From 0d3122e4896d3a328d2839a00f19267355785776 Mon Sep 17 00:00:00 2001 From: Bishwas Praveen Date: Mon, 22 Jan 2024 11:07:52 -0600 Subject: [PATCH 1/7] added the source field to the display list on admin panel --- feedback/admin.py | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/feedback/admin.py b/feedback/admin.py index 884acc0c..97f58a90 100644 --- a/feedback/admin.py +++ b/feedback/admin.py @@ -5,7 +5,7 @@ @admin.register(Feedback) class ContactFormAdmin(admin.ModelAdmin): - list_display = ["name", "email", "subject", "comments"] + list_display = ["name", "email", "subject", "comments", "source"] search_fields = ["name", "email"] list_filter = ["subject"] From 84a136ee7288d1c7d5e5cd1d9d332c5aa5c242b5 Mon Sep 17 00:00:00 2001 From: Bishwas Praveen Date: Mon, 22 Jan 2024 11:08:20 -0600 Subject: [PATCH 2/7] added the source field to the updated model --- feedback/models.py | 1 + 1 file changed, 1 insertion(+) diff --git a/feedback/models.py b/feedback/models.py index bc82b41a..f1e475f6 100644 --- a/feedback/models.py +++ b/feedback/models.py @@ -6,6 +6,7 @@ class Feedback(models.Model): email = models.EmailField() subject = models.CharField(max_length=400) comments = models.TextField() + source = models.CharField(max_length=50, default="SDE") class Meta: verbose_name = "Feedback Response" From 53ed13a192f6ffc380c558378ff03557186c82d7 Mon Sep 17 00:00:00 2001 From: Bishwas Praveen Date: Mon, 22 Jan 2024 11:08:43 -0600 Subject: [PATCH 3/7] added source into serializer --- feedback/serializers.py | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/feedback/serializers.py b/feedback/serializers.py index 2903a851..faf2415e 100644 --- a/feedback/serializers.py +++ b/feedback/serializers.py @@ -6,7 +6,7 @@ class FeedbackSerializer(serializers.ModelSerializer): class Meta: model = Feedback - fields = ["name", "email", "subject", "comments"] + fields = ["name", "email", "subject", "comments", "source"] class ContentCurationRequestSerializer(serializers.ModelSerializer): From fc9337dca7745a262a60c7fd13d69db65cc2cff5 Mon Sep 17 00:00:00 2001 From: Bishwas Praveen Date: Mon, 22 Jan 2024 11:09:01 -0600 Subject: [PATCH 4/7] updated migration file --- feedback/migrations/0003_feedback_source.py | 17 +++++++++++++++++ 1 file changed, 17 insertions(+) create mode 100644 feedback/migrations/0003_feedback_source.py diff --git a/feedback/migrations/0003_feedback_source.py b/feedback/migrations/0003_feedback_source.py new file mode 100644 index 00000000..604a2c68 --- /dev/null +++ b/feedback/migrations/0003_feedback_source.py @@ -0,0 +1,17 @@ +# Generated by Django 4.2.6 on 2024-01-22 17:00 + +from django.db import migrations, models + + +class Migration(migrations.Migration): + dependencies = [ + ("feedback", "0002_alter_contentcurationrequest_additional_info"), + ] + + operations = [ + migrations.AddField( + model_name="feedback", + name="source", + field=models.CharField(default="SDE", max_length=50), + ), + ] From 25ce8b66771da12c9554a8df130ba40ed08a9d23 Mon Sep 17 00:00:00 2001 From: Bishwas Praveen Date: Mon, 22 Jan 2024 11:17:13 -0600 Subject: [PATCH 5/7] deleted the notebook which was accidentally added to the PR --- jupyter_notebooks/SciX-API-Experiments.ipynb | 11764 ----------------- 1 file changed, 11764 deletions(-) delete mode 100644 jupyter_notebooks/SciX-API-Experiments.ipynb diff --git a/jupyter_notebooks/SciX-API-Experiments.ipynb b/jupyter_notebooks/SciX-API-Experiments.ipynb deleted file mode 100644 index 1a306cb3..00000000 --- a/jupyter_notebooks/SciX-API-Experiments.ipynb +++ /dev/null @@ -1,11764 +0,0 @@ -{ - 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"* ALPN: curl offers h2,http/1.1\n", - "* (304) (OUT), TLS handshake, Client hello (1):\n", - "} [319 bytes data]\n", - "* CAfile: /etc/ssl/cert.pem\n", - "* CApath: none\n", - "* (304) (IN), TLS handshake, Server hello (2):\n", - "{ [122 bytes data]\n", - "* (304) (IN), TLS handshake, Unknown (8):\n", - "{ [19 bytes data]\n", - "* (304) (IN), TLS handshake, Certificate (11):\n", - "{ [4969 bytes data]\n", - "* (304) (IN), TLS handshake, CERT verify (15):\n", - "{ [264 bytes data]\n", - "* (304) (IN), TLS handshake, Finished (20):\n", - "{ [36 bytes data]\n", - "* (304) (OUT), TLS handshake, Finished (20):\n", - "} [36 bytes data]\n", - "* SSL connection using TLSv1.3 / AEAD-AES128-GCM-SHA256\n", - "* ALPN: server accepted h2\n", - "* Server certificate:\n", - "* subject: CN=scixplorer.org\n", - "* start date: Nov 6 00:00:00 2023 GMT\n", - "* expire date: Dec 4 23:59:59 2024 GMT\n", - "* subjectAltName: host \"scixplorer.org\" matched cert's \"scixplorer.org\"\n", - "* issuer: C=US; O=Amazon; CN=Amazon RSA 2048 M02\n", - "* SSL certificate verify ok.\n", - "* using HTTP/2\n", - "* [HTTP/2] [1] OPENED stream for https://scixplorer.org/v1/search/query?q=star\n", - "* [HTTP/2] [1] [:method: GET]\n", - "* [HTTP/2] [1] [:scheme: https]\n", - "* [HTTP/2] [1] [:authority: scixplorer.org]\n", - "* [HTTP/2] [1] [:path: /v1/search/query?q=star]\n", - "* [HTTP/2] [1] [user-agent: curl/8.4.0]\n", - "* [HTTP/2] [1] [accept: */*]\n", - "* [HTTP/2] [1] [authorization: Bearer fmHQTYXdYU8Cl4yjs84fiuY3IYqoKqIO6RrXJngy]\n", - "> GET /v1/search/query?q=star HTTP/2\n", - "> Host: scixplorer.org\n", - "> User-Agent: curl/8.4.0\n", - "> Accept: */*\n", - "> Authorization: Bearer fmHQTYXdYU8Cl4yjs84fiuY3IYqoKqIO6RrXJngy\n", - "> \n", - "< HTTP/2 200 \n", - "< date: Thu, 18 Jan 2024 18:22:16 GMT\n", - "< content-type: application/json\n", - "< content-length: 648\n", - "< access-control-allow-origin: http://0.0.0.0:8000, http://adsabs.harvard.edu, http://adsx.cfa.harvard.edu:8888, http://hourly.adslabs.org, http://localhost:8000, http://playground.scixplorer.org, http://scixplorer.org, http://testing.scixlabs.org, http://ui.adsabs.harvard.edu, http://ui.adslabs.org, http://www.scixplorer.org, https://arxiv.org, https://beta.arxiv.org, https://demo.adsabs.harvard.edu, https://dev.adsabs.harvard.edu, https://dev.scixplorer.org, https://devui.adsabs.harvard.edu, https://experimental-bumblebee.us-east-1.elasticbeanstalk.com, https://playground.scixplorer.org, https://prod.adsabs.harvard.edu, https://scixplorer.org, https://staging-bumblebee.elasticbeanstalk.com, https://staging-bumblebee.us-east-1.elasticbeanstalk.com, https://testing.scixlabs.org, https://ui.adsabs.harvard.edu, https://www.scixplorer.org\n", - "< access-control-allow-methods: DELETE, GET, OPTIONS, POST, PUT\n", - "< access-control-allow-headers: Accept, Authorization, Content-Type, Orcid-Authorization, X-BB-Api-Client-Version, X-CSRFToken\n", - "< access-control-allow-credentials: true\n", - "< vary: Origin\n", - "< x-ratelimit-limit: 5000\n", - "< x-ratelimit-remaining: 4999\n", - "< x-ratelimit-reset: 1705688536\n", - "< retry-after: 86399\n", - "< set-cookie: session=.eJyrVopPK0otzlCyKikqTdVRis9MUbKqVlJIUrJS8s1yNPULca2KcvHKjgrxNIgKccv0zXLK8Q9xLPc1iiz3rcrJ9nOPNPZzibRVqgXqLUgtyk3MS80rgZlWWpxaBDZRydTAxMxEqRYA0rojig.ZalsWA.HovDzCyXZ5BnjPN55v2KQpVJ6rg; Expires=Sat, 18-Jan-2025 00:22:16 GMT; Secure; HttpOnly; Path=/; SameSite=None\n", - "< \n", - "{ [648 bytes data]\n", - "\n", - "100 648 100 648 0 0 757 0 --:--:-- --:--:-- --:--:-- 758\n", - "* Connection #0 to host scixplorer.org left intact\n", - "\n" - ] - } - ], - "source": [ - "process = subprocess.run(command, shell=True, stdout=subprocess.PIPE, stderr=subprocess.PIPE, text=True)\n", - "\n", - "print(process.stdout)\n", - "print(process.stderr)" - ] - }, - { - "cell_type": "code", - "execution_count": 14, - "id": "6849e200-08c3-4d1a-825a-a1ad97a4c8a1", - "metadata": {}, - "outputs": [ - { - "data": { - "text/plain": [ - "{'responseHeader': {'status': 0,\n", - " 'QTime': 485,\n", - " 'params': {'q': 'mouse liver',\n", - " 'fl': 'title,bibcode,links_data,author,abstract',\n", - " 'start': '0',\n", - " 'internal_logging_params': 'X-Amzn-Trace-Id=Root=1-65a9929f-168ffa1a36539a3f37553e08',\n", - " 'sort': 'score desc',\n", - " 'rows': '2000',\n", - " 'wt': 'json'}},\n", - " 'response': {'numFound': 6414,\n", - " 'start': 0,\n", - " 'docs': [{'bibcode': '2007PNAS..104.1488V',\n", - " 'abstract': 'Protein phosphorylation is a complex network of signaling and regulatory events that affects virtually every cellular process. Our understanding of the nature of this network as a whole remains limited, largely because of an array of technical challenges in the isolation and high-throughput sequencing of phosphorylated species. In the present work, we demonstrate that a combination of tandem phosphopeptide enrichment methods, high performance MS, and optimized database search/data filtering strategies is a powerful tool for surveying the phosphoproteome. Using our integrated analytical platform, we report the identification of 5,635 nonredundant phosphorylation sites from 2,328 proteins from mouse liver. From this list of sites, we extracted both novel and known motifs for specific Ser/Thr kinases including a \"dipolar\" motif. We also found that C-terminal phosphorylation was more frequent than at any other location and that the distribution of potential kinases for these sites was unique. Finally, we identified double phosphorylation motifs that may be involved in ordered phosphorylation.',\n", - " 'author': ['Villén, Judit',\n", - " 'Beausoleil, Sean A.',\n", - " 'Gerber, Scott A.',\n", - " 'Gygi, Steven P.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/104/5/1488\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0609836104\"}'],\n", - " 'title': ['Large-scale phosphorylation analysis of mouse liver']},\n", - " {'bibcode': '2008Sci...321..699A',\n", - " 'abstract': 'Induced pluripotent stem (iPS) cells have been generated from mouse and human fibroblasts by the retroviral transduction of four transcription factors. However, the cell origins and molecular mechanisms of iPS cell induction remain elusive. This report describes the generation of iPS cells from adult mouse hepatocytes and gastric epithelial cells. These iPS cell clones appear to be equivalent to embryonic stem cells in gene expression and are competent to generate germline chimeras. Genetic lineage tracings show that liver-derived iPS cells are derived from albumin-expressing cells. No common retroviral integration sites are found among multiple clones. These data suggest that iPS cells are generated by direct reprogramming of lineage-committed somatic cells and that retroviral integration into specific sites is not required.',\n", - " 'author': ['Aoi, Takashi',\n", - " 'Yae, Kojiro',\n", - " 'Nakagawa, Masato',\n", - " 'Ichisaka, Tomoko',\n", - " 'Okita, Keisuke',\n", - " 'Takahashi, Kazutoshi',\n", - " 'Chiba, Tsutomu',\n", - " 'Yamanaka, Shinya'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.1154884\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.1154884\"}'],\n", - " 'title': ['Generation of Pluripotent Stem Cells from Adult Mouse Liver and Stomach Cells']},\n", - " {'bibcode': '2014Natur.514..380X',\n", - " 'abstract': 'The study of cancer genes in mouse models has traditionally relied on genetically-engineered strains made via transgenesis or gene targeting in embryonic stem cells. Here we describe a new method of cancer model generation using the CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins) system in vivo in wild-type mice. We used hydrodynamic injection to deliver a CRISPR plasmid DNA expressing Cas9 and single guide RNAs (sgRNAs) to the liver that directly target the tumour suppressor genes Pten (ref. 5) and p53 (also known as TP53 and Trp53) (ref. 6), alone and in combination. CRISPR-mediated Pten mutation led to elevated Akt phosphorylation and lipid accumulation in hepatocytes, phenocopying the effects of deletion of the gene using Cre-LoxP technology. Simultaneous targeting of Pten and p53 induced liver tumours that mimicked those caused by Cre-loxP-mediated deletion of Pten and p53. DNA sequencing of liver and tumour tissue revealed insertion or deletion mutations of the tumour suppressor genes, including bi-allelic mutations of both Pten and p53 in tumours. Furthermore, co-injection of Cas9 plasmids harbouring sgRNAs targeting the β-catenin gene and a single-stranded DNA oligonucleotide donor carrying activating point mutations led to the generation of hepatocytes with nuclear localization of β-catenin. This study demonstrates the feasibility of direct mutation of tumour suppressor genes and oncogenes in the liver using the CRISPR/Cas system, which presents a new avenue for rapid development of liver cancer models and functional genomics.',\n", - " 'author': ['Xue, Wen',\n", - " 'Chen, Sidi',\n", - " 'Yin, Hao',\n", - " 'Tammela, Tuomas',\n", - " 'Papagiannakopoulos, Thales',\n", - " 'Joshi, Nikhil S.',\n", - " 'Cai, Wenxin',\n", - " 'Yang, Gillian',\n", - " 'Bronson, Roderick',\n", - " 'Crowley, Denise G.',\n", - " 'Zhang, Feng',\n", - " 'Anderson, Daniel G.',\n", - " 'Sharp, Phillip A.',\n", - " 'Jacks, Tyler'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature13589\"}'],\n", - " 'title': ['CRISPR-mediated direct mutation of cancer genes in the mouse liver']},\n", - " {'bibcode': '2021zndo...4694749M',\n", - " 'abstract': 'Analysis of snRNA-seq2 data coming from 3 months old mouse liver, dissecting the influence ploidy has on gene expression.',\n", - " 'author': ['Mrichter23', 'Laboratory, Martinez-Jimenez'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.5281/zenodo.4694749\"}'],\n", - " 'title': ['snRNA-seq2 analysis pipeline']},\n", - " {'bibcode': '2003PNAS..100.6795T',\n", - " 'abstract': 'A main oscillator in the suprachiasmatic nucleus (SCN) conveys circadian information to the peripheral clock systems for the regulation of fundamental physiological functions. Although polysynaptic autonomic neural pathways between the SCN and the liver were observed in rats, whether activation of the sympathetic nervous system entrains clock gene expression in the liver has yet to be understood. To assess sympathetic innervation from the SCN to liver tissue, we investigated whether injection of adrenaline/noradrenaline (epinephrine/norepinephrine) or sympathetic nerve stimulation could induce mPer gene expression in mouse liver. Acute administration of adrenaline or noradrenaline increased mPer1 but not mPer2 expression in the liver of mice in vivo and in hepatic slices in vitro. Electrical stimulation of the sympathetic nerves or adrenaline injection caused an elevation of bioluminescence in the liver area of transgenic mice carrying mPer1 promoter-luciferase. Under a light-dark cycle, destruction of the SCN flattened the daily rhythms of not only mPer1, mPer2, and mBmal1 genes but also noradrenaline content in the liver. Daily injection of adrenaline, administered at a fixed time for 6 days, recovered oscillations of mPer2 and mBmal1 gene expression in the liver of mice with SCN lesion on day 7. Sympathetic nerve denervation by 6-hydroxydopamine flattened the daily rhythm of mPer1 and mPer2 gene expression. Thus, on the basis of the present results, activation of the sympathetic nerves through noradrenaline and/or adrenaline release was a factor controlling the peripheral clock.',\n", - " 'author': ['Terazono, Hideyuki',\n", - " 'Mutoh, Tatsushi',\n", - " 'Yamaguchi, Shun',\n", - " 'Kobayashi, Masaki',\n", - " 'Akiyama, Masashi',\n", - " 'Udo, Rhyuta',\n", - " 'Ohdo, Shigehiro',\n", - " 'Okamura, Hitoshi',\n", - " 'Shibata, Shigenobu'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/100/11/6795\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0936797100\"}'],\n", - " 'title': ['Adrenergic regulation of clock gene expression in mouse liver']},\n", - " {'bibcode': '2014Natur.508...93Z',\n", - " 'abstract': 'Human induced pluripotent stem cells (iPSCs) have the capability of revolutionizing research and therapy of liver diseases by providing a source of hepatocytes for autologous cell therapy and disease modelling. However, despite progress in advancing the differentiation of iPSCs into hepatocytes (iPSC-Heps) in vitro, cells that replicate the ability of human primary adult hepatocytes (aHeps) to proliferate extensively in vivo have not been reported. This deficiency has hampered efforts to recreate human liver diseases in mice, and has cast doubt on the potential of iPSC-Heps for liver cell therapy. The reason is that extensive post-transplant expansion is needed to establish and sustain a therapeutically effective liver cell mass in patients, a lesson learned from clinical trials of aHep transplantation. Here, as a solution to this problem, we report the generation of human fibroblast-derived hepatocytes that can repopulate mouse livers. Unlike current protocols for deriving hepatocytes from human fibroblasts, ours did not generate iPSCs but cut short reprogramming to pluripotency to generate an induced multipotent progenitor cell (iMPC) state from which endoderm progenitor cells and subsequently hepatocytes (iMPC-Heps) could be efficiently differentiated. For this purpose we identified small molecules that aided endoderm and hepatocyte differentiation without compromising proliferation. After transplantation into an immune-deficient mouse model of human liver failure, iMPC-Heps proliferated extensively and acquired levels of hepatocyte function similar to those of aHeps. Unfractionated iMPC-Heps did not form tumours, most probably because they never entered a pluripotent state. Our results establish the feasibility of significant liver repopulation of mice with human hepatocytes generated in vitro, which removes a long-standing roadblock on the path to autologous liver cell therapy.',\n", - " 'author': ['Zhu, Saiyong',\n", - " 'Rezvani, Milad',\n", - " 'Harbell, Jack',\n", - " 'Mattis, Aras N.',\n", - " 'Wolfe, Alan R.',\n", - " 'Benet, Leslie Z.',\n", - " 'Willenbring, Holger',\n", - " 'Ding, Sheng'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature13020\"}'],\n", - " 'title': ['Mouse liver repopulation with hepatocytes generated from human fibroblasts']},\n", - " {'bibcode': '2018NatCo...9.1553W',\n", - " 'abstract': 'As a circadian organ, liver executes diverse functions in different phase of the circadian clock. This process is believed to be driven by a transcription program. Here, we present a transcription factor (TF) DNA-binding activity-centered multi-dimensional proteomics landscape of the mouse liver, which includes DNA-binding profiles of different TFs, phosphorylation, and ubiquitylation patterns, the nuclear sub-proteome, the whole proteome as well as the transcriptome, to portray the hierarchical circadian clock network of this tissue. The TF DNA-binding activity indicates diurnal oscillation in four major pathways, namely the immune response, glucose metabolism, fatty acid metabolism, and the cell cycle. We also isolate the mouse liver Kupffer cells and measure their proteomes during the circadian cycle to reveal a cell-type resolved circadian clock. These comprehensive data sets provide a rich data resource for the understanding of mouse hepatic physiology around the circadian clock.',\n", - " 'author': ['Wang, Yunzhi',\n", - " 'Song, Lei',\n", - " 'Liu, Mingwei',\n", - " 'Ge, Rui',\n", - " 'Zhou, Quan',\n", - " 'Liu, Wanlin',\n", - " 'Li, Ruiyang',\n", - " 'Qie, Jingbo',\n", - " 'Zhen, Bei',\n", - " 'Wang, Yi',\n", - " 'He, Fuchu',\n", - " 'Qin, Jun',\n", - " 'Ding, Chen'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41467-018-03898-2\"}'],\n", - " 'title': ['A proteomics landscape of circadian clock in mouse liver']},\n", - " {'bibcode': '2016PLoSO..1152877J',\n", - " 'author': ['Jonscher, Karen R.',\n", - " 'Alfonso-Garcia, Alba',\n", - " 'Suhalim, Jeffrey L.',\n", - " 'Orlicky, David J.',\n", - " 'Potma, Eric O.',\n", - " 'Ferguson, Virginia L.',\n", - " 'Bouxsein, Mary L.',\n", - " 'Bateman, Ted A.',\n", - " 'Stodieck, Louis S.',\n", - " 'Levi, Moshe',\n", - " 'Friedman, Jacob E.',\n", - " 'Gridley, Daila S.',\n", - " 'Pecaut, Michael J.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0152877\"}'],\n", - " 'title': ['Spaceflight Activates Lipotoxic Pathways in Mouse Liver']},\n", - " {'bibcode': '2012EnST...4610758W',\n", - " 'author': ['Wu, Bing',\n", - " 'Liu, Su',\n", - " 'Guo, Xuechao',\n", - " 'Zhang, Yan',\n", - " 'Zhang, Xuxiang',\n", - " 'Li, Mei',\n", - " 'Cheng, Shupei'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1021%2Fes301804t\"}'],\n", - " 'title': ['Responses of Mouse Liver to Dechlorane Plus Exposure by Integrative Transcriptomic and Metabonomic Studies']},\n", - " {'bibcode': '1981Natur.291..340H',\n", - " 'abstract': \"Glucocorticoid hormones play an important part in the regulation of many essential metabolic processes1. These include the synthesis of stress-related `acute-phase' proteins2 and the timing of developmental events in numerous tissues including fetal lung, liver and intestine, and adult mammary gland1. Among the proteins that are induced by glucocorticoids during stress and fetal development are the metallothioneins (MT)3-6. These small, cysteine-rich proteins are found primarily in the liver and kidney. They bind heavy metals and are thought to be involved in zinc homeostasis and heavy metal detoxification7. We show here that the accumulation of MT mRNA in mouse liver in response to the synthetic glucocorticoid, dexamethasone, is due to transcriptional activation of the metallothionein gene.\",\n", - " 'author': ['Hager, Lisa J.', 'Palmiter, Richard D.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F291340a0\"}'],\n", - " 'title': ['Transcriptional regulation of mouse liver metallothionein-I gene by glucocorticoids']},\n", - " {'bibcode': '1994Sci...263.1149R',\n", - " 'abstract': 'Adult liver has the unusual ability to fully regenerate after injury. Although regeneration is accomplished by the division of mature hepatocytes, the replicative potential of these cells is unknown. Here, the replicative capacity of adult liver cells and their medical usefulness as donor cells for transplantation were investigated by transfer of adult mouse liver cells into transgenic mice that display an endogenous defect in hepatic growth potential and function. The transplanted liver cell populations replaced up to 80 percent of the diseased recipient liver. These findings demonstrate the enormous growth potential of adult hepatocytes, indicating the feasibility of liver cell transplantation as a method to replace lost or diseased hepatic parenchyma.',\n", - " 'author': ['Rhim, Jonathan A.',\n", - " 'Sandgren, Eric P.',\n", - " 'Degen, Jay L.',\n", - " 'Palmiter, Richard D.',\n", - " 'Brinster, Ralph L.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.8108734\"}'],\n", - " 'title': ['Replacement of Diseased Mouse Liver by Hepatic Cell Transplantation']},\n", - " {'bibcode': '1963Sci...140.1408H',\n", - " 'abstract': 'The rapidly labeled RNA from both the nuclei and cytoplasm of mouse liver cells can be bound specifically to mouse DNA. The bound fraction differs in base composition and metabolic stability from the bulk RNA. There is considerable cross reaction between this RNA and the DNA obtained from calf thymus.',\n", - " 'author': ['Hoyer, Bill H.', 'McCarthy, Brian J.', 'Bolton, Ellis T.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.jstor.org/stable/1711431?origin=ads\"}'],\n", - " 'title': ['Complementary RNA in Nucleus and Cytoplasm of Mouse Liver Cells']},\n", - " {'bibcode': '2011Sci...331.1315F',\n", - " 'abstract': 'Disruption of the circadian clock exacerbates metabolic diseases, including obesity and diabetes. We show that histone deacetylase 3 (HDAC3) recruitment to the genome displays a circadian rhythm in mouse liver. Histone acetylation is inversely related to HDAC3 binding, and this rhythm is lost when HDAC3 is absent. Although amounts of HDAC3 are constant, its genomic recruitment in liver corresponds to the expression pattern of the circadian nuclear receptor Rev-erbα. Rev-erbα colocalizes with HDAC3 near genes regulating lipid metabolism, and deletion of HDAC3 or Rev-erbα in mouse liver causes hepatic steatosis. Thus, genomic recruitment of HDAC3 by Rev-erbα directs a circadian rhythm of histone acetylation and gene expression required for normal hepatic lipid homeostasis.',\n", - " 'author': ['Feng, Dan',\n", - " 'Liu, Tao',\n", - " 'Sun, Zheng',\n", - " 'Bugge, Anne',\n", - " 'Mullican, Shannon E.',\n", - " 'Alenghat, Theresa',\n", - " 'Liu, X. Shirley',\n", - " 'Lazar, Mitchell A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.1198125\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.1198125\"}'],\n", - " 'title': ['A Circadian Rhythm Orchestrated by Histone Deacetylase 3 Controls Hepatic Lipid Metabolism']},\n", - " {'bibcode': '2012PLoSO...746835K',\n", - " 'author': ['Korenčič, Anja',\n", - " 'Bordyugov, Grigory',\n", - " 'Košir, Rok',\n", - " 'Rozman, Damjana',\n", - " 'Goličnik, Marko',\n", - " 'Herzel, Hanspeter'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0046835\"}'],\n", - " 'title': ['The Interplay of cis-Regulatory Elements Rules Circadian Rhythms in Mouse Liver']},\n", - " {'bibcode': '2014PNAS..111..167M',\n", - " 'abstract': 'Circadian clocks orchestrate daily rhythms in behavior and physiology using temporal regulation of gene expression to control core clock genes and rhythmic output programs. Although transcription regulation was shown to drive extensive diurnal mRNA rhythms, less is known about the proteins. Here, we provide a proteome-wide study of rhythmic protein accumulation in mouse liver, showing that proteins preferentially accumulate in the morning and during the night. About one-half of these rhythmic proteins could not be explained by rhythmic mRNAs, suggesting that translational or posttranslational regulation plays an important role. Moreover, such rhythms involved many secreted proteins and were clock-independent. Hence, these findings indicate that feeding behavior might determine the rhythmic functions of circulating proteins in the blood.',\n", - " 'author': ['Mauvoisin, Daniel',\n", - " 'Wang, Jingkui',\n", - " 'Jouffe, Céline',\n", - " 'Martin, Eva',\n", - " 'Atger, Florian',\n", - " 'Waridel, Patrice',\n", - " 'Quadroni, Manfredo',\n", - " 'Gachon, Frédéric',\n", - " 'Naef, Felix'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/111/1/167\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1314066111\"}'],\n", - " 'title': ['Circadian clock-dependent and -independent rhythmic proteomes implement distinct diurnal functions in mouse liver']},\n", - " {'bibcode': '1970Natur.225..462W',\n", - " 'abstract': 'TETRAPARENTAL mice are produced by fusing two eight-cell stage embryos. If the two embryos originate from different inbred strains, allelic differences between the strains produce mosaic patterns in the adult tetraparental which make possible inferences about development1-3. Mintz and Baker have elegantly used this concept to confirm that somatic muscle cells fuse during development4. They used an isozyme variant of isocitrate dehydrogenase, and found hybrid enzyme patterns in somatic muscle tissue. Only parental patterns were demonstrable in other tissues, such as the liver.',\n", - " 'author': ['Wegmann, Thomas G.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F225462a0\"}'],\n", - " 'title': ['Enzyme Patterns in Tetraparental Mouse Liver']},\n", - " {'bibcode': '1987Sci...237.1309R',\n", - " 'abstract': 'The validity of mouse liver tumor end points in assessing the potential hazards of chemical exposure to humans is a controversial but important issue, since liver neoplasia in mice is the most frequent tumor target tissue end point in 2-year carcinogenicity studies. The ability to distinguish between promotion of background tumors versus a genotoxic mechanism of tumor initiation by chemical treatment would aid in the interpretation of rodent carcinogenesis data. Activated oncogenes in chemically induced and spontaneously occurring mouse liver tumors were examined and compared as one approach to determine the mechanism by which chemical treatment caused an increased incidence of mouse liver tumors. Data suggest that furan and furfural caused an increased incidence in mouse liver tumors at least in part by induction of novel weakly activating point mutations in ras genes even though both chemicals did not induce mutations in Salmonella assays. In addition to ras oncogenes, two activated raf genes and four non-ras transforming genes were detected. The B6C3F1 mouse liver may thus provide a sensitive assay system to detect various classes of proto-oncogenes that are susceptible to activation by carcinogenic insult. As illustrated with mouse liver tumors, analysis of activated oncogenes in spontaneously occurring and chemically induced rodent tumors will provide information at a molecular level to aid in the use of rodent carcinogenesis data for risk assessment.',\n", - " 'author': ['Reynolds, Steven H.',\n", - " 'Stowers, Shari J.',\n", - " 'Patterson, Rachel M.',\n", - " 'Maronpot, Robert R.',\n", - " 'Aaronson, Stuart A.',\n", - " 'Anderson, Marshall W.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.3629242\"}'],\n", - " 'title': ['Activated Oncogenes in B6C3F1 Mouse Liver Tumors: Implications for Risk Assessment']},\n", - " {'bibcode': '1995PNAS...92.4942R',\n", - " 'abstract': 'We have developed a system for studying hepatocellular growth potential in which liver cells are introduced into the diseased livers of albumin-urokinase (Alb-uPA) transgenic mice. To use this system to study xenogeneic cell transplantation, rat liver cells were introduced into immunotolerant Alb-uPA transgenic mice. In regenerated recipient livers, up to 100% of hepatocellular gene expression was of rat origin, demonstrating the creation of a functional mouse liver in which parenchyma is derived from xenogeneic (rat) hepatocytes. Immunotolerant Alb-uPA transgenic mice provide a tool for studying hepatocellular biology of any species, including humans, in a controlled experimental setting.',\n", - " 'author': ['Rhim, Jonathan A.',\n", - " 'Sandgren, Eric P.',\n", - " 'Palmiter, Richard D.',\n", - " 'Brinster, Ralph L.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/92/11/4942\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/92/11/4942\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/92/11/4942\"}'],\n", - " 'title': ['Complete reconstitution of mouse liver with xenogeneic hepatocytes.']},\n", - " {'bibcode': '1963Natur.197.1106N',\n", - " 'abstract': 'INCUBATION of mitochondria isolated from normal cells or cancer cells liberate two substances into the medium-a lipoprotein arid adenine nucleotide. When separated from the mitochondria and added to the soluble cell fraction, these have been found to exert a highly stimulating effect on glycolysis1,2. In the case of mitochondria from normal cells, liberation of both these factors has been shown to depend on reversible changes in configuration of mitochondrial membranes. Pre-incubation of mitochondria with adenosine triphosphate, magnesium ions or ethylenediamine tetraacetic acid-that is, agents provoking shrinkage of mitochondria-proved to diminish or to prevent liberation of the stimulating factors and their retention within the mitochondria. On the contrary, pre-incubation with inorganic phosphate, calcium ions or potassium chloride, known to cause membrane relaxation and swelling of mitochondria, increased the release of the stimulating factors into the medium1,3.',\n", - " 'author': ['Neifakh, S. A.', 'Kazakova, T. B.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F1971106a0\"}'],\n", - " 'title': ['Actomyosin-like Protein in Mitochondria of the Mouse Liver']},\n", - " {'bibcode': '2009PLoSO...4.6909H',\n", - " 'author': ['Hirao, Akiko',\n", - " 'Tahara, Yu',\n", - " 'Kimura, Ichiro',\n", - " 'Shibata, Shigenobu'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0006909\"}'],\n", - " 'title': ['A Balanced Diet Is Necessary for Proper Entrainment Signals of the Mouse Liver Clock']},\n", - " {'bibcode': '2008JRadR..49...29R',\n", - " 'author': ['Roudkenar, Mehryar Habibi',\n", - " 'Li, Li',\n", - " 'Baba, Taisuke',\n", - " 'Kuwahara, Yoshikazu',\n", - " 'Nakagawa, Hironobu',\n", - " 'Wang, Lu',\n", - " 'Kasaoka, Satoshi',\n", - " 'Ohkubo, Yasuhito',\n", - " 'Ono, Koji',\n", - " 'Fukumoto, Manabu'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1269%2Fjrr.07078\"}'],\n", - " 'title': ['Gene Expression Profiles in Mouse Liver Cells after Exposure to Different Types of Radiation']},\n", - " {'bibcode': '2009Natur.458.1131S',\n", - " 'abstract': 'The intracellular storage and utilization of lipids are critical to maintain cellular energy homeostasis. During nutrient deprivation, cellular lipids stored as triglycerides in lipid droplets are hydrolysed into fatty acids for energy. A second cellular response to starvation is the induction of autophagy, which delivers intracellular proteins and organelles sequestered in double-membrane vesicles (autophagosomes) to lysosomes for degradation and use as an energy source. Lipolysis and autophagy share similarities in regulation and function but are not known to be interrelated. Here we show a previously unknown function for autophagy in regulating intracellular lipid stores (macrolipophagy). Lipid droplets and autophagic components associated during nutrient deprivation, and inhibition of autophagy in cultured hepatocytes and mouse liver increased triglyceride storage in lipid droplets. This study identifies a critical function for autophagy in lipid metabolism that could have important implications for human diseases with lipid over-accumulation such as those that comprise the metabolic syndrome.',\n", - " 'author': ['Singh, Rajat',\n", - " 'Kaushik, Susmita',\n", - " 'Wang, Yongjun',\n", - " 'Xiang, Youqing',\n", - " 'Novak, Inna',\n", - " 'Komatsu, Masaaki',\n", - " 'Tanaka, Keiji',\n", - " 'Cuervo, Ana Maria',\n", - " 'Czaja, Mark J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature07976\"}'],\n", - " 'title': ['Autophagy regulates lipid metabolism']},\n", - " {'bibcode': '2015PNAS..112E6579A',\n", - " 'abstract': \"Rhythmic gene regulation in mouse liver results from an intertwined relationship between feeding cycles and the circadian clock. Significant efforts have been made to understand this interaction but a complete picture of the resulting diurnal transcription-translation processes is still missing. Through the simultaneous quantification of temporal transcription, accumulation, and translation of mRNA in the liver, we investigated the regulatory landscape of mice with intact or deficient circadian clock subjected to different feeding regimens. We showed that circadian clock and feeding rhythms coordinate rhythmic transcription to drive downstream rhythmic mRNA accumulation and translation. However, a subset of genes harboring 5'-Terminal Oligo Pyrimidine tract or Translation Initiator of Short 5'-UTR elements encoding proteins involved in translation and mitochondrial activity, respectively, present a transcription-independent rhythmic translation mainly regulated by feeding.\",\n", - " 'author': ['Atger, Florian',\n", - " 'Gobet, Cédric',\n", - " 'Marquis, Julien',\n", - " 'Martin, Eva',\n", - " 'Wang, Jingkui',\n", - " 'Weger, Benjamin',\n", - " 'Lefebvre, Grégory',\n", - " 'Descombes, Patrick',\n", - " 'Naef, Felix',\n", - " 'Gachon, Frédéric'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/112/47/E6579\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1515308112\"}'],\n", - " 'title': ['Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver']},\n", - " {'bibcode': '2019ScTEn.655.1334Z',\n", - " 'author': ['Zhang, Rui', 'Zhang, Xun', 'Gao, Sichen', 'Liu, Rutao'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.scitotenv.2018.11.295\"}'],\n", - " 'title': ['Assessing the in vitro and in vivo toxicity of ultrafine carbon black to mouse liver']},\n", - " {'bibcode': '2013ITM....49..394G',\n", - " 'author': ['Gabbasov, Raul',\n", - " 'Cherepanov, Valery',\n", - " 'Chuev, Mikhail',\n", - " 'Polikarpov, Mikhail',\n", - " 'Nikitin, Maxim',\n", - " 'Deyev, Sergey',\n", - " 'Panchenko, Vladislav'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1109%2FTMAG.2012.2226148\"}'],\n", - " 'title': ['Biodegradation of Magnetic Nanoparticles in Mouse Liver From Combined Analysis of Mössbauer and Magnetization Data']},\n", - " {'bibcode': '2015Natur.520..186R',\n", - " 'abstract': 'The RNA-guided endonuclease Cas9 has emerged as a versatile genome-editing platform. However, the size of the commonly used Cas9 from Streptococcus pyogenes (SpCas9) limits its utility for basic research and therapeutic applications that use the highly versatile adeno-associated virus (AAV) delivery vehicle. Here, we characterize six smaller Cas9 orthologues and show that Cas9 from Staphylococcus aureus (SaCas9) can edit the genome with efficiencies similar to those of SpCas9, while being more than 1 kilobase shorter. We packaged SaCas9 and its single guide RNA expression cassette into a single AAV vector and targeted the cholesterol regulatory gene Pcsk9 in the mouse liver. Within one week of injection, we observed >40% gene modification, accompanied by significant reductions in serum Pcsk9 and total cholesterol levels. We further assess the genome-wide targeting specificity of SaCas9 and SpCas9 using BLESS, and demonstrate that SaCas9-mediated in vivo genome editing has the potential to be efficient and specific.',\n", - " 'author': ['Ran, F. Ann',\n", - " 'Cong, Le',\n", - " 'Yan, Winston X.',\n", - " 'Scott, David A.',\n", - " 'Gootenberg, Jonathan S.',\n", - " 'Kriz, Andrea J.',\n", - " 'Zetsche, Bernd',\n", - " 'Shalem, Ophir',\n", - " 'Wu, Xuebing',\n", - " 'Makarova, Kira S.',\n", - " 'Koonin, Eugene V.',\n", - " 'Sharp, Phillip A.',\n", - " 'Zhang, Feng'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature14299\"}'],\n", - " 'title': ['In vivo genome editing using Staphylococcus aureus Cas9']},\n", - " {'bibcode': '2002PNAS...9916881W',\n", - " 'abstract': 'The Forkhead Box (Fox) proteins are an extensive family of transcription factors that shares homology in the winged helix DNA-binding domain and whose members play essential roles in cellular proliferation, differentiation, transformation, longevity, and metabolic homeostasis. Liver regeneration studies with transgenic mice demonstrated that FoxM1B regulates the onset of hepatocyte DNA replication and mitosis by stimulating expression of cell cycle genes. Here, we demonstrate that albumin-promoter-driven Cre recombinase-mediated hepatocyte-specific deletion of the Foxm1b Floxed (fl) targeted allele resulted in significant reduction in hepatocyte DNA replication and inhibition of mitosis after partial hepatectomy. Reduced DNA replication in regenerating Foxm1b-/- hepatocytes was associated with sustained increase in nuclear staining of the cyclin-dependent kinase (Cdk) inhibitor p21Cip1 (p21) protein between 24 and 40 h after partial hepatectomy. Furthermore, increased nuclear p21 levels and reduced expression of Cdc25A phosphatase coincided with decreases in Cdk2 activation and hepatocyte progression into S-phase. Moreover, the significant reduction in hepatocyte mitosis was associated with diminished mRNA levels and nuclear expression of Cdc25B phosphatase and delayed accumulation of cyclin B1 protein, which is required for Cdk1 activation and entry into mitosis. Cotransfection studies demonstrate that FoxM1B protein directly activated transcription of the Cdc25B promoter region. Our present study shows that the mammalian Foxm1b transcription factor regulates expression of cell cycle proteins essential for hepatocyte entry into DNA replication and mitosis.',\n", - " 'author': ['Wang, Xinhe',\n", - " 'Kiyokawa, Hiroaki',\n", - " 'Dennewitz, Margaret B.',\n", - " 'Costa, Robert H.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/99/26/16881\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/99/26/16881\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/99/26/16881\"}'],\n", - " 'title': ['The Forkhead Box m1b transcription factor is essential for hepatocyte DNA replication and mitosis during mouse liver regeneration']},\n", - " {'bibcode': '1994PNAS...91.6196E',\n", - " 'abstract': 'First-generation recombinant adenoviruses that lack E1 sequences have shown tremendous promise in animal and human models of gene therapy. Important limitations of these vectors are that recombinant gene expression is transient and inflammation occurs at the site of gene transfer. Our hypothesis for generating vectors with increased persistence is that present recombinant adenoviruses express viral proteins that stimulate cellular immune responses leading to destruction of the infected cells and repopulation of the organ with non-transgene-containing cells. This model predicts that further crippling of the virus will improve persistence and diminish pathology. We describe in this report second-generation recombinant adenoviruses harboring a beta-galactosidase-expressing transgene in which a temperature-sensitive mutation has been introduced into the E2A gene of an E1-deleted recombinant. At nonpermissive temperature, this virus fails to express late gene products, even when E1 is expressed in trans. The biology of this recombinant was studied in vivo in the context of mouse liver, a setting that is permissive for adenovirus type 5 replication. Animals that received the second-generation virus expressed the transgene for at least 70 days, whereas expression of the first-generation virus was no longer than 14 days. In addition, the inflammatory response, as measured by infiltration of CD8+ T cells, was blunted and delayed in livers infected with second-generation virus. These studies illustrate that modifications that disrupt structural protein expression in recombinant adenoviruses may be useful in enhancing their utility for gene therapy.',\n", - " 'author': ['Engelhardt, John F.',\n", - " 'Ye, Xuehai',\n", - " 'Doranz, Benjamin',\n", - " 'Wilson, James M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/91/13/6196\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/91/13/6196\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/91/13/6196\"}'],\n", - " 'title': ['Ablation of E2A in recombinant adenoviruses improves transgene persistence and decreases inflammatory response in mouse liver.']},\n", - " {'bibcode': '2021NatCo..12.7046H',\n", - " 'abstract': 'Reconstruction of heterogeneity through single cell transcriptional profiling has greatly advanced our understanding of the spatial liver transcriptome in recent years. However, global transcriptional differences across lobular units remain elusive in physical space. Here, we apply Spatial Transcriptomics to perform transcriptomic analysis across sectioned liver tissue. We confirm that the heterogeneity in this complex tissue is predominantly determined by lobular zonation. By introducing novel computational approaches, we enable transcriptional gradient measurements between tissue structures, including several lobules in a variety of orientations. Further, our data suggests the presence of previously transcriptionally uncharacterized structures within liver tissue, contributing to the overall spatial heterogeneity of the organ. This study demonstrates how comprehensive spatial transcriptomic technologies can be used to delineate extensive spatial gene expression patterns in the liver, indicating its future impact for studies of liver function, development and regeneration as well as its potential in pre-clinical and clinical pathology.',\n", - " 'author': ['Hildebrandt, Franziska',\n", - " 'Andersson, Alma',\n", - " 'Saarenpää, Sami',\n", - " 'Larsson, Ludvig',\n", - " 'Van Hul, Noémi',\n", - " 'Kanatani, Sachie',\n", - " 'Masek, Jan',\n", - " 'Ellis, Ewa',\n", - " 'Barragan, Antonio',\n", - " 'Mollbrink, Annelie',\n", - " 'Andersson, Emma R.',\n", - " 'Lundeberg, Joakim',\n", - " 'Ankarklev, Johan'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41467-021-27354-w\"}'],\n", - " 'title': ['Spatial Transcriptomics to define transcriptional patterns of zonation and structural components in the mouse liver']},\n", - " {'bibcode': '2021EnST...55.8191Y',\n", - " 'author': ['Yao, Linlin',\n", - " 'Wang, Yuanyuan',\n", - " 'Shi, Jianbo',\n", - " 'Liu, Yanna',\n", - " 'Guo, Hao',\n", - " 'Yang, Xiaoxi',\n", - " 'Liu, Yaquan',\n", - " 'Ma, Junjie',\n", - " 'Li, Danyang',\n", - " 'Wang, Ziniu',\n", - " 'Li, Zikang',\n", - " 'Luo, Qian',\n", - " 'Fu, Jianjie',\n", - " 'Zhang, Qinghua',\n", - " 'Qu, Guangbo',\n", - " 'Wang, Yanxin',\n", - " 'Jiang, Guibin'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1021%2Facs.est.1c01726\"}'],\n", - " 'title': ['Toxicity of Tetrabromobisphenol A and Its Derivative in the Mouse Liver Following Oral Exposure at Environmentally Relevant Levels']},\n", - " {'bibcode': '1993Sci...261.1733R',\n", - " 'abstract': 'Intraperitoneal injection of epidermal growth factor (EGF) into mice resulted in the appearance in liver nuclei of three tyrosine phosphorylated proteins (84, 91, and 92 kilodaltons) within minutes after administration of EGF. Administration of interferon-γ (IFN-γ) resulted in the appearance in liver nuclei of two tyrosine phosphorylated proteins (84 and 91 kilodaltons). The 84- and 91-kilodalton proteins detected after either EGF or IFN-γ administration were identified as the IFN-γ activation factors (GAF). Furthermore, gel shift analysis revealed that these GAF proteins, detected after either EGF or IFN-γ administration, specifically bound to the sis-inducible element of the c-fos promoter. Thus, GAF proteins participate in nuclear signaling in both IFN-γ and EGF pathways.',\n", - " 'author': ['Ruff-Jamison, Susan', 'Chen, Katherine', 'Cohen, Stanley'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.8378774\"}'],\n", - " 'title': ['Induction by EGF and Interferon-γ of Tyrosine Phosphorylated DNA Binding Proteins in Mouse Liver Nuclei']},\n", - " {'bibcode': '2012Sci...338..349K',\n", - " 'abstract': 'The mammalian circadian clock involves a transcriptional feed back loop in which CLOCK and BMAL1 activate the Period and Cryptochrome genes, which then feedback and repress their own transcription. We have interrogated the transcriptional architecture of the circadian transcriptional regulatory loop on a genome scale in mouse liver and find a stereotyped, time-dependent pattern of transcription factor binding, RNA polymerase II (RNAPII) recruitment, RNA expression, and chromatin states. We find that the circadian transcriptional cycle of the clock consists of three distinct phases: a poised state, a coordinated de novo transcriptional activation state, and a repressed state. Only 22% of messenger RNA (mRNA) cycling genes are driven by de novo transcription, suggesting that both transcriptional and posttranscriptional mechanisms underlie the mammalian circadian clock. We also find that circadian modulation of RNAPII recruitment and chromatin remodeling occurs on a genome-wide scale far greater than that seen previously by gene expression profiling.',\n", - " 'author': ['Koike, Nobuya',\n", - " 'Yoo, Seung-Hee',\n", - " 'Huang, Hung-Chung',\n", - " 'Kumar, Vivek',\n", - " 'Lee, Choogon',\n", - " 'Kim, Tae-Kyung',\n", - " 'Takahashi, Joseph S.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.1226339\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.1226339\"}'],\n", - " 'title': ['Transcriptional Architecture and Chromatin Landscape of the Core Circadian Clock in Mammals']},\n", - " {'bibcode': '2019OExpr..2726014H',\n", - " 'author': ['Huang, Pingjie',\n", - " 'Cao, Yuqi',\n", - " 'Chen, Jiani',\n", - " 'Ge, Weiting',\n", - " 'Hou, Dibo',\n", - " 'Zhang, Guangxin'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1364%2FOE.27.026014\"}'],\n", - " 'title': ['Analysis and inspection techniques for mouse liver injury based on terahertz spectroscopy']},\n", - " {'bibcode': '2010RadR..174..611U',\n", - " 'author': ['Uehara, Yoshihiko',\n", - " 'Ito, Yasuko',\n", - " 'Taki, Keiko',\n", - " 'Nenoi, Mitsuru',\n", - " 'Ichinohe, Kazuaki',\n", - " 'Nakamura, Shingo',\n", - " 'Tanaka, Satoshi',\n", - " 'Oghiso, Yoichi',\n", - " 'Tanaka, Kimio',\n", - " 'Matsumoto, Tsuneya',\n", - " 'Paunesku, Tatjana',\n", - " 'Woloschak, Gayle E.',\n", - " 'Ono, Tetsuya'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1667%2FRR2195.1\"}'],\n", - " 'title': ['Gene Expression Profiles in Mouse Liver after Long-Term Low-Dose-Rate Irradiation with Gamma Rays']},\n", - " {'bibcode': '2013PLoSO...883723Z',\n", - " 'author': ['Zheng, Rena',\n", - " 'Rebolledo-Jaramillo, Boris',\n", - " 'Zong, Yiwei',\n", - " 'Wang, Liqing',\n", - " 'Russo, Pierre',\n", - " 'Hancock, Wayne',\n", - " 'Stanger, Ben Z.',\n", - " 'Hardison, Ross C.',\n", - " 'Blobel, Gerd A.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0083723\"}'],\n", - " 'title': ['Function of GATA Factors in the Adult Mouse Liver']},\n", - " {'bibcode': '1990RadR..124..227M',\n", - " 'author': ['Majo, V. Di', 'Coppola, M.', 'Rebessi, S.', 'Covelli, V.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.2307%2F3577870\"}'],\n", - " 'title': ['Age-Related Susceptibility of Mouse Liver to Induction of Tumors by Neutrons']},\n", - " {'bibcode': '1961PNAS...47..762H',\n", - " 'author': ['Herzenberg, Leonard A.', 'Herzenberg, Leonore A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/47/6/762\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.47.6.762\"}'],\n", - " 'title': ['Association of H-2 Antigens with the Cell Membrane Fraction of Mouse Liver']},\n", - " {'bibcode': '2006ApPhL..88o3903K',\n", - " 'abstract': 'We present biomedical imaging using a single frequency terahertz imaging system based on a low threshold quantum cascade laser emitting at 3.7THz (λ=81μm). With a peak output power of 4mW, coherent terahertz radiation and detection provide a relatively large dynamic range and high spatial resolution. We study image contrast based on water/fat content ratios in different tissues. Terahertz transmission imaging demonstrates a distinct anatomy in a rat brain slice. We also demonstrate malignant tissue contrast in an image of a mouse liver with developed tumors, indicating potential use of terahertz imaging for probing cancerous tissues.',\n", - " 'author': ['Kim, Seongsin M.',\n", - " 'Hatami, Fariba',\n", - " 'Harris, James S.',\n", - " 'Kurian, Allison W.',\n", - " 'Ford, James',\n", - " 'King, Douglas',\n", - " 'Scalari, Giacomo',\n", - " 'Giovannini, Marcella',\n", - " 'Hoyler, Nicolas',\n", - " 'Faist, Jerome',\n", - " 'Harris, Geoff'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1063%2F1.2194229\"}'],\n", - " 'title': ['Biomedical terahertz imaging with a quantum cascade laser']},\n", - " {'bibcode': '2003RadR..160..549F',\n", - " 'author': ['Furuno-Fukushi, Ikuko',\n", - " 'Masumura, Ken-ichi',\n", - " 'Furuse, Takeshi',\n", - " 'Noda, Yuko',\n", - " 'Takahagi, Masahiko',\n", - " 'Saito, Toshiyuki',\n", - " 'Hoki, Yuko',\n", - " 'Suzuki, Hiroshi',\n", - " 'Wynshaw-Boris, Anthony',\n", - " 'Nohmi, Takehiko',\n", - " 'Tatsumi, Kouichi'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1667%2FRR3073\"}'],\n", - " 'title': ['Effect ofAtmDisruption on Spontaneously Arising and Radiation-Induced Deletion Mutations in Mouse Liver']},\n", - " {'bibcode': '2010PLoSO...511264K',\n", - " 'author': ['Kojima, Shihoko',\n", - " 'Gatfield, David',\n", - " 'Esau, Christine C.',\n", - " 'Green, Carla B.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0011264\"}'],\n", - " 'title': ['MicroRNA-122 Modulates the Rhythmic Expression Profile of the Circadian Deadenylase Nocturnin in Mouse Liver']},\n", - " {'bibcode': '1984JESHB..19..501C',\n", - " 'author': ['Chukwudebe, A. C.', 'Hussain, M. A.', 'Oloffs, P. C.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1080%2F03601238409372447\"}'],\n", - " 'title': ['Hydrolytic and metabolic products of acephate in water and mouse liver']},\n", - " {'bibcode': '2011PLoSO...624993D',\n", - " 'author': [\"D'Ambrosio, Diana N.\",\n", - " 'Walewski, José L.',\n", - " 'Clugston, Robin D.',\n", - " 'Berk, Paul D.',\n", - " 'Rippe, Richard A.',\n", - " 'Blaner, William S.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0024993\"}'],\n", - " 'title': ['Distinct Populations of Hepatic Stellate Cells in the Mouse Liver Have Different Capacities for Retinoid and Lipid Storage']},\n", - " {'bibcode': '2019NatSR...919195B',\n", - " 'abstract': 'Spaceflight has several detrimental effects on the physiology of astronauts, many of which are recapitulated in rodent models. Mouse studies performed on the Space Shuttle showed disruption of lipid metabolism in liver. However, given that these animals were not sacrificed on-orbit and instead returned live to earth, it is unclear if these disruptions were solely induced by space stressors (e.g. microgravity, space radiation) or in part explained by the stress of return to Earth. In this work we analyzed three liver datasets from two different strains of mice (C57BL/6 (Jackson) & BALB/c (Taconic)) flown aboard the International Space Station (ISS). Notably, these animals were sacrificed on-orbit and exposed to varying spaceflight durations (i.e. 21, 37, and 42 days vs 13 days for the Shuttle mice). Oil Red O (ORO) staining showed abnormal lipid accumulation in all space-flown mice compared to ground controls regardless of strain or exposure duration. Similarly, transcriptomic analysis by RNA-sequencing revealed several pathways that were affected in both strains related to increased lipid metabolism, fatty acid metabolism, lipid and fatty acid processing, lipid catabolic processing, and lipid localization. In addition, key upstream regulators were predicted to be commonly regulated across all conditions including Glucagon (GCG) and Insulin (INS). Moreover, quantitative proteomic analysis showed that a number of lipid related proteins were changed in the livers during spaceflight. Taken together, these data indicate that activation of lipotoxic pathways are the result of space stressors alone and this activation occurs in various genetic backgrounds during spaceflight exposures of weeks to months. If similar responses occur in humans, a prolonged change of these pathways may result in the development of liver disease and should be investigated further.',\n", - " 'author': ['Beheshti, Afshin',\n", - " 'Chakravarty, Kaushik',\n", - " 'Fogle, Homer',\n", - " 'Fazelinia, Hossein',\n", - " 'Silveira, Willian A. da',\n", - " 'Boyko, Valery',\n", - " 'Polo, San-Huei Lai',\n", - " 'Saravia-Butler, Amanda M.',\n", - " 'Hardiman, Gary',\n", - " 'Taylor, Deanne',\n", - " 'Galazka, Jonathan M.',\n", - " 'Costes, Sylvain V.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-019-55869-2\"}'],\n", - " 'title': ['Multi-omics analysis of multiple missions to space reveal a theme of lipid dysregulation in mouse liver']},\n", - " {'bibcode': '2012PLoSO...735143P',\n", - " 'author': ['Patel, Raza',\n", - " 'Baker, Susan S.',\n", - " 'Liu, Wensheng',\n", - " 'Desai, Sonal',\n", - " 'Alkhouri, Razan',\n", - " 'Kozielski, Rafal',\n", - " 'Mastrandrea, Lucy',\n", - " 'Sarfraz, Adil',\n", - " 'Cai, Weijing',\n", - " 'Vlassara, Helen',\n", - " 'Patel, Mulchand S.',\n", - " 'Baker, Robert D.',\n", - " 'Zhu, Lixin'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0035143\"}'],\n", - " 'title': ['Effect of Dietary Advanced Glycation End Products on Mouse Liver']},\n", - " {'bibcode': '2015NatCo...6.6479E',\n", - " 'abstract': 'Across phyla, reduced nicotinamide adenine dinucleotide phosphate (NADPH) transfers intracellular reducing power to thioredoxin reductase-1 (TrxR1) and glutathione reductase (GR), thereby supporting fundamental housekeeping and antioxidant pathways. Here we show that a third, NADPH-independent pathway can bypass the need for TrxR1 and GR in mammalian liver. Most mice genetically engineered to lack both TrxR1 and GR in all hepatocytes (‘TR/GR-null livers’) remain long-term viable. TR/GR-null livers cannot reduce oxidized glutathione disulfide using NADPH but still require continuous glutathione synthesis. Inhibition of cystathionine γ-lyase causes rapid necrosis of TR/GR-null livers, indicating that methionine-fueled trans-sulfuration supplies the necessary cysteine precursor for glutathione synthesis via an NADPH-independent pathway. We further show that dietary methionine provides the cytosolic disulfide-reducing power and all sulfur amino acids in TR/GR-null livers. Although NADPH is generally considered an essential reducing currency, these results indicate that hepatocytes can adequately sustain cytosolic redox homeostasis pathways using either NADPH or methionine.',\n", - " 'author': ['Eriksson, Sofi',\n", - " 'Prigge, Justin R.',\n", - " 'Talago, Emily A.',\n", - " 'Arnér, Elias S. J.',\n", - " 'Schmidt, Edward E.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fncomms7479\"}'],\n", - " 'title': ['Dietary methionine can sustain cytosolic redox homeostasis in the mouse liver']},\n", - " {'bibcode': '2023iSci...26j8555F',\n", - " 'author': ['Fisher, Allison L.',\n", - " 'Wang, Chia-Yu',\n", - " 'Xu, Yang',\n", - " 'Phillips, Sydney',\n", - " 'Paulo, Joao A.',\n", - " 'Małachowska, Beata',\n", - " 'Xiao, Xia',\n", - " 'Fendler, Wojciech',\n", - " 'Mancias, Joseph D.',\n", - " 'Babitt, Jodie L.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.isci.2023.108555\"}'],\n", - " 'title': ['Quantitative proteomics and RNA-sequencing of mouse liver endothelial cells identify novel regulators of BMP6 by iron']},\n", - " {'bibcode': '2014PLoSO...9k6179J',\n", - " 'author': ['Jiang, Yan', 'Chen, Jiahong', 'Tong, Jian', 'Chen, Tao'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0116179\"}'],\n", - " 'title': ['Trichloroethylene-Induced Gene Expression and DNA Methylation Changes in B6C3F1 Mouse Liver']},\n", - " {'bibcode': '2004NYASA1030...86A',\n", - " 'abstract': 'Since radiation treatment has been reappraised in the treatment of hepatic tumors, radiation response in the liver is emerging as an interesting new area of investigation. In this study, identification of the repertoire of signaling proteins was performed using a proteomics approach involving cellular responses of liver tissue to ionizing radiation. Approximately 800 protein spots were detected. Among them, at least 28 proteins showed significant quantitative alterations after radiation. The significantly altered proteins were categorized as those related to reactive oxygen species (ROS) metabolism, metabolic pathway proteins, and G‑type proteins. Particularly, the expression levels of proteins related to ROS metabolism, including cytochrome c, glutathione S‑transferase Pi, NADH dehydrogenase, and peroxiredoxin VI, were increased after radiation. It is suggested that although radiation initiates cytotoxic effects, it can also induce a radioprotective antioxidant system.',\n", - " 'author': ['An, Jeung Hee', 'Kim, Jiyoung', 'Seong, Jinsil'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1196%2Fannals.1329.011\"}'],\n", - " 'title': ['Redox Signaling by Ionizing Radiation in Mouse Liver']},\n", - " {'bibcode': '2015PLoSO..1041220G',\n", - " 'author': ['Gunewardena, Sumedha S.',\n", - " 'Yoo, Byunggil',\n", - " 'Peng, Lai',\n", - " 'Lu, Hong',\n", - " 'Zhong, Xiaobo',\n", - " 'Klaassen, Curtis D.',\n", - " 'Cui, Julia Yue'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0141220\"}'],\n", - " 'title': ['Deciphering the Developmental Dynamics of the Mouse Liver Transcriptome']},\n", - " {'bibcode': '1996PNAS...93.9443M',\n", - " 'abstract': 'Peroxisome proliferators induce stearoyl-CoA desaturase activity (EC 1.14.99.5) in liver [Kawashima, Y., Hanioka, N., Matsumura, M. & Kozuka, H. (1983) Biochim. Biophys. Acta 752, 259-264]. We analyzed the changes in stearoyl-CoA desaturase 1 (SCD1) mRNA to further define the molecular mechanism for the induction of stearoyl-CoA desaturase by peroxisome proliferators. SCD1 mRNA was analyzed from the livers of BALB/c mice that had been fed diets supplemented with clofibrate or gemfibrozil. Clofibrate was found to induce liver SCD1 mRNA levels 3-fold within 6 hr to a maximum of 22-fold in 30 hr. Gemfibrozil administration resulted in a similar induction pattern. This induction is primarily due to an increase in transcription of the SCD1 gene, as shown by nuclear run-on transcription assays and DNA deletion analysis of transfected SCD1-chloramphenicol acetyltransferase fusion genes. The cis-linked response element for peroxisome proliferator-activated receptor (PPAR) was localized to an AGGTCA consensus sequence between base pairs -664 to -642 of the SCD1 promoter. Clofibrate-mediated induction of SCD1 mRNA was shown to be independent of polyunsaturated fatty acids, with peroxisome proliferators and arachidonic acid having opposite effects on SCD1 mRNA levels. Additionally, the activation of SCD1 mRNA by clofibrate was inhibited 77% by cycloheximide administration. Levels of liver beta-actin and albumin mRNAs were unchanged by these dietary manipulations. Our data show that hepatic SCD1 gene expression is regulated by PPARs and suggest that peroxisome proliferators and poly-unsaturated fatty acids act through distinct mechanisms.',\n", - " 'author': ['Miller, Carolyn Wilson', 'Ntambi, James M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/93/18/9443\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/93/18/9443\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/93/18/9443\"}'],\n", - " 'title': ['Peroxisome proliferators induce mouse liver stearoyl-CoA desaturase 1 gene expression.']},\n", - " {'bibcode': '2010PLoSO...5.9148B',\n", - " 'author': ['Beck, Laurent',\n", - " 'Leroy, Christine',\n", - " 'Beck-Cormier, Sarah',\n", - " 'Forand, Anne',\n", - " 'Salaün, Christine',\n", - " 'Paris, Nadine',\n", - " 'Bernier, Adeline',\n", - " 'Ureña-Torres, Pablo',\n", - " 'Prié, Dominique',\n", - " 'Ollero, Mario',\n", - " 'Coulombel, Laure',\n", - " 'Friedlander, Gérard'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0009148\"}'],\n", - " 'title': ['The Phosphate Transporter PiT1 (Slc20a1) Revealed As a New Essential Gene for Mouse Liver Development']},\n", - " {'bibcode': '1982PNAS...79.6237C',\n", - " 'abstract': 'We have purified the epidermal growth factor (EGF) receptor/protein kinase from the livers of normal mice by affinity chromatography. The biochemical properties of the liver receptor are very similar to those of the EGF receptor previously prepared from the human tumor cell line A-431 [Cohen, S., Ushiro, H., Stoscheck, C. & Chinkers, M. (1982) J. Biol. Chem. 257, 1523-1531]. The liver receptor for EGF is a glycoprotein of Mr 170,000. It binds 125I-labeled EGF and possesses an EGF-stimulable protein kinase activity specific for tyrosine residues. Both autophosphorylation and kinase activity toward exogenous substrates are demonstrable. The EGF receptor purified from normal mouse liver is antigenically related to the receptor purified from human A-431 cells.',\n", - " 'author': ['Cohen, Stanley', 'Fava, Roy A.', 'Sawyer, Stephen T.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/79/20/6237\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/79/20/6237\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/79/20/6237\"}'],\n", - " 'title': ['Purification and characterization of epidermal growth factor receptor/protein kinase from normal mouse liver.']},\n", - " {'bibcode': '2000PNAS...97.2214F',\n", - " 'abstract': \"Hereditary hemochromatosis (HH) is a common autosomal recessive disorder characterized by excess absorption of dietary iron and progressive iron deposition in several tissues, particularly liver. Liver disease resulting from iron toxicity is the major cause of death in HH. Hepatic iron loading in HH is progressive despite down-regulation of the classical transferrin receptor (TfR). Recently a human cDNA highly homologous to TfR was identified and reported to encode a protein (TfR2) that binds holotransferrin and mediates uptake of transferrin-bound iron. We independently identified a full-length murine EST encoding the mouse orthologue of the human TfR2. Although homologous to murine TfR in the coding region, the TfR2 transcript does not contain the iron-responsive elements found in the 3' untranslated sequence of TfR mRNA. To determine the potential role for TfR2 in iron uptake by liver, we investigated TfR and TfR2 expression in normal mice and murine models of dietary iron overload (2% carbonyl iron), dietary iron deficiency (gastric parietal cell ablation), and HH (HFE -/-). Northern blot analyses demonstrated distinct tissue-specific patterns of expression for TfR and TfR2, with TfR2 expressed highly only in liver where TfR expression is low. In situ hybridization demonstrated abundant TfR2 expression in hepatocytes. In contrast to TfR, TfR2 expression in liver was not increased in iron deficiency. Furthermore, hepatic expression of TfR2 was not down-regulated with dietary iron loading or in the HFE -/- model of HH. From these observations, we propose that TfR2 allows continued uptake of Tf-bound iron by hepatocytes even after TfR has been down-regulated by iron overload, and this uptake contributes to the susceptibility of liver to iron loading in HH.\",\n", - " 'author': ['Fleming, Robert E.',\n", - " 'Migas, Mary C.',\n", - " 'Holden, Christopher C.',\n", - " 'Waheed, Abdul',\n", - " 'Britton, Robert S.',\n", - " 'Tomatsu, Shunji',\n", - " 'Bacon, Bruce R.',\n", - " 'Sly, William S.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/97/5/2214\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/97/5/2214\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/97/5/2214\"}'],\n", - " 'title': ['Transferrin receptor 2: Continued expression in mouse liver in the face of iron overload and in hereditary hemochromatosis']},\n", - " {'bibcode': '2004RCMS...18.2169J',\n", - " 'author': ['Jin, Wen-Hai',\n", - " 'Dai, Jie',\n", - " 'Zhou, Hu',\n", - " 'Xia, Qi-Chang',\n", - " 'Zou, Han-Fa',\n", - " 'Zeng, Rong'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Frcm.1604\"}'],\n", - " 'title': ['Phosphoproteome analysis of mouse liver using immobilized metal affinity purification and linear ion trap mass spectrometry']},\n", - " {'bibcode': '2017Natur.551...51S',\n", - " 'abstract': 'Imaging and chromosome conformation capture studies have revealed several layers of chromosome organization, including segregation into megabase-sized active and inactive compartments, and partitioning into sub-megabase domains (TADs). It remains unclear, however, how these layers of organization form, interact with one another and influence genome function. Here we show that deletion of the cohesin-loading factor Nipbl in mouse liver leads to a marked reorganization of chromosomal folding. TADs and associated Hi-C peaks vanish globally, even in the absence of transcriptional changes. By contrast, compartmental segregation is preserved and even reinforced. Strikingly, the disappearance of TADs unmasks a finer compartment structure that accurately reflects the underlying epigenetic landscape. These observations demonstrate that the three-dimensional organization of the genome results from the interplay of two independent mechanisms: cohesin-independent segregation of the genome into fine-scale compartments, defined by chromatin state; and cohesin-dependent formation of TADs, possibly by loop extrusion, which helps to guide distant enhancers to their target genes.',\n", - " 'author': ['Schwarzer, Wibke',\n", - " 'Abdennur, Nezar',\n", - " 'Goloborodko, Anton',\n", - " 'Pekowska, Aleksandra',\n", - " 'Fudenberg, Geoffrey',\n", - " 'Loe-Mie, Yann',\n", - " 'Fonseca, Nuno A.',\n", - " 'Huber, Wolfgang',\n", - " 'H. Haering, Christian',\n", - " 'Mirny, Leonid',\n", - " 'Spitz, Francois'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"data\", \"url\": \"http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse93431\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature24281\"}'],\n", - " 'title': ['Two independent modes of chromatin organization revealed by cohesin removal']},\n", - " {'bibcode': '2002Natur.417...78S',\n", - " 'abstract': 'Many mammalian peripheral tissues have circadian clocks; endogenous oscillators that generate transcriptional rhythms thought to be important for the daily timing of physiological processes. The extent of circadian gene regulation in peripheral tissues is unclear, and to what degree circadian regulation in different tissues involves common or specialized pathways is unknown. Here we report a comparative analysis of circadian gene expression in vivo in mouse liver and heart using oligonucleotide arrays representing 12,488 genes. We find that peripheral circadian gene regulation is extensive (>=8-10% of the genes expressed in each tissue), that the distributions of circadian phases in the two tissues are markedly different, and that very few genes show circadian regulation in both tissues. This specificity of circadian regulation cannot be accounted for by tissue-specific gene expression. Despite this divergence, the clock-regulated genes in liver and heart participate in overlapping, extremely diverse processes. A core set of 37 genes with similar circadian regulation in both tissues includes candidates for new clock genes and output genes, and it contains genes responsive to circulating factors with circadian or diurnal rhythms.',\n", - " 'author': ['Storch, Kai-Florian',\n", - " 'Lipan, Ovidiu',\n", - " 'Leykin, Igor',\n", - " 'Viswanathan, N.',\n", - " 'Davis, Fred C.',\n", - " 'Wong, Wing H.',\n", - " 'Weitz, Charles J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature744\"}'],\n", - " 'title': ['Extensive and divergent circadian gene expression in liver and heart']},\n", - " {'bibcode': '2013SMat....9.8705K',\n", - " 'author': ['Ko, Tae-Jun',\n", - " 'Kim, Eunkyung',\n", - " 'Nagashima, So',\n", - " 'Oh, Kyu Hwan',\n", - " 'Lee, Kwang-Ryeol',\n", - " 'Kim, Soyoun',\n", - " 'Moon, Myoung-Woon'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1039%2Fc3sm51147b\"}'],\n", - " 'title': ['Adhesion behavior of mouse liver cancer cells on nanostructured superhydrophobic and superhydrophilic surfaces']},\n", - " {'bibcode': '1979PNAS...76.4808C',\n", - " 'abstract': 'Time courses of 13C labeling from alanine and ethanol in perfused mouse livers have been followed by NMR. The enrichment at specific carbons of glucose, glutamate, glutamine, aspartate, acetate, acetoacetate, beta-hydroxybutyrate, and lactate has been measured. The specific labeling of glutamate in the presence of labeled alanine and labeled or unlabeled ethanol shows that, under these conditions, alanine enters the tricarboxylic acid cycle almost exclusively through pyruvate carboxylation, whereas ethanol is the exclusive source of acetyl-CoA. In the absence of ethanol, the alanine label flows through both paths. By comparing the scrambling of 13C between C3 and C2 of glutamate it is possible to estimate the mitochondrial fumarase activity; the C6-to-C5 ratios in glucose give the additional scrambling by cytosolic fumarase activity. In addition, the C6-to-C1 and C5-to-C2 ratios in glucose show that there is about 15% flux through the pentose cycle. Finally, the C4-to-C2 ratios in glutamine and glutamate are unequal at any time (the glutamine labels reflect the label distribution in glutamate measured 1 hr earlier), providing a method for studying flow through glutamine synthetase in situ.',\n", - " 'author': ['Cohen, S. M.', 'Shulman, R. G.', 'McLaughlin, A. C.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/76/10/4808\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/76/10/4808\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/76/10/4808\"}'],\n", - " 'title': ['Effects of Ethanol on Alanine Metabolism in Perfused Mouse Liver Studied by 13C NMR']},\n", - " {'bibcode': '1982PNAS...79..500B',\n", - " 'abstract': 'The mouse liver contains a group of 10--12 different tissue-specific mRNAs, each present at an average concentration of 12,000--15,000 copies per cell [Hastie, N. D. & Bishop, J. O. (1976) Cell 9, 761--774]. We have determined, by translation in vitro, that these mRNAs are developmentally regulated in the liver. We have also used specific cloned probes to quantitate the developmental time course of expression of five different abundant liver mRNAs. We have found that there are at least three periods during liver development when specific abundant mRNAs are first detectable: prior to 14 days postconception, at birth, and during the onset of sexual maturity. These results indicate that all the members of this mRNA group are not under common developmental regulation. One of the abundant liver mRNAs (p54 mRNA) increases more than 1000-fold in the liver 1 day before birth. We discuss factors that may be involved in the developmental regulation of expression of the genes encoding these mRNAs.',\n", - " 'author': ['Barth, Richard K.',\n", - " 'Gross, Kenneth W.',\n", - " 'Gremke, Linda C.',\n", - " 'Hastie, Nicholas D.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/79/2/500\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/79/2/500\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/79/2/500\"}'],\n", - " 'title': ['Developmentally regulated mRNAs in mouse liver.']},\n", - " {'bibcode': '2013JBO....18d0505Z',\n", - " 'abstract': 'Pharmacokinetic rates have the potential to provide quantitative physiological and pathological information for biological studies and drug development. Fluorescence molecular tomography (FMT) is an attractive imaging tool for three-dimensionally resolving fluorophore distribution in small animals. In this letter, pharmacokinetic rates of indocyanine green (ICG) in mouse liver are imaged with a hybrid FMT and x-ray computed tomography (XCT) system. A recently developed FMT method using structural priors from an XCT system is adopted to improve the quality of FMT reconstruction. In the in vivo experiments, images of uptake and excretion rates of ICG in mouse liver are obtained, which can be used to quantitatively evaluate liver function. The accuracy of the results is validated by a fiber-based fluorescence measurement system.',\n", - " 'author': ['Zhang, Guanglei',\n", - " 'Liu, Fei',\n", - " 'Zhang, Bin',\n", - " 'He, Yun',\n", - " 'Luo, Jianwen',\n", - " 'Bai, Jing'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1117%2F1.JBO.18.4.040505\"}'],\n", - " 'title': ['Imaging of pharmacokinetic rates of indocyanine green in mouse liver with a hybrid fluorescence molecular tomography/x-ray computed tomography system']},\n", - " {'bibcode': '1979Sci...203.1019S',\n", - " 'abstract': \"The restriction enzymes Hpa II and Msp I both recognize the sequence 5'-CCGG (C, cytosine; G, guanine). However, Hpa II cuts mouse liver DNA to fragments four times larger than does Msp I. The size of DNA cut by Msp I is close to that predicted from base composition and nearest neighbor analysis. The most probable explanation of these results is that in mouse the site 5'-CCGG is highly methylated.\",\n", - " 'author': ['Singer, Judith', 'Roberts-Ems, Joan', 'Riggs, Arthur D.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.424726\"}'],\n", - " 'title': ['Methylation of Mouse Liver DNA Studied by Means of the Restriction Enzymes Msp I and Hpa II']},\n", - " {'bibcode': '2007JRadR..48..233J',\n", - " 'author': ['Jeong, Won-Il',\n", - " 'Do, Sun-Hee',\n", - " 'Kim, Tae-Hwan',\n", - " 'Jeong, Da-Hee',\n", - " 'Hong, Il-Hwa',\n", - " 'Ki, Mi-Ran',\n", - " 'Kwak, Dong-Mi',\n", - " 'Lee, Seung-Sook',\n", - " 'Jee, Young-Heun',\n", - " 'Kim, Soon-Bok',\n", - " 'Jeong, Kyu-Shik'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1269%2Fjrr.0629\"}'],\n", - " 'title': ['Acute Effects of Fast Neutron Irradiation on Mouse Liver']},\n", - " {'bibcode': '2015PLoSO..1042374M',\n", - " 'author': ['Moskaleva, Natalia',\n", - " 'Moysa, Alexander',\n", - " 'Novikova, Svetlana',\n", - " 'Tikhonova, Olga',\n", - " 'Zgoda, Victor',\n", - " 'Archakov, Alexander'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0142374\"}'],\n", - " 'title': ['Spaceflight Effects on Cytochrome P450 Content in Mouse Liver']},\n", - " {'bibcode': '1986PNAS...83.8356L',\n", - " 'abstract': 'It has been proposed that a ring-opened form may be responsible for the toxicity of benzene. The present studies demonstrate that incubation of [14C]benzene with liver microsomes (obtained from male CD-1 mice treated with benzene) in the presence of NADPH results in the formation of a ring-opened product. Evidence for the identity of this product was obtained by derivatizing with 2-thiobarbituric acid (TBA), which resulted in the formation of an adduct with a 490-nm absorbance maximum. This maximum is identical to that observed after authentic trans,trans-muconaldehyde has reacted with TBA. Separation of muconaldehyde, both with and without trapping with TBA, from other benzene metabolites in the incubation mixture was accomplished by HPLC. The radioactivity profile of fractions collected during HPLC analysis contained peaks that eluted with muconaldehyde and the muconaldehyde-TBA adduct. The structure of the ring-opened product was confirmed by mass spectrometry, studies in which the HPLC peak from the microsomal incubation mixture that eluted at the retention time of authentic muconaldehyde was collected and derivatized with 2,4-dinitrophenylhydrazine. The high-resolution mass spectrum of this sample contained an ion with an m/z of 291.0729, corresponding to muconaldehyde mono-dinitrophenylhydrazone. These results indicate that benzene is metabolized in vitro to a ring-opened product identified as muconaldehyde.',\n", - " 'author': ['Latriano, Louise', 'Goldstein, Bernard D.', 'Witz, Gisela'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/83/21/8356\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/83/21/8356\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/83/21/8356\"}'],\n", - " 'title': ['Formation of muconaldehyde, an open-ring metabolite of benzene, in mouse liver microsomes: an additional pathway for toxic metabolites.']},\n", - " {'bibcode': '2020NatCo..11.1961C',\n", - " 'abstract': 'Cancer stem cells (CSCs) or tumor-initiating cells (TICs) are thought to be the main drivers for disease progression and treatment resistance across various cancer types. Identifying and targeting these rare cancer cells, however, remains challenging with respect to therapeutic benefit. Here, we report the enrichment of LGR5 expressing cells, a well-recognized stem cell marker, in mouse liver tumors, and the upregulation of LGR5 expression in human hepatocellular carcinoma. Isolated LGR5 expressing cells from mouse liver tumors are superior in initiating organoids and forming tumors upon engraftment, featuring candidate TICs. These cells are resistant to conventional treatment including sorafenib and 5-FU. Importantly, LGR5 lineage ablation significantly inhibits organoid initiation and tumor growth. The combination of LGR5 ablation with 5-FU, but not sorafenib, further augments the therapeutic efficacy in vivo. Thus, we have identified the LGR5+ compartment as an important TIC population, representing a viable therapeutic target for combating liver cancer.',\n", - " 'author': ['Cao, Wanlu',\n", - " 'Li, Meng',\n", - " 'Liu, Jiaye',\n", - " 'Zhang, Shaoshi',\n", - " 'Noordam, Lisanne',\n", - " 'Verstegen, Monique M. A.',\n", - " 'Wang, Ling',\n", - " 'Ma, Buyun',\n", - " 'Li, Shan',\n", - " 'Wang, Wenshi',\n", - " 'Bolkestein, Michiel',\n", - " 'Doukas, Michael',\n", - " 'Chen, Kan',\n", - " 'Ma, Zhongren',\n", - " 'Bruno, Marco',\n", - " 'Sprengers, Dave',\n", - " 'Kwekkeboom, Jaap',\n", - " 'van der Laan, Luc J. W.',\n", - " 'Smits, Ron',\n", - " 'Peppelenbosch, Maikel P.',\n", - " 'Pan, Qiuwei'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41467-020-15846-0\"}'],\n", - " 'title': ['LGR5 marks targetable tumor-initiating cells in mouse liver cancer']},\n", - " {'bibcode': '2013PLoSO...857766Z',\n", - " 'author': ['Zhang, Fang',\n", - " 'Xu, Xiang',\n", - " 'Zhang, Yi',\n", - " 'Zhou, Ben',\n", - " 'He, Zhishui',\n", - " 'Zhai, Qiwei'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0057766\"}'],\n", - " 'title': ['Gene Expression Profile Analysis of Type 2 Diabetic Mouse Liver']},\n", - " {'bibcode': '2017ESPR...2424201W',\n", - " 'author': ['Wu, Xinmou',\n", - " 'Liang, Minqing',\n", - " 'Yang, Zhao',\n", - " 'Su, Min',\n", - " 'Yang, Bin'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1007%2Fs11356-017-0072-5\"}'],\n", - " 'title': ['Effect of acute exposure to PFOA on mouse liver cells in vivo and in vitro']},\n", - " {'bibcode': '2011PLoSO...624738L',\n", - " 'author': ['Le Saux, Olivier',\n", - " 'Fülöp, Krisztina',\n", - " 'Yamaguchi, Yukiko',\n", - " 'Iliás, Attila',\n", - " 'Szabó, Zalán',\n", - " 'Brampton, Christopher N.',\n", - " 'Pomozi, Viola',\n", - " 'Huszár, Krisztina',\n", - " 'Arányi, Tamás',\n", - " 'Váradi, András'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0024738\"}'],\n", - " 'title': ['Expression and In Vivo Rescue of Human ABCC6 Disease-Causing Mutants in Mouse Liver']},\n", - " {'bibcode': '1978IJBm...22...43B',\n", - " 'abstract': 'The effects of small negative air ions on the oxygen uptake of isolated mouse liver cells were studied by exposing the liver cells to varying ion concentrations. For concentrations of the order of 1 2 × 105 ions/cm3, the oxygen uptake was always higher than in the normal atmospheric conditions of 3 8 × 102/ions/cm3. For intermediate concentrations varying effects of activation and inhibition were observed. A statistical analysis showed that the oxygen uptake increased by approximately 14% when liver cells were exposed to ion concentrations of values 1 9 times the normal, by approximately 9% when exposed to 10 99 times the normal, and by approximately 38% when exposed to 100 999 times the normal. The significance and possible implications of the results are discussed.',\n", - " 'author': ['Bhartendu', 'Menon, I. A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1007%2FBF01553139\"}'],\n", - " 'title': ['Effects of atmospheric small negative ions on the oxygen consumption of mouse liver cells']},\n", - " {'bibcode': '2018NatCo...9..636Y',\n", - " 'abstract': 'The nutritional environment to which animals are exposed in early life can lead to epigenetic changes in the genome that influence the risk of obesity in later life. Here, we demonstrate that the fibroblast growth factor-21 gene (Fgf21) is subject to peroxisome proliferator-activated receptor (PPAR) α-dependent DNA demethylation in the liver during the postnatal period. Reductions in Fgf21 methylation can be enhanced via pharmacologic activation of PPARα during the suckling period. We also reveal that the DNA methylation status of Fgf21, once established in early life, is relatively stable and persists into adulthood. Reduced DNA methylation is associated with enhanced induction of hepatic FGF21 expression after PPARα activation, which may partly explain the attenuation of diet-induced obesity in adulthood. We propose that Fgf21 methylation represents a form of epigenetic memory that persists into adulthood, and it may have a role in the developmental programming of obesity.',\n", - " 'author': ['Yuan, Xunmei',\n", - " 'Tsujimoto, Kazutaka',\n", - " 'Hashimoto, Koshi',\n", - " 'Kawahori, Kenichi',\n", - " 'Hanzawa, Nozomi',\n", - " 'Hamaguchi, Miho',\n", - " 'Seki, Takami',\n", - " 'Nawa, Makiko',\n", - " 'Ehara, Tatsuya',\n", - " 'Kitamura, Yohei',\n", - " 'Hatada, Izuho',\n", - " 'Konishi, Morichika',\n", - " 'Itoh, Nobuyuki',\n", - " 'Nakagawa, Yoshimi',\n", - " 'Shimano, Hitoshi',\n", - " 'Takai-Igarashi, Takako',\n", - " 'Kamei, Yasutomi',\n", - " 'Ogawa, Yoshihiro'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41467-018-03038-w\"}'],\n", - " 'title': ['Epigenetic modulation of Fgf21 in the perinatal mouse liver ameliorates diet-induced obesity in adulthood']},\n", - " {'bibcode': '1981PNAS...78.2253P',\n", - " 'abstract': 'We have isolated three cDNA clones for beta 2-microglobulin, the small subunit of the major histocompatibility antigens. beta 2-Microglobulin makes up less than 0.1% of mouse liver protein, and its mRNA is approximately 0.03% of liver poly(A)+ mRNA. The cDNA clones were identified by screening 1400 cDNA clones made from 9--10S mouse liver poly(A)+ mRNA. The procedure for screening the cDNA clones involved binding pooled plasmid DNA to nitrocellulose filters and testing the ability of each filter to select beta 2-microglobulin mRNA. The filter-selected mRNAs were assayed for their ability to direct the synthesis of beta 2-microglobulin in translation reactions in vitro. The isolated clones were shown by nucleotide sequence analysis to encode beta 2-microglobulin. The positive-selection--hybridization assay has been modified to facilitate the screening of large numbers of cDNA clones, and the modified assay should allow the isolation of cDNAs corresponding to any mRNA whose in vitro translation products can be immunoprecipitated. These modifications are of particular value in the isolation of cDNA clones corresponding to rare species of mRNA.',\n", - " 'author': ['Parnes, Jane R.',\n", - " 'Velan, Baruch',\n", - " 'Felsenfeld, Adam',\n", - " 'Ramanathan, Lata',\n", - " 'Ferrini, Umberto',\n", - " 'Appella, Ettore',\n", - " 'Seidman, J. G.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/78/4/2253\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/78/4/2253\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/78/4/2253\"}'],\n", - " 'title': ['Mouse β 2-microglobulin cDNA Clones: A Screening Procedure for cDNA Clones Corresponding to Rare mRNAs']},\n", - " {'bibcode': '1979PNAS...76.5445M',\n", - " 'abstract': '31P NMR was used to continuously monitor ATP and inorganic phosphate levels in perfused mouse liver. Under \"optimal\" conditions, the time resolution of the technique was approximately 1 min. In the absence of any metabolic perturbations the ATP level remained constant for at least 2 hr and decreased by only approximately 20% in 18 hr. Both ATP and inorganic phosphate levels responded to alterations in the oxygen supply to the liver. The half-time for this response was approximately 1 min, and the response to short periods of hypoxia or ischemia was partially reversible. The addition of insulin caused only a minor decrease in the ATP level but significantly decreased the rate of response of ATP and phosphate levels to hypoxia and ischemia.',\n", - " 'author': ['McLaughlin, A. C.', 'Takeda, H.', 'Chance, B.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/76/11/5445\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/76/11/5445\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/76/11/5445\"}'],\n", - " 'title': ['Rapid ATP Assays in Perfused Mouse Liver by 31P NMR']},\n", - " {'bibcode': '2015PLoSO..1012655O',\n", - " 'author': ['Oshida, Keiyu',\n", - " 'Vasani, Naresh',\n", - " 'Thomas, Russell S.',\n", - " 'Applegate, Dawn',\n", - " 'Rosen, Mitch',\n", - " 'Abbott, Barbara',\n", - " 'Lau, Christopher',\n", - " 'Guo, Grace',\n", - " 'Aleksunes, Lauren M.',\n", - " 'Klaassen, Curtis',\n", - " 'Corton, J. Christopher'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0112655\"}'],\n", - " 'title': ['Identification of Modulators of the Nuclear Receptor Peroxisome Proliferator-Activated Receptor α (PPARα) in a Mouse Liver Gene Expression Compendium']},\n", - " {'bibcode': '2017Natur.542..352H',\n", - " 'abstract': 'The mammalian liver consists of hexagon-shaped lobules that are radially polarized by blood flow and morphogens. Key liver genes have been shown to be differentially expressed along the lobule axis, a phenomenon termed zonation, but a detailed genome-wide reconstruction of this spatial division of labour has not been achieved. Here we measure the entire transcriptome of thousands of mouse liver cells and infer their lobule coordinates on the basis of a panel of zonated landmark genes, characterized with single-molecule fluorescence in situ hybridization. Using this approach, we obtain the zonation profiles of all liver genes with high spatial resolution. We find that around 50% of liver genes are significantly zonated and uncover abundant non-monotonic profiles that peak at the mid-lobule layers. These include a spatial order of bile acid biosynthesis enzymes that matches their position in the enzymatic cascade. Our approach can facilitate the reconstruction of similar spatial genomic blueprints for other mammalian organs.',\n", - " 'author': ['Halpern, Keren Bahar',\n", - " 'Shenhav, Rom',\n", - " 'Matcovitch-Natan, Orit',\n", - " 'Tóth, Beáta',\n", - " 'Lemze, Doron',\n", - " 'Golan, Matan',\n", - " 'Massasa, Efi E.',\n", - " 'Baydatch, Shaked',\n", - " 'Landen, Shanie',\n", - " 'Moor, Andreas E.',\n", - " 'Brandis, Alexander',\n", - " 'Giladi, Amir',\n", - " 'Stokar-Avihail, Avigail',\n", - " 'David, Eyal',\n", - " 'Amit, Ido',\n", - " 'Itzkovitz, Shalev'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature21065\"}'],\n", - " 'title': ['Single-cell spatial reconstruction reveals global division of labour in the mammalian liver']},\n", - " {'bibcode': '2020PMB....65u5024L',\n", - " 'abstract': 'Magneto-acousto-electrical tomography (MAET) is an imaging method coupled with sound field and magnetic field. The aim of this study is to present some novel experimental results of the mouse liver for the magneto-acousto-electrical tomography measured by two electrodes. The magnetic field in the space of 60 mm3 is about 300 mT which generate by two permanent magnets. A plane transducer with 2.25 MHz center frequency is utilized to generate acoustic waves inside the object. The signal is detected by two similar 1 mm copper foil electrodes. An amplifier is designed to receive the MAET signal, and the gain of the amplifier is adjusted to be 54 dB. The phantom used in this paper is a mouse liver surrounded by a gel phantom with the conductivity of 0.7 S m-1. The gel phantom with the conductivity of 0.7 S m-1 is used to simulate the liver tumor, and the normal mouse liver is filled in the phantom. A series of the MAET signals are detected by the electrodes when the transducer is moved on a pre-set line route, then a B-scan image is realized. The experimental system can provide more information about the tumor and the results show that the MAET is sensitive enough for the potential clinical application of tumor in animal or human.',\n", - " 'author': ['Li, Yuanyuan', 'Song, Jiaxiang', 'Xia, Hui', 'Liu, Guoqiang'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1088%2F1361-6560%2Fabb4bb\"}'],\n", - " 'title': ['The experimental study of mouse liver in magneto-acousto-electrical tomography by scan mode']},\n", - " {'bibcode': '2003Natur.423..550P',\n", - " 'abstract': 'Hepatic gluconeogenesis is absolutely required for survival during prolonged fasting or starvation, but is inappropriately activated in diabetes mellitus. Glucocorticoids and glucagon have strong gluconeogenic actions on the liver. In contrast, insulin suppresses hepatic gluconeogenesis. Two components known to have important physiological roles in this process are the forkhead transcription factor FOXO1 (also known as FKHR) and peroxisome proliferative activated receptor-γ co-activator 1 (PGC-1α also known as PPARGC1), a transcriptional co-activator; whether and how these factors collaborate has not been clear. Using wild-type and mutant alleles of FOXO1, here we show that PGC-1α binds and co-activates FOXO1 in a manner inhibited by Akt-mediated phosphorylation. Furthermore, FOXO1 function is required for the robust activation of gluconeogenic gene expression in hepatic cells and in mouse liver by PGC-1α. Insulin suppresses gluconeogenesis stimulated by PGC-1α but co-expression of a mutant allele of FOXO1 insensitive to insulin completely reverses this suppression in hepatocytes or transgenic mice. We conclude that FOXO1 and PGC-1α interact in the execution of a programme of powerful, insulin-regulated gluconeogenesis.',\n", - " 'author': ['Puigserver, Pere',\n", - " 'Rhee, James',\n", - " 'Donovan, Jerry',\n", - " 'Walkey, Christopher J.',\n", - " 'Yoon, J. Cliff',\n", - " 'Oriente, Francesco',\n", - " 'Kitamura, Yukari',\n", - " 'Altomonte, Jennifer',\n", - " 'Dong, Hengjiang',\n", - " 'Accili, Domenico',\n", - " 'Spiegelman, Bruce M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature01667\"}'],\n", - " 'title': ['Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1α interaction']},\n", - " {'bibcode': '2003JAPco..15..507W',\n", - " 'author': ['Wei, Yuxi', \"Li, Zhi'en\", 'Hu, Yingfen', 'Xu, Zuhong'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1023%2FB%3AJAPH.0000004344.45697.0f\"}'],\n", - " 'title': ['Inhibition of mouse liver lipid peroxidation by high molecular weight phlorotannins fromSargassum kjellmanianum']},\n", - " {'bibcode': '2011PLoSO...623709O',\n", - " 'author': ['Oike, Hideaki',\n", - " 'Nagai, Kanji',\n", - " 'Fukushima, Tatsunobu',\n", - " 'Ishida, Norio',\n", - " 'Kobori, Masuko'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0023709\"}'],\n", - " 'title': ['Feeding Cues and Injected Nutrients Induce Acute Expression of Multiple Clock Genes in the Mouse Liver']},\n", - " {'bibcode': '2016NatSR...634989A',\n", - " 'abstract': 'The aryl hydrocarbon receptor (Ahr) is a highly conserved nuclear receptor that plays an important role in the manifestation of toxicity induced by polycyclic aromatic hydrocarbons. As a xenobiotic sensor, Ahr is involved in chemical biotransformation through activation of drug metabolizing enzymes. The activated Ahr cooperates with coactivator complexes to induce epigenetic modifications at target genes. Thus, it is conceivable that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent Ahr ligand, may elicit robust epigenetic changes in vivo at the Ahr target gene cytochrome P450 1a1 (Cyp1a1). A single dose of TCDD administered to adult mice induced Ahr-dependent CpG hypomethylation, changes in histone modifications, and thymine DNA glycosylase (Tdg) recruitment at the Cyp1a1 promoter in the liver within 24\\u2009hrs. These epigenetic changes persisted until 40 days post-TCDD treatment and there was Cyp1a1 mRNA hyperinduction upon repeat administration of TCDD at this time-point. Our demethylation assay using siRNA knockdown and an in vitro methylated plasmid showed that Ahr, Tdg, and the ten-eleven translocation methyldioxygenases Tet2 and Tet3 are required for the TCDD-induced DNA demethylation. These results provide novel evidence of Ahr-driven active DNA demethylation and epigenetic memory. The epigenetic alterations influence response to subsequent chemical exposure and imply an adaptive mechanism to xenobiotic stress.',\n", - " 'author': ['Amenya, Hesbon Z.', 'Tohyama, Chiharu', 'Ohsako, Seiichiroh'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep34989\"}'],\n", - " 'title': ['Dioxin induces Ahr-dependent robust DNA demethylation of the Cyp1a1 promoter via Tdg in the mouse liver']},\n", - " {'bibcode': '2010Natur.466..714M',\n", - " 'abstract': 'Recent genome-wide association studies (GWASs) have identified a locus on chromosome 1p13 strongly associated with both plasma low-density lipoprotein cholesterol (LDL-C) and myocardial infarction (MI) in humans. Here we show through a series of studies in human cohorts and human-derived hepatocytes that a common noncoding polymorphism at the 1p13 locus, rs12740374, creates a C/EBP (CCAAT/enhancer binding protein) transcription factor binding site and alters the hepatic expression of the SORT1 gene. With small interfering RNA (siRNA) knockdown and viral overexpression in mouse liver, we demonstrate that Sort1 alters plasma LDL-C and very low-density lipoprotein (VLDL) particle levels by modulating hepatic VLDL secretion. Thus, we provide functional evidence for a novel regulatory pathway for lipoprotein metabolism and suggest that modulation of this pathway may alter risk for MI in humans. We also demonstrate that common noncoding DNA variants identified by GWASs can directly contribute to clinical phenotypes.',\n", - " 'author': ['Musunuru, Kiran',\n", - " 'Strong, Alanna',\n", - " 'Frank-Kamenetsky, Maria',\n", - " 'Lee, Noemi E.',\n", - " 'Ahfeldt, Tim',\n", - " 'Sachs, Katherine V.',\n", - " 'Li, Xiaoyu',\n", - " 'Li, Hui',\n", - " 'Kuperwasser, Nicolas',\n", - " 'Ruda, Vera M.',\n", - " 'Pirruccello, James P.',\n", - " 'Muchmore, Brian',\n", - " 'Prokunina-Olsson, Ludmila',\n", - " 'Hall, Jennifer L.',\n", - " 'Schadt, Eric E.',\n", - " 'Morales, Carlos R.',\n", - " 'Lund-Katz, Sissel',\n", - " 'Phillips, Michael C.',\n", - " 'Wong, Jamie',\n", - " 'Cantley, William',\n", - " 'Racie, Timothy',\n", - " 'Ejebe, Kenechi G.',\n", - " 'Orho-Melander, Marju',\n", - " 'Melander, Olle',\n", - " 'Koteliansky, Victor',\n", - " 'Fitzgerald, Kevin',\n", - " 'Krauss, Ronald M.',\n", - " 'Cowan, Chad A.',\n", - " 'Kathiresan, Sekar',\n", - " 'Rader, Daniel J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature09266\"}'],\n", - " 'title': ['From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus']},\n", - " {'bibcode': '2013EnTox..28..349L',\n", - " 'author': ['Li, Na',\n", - " 'Cheng, Jie',\n", - " 'Cheng, Zhe',\n", - " 'Hu, Renping',\n", - " 'Cai, Jingwei',\n", - " 'Gao, Guodong',\n", - " 'Cui, Yaling',\n", - " 'Wang, Ling',\n", - " 'Hong, Fashui'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Ftox.20727\"}'],\n", - " 'title': ['Molecular mechanism of inflammatory response in mouse liver caused by exposure to CeCl3']},\n", - " {'bibcode': '1998PNAS...95.5987H',\n", - " 'abstract': 'Hepatic lipid synthesis is known to be regulated by food consumption. In rodents fasting decreases the synthesis of cholesterol as well as fatty acids. Refeeding a high carbohydrate/low fat diet enhances fatty acid synthesis by 5- to 20-fold above the fed state, whereas cholesterol synthesis returns only to the prefasted level. Sterol regulatory element binding proteins (SREBPs) are transcription factors that regulate genes involved in cholesterol and fatty acid synthesis. Here, we show that fasting markedly reduces the amounts of SREBP-1 and -2 in mouse liver nuclei, with corresponding decreases in the mRNAs for SREBP-activated target genes. Refeeding a high carbohydrate/low fat diet resulted in a 4- to 5-fold increase of nuclear SREBP-1 above nonfasted levels, whereas nuclear SREBP-2 protein returned only to the nonfasted level. The hepatic mRNAs for fatty acid biosynthetic enzymes increased 5- to 10-fold above nonfasted levels, a pattern that paralleled the changes in nuclear SREBP-1. The hepatic mRNAs for enzymes involved in cholesterol synthesis returned to the nonfasted level, closely following the pattern of nuclear SREBP-2 regulation. Transgenic mice that overproduce nuclear SREBP-1c failed to show the normal decrease in hepatic mRNA levels for cholesterol and fatty acid synthetic enzymes upon fasting. We conclude that SREBPs are regulated by food consumption in the mouse liver and that the decline in nuclear SREBP-1c upon fasting may explain in part the decrease in mRNAs encoding enzymes of the fatty acid biosynthetic pathway.',\n", - " 'author': ['Horton, Jay D.',\n", - " 'Bashmakov, Yuriy',\n", - " 'Shimomura, Iichiro',\n", - " 'Shimano, Hitoshi'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/95/11/5987\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/95/11/5987\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/95/11/5987\"}'],\n", - " 'title': ['Regulation of Sterol Regulatory Element Binding Proteins in Livers of Fasted and Refed Mice']},\n", - " {'bibcode': '2015RScI...86a4905L',\n", - " 'abstract': 'Accurate knowledge of the thermal conductivity (k) of biological tissues is important for cryopreservation, thermal ablation, and cryosurgery. Here, we adapt the 3ω method—widely used for rigid, inorganic solids—as a reusable sensor to measure k of soft biological samples two orders of magnitude thinner than conventional tissue characterization methods. Analytical and numerical studies quantify the error of the commonly used \"boundary mismatch approximation\" of the bi-directional 3ω geometry, confirm that the generalized slope method is exact in the low-frequency limit, and bound its error for finite frequencies. The bi-directional 3ω measurement device is validated using control experiments to within ±2% (liquid water, standard deviation) and ±5% (ice). Measurements of mouse liver cover a temperature ranging from -69 °C to +33 °C. The liver results are independent of sample thicknesses from 3 mm down to 100 μm and agree with available literature for non-mouse liver to within the measurement scatter.',\n", - " 'author': ['Lubner, Sean D.',\n", - " 'Choi, Jeunghwan',\n", - " 'Wehmeyer, Geoff',\n", - " 'Waag, Bastian',\n", - " 'Mishra, Vivek',\n", - " 'Natesan, Harishankar',\n", - " 'Bischof, John C.',\n", - " 'Dames, Chris'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1063%2F1.4905680\"}'],\n", - " 'title': ['Reusable bi-directional 3ω sensor to measure thermal conductivity of 100-μm thick biological tissues']},\n", - " {'bibcode': '2006PNAS..10318586F',\n", - " 'abstract': 'Dividing cultured cells contain much larger pools of the four dNTPs than resting cells. In both cases the sizes of the individual pools are only moderately different. The same applies to mitochondrial (mt) pools of cultured cells. Song et al. [Song S, Pursell ZF, Copeland WC, Longley MJ, Kunkel TA, Mathews CK (2005) Proc Natl Acad Sci USA 102:4990-4995] reported that mt pools of rat tissues instead are highly asymmetric, with the dGTP pool in some cases being several-hundred-fold larger than the dTTP pool, and suggested that the asymmetry contributes to increased mutagenesis during mt DNA replication. We have now investigated this discrepancy and determined the size of each dNTP pool in mouse liver mitochondria. We found large variations in pool sizes that closely followed variations in the ATP pool and depended on the length of time spent in the preparation of mitochondria. The proportion between dNTPs was in all cases without major asymmetries and similar to those found earlier in cultured resting cells. We also investigated the import and export of thymidine phosphates in mouse liver mitochondria and provide evidence for a rapid, highly selective, and saturable import of dTMP, not depending on a functional respiratory chain. At nM external dTMP the nucleotide is concentrated 100-fold inside the mt matrix. Export of thymidine phosphates was much slower and possibly occurred at the level of dTDP.',\n", - " 'author': ['Ferraro, Paola',\n", - " 'Nicolosi, Luca',\n", - " 'Bernardi, Paolo',\n", - " 'Reichard, Peter',\n", - " 'Bianchi, Vera'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/103/49/18586\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0609020103\"}'],\n", - " 'title': ['Mitochondrial deoxynucleotide pool sizes in mouse liver and evidence for a transport mechanism for thymidine monophosphate']},\n", - " {'bibcode': '2014EnTox..29..837C',\n", - " 'author': ['Cheng, Jie',\n", - " 'Fei, Min',\n", - " 'Fei, Min',\n", - " 'Sang, Xuezi',\n", - " 'Sang, Xuezi',\n", - " 'Cheng, Zhe',\n", - " 'Gui, Suxin',\n", - " 'Zhao, Xiaoyang',\n", - " 'Sheng, Lei',\n", - " 'Sun, Qingqing',\n", - " 'Hu, Renping',\n", - " 'Wang, Ling',\n", - " 'Hong, Fashui'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Ftox.21826\"}'],\n", - " 'title': ['Gene expression profile in chronic mouse liver injury caused by long-term exposure to CeCl3']},\n", - " {'bibcode': '1981Natur.289..643H',\n", - " 'abstract': \"The sequence of the 1,773-nucleotide major and 1,806-nucleotide minor mouse liver α-amylase mRNAs differ only with respect to approximately 30 additional residues at the extreme 5' terminus of the minor species. Comparison of the liver α-amylase mRNAs with their salivary gland counterpart reveals that these mRNAs share identical coding and 3'-noncoding sequences, but contain distinct 5'-terminal residues. These data suggest that all three mRNAs might be transcribed from the same gene.\",\n", - " 'author': ['Hagenbüchle, Otto',\n", - " 'Tosi, Mario',\n", - " 'Schibler, Ueli',\n", - " 'Bovey, Raymonde',\n", - " 'Wellauer, Peter K.',\n", - " 'Young, Richard A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F289643a0\"}'],\n", - " 'title': [\"Mouse liver and salivary gland α-amylase mRNAs differ only in 5' non-translated sequences\"]},\n", - " {'bibcode': '1995PNAS...92.4215R',\n", - " 'abstract': 'Intraperitoneal injection of epidermal growth factor into mice results in the appearance of multiple tyrosine-phosphorylated proteins in liver nuclei within minutes after administration. We have previously identified three of these proteins as Stat 1 alpha, Stat 1 beta (p91, p84), and Stat 3 (p89). In the present report we demonstrate that Stat 5 (p92), the recently described prolactin inducible transcription factor detected in mammary glands, is the major tyrosine-phosphorylated protein translocated to the nucleus in mouse liver in response to epidermal growth factor. Furthermore, gel-shift analysis and affinity purification revealed that Stat 5, Stat 1 alpha, and Stat 1 beta specifically bind to the prolactin inducible element upstream of the beta-casein promoter.',\n", - " 'author': ['Ruff-Jamison, Susan', 'Chen, Katherine', 'Cohen, Stanley'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/92/10/4215\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/92/10/4215\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/92/10/4215\"}'],\n", - " 'title': ['Epidermal growth factor induces the tyrosine phosphorylation and nuclear translocation of Stat 5 in mouse liver.']},\n", - " {'bibcode': '2015NatCo...6.6790W',\n", - " 'abstract': 'DNA damage has been implicated in ageing, but direct evidence for a causal relationship is lacking, owing to the difficulty of inducing defined DNA lesions in cells and tissues without simultaneously damaging other biomolecules and cellular structures. Here we directly test whether highly toxic DNA double-strand breaks (DSBs) alone can drive an ageing phenotype using an adenovirus-based system based on tetracycline-controlled expression of the SacI restriction enzyme. We deliver the adenovirus to mice and compare molecular and cellular end points in the liver with normally aged animals. Treated, 3-month-old mice display many, but not all signs of normal liver ageing as early as 1 month after treatment, including ageing pathologies, markers of senescence, fused mitochondria and alterations in gene expression profiles. These results, showing that DSBs alone can cause distinct ageing phenotypes in mouse liver, provide new insights in the role of DNA damage as a driver of tissue ageing.',\n", - " 'author': ['White, Ryan R.',\n", - " 'Milholland, Brandon',\n", - " 'de Bruin, Alain',\n", - " 'Curran, Samuel',\n", - " 'Laberge, Remi-Martin',\n", - " 'van Steeg, Harry',\n", - " 'Campisi, Judith',\n", - " 'Maslov, Alexander Y.',\n", - " 'Vijg, Jan'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fncomms7790\"}'],\n", - " 'title': ['Controlled induction of DNA double-strand breaks in the mouse liver induces features of tissue ageing']},\n", - " {'bibcode': '2020Chmsp.241l5092B',\n", - " 'author': ['Brulport, Axelle',\n", - " 'Vaiman, Daniel',\n", - " 'Chagnon, Marie-Christine',\n", - " 'Le Corre, Ludovic'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.chemosphere.2019.125092\"}'],\n", - " 'title': ['Obesogen effect of bisphenol S alters mRNA expression and DNA methylation profiling in male mouse liver']},\n", - " {'bibcode': '1967PNAS...57..790D',\n", - " 'author': ['du Buy, H. G.', 'Riley, F. L.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/57/3/790\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/57/3/790\"}'],\n", - " 'title': [\"Hybridization Between the Nuclear and Kinetoplast Dna's of Leishmania enriettii and Between Nuclear and Mitochondrial Dna's of Mouse Liver\"]},\n", - " {'bibcode': '1968PNAS...59..854T',\n", - " 'author': ['Trakatellis, Anthony C.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/59/3/854\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/59/3/854\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.59.3.854\"}'],\n", - " 'title': ['Effect of sparsomycin on protein synthesis in the mouse liver.']},\n", - " {'bibcode': '1987RadR..109..143N',\n", - " 'author': ['Nakamura, Jiro', 'Shaw, Leslie M.', 'Brown, Darrell Q.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.2307%2F3576875\"}'],\n", - " 'title': ['Hydrolysis of WR2721 by Mouse Liver Cell Fractions']},\n", - " {'bibcode': '1973RadR...53..102R',\n", - " 'author': ['Rosenthal, M. W.',\n", - " 'Brown, H.',\n", - " 'Chladek, D. L.',\n", - " 'Moretti, E. S.',\n", - " 'Russell, J. J.',\n", - " 'Lindenbaum, A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.2307%2F3573451\"}'],\n", - " 'title': ['Removal of Plutonium from Mouse Liver by Glucan and DTPA']},\n", - " {'bibcode': '1997PNAS...94.2284U',\n", - " 'abstract': 'Methylation of CpG sites in the genome, which is generally conserved during cell replication, is considered to play important roles in cell differentiation and carcinogenesis. However, investigations on changes in methylation status have been limited to known genes. To make a genome-wide search for differentially methylated genes, we developed a methylation-sensitive-representational difference analysis (MS-RDA) method. The representation of the genome was prepared using the methylation-sensitive restriction enzyme HpaII, and the mixture ratio of tester and driver DNAs was optimized to detect differences in methylation status of a single copy per diploid mammalian genome. By performing comparative MS-RDA of one hepatocellular carcinoma and of background liver tissue of one mouse treated with a food carcinogen (2-amino-3,4-dimethylimidazo[4,5-f]quinoline), we were able to identify (i) extensive hypomethylation of long interspersed nuclear element repetitive sequences in a number of hepatocellular carcinomas, (ii) reduction of the gene dosage of their mitochondrial DNA, and (iii) a hypermethylated DNA fragment of unknown origin. Furthermore, by adding the clones obtained in the first MS-RDA to the driver DNA [MS-RDA with elimination of excessive clones (MS-RDA-WEEC)], nine DNA fragments that could not be detected at the first MS-RDA were isolated as differentially methylated DNA fragments. MS-RDA, combined with MS-RDA-WEEC, is thus a promising approach to identify DNA fragments differentially methylated in two DNA sources.',\n", - " 'author': ['Ushijima, Toshikazu',\n", - " 'Morimura, Keiichirou',\n", - " 'Hosoya, Yoko',\n", - " 'Okonogi, Hideo',\n", - " 'Tatematsu, Masae',\n", - " 'Sugimura, Takashi',\n", - " 'Nagao, Minako'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/94/6/2284\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/94/6/2284\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/94/6/2284\"}'],\n", - " 'title': ['Establishment of Methylation-Sensitive-Representational Difference Analysis and Isolation of Hypo- and Hypermethylated Genomic Fragments in Mouse Liver Tumors']},\n", - " {'bibcode': '2014PNAS..11117200Y',\n", - " 'abstract': 'Triclosan [5-chloro-2-(2,4-dichlorophenoxy)phenol; TCS] is a broad-spectrum antimicrobial agent that has become one of the most common additives used in consumer products. As a result, TCS has significantly affected the environment and has been frequently detected in human body fluids. Through a long-term feeding study, we found that TCS enhances hepatocyte proliferation, fibrogenesis, and oxidative stress, which, we believe, can be the driving force for developing advanced liver disease in mice. Indeed, TCS strongly enhances hepatocarcinogenesis after diethylnitrosamine initiation, accelerating hepatocellular carcinoma (HCC) development. Although animal studies require higher chemical concentrations than predicted for human exposure, this study demonstrates that TCS acts as a HCC tumor promoter and that the mechanism of TCS-induced mouse liver pathology may be relevant to humans.',\n", - " 'author': ['Yueh, Mei-Fei',\n", - " 'Taniguchi, Koji',\n", - " 'Chen, Shujuan',\n", - " 'Evans, Ronald M.',\n", - " 'Hammock, Bruce D.',\n", - " 'Karin, Michael',\n", - " 'Tukey, Robert H.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/111/48/17200\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1419119111\"}'],\n", - " 'title': ['The commonly used antimicrobial additive triclosan is a liver tumor promoter']},\n", - " {'bibcode': '2018JASMS..29..711R',\n", - " 'abstract': 'Bile acids (BAs) play two vital roles in living organisms, as they are involved in (1) the secretion of cholesterol from liver, and (2) the lipid digestion/absorption in the intestine. Abnormal bile acid synthesis or secretion can lead to severe liver disorders. Even though there is extensive literature on the mass spectrometric determination of BAs in biofluids and tissue homogenates, there are no reports on the spatial distribution in the biliary network of the liver. Here, we demonstrate the application of high mass resolution/mass accuracy matrix-assisted laser desorption/ionization (MALDI)-Fourier-transform ion cyclotron resonance (FTICR) to MS imaging (MSI) of BAs at high spatial resolutions (pixel size, 25 μm). The results show chemical heterogeneity of the mouse liver sections with a number of branching biliary and blood ducts. In addition to ion signals from deprotonation of the BA molecules, MALDI-MSI generated several further intense signals at larger m/z for the BAs. These signals were spatially co-localized with the deprotonated molecules and easily misinterpreted as additional products of BA biotransformations. In-depth analysis of accurate mass shifts and additional electrospray ionization and MALDI-FTICR experiments, however, confirmed them as proton-bound dimers. Interestingly, dimers of bile acids, but also unusual mixed dimers of different taurine-conjugated bile acids and free taurine, were identified. Since formation of these complexes will negatively influence signal intensities of the desired [M - H]- ions and significantly complicate mass spectral interpretations, two simple broadband techniques were proposed for non-selective dissociation of dimers that lead to increased signals for the deprotonated BAs.

[Figure not available: see fulltext.]',\n", - " 'author': ['Rzagalinski, Ignacy',\n", - " 'Hainz, Nadine',\n", - " 'Meier, Carola',\n", - " 'Tschernig, Thomas',\n", - " 'Volmer, Dietrich A.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://dx.doi.org/10.1007/s13361-017-1886-6\"}'],\n", - " 'title': ['MALDI Mass Spectral Imaging of Bile Acids Observed as Deprotonated Molecules and Proton-Bound Dimers from Mouse Liver Sections']},\n", - " {'bibcode': '2011Natur.476..341B',\n", - " 'abstract': \"Mitochondria from diverse organisms are capable of transporting large amounts of Ca2+ via a ruthenium-red-sensitive, membrane-potential-dependent mechanism called the uniporter. Although the uniporter's biophysical properties have been studied extensively, its molecular composition remains elusive. We recently used comparative proteomics to identify MICU1 (also known as CBARA1), an EF-hand-containing protein that serves as a putative regulator of the uniporter. Here, we use whole-genome phylogenetic profiling, genome-wide RNA co-expression analysis and organelle-wide protein coexpression analysis to predict proteins functionally related to MICU1. All three methods converge on a novel predicted transmembrane protein, CCDC109A, that we now call `mitochondrial calcium uniporter' (MCU). MCU forms oligomers in the mitochondrial inner membrane, physically interacts with MICU1, and resides within a large molecular weight complex. Silencing MCU in cultured cells or in vivo in mouse liver severely abrogates mitochondrial Ca2+ uptake, whereas mitochondrial respiration and membrane potential remain fully intact. MCU has two predicted transmembrane helices, which are separated by a highly conserved linker facing the intermembrane space. Acidic residues in this linker are required for its full activity. However, an S259A point mutation retains function but confers resistance to Ru360, the most potent inhibitor of the uniporter. Our genomic, physiological, biochemical and pharmacological data firmly establish MCU as an essential component of the mitochondrial Ca2+ uniporter.\",\n", - " 'author': ['Baughman, Joshua M.',\n", - " 'Perocchi, Fabiana',\n", - " 'Girgis, Hany S.',\n", - " 'Plovanich, Molly',\n", - " 'Belcher-Timme, Casey A.',\n", - " 'Sancak, Yasemin',\n", - " 'Bao, X. Robert',\n", - " 'Strittmatter, Laura',\n", - " 'Goldberger, Olga',\n", - " 'Bogorad, Roman L.',\n", - " 'Koteliansky, Victor',\n", - " 'Mootha, Vamsi K.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature10234\"}'],\n", - " 'title': ['Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter']},\n", - " {'bibcode': '2014PLoSO...990137L',\n", - " 'author': ['Lim, Jihyeon',\n", - " 'Liu, Zhongbo',\n", - " 'Apontes, Pasha',\n", - " 'Feng, Daorong',\n", - " 'Pessin, Jeffrey E.',\n", - " 'Sauve, Anthony A.',\n", - " 'Angeletti, Ruth H.',\n", - " 'Chi, Yuling'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0090137\"}'],\n", - " 'title': ['Dual Mode Action of Mangiferin in Mouse Liver under High Fat Diet']},\n", - " {'bibcode': '1980Sci...209.1348L',\n", - " 'abstract': \"A single DNA fragment containing both μ and δ immunoglobulin heavy chain genes has been cloned from normal BALB/c mouse liver DNA with a new λ phage vector Charon 28. The physical distance between the membrane terminal exon of μ and the first domain of δ is 2466 base pairs, with δ on the 3' side of μ . A single transcript could contain a variable region and both μ and δ constant regions. The dual expression of immunoglobulins M and D on spleen B cells may be due to alternate splicing of this transcript.\",\n", - " 'author': ['Liu, Chih-Ping',\n", - " 'Tucker, Philip W.',\n", - " 'Mushinski, J. Frederic',\n", - " 'Blattner, Frederick R.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.6774414\"}'],\n", - " 'title': ['Mapping of Heavy Chain Genes for Mouse Immunoglobulins M and D']},\n", - " {'bibcode': '2013PLoSO...859611N',\n", - " 'author': ['Nakagawa, Shin-ichiro',\n", - " 'Hirata, Yuichi',\n", - " 'Kameyama, Takeshi',\n", - " 'Tokunaga, Yuko',\n", - " 'Nishito, Yasumasa',\n", - " 'Hirabayashi, Kazuko',\n", - " 'Yano, Junichi',\n", - " 'Ochiya, Takahiro',\n", - " 'Tateno, Chise',\n", - " 'Tanaka, Yasuhito',\n", - " 'Mizokami, Masashi',\n", - " 'Tsukiyama-Kohara, Kyoko',\n", - " 'Inoue, Kazuaki',\n", - " 'Yoshiba, Makoto',\n", - " 'Takaoka, Akinori',\n", - " 'Kohara, Michinori'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0059611\"}'],\n", - " 'title': ['Targeted Induction of Interferon-λ in Humanized Chimeric Mouse Liver Abrogates Hepatotropic Virus Infection']},\n", - " {'bibcode': '2002JMMM..248..276H',\n", - " 'abstract': 'In the previous work, we incubated THP1 cells and macrophages in vitro with unsubstituted ferrofluid (FF) and placed them in an alternating magnetic field. This resulted in the destruction of the cells (magnetocytolysis). Cell-specific magnetocytolysis in vitro was achieved in MCF7 human breast cancer cells incubated with tamoxifen-bound FF and treated in an alternating magnetic field. In this work, in a search of a model for magnetocytolysis in vivo, we injected mice intravenously with hepatospecific magnetic nanoparticles (HS-USPIO) and subjected the mice to magnetocytolysis in an alternating magnetic field (1 h at 200 A/m). This treatment resulted in a prolongation of blood coagulation time due to depletion of protein coagulation factors that are synthesized exclusively in the liver. The attendant derangement of liver protein synthesis was characterized in cell-free preparations by an inhibition of the endogenously coded protein synthesis coupled with an enhancement of phenylalanine polymerization directed by polyuridylic acid (Poly U). This indication of polyribosome dispersion was confirmed by electron microscopy. Magnetocytolysis did not cause liver necrosis and was neither accompanied by any increase in body or liver temperature, nor damage to any other tissue. The effects of magnetocytolysis were proportional to the amount of injected HS-USPIO, field strength and its application time. Magnetocytolysis did not occur when non-magnetic PolyGalactoseGold particles were substituted for HS-USPIO. PolyGalactoseGold particles were employed to measure asialoglycoprotein receptor (ASGP-R) activity in liver using neutron activation analysis. Injection of PolyGalactoseGold particles to mice, pre-treated by HS-USPIO driven magnetocytolysis, revealed a transient diminution of hepatic ASGP-R. Liver damage from magnetocytolysis was followed by liver regeneration, manifested by the appearance of thymidylate kinase activity, diminution of ASGP-R and return to normal blood coagulation time.',\n", - " 'author': ['Halbreich, Avraham',\n", - " 'Groman, Ernest V.',\n", - " 'Raison, Danielle',\n", - " 'Bouchaud, Claude',\n", - " 'Paturance, Sébastien'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2FS0304-8853%2802%2900356-6\"}'],\n", - " 'title': ['Damage to the protein synthesizing apparatus in mouse liver in vivo by magnetocytolysis in the presence of hepatospecific magnetic nanoparticles']},\n", - " {'bibcode': '2009PNAS..10621453V',\n", - " 'abstract': 'In mammals, the circadian oscillator generates approximately 24-h rhythms in feeding behavior, even under constant environmental conditions. Livers of mice held under constant darkness exhibit circadian rhythm in abundance in up to 15% of expressed transcripts. Therefore, oscillations in hepatic transcripts could be driven by rhythmic food intake or sustained by the hepatic circadian oscillator, or a combination of both. To address this question, we used distinct feeding and fasting paradigms on wild-type (WT) and circadian clock-deficient mice. We monitored temporal patterns of feeding and hepatic transcription. Both food availability and the temporal pattern of feeding determined the repertoire, phase, and amplitude of the circadian transcriptome in WT liver. In the absence of feeding, only a small subset of transcripts continued to express circadian patterns. Conversely, temporally restricted feeding restored rhythmic transcription of hundreds of genes in oscillator-deficient mouse liver. Our findings show that both temporal pattern of food intake and the circadian clock drive rhythmic transcription, thereby highlighting temporal regulation of hepatic transcription as an emergent property of the circadian system.',\n", - " 'author': ['Vollmers, Christopher',\n", - " 'Gill, Shubhroz',\n", - " 'DiTacchio, Luciano',\n", - " 'Pulivarthy, Sandhya R.',\n", - " 'Le, Hiep D.',\n", - " 'Panda, Satchidananda'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/106/50/21453\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0909591106\"}'],\n", - " 'title': ['Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression']},\n", - " {'bibcode': '1974Sci...183..208R',\n", - " 'abstract': 'Homogenates of mouse liver and brain at 37 degrees C spontaneously formed lipid peroxides and simultaneously evolved ethane. α -Tocopherol, a lipid antioxidant, blocked ethane formation. When mice were injected with carbon tetrachloride (a liquid prooxidant for liver), the animals produced ethane. Ethane evolution in vivo was stimulated by prior administration of phenobarbital and it was diminished by prior injection of α -tocopherol. These data suggest that ethane production may be a useful index of lipid peroxidation in tissue homogenates and in intact animals.',\n", - " 'author': ['Riely, Caroline A.', 'Cohen, Gerald', 'Lieberman, Morris'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.jstor.org/stable/1737370?origin=ads\"}'],\n", - " 'title': ['Ethane Evolution: A New Index of Lipid Peroxidation']},\n", - " {'bibcode': '2012PLoSO...739006W',\n", - " 'author': ['Wu, Kai Connie', 'Cui, Julia Yue', 'Klaassen, Curtis D.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0039006\"}'],\n", - " 'title': ['Effect of Graded Nrf2 Activation on Phase-I and -II Drug Metabolizing Enzymes and Transporters in Mouse Liver']},\n", - " {'bibcode': '2010PLoSO...510288F',\n", - " 'author': ['Fang, Xianfeng', 'Du, Peishuang', 'Liu, Yang', 'Tang, Jie'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0010288\"}'],\n", - " 'title': ['Efficient Isolation of Mouse Liver NKT Cells by Perfusion']},\n", - " {'bibcode': '2016PLoSO..1155282J',\n", - " 'author': ['Jonscher, Karen R.',\n", - " 'Alfonso-Garcia, Alba',\n", - " 'Suhalim, Jeffrey L.',\n", - " 'Orlicky, David J.',\n", - " 'Potma, Eric O.',\n", - " 'Ferguson, Virginia L.',\n", - " 'Bouxsein, Mary L.',\n", - " 'Bateman, Ted A.',\n", - " 'Stodieck, Louis S.',\n", - " 'Levi, Moshe',\n", - " 'Friedman, Jacob E.',\n", - " 'Gridley, Daila S.',\n", - " 'Pecaut, Michael J.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0155282\"}'],\n", - " 'title': ['Correction: Spaceflight Activates Lipotoxic Pathways in Mouse Liver']},\n", - " {'bibcode': '1967PNAS...58.1548C',\n", - " 'author': ['Church, Robert', 'McCarthy, Brian J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/58/4/1548\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/58/4/1548\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.58.4.1548\"}'],\n", - " 'title': ['Changes in nuclear and cytoplasmic RNA in regenerating mouse liver.']},\n", - " {'bibcode': '2012HyInt.206...71G',\n", - " 'abstract': 'In this work the first fast stage of the biodegradation in vivo of magnetic ferrofluid was investigated. The appearance of a paramagnetic doublet was observed in Mössbauer spectra of mouse liver within 2 h after intravenous injection of the ferrofluid. It was shown that nanosized superparamagnetic particles were combined into groups in the initial magnetic beads of the ferrofluid and were connected inside each group by magnetic dipole interaction. It was found that the appearance of a paramagnetic doublet in the spectrum of mouse liver is caused by the decrease of the magneto-dipole interaction between the superparamagnetic nanoparticles.',\n", - " 'author': ['Gabbasov, Raul R.',\n", - " 'Cherepanov, Valery M.',\n", - " 'Chuev, Michael A.',\n", - " 'Polikarpov, Michael A.',\n", - " 'Panchenko, Vladislav Y.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1007%2Fs10751-011-0530-2\"}'],\n", - " 'title': ['Study of interparticle interaction in conjugates of magnetic nanoparticles injected into mice']},\n", - " {'bibcode': '2019NatSR...914937K',\n", - " 'abstract': 'ALDH1L1 (10-formyltetrahydrofolate dehydrogenase), an enzyme of folate metabolism highly expressed in liver, metabolizes 10-formyltetrahydrofolate to produce tetrahydrofolate (THF). This reaction might have a regulatory function towards reduced folate pools, de novo purine biosynthesis, and the flux of folate-bound methyl groups. To understand the role of the enzyme in cellular metabolism, Aldh1l1-/- mice were generated using an ES cell clone (C57BL/6N background) from KOMP repository. Though Aldh1l1-/- mice were viable and did not have an apparent phenotype, metabolomic analysis indicated that they had metabolic signs of folate deficiency. Specifically, the intermediate of the histidine degradation pathway and a marker of folate deficiency, formiminoglutamate, was increased more than 15-fold in livers of Aldh1l1-/- mice. At the same time, blood folate levels were not changed and the total folate pool in the liver was decreased by only 20%. A two-fold decrease in glycine and a strong drop in glycine conjugates, a likely result of glycine shortage, were also observed in Aldh1l1-/- mice. Our study indicates that in the absence of ALDH1L1 enzyme, 10-formyl-THF cannot be efficiently metabolized in the liver. This leads to the decrease in THF causing reduced generation of glycine from serine and impaired histidine degradation, two pathways strictly dependent on THF.',\n", - " 'author': ['Krupenko, Natalia I.',\n", - " 'Sharma, Jaspreet',\n", - " 'Pediaditakis, Peter',\n", - " 'Fekry, Baharan',\n", - " 'Helke, Kristi L.',\n", - " 'Du, Xiuxia',\n", - " 'Sumner, Susan',\n", - " 'Krupenko, Sergey A.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-019-51397-1\"}'],\n", - " 'title': ['Cytosolic 10-formyltetrahydrofolate dehydrogenase regulates glycine metabolism in mouse liver']},\n", - " {'bibcode': '2018NatSR...810138D',\n", - " 'abstract': 'DNA methylation plays a key role in X-chromosome inactivation (XCI), a process that achieves dosage compensation for X-encoded gene products between mammalian female and male cells. However, differential sex chromosome dosage complicates genome-wide epigenomic assessments, and the X chromosome is frequently excluded from female-to-male comparative analyses. Using the X chromosome in the sexually dimorphic mouse liver as a model, we provide a general framework for comparing base-resolution DNA methylation patterns across samples that have different chromosome numbers and ask at a systematic level if predictions by historical analyses of X-linked DNA methylation hold true at a base-resolution chromosome-wide level. We demonstrate that sex-specific methylation patterns on the X chromosome largely reflect the effects of XCI. While our observations concur with longstanding observations of XCI at promoter-proximal CpG islands, we provide evidence that sex-specific DNA methylation differences are not limited to CpG island boundaries. Moreover, these data support a model in which maintenance of CpG islands in the inactive state does not require complete regional methylation. Further, we validate an intragenic non-CpG methylation signature in genes escaping XCI in mouse liver. Our analyses provide insight into underlying methylation patterns that should be considered when assessing sex differences in genome-wide methylation analyses.',\n", - " 'author': ['Duncan, Christopher G.',\n", - " 'Grimm, Sara A.',\n", - " 'Morgan, Daniel L.',\n", - " 'Bushel, Pierre R.',\n", - " 'Bennett, Brian D.',\n", - " 'NISC Comparative Sequencing Program',\n", - " 'Roberts, John D.',\n", - " 'Tyson, Frederick L.',\n", - " 'Merrick, B. Alex',\n", - " 'Wade, Paul A.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-018-28356-3\"}'],\n", - " 'title': ['Dosage compensation and DNA methylation landscape of the X chromosome in mouse liver']},\n", - " {'bibcode': '1950Sci...111..149F',\n", - " 'author': ['Feinstein, Robert N.',\n", - " 'Butler, Carrie L.',\n", - " 'Hendley, Daniel D.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.jstor.org/stable/1676119?origin=ads\"}'],\n", - " 'title': ['Effect of Whole Body X-Radiation and of Intraperitoneal Hydrogen Peroxide on Mouse Liver Catalase']},\n", - " {'bibcode': '1973PNAS...70..909G',\n", - " 'abstract': 'Evidence is presented that there is a considerable accumulation of inactive fructose-1,6-diphosphate aldolase (EC 4.1.2.7) in the liver of senescent mice. Liver aldolase was purified from 3-month-old mice and used to immunize rabbits. It was demonstrated with the monospecific antibody thus produced that the liver aldolase of young adult (3 month) and aged (31 month) mice are antigenically identical. With the antibody, inactive enzyme molecules (crossreacting material) in liver homogenate of old mice were detected. The liver aldolase of senescent mice had half as much active enzyme per mg of protein, as well as per antigenic unit, as did the liver aldolase of young adult mice. The accumulation of faulty enzyme molecules may be one of the causes of debilitation leading to senescence and death.',\n", - " 'author': ['Gershon, Harriet', 'Gershon, David'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/70/3/909\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/70/3/909\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/70/3/909\"}'],\n", - " 'title': ['Inactive Enzyme Molecules in Aging Mice: Liver Aldolase']},\n", - " {'bibcode': '2013Natur.494..247H',\n", - " 'abstract': 'The Wnt target gene Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5) marks actively dividing stem cells in Wnt-driven, self-renewing tissues such as small intestine and colon, stomach and hair follicles. A three-dimensional culture system allows long-term clonal expansion of single Lgr5+ stem cells into transplantable organoids (budding cysts) that retain many characteristics of the original epithelial architecture. A crucial component of the culture medium is the Wnt agonist RSPO1, the recently discovered ligand of LGR5. Here we show that Lgr5-lacZ is not expressed in healthy adult liver, however, small Lgr5-LacZ+ cells appear near bile ducts upon damage, coinciding with robust activation of Wnt signalling. As shown by mouse lineage tracing using a new Lgr5-IRES-creERT2 knock-in allele, damage-induced Lgr5+ cells generate hepatocytes and bile ducts in vivo. Single Lgr5+ cells from damaged mouse liver can be clonally expanded as organoids in Rspo1-based culture medium over several months. Such clonal organoids can be induced to differentiate in vitro and to generate functional hepatocytes upon transplantation into Fah-/- mice. These findings indicate that previous observations concerning Lgr5+ stem cells in actively self-renewing tissues can also be extended to damage-induced stem cells in a tissue with a low rate of spontaneous proliferation.',\n", - " 'author': ['Huch, Meritxell',\n", - " 'Dorrell, Craig',\n", - " 'Boj, Sylvia F.',\n", - " 'van Es, Johan H.',\n", - " 'Li, Vivian S. W.',\n", - " 'van de Wetering, Marc',\n", - " 'Sato, Toshiro',\n", - " 'Hamer, Karien',\n", - " 'Sasaki, Nobuo',\n", - " 'Finegold, Milton J.',\n", - " 'Haft, Annelise',\n", - " 'Vries, Robert G.',\n", - " 'Grompe, Markus',\n", - " 'Clevers, Hans'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature11826\"}'],\n", - " 'title': ['In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration']},\n", - " {'bibcode': '2011PLoSO...627553Z',\n", - " 'author': ['Zhang, Fang',\n", - " 'Xu, Xiang',\n", - " 'Zhou, Ben',\n", - " 'He, Zhishui',\n", - " 'Zhai, Qiwei'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0027553\"}'],\n", - " 'title': ['Gene Expression Profile Change and Associated Physiological and Pathological Effects in Mouse Liver Induced by Fasting and Refeeding']},\n", - " {'bibcode': '1997PNAS...94.1426K',\n", - " 'abstract': 'We previously found that gene transduction by adeno-associated virus (AAV) vectors in cell culture can be stimulated over 100-fold by treatment of the target cells with agents that affect DNA metabolism, such as irradiation or topoisomerase inhibitors. Here we show that previous γ-irradiation increased the transduction rate in mouse liver by up to 900-fold, and the topoisomerase inhibitor etoposide increased transduction by about 20-fold. Similar rates of hepatic transduction were obtained by direct injection of the liver or by systemic delivery via tail vein injection. Hepatocytes were much more efficiently transduced than other cells after systemic delivery, and up to 3% of all hepatocytes could be transduced after one vector injection. The presence of wild-type AAV, which contaminates many AAV vector preparations, was required to observe a full response to γ-irradiation. Injection of mice with AAV vectors encoding human clotting factor IX after γ-irradiation resulted in synthesis of low levels of human clotting factor IX for the 5-month period of observation. These studies show the potential of targeted gene transduction of the liver by AAV vectors for treatment of various hematological or metabolic diseases.',\n", - " 'author': ['Koeberl, Dwight D.',\n", - " 'Alexander, Ian E.',\n", - " 'Halbert, Christine L.',\n", - " 'Russell, David W.',\n", - " 'Miller, A. Dusty'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/94/4/1426\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/94/4/1426\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/94/4/1426\"}'],\n", - " 'title': ['Persistent Expression of Human Clotting Factor IX from Mouse Liver after Intravenous Injection of Adeno-Associated Virus Vectors']},\n", - " {'bibcode': '2009Sci...325..100Z',\n", - " 'abstract': 'Cellular cholesterol levels reflect a balance between uptake, efflux, and endogenous synthesis. Here we show that the sterol-responsive nuclear liver X receptor (LXR) helps maintain cholesterol homeostasis, not only through promotion of cholesterol efflux but also through suppression of low-density lipoprotein (LDL) uptake. LXR inhibits the LDL receptor (LDLR) pathway through transcriptional induction of Idol (inducible degrader of the LDLR), an E3 ubiquitin ligase that triggers ubiquitination of the LDLR on its cytoplasmic domain, thereby targeting it for degradation. LXR ligand reduces, whereas LXR knockout increases, LDLR protein levels in vivo in a tissue-selective manner. Idol knockdown in hepatocytes increases LDLR protein levels and promotes LDL uptake. Conversely, adenovirus-mediated expression of Idol in mouse liver promotes LDLR degradation and elevates plasma LDL levels. The LXR-Idol-LDLR axis defines a complementary pathway to sterol response element-binding proteins for sterol regulation of cholesterol uptake.',\n", - " 'author': ['Zelcer, Noam',\n", - " 'Hong, Cynthia',\n", - " 'Boyadjian, Rima',\n", - " 'Tontonoz, Peter'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.1168974\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.1168974\"}'],\n", - " 'title': ['LXR Regulates Cholesterol Uptake Through Idol-Dependent Ubiquitination of the LDL Receptor']},\n", - " {'bibcode': '1984JMagR..60..430R',\n", - " 'abstract': '1H NMR studies of many mammalian tissues are complicated by the presence of large lipid resonances that obscure much of the spectrum. In this communication a simple spin-echo homonuclear double-resonance difference sequence was used to separate the resonances of alanine, lactate, β-hydroxybutyrate, glutamate, and glutamine from the lipid resonances which overlap them in excised rat leg muscle and heart, and in an excised mouse liver which had been perfused with [3- 13C]alanine.',\n", - " 'author': ['Rothman, D. L.',\n", - " 'Arias-Mendoza, F.',\n", - " 'Shulman, G. I.',\n", - " 'Shulman, R. G.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2F0022-2364%2884%2990054-4\"}'],\n", - " 'title': ['A pulse sequence for simplifying hydrogen NMR spectra of biological tissues']},\n", - " {'bibcode': '2004Natur.427..461K',\n", - " 'abstract': 'A sudden increase in permeability of the inner mitochondrial membrane, the so-called mitochondrial permeability transition, is a common feature of apoptosis and is mediated by the mitochondrial permeability transition pore (mtPTP). It is thought that the mtPTP is a protein complex formed by the voltage-dependent anion channel, members of the pro- and anti-apoptotic BAX-BCL2 protein family, cyclophilin D, and the adenine nucleotide (ADP/ATP) translocators (ANTs). The latter exchange mitochondrial ATP for cytosolic ADP and have been implicated in cell death. To investigate the role of the ANTs in the mtPTP, we genetically inactivated the two isoforms of ANT in mouse liver and analysed mtPTP activation in isolated mitochondria and the induction of cell death in hepatocytes. Mitochondria lacking ANT could still be induced to undergo permeability transition, resulting in release of cytochrome c. However, more Ca2+ than usual was required to activate the mtPTP, and the pore could no longer be regulated by ANT ligands. Moreover, hepatocytes without ANT remained competent to respond to various initiators of cell death. Therefore, ANTs are non-essential structural components of the mtPTP, although they do contribute to its regulation.',\n", - " 'author': ['Kokoszka, Jason E.',\n", - " 'Waymire, Katrina G.',\n", - " 'Levy, Shawn E.',\n", - " 'Sligh, James E.',\n", - " 'Cai, Jiyang',\n", - " 'Jones, Dean P.',\n", - " 'MacGregor, Grant R.',\n", - " 'Wallace, Douglas C.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature02229\"}'],\n", - " 'title': ['The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore']},\n", - " {'bibcode': '1965Sci...149..981F',\n", - " 'abstract': 'Mouse serum contains protein having the same charge density and molecular size as the major urinary protein complex of mice. Mouse liver (but not eight other tissues examined) incorporated amino acids labeled with carbon-14 into the complex in vitro. The degree of incorporation was greater in livers from males than from females, and was intermediate in livers from females treated with testosterone.',\n", - " 'author': ['Finlayson, J. S.',\n", - " 'Asofsky, R.',\n", - " 'Potter, M.',\n", - " 'Runner, C. C.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.jstor.org/stable/1716620?origin=ads\"}'],\n", - " 'title': ['Major Urinary Protein Complex of Normal Mice: Origin']},\n", - " {'bibcode': '2003Natur.421..177E',\n", - " 'abstract': 'In the mouse circadian clock, a transcriptional feedback loop is at the centre of the clockwork mechanism. Clock and Bmal1 are essential transcription factors that drive the expression of three period genes (Per1-3) and two cryptochrome genes (Cry1 and Cry2). The Cry proteins feedback to inhibit Clock/Bmal1-mediated transcription by a mechanism that does not alter Clock/Bmal1 binding to DNA. Here we show that transcriptional regulation of the core clock mechanism in mouse liver is accompanied by rhythms in H3 histone acetylation, and that H3 acetylation is a potential target of the inhibitory action of Cry. The promoter regions of the Per1, Per2 and Cry1 genes exhibit circadian rhythms in H3 acetylation and RNA polymerase II binding that are synchronous with the corresponding steady-state messenger RNA rhythms. The histone acetyltransferase p300 precipitates together with Clock in vivo in a time-dependent manner. Moreover, the Cry proteins inhibit a p300-induced increase in Clock/Bmal1-mediated transcription. The delayed timing of the Cry1 mRNA rhythm, relative to the Per rhythms, is due to the coordinated activities of Rev-Erbα and Clock/Bmal1, and defines a new mechanism for circadian phase control.',\n", - " 'author': ['Etchegaray, Jean-Pierre',\n", - " 'Lee, Choogon',\n", - " 'Wade, Paul A.',\n", - " 'Reppert, Steven M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature01314\"}'],\n", - " 'title': ['Rhythmic histone acetylation underlies transcription in the mammalian circadian clock']},\n", - " {'bibcode': '1963RadR...20..510S',\n", - " 'author': ['Stevens, Walter', 'Berliner, David L.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.2307%2F3571382\"}'],\n", - " 'title': ['The Effect of X-Irradiation on the Conjugation of Steroids by Mouse Liver and Kidney']},\n", - " {'bibcode': '2022PLoSO..1764743K',\n", - " 'abstract': 'Fibroblast growth factor 23 (FGF23) is a bone marrow cell produced hormone that functions in the intestine and kidney to regulate phosphate homeostasis. Increased serum FGF23 is a well-established predictor of mortality in renal disease, but recent findings linking increased levels to hepatic and cardiac diseases have suggested that other organs are sources of FGF23 or targets of its effects. The potential ability of the liver to produce FGF23 in response to hepatocellular injury was therefore examined. Very low levels of Fgf23 mRNA and FGF23 protein were detected in normal mouse liver, but the amounts increased markedly during acute liver injury from the hepatotoxin carbon tetrachloride. Serum levels of intact FGF23 were elevated during liver injury from carbon tetrachloride. Chronic liver injury induced by a high fat diet or elevated bile acids also increased hepatic FGF23 levels. Stimulation of toll-like receptor (TLR) 4-driven inflammation by gut-derived lipopolysaccharide (LPS) underlies many forms of liver injury, and LPS induced Fgf23 in the liver as well as in other organs. The LPS-inducible cytokines IL-1β and TNF increased hepatic Fgf23 expression as did a TLR2 agonist Pam2CSK3. Analysis of Fgf23 expression and FGF23 secretion in different hepatic cell types involved in liver injury identified the resident liver macrophage or Kupffer cell as a source of hepatic FGF23. LPS and cytokines selectively induced the hormone in these cells but not in hepatocytes or hepatic stellate cells. FGF23 failed to exert any autocrine effect on the inflammatory state of Kupffer cells but did trigger proinflammatory activation of hepatocytes. During liver injury inflammatory factors induce Kupffer cell production of FGF23 that may have a paracrine proinflammatory effect on hepatocytes. Liver-produced FGF23 may have systemic hormonal effects as well that influence diseases in in other organs.',\n", - " 'author': ['Kumar, Pradeep',\n", - " 'Liu, Yunshan',\n", - " 'Shen, Yang',\n", - " 'Maher, Jacquelyn J.',\n", - " 'Cingolani, Francesca',\n", - " 'Czaja, Mark J.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0264743\"}'],\n", - " 'title': ['Mouse liver injury induces hepatic macrophage FGF23 production']},\n", - " {'bibcode': '2016Natur.534..124S',\n", - " 'abstract': 'Liver X receptors (LXRs) are transcriptional regulators of cellular and systemic cholesterol homeostasis. Under conditions of excess cholesterol, LXR activation induces the expression of several genes involved in cholesterol efflux, facilitates cholesterol esterification by promoting fatty acid synthesis, and inhibits cholesterol uptake by the low-density lipoprotein receptor. The fact that sterol content is maintained in a narrow range in most cell types and in the organism as a whole suggests that extensive crosstalk between regulatory pathways must exist. However, the molecular mechanisms that integrate LXRs with other lipid metabolic pathways are incompletely understood. Here we show that ligand activation of LXRs in mouse liver not only promotes cholesterol efflux, but also simultaneously inhibits cholesterol biosynthesis. We further identify the long non-coding RNA LeXis as a mediator of this effect. Hepatic LeXis expression is robustly induced in response to a Western diet (high in fat and cholesterol) or to pharmacological LXR activation. Raising or lowering LeXis levels in the liver affects the expression of genes involved in cholesterol biosynthesis and alters the cholesterol levels in the liver and plasma. LeXis interacts with and affects the DNA interactions of RALY, a heterogeneous ribonucleoprotein that acts as a transcriptional cofactor for cholesterol biosynthetic genes in the mouse liver. These findings outline a regulatory role for a non-coding RNA in lipid metabolism and advance our understanding of the mechanisms that coordinate sterol homeostasis.',\n", - " 'author': ['Sallam, Tamer',\n", - " 'Jones, Marius C.',\n", - " 'Gilliland, Thomas',\n", - " 'Zhang, Li',\n", - " 'Wu, Xiaohui',\n", - " 'Eskin, Ascia',\n", - " 'Sandhu, Jaspreet',\n", - " 'Casero, David',\n", - " 'Vallim, Thomas Q. De Aguiar',\n", - " 'Hong, Cynthia',\n", - " 'Katz, Melanie',\n", - " 'Lee, Richard',\n", - " 'Whitelegge, Julian',\n", - " 'Tontonoz, Peter'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature17674\"}'],\n", - " 'title': ['Feedback modulation of cholesterol metabolism by the lipid-responsive non-coding RNA LeXis']},\n", - " {'bibcode': '2013PJAB...89...59T',\n", - " 'author': ['Tsuchiya, Yoshiki',\n", - " 'Minami, Itsunari',\n", - " 'Kadotani, Hiroshi',\n", - " 'Todo, Takeshi',\n", - " 'Nishida, Eisuke'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.2183%2Fpjab.89.59\"}'],\n", - " 'title': ['Circadian clock-controlled diurnal oscillation of Ras/ERK signaling in mouse liver']},\n", - " {'bibcode': '2016APS..MARY41008F',\n", - " 'abstract': \"Our study aims to construct a structurally plausible in silico model of a mouse liver lobule to simulate the transport of xenobiotics and the production of their metabolites. We use a physiologically-based model to calculate blood-flow rates in a network of mouse liver sinusoids and simulate transport, uptake and biotransformation of xenobiotics within the in silico lobule. Using our base model, we then explore the effects of variations of compound-specific (diffusion, transport and metabolism) and compound-independent (temporal alteration of blood flow pattern) parameters, and examine their influence on the distribution of xenobiotics and metabolites. Our simulations show that the transport mechanism (diffusive and transporter-mediated) of xenobiotics and blood flow both impact the regional distribution of xenobiotics in a mouse hepatic lobule. Furthermore, differential expression of metabolic enzymes along each sinusoid's portal to central axis, together with differential cellular availability of xenobiotics, induce non-uniform production of metabolites. Thus, the heterogeneity of the biochemical and biophysical properties of xenobiotics, along with the complexity of blood flow, result in different exposures to xenobiotics for hepatocytes at different lobular locations.

We acknowledge support from National Institute of Health GM 077138 and GM 111243.\",\n", - " 'author': ['Fu, Xiao',\n", - " 'Sluka, James',\n", - " 'Clendenon, Sherry',\n", - " 'Glazier, James',\n", - " 'Ryan, Jennifer',\n", - " 'Dunn, Kenneth',\n", - " 'Wang, Zemin',\n", - " 'Klaunig, James'],\n", - " 'title': ['Spatio-temporal Model of Xenobiotic Distribution and Metabolism in an in Silico Mouse Liver Lobule']},\n", - " {'bibcode': '2016NatSR...634635S',\n", - " 'abstract': 'Spinal Muscular Atrophy (SMA) is caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene. Decreased levels of, cell-ubiquitous, SMN protein is associated with a range of systemic pathologies reported in severe patients. Despite high levels of SMN protein in normal liver, there is no comprehensive study of liver pathology in SMA. We describe failed liver development in response to reduced SMN levels, in a mouse model of severe SMA. The SMA liver is dark red, small and has: iron deposition; immature sinusoids congested with blood; persistent erythropoietic elements and increased immature red blood cells; increased and persistent megakaryocytes which release high levels of platelets found as clot-like accumulations in the heart. Myelopoiesis in contrast, was unaffected. Further analysis revealed significant molecular changes in SMA liver, consistent with the morphological findings. Antisense treatment from birth with PMO25, increased lifespan and ameliorated all morphological defects in liver by postnatal day 21. Defects in the liver are evident at birth, prior to motor system pathology, and impair essential liver function in SMA. Liver is a key recipient of SMA therapies, and systemically delivered antisense treatment, completely rescued liver pathology. Liver therefore, represents an important therapeutic target in SMA.',\n", - " 'author': ['Szunyogova, Eva',\n", - " 'Zhou, Haiyan',\n", - " 'Maxwell, Gillian K.',\n", - " 'Powis, Rachael A.',\n", - " 'Francesco, Muntoni',\n", - " 'Gillingwater, Thomas H.',\n", - " 'Parson, Simon H.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep34635\"}'],\n", - " 'title': ['Survival Motor Neuron (SMN) protein is required for normal mouse liver development']},\n", - " {'bibcode': '2014Natur.508...66S',\n", - " 'abstract': \"Poly(A) tails enhance the stability and translation of most eukaryotic messenger RNAs, but difficulties in globally measuring poly(A)-tail lengths have impeded greater understanding of poly(A)-tail function. Here we describe poly(A)-tail length profiling by sequencing (PAL-seq) and apply it to measure tail lengths of millions of individual RNAs isolated from yeasts, cell lines, Arabidopsis thaliana leaves, mouse liver, and zebrafish and frog embryos. Poly(A)-tail lengths were conserved between orthologous mRNAs, with mRNAs encoding ribosomal proteins and other `housekeeping' proteins tending to have shorter tails. As expected, tail lengths were coupled to translational efficiencies in early zebrafish and frog embryos. However, this strong coupling diminished at gastrulation and was absent in non-embryonic samples, indicating a rapid developmental switch in the nature of translational control. This switch complements an earlier switch to zygotic transcriptional control and explains why the predominant effect of microRNA-mediated deadenylation concurrently shifts from translational repression to mRNA destabilization.\",\n", - " 'author': ['Subtelny, Alexander O.',\n", - " 'Eichhorn, Stephen W.',\n", - " 'Chen, Grace R.',\n", - " 'Sive, Hazel',\n", - " 'Bartel, David P.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"data\", \"url\": \"http://www.ncbi.nlm.nih.gov/geo\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"data\", \"url\": \"http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse52809\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature13007\"}'],\n", - " 'title': ['Poly(A)-tail profiling reveals an embryonic switch in translational control']},\n", - " {'bibcode': '2008Chmsp..74..155T',\n", - " 'author': ['Takeuchi, Shinji',\n", - " 'Iida, Mitsuru',\n", - " 'Yabushita, Hisatoshi',\n", - " 'Matsuda, Tadashi',\n", - " 'Kojima, Hiroyuki'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.chemosphere.2008.08.015\"}'],\n", - " 'title': ['In vitro screening for aryl hydrocarbon receptor agonistic activity in 200 pesticides using a highly sensitive reporter cell line, DR-EcoScreen cells, and in vivo mouse liver cytochrome P450-1A induction by propanil, diuron and linuron']},\n", - " {'bibcode': '2018NatCo...9.2784Z',\n", - " 'abstract': 'Developing injectable antibacterial and conductive shape memory hemostatic with high blood absorption and fast recovery for irregularly shaped and noncompressible hemorrhage remains a challenge. Here we report injectable antibacterial conductive cryogels based on carbon nanotube (CNT) and glycidyl methacrylate functionalized quaternized chitosan for lethal noncompressible hemorrhage hemostasis and wound healing. These cryogels present robust mechanical strength, rapid blood-triggered shape recovery and absorption speed, and high blood uptake capacity. Moreover, cryogels show better blood-clotting ability, higher blood cell and platelet adhesion and activation than gelatin sponge and gauze. Cryogel with 4 mg/mL CNT (QCSG/CNT4) shows better hemostatic capability than gauze and gelatin hemostatic sponge in mouse-liver injury model and mouse-tail amputation model, and better wound healing performance than Tegaderm™ film. Importantly, QCSG/CNT4 presents excellent hemostatic performance in rabbit liver defect lethal noncompressible hemorrhage model and even better hemostatic ability than Combat Gauze in standardized circular liver bleeding model.',\n", - " 'author': ['Zhao, Xin',\n", - " 'Guo, Baolin',\n", - " 'Wu, Hao',\n", - " 'Liang, Yongping',\n", - " 'Ma, Peter X.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41467-018-04998-9\"}'],\n", - " 'title': ['Injectable antibacterial conductive nanocomposite cryogels with rapid shape recovery for noncompressible hemorrhage and wound healing']},\n", - " {'bibcode': '1986BuECT..37..169S',\n", - " 'author': ['Swartz, William J.', 'Schutzmann, Roy L.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1007%2FBF01607745\"}'],\n", - " 'title': ['Reaction of the mouse liver to kepone exposure']},\n", - " {'bibcode': '2005Sci...309.1390C',\n", - " 'abstract': 'The molecular machinery that governs circadian rhythmicity is based on clock proteins organized in regulatory feedback loops. Although posttranslational modification of clock proteins is likely to finely control their circadian functions, only limited information is available to date. Here, we show that BMAL1, an essential transcription factor component of the clock mechanism, is SUMOylated on a highly conserved lysine residue (Lys259) in vivo. BMAL1 shows a circadian pattern of SUMOylation that parallels its activation in the mouse liver. SUMOylation of BMAL1 requires and is induced by CLOCK, the heterodimerization partner of BMAL1. Ectopic expression of a SUMO-deficient BMAL1 demonstrates that SUMOylation plays an important role in BMAL1 circadian expression and clock rhythmicity. This reveals an additional level of regulation within the core mechanism of the circadian clock.',\n", - " 'author': ['Cardone, Luca',\n", - " 'Hirayama, Jun',\n", - " 'Giordano, Francesca',\n", - " 'Tamaru, Teruya',\n", - " 'Palvimo, Jorma J.',\n", - " 'Sassone-Corsi, Paolo'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.1110689\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.1110689\"}'],\n", - " 'title': ['Circadian Clock Control by SUMOylation of BMAL1']},\n", - " {'bibcode': '1985PNAS...82.2262E',\n", - " 'abstract': \"The main ethanol-active alcohol dehydrogenase (ADH; alcohol:NAD+ oxidoreductase, EC 1.1.1.1) in mouse liver (ADH-AA) is similar in catalytic and molecular properties to horse liver ADH-EE and to the human class I ADHs. We have isolated cDNA clones encoding the entire mouse liver enzyme plus flanking regions. A mixture of 16 different oligonucleotides, each 14 bases long, was used to screen a liver cDNA library made from a DBA/2J mouse. A strongly hybridizing clone was found and identified as an ADH-encoding cDNA by partial DNA sequencing. This clone was used as a probe to identify others. Two overlapping cDNA clones together contained the entire protein-encoding region plus 100 nucleotides of the 5' noncoding region and 133 nucleotides of the 3' noncoding region culminating in a short poly(dA) tail. The amino acid sequence of the mouse liver enzyme deduced from this cDNA closely resembles that of horse liver ADH-E: 316 of 374 residues are identical, and 29 of the differences are conservative substitutions. The 5' region of this cDNA is interesting: the AUG that initiates the ADH polypeptide is preceded by an AUG that would encode the first amino acid of a tripeptide. Presumably termination of this tripeptide is followed by reinitiation at the AUG immediately preceding the sequence of the mature ADH polypeptide.\",\n", - " 'author': ['Edenberg, Howard J.',\n", - " 'Zhang, Ke',\n", - " 'Fong, Kenneth',\n", - " 'Bosron, William F.',\n", - " 'Li, Ting-Kai'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/82/8/2262\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/82/8/2262\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/82/8/2262\"}'],\n", - " 'title': ['Cloning and sequencing of cDNA encoding the complete mouse liver alcohol dehydrogenase.']},\n", - " {'bibcode': '2013RadR..179...69W',\n", - " 'author': ['Wang, Sihyung',\n", - " 'Hyun, Jeongeun',\n", - " 'Youn, BuHyun',\n", - " 'Jung, Youngmi'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1667%2FRR3091.1\"}'],\n", - " 'title': ['Hedgehog Signaling Regulates the Repair Response in Mouse Liver Damaged by Irradiation']},\n", - " {'bibcode': '2019PNAS..116.6313Q',\n", - " 'abstract': 'Taurine transporter deficiency in mice results in hyperammonemia and reduced glutamine formation in hepatic scavenger cells due to an impaired ammonia transport at 3 months of age and a tyrosine nitration-dependent inactivation of glutamine synthetase in 12-month-old mice. The data suggest that down-regulation of the ammonia transporter RhBG can be rate limiting for the synthesis of glutamine in mouse liver.',\n", - " 'author': ['Qvartskhava, Natalia',\n", - " 'Jin, Cheng Jun',\n", - " 'Buschmann, Tobias',\n", - " 'Albrecht, Ute',\n", - " 'Bode, Johannes Georg',\n", - " 'Monhasery, Niloufar',\n", - " 'Oenarto, Jessica',\n", - " 'Bidmon, Hans Jürgen',\n", - " 'Görg, Boris',\n", - " 'Häussinger, Dieter'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1813100116\"}'],\n", - " 'title': ['Taurine transporter (TauT) deficiency impairs ammonia detoxification in mouse liver']},\n", - " {'bibcode': '1968SpecL...1..121D',\n", - " 'author': ['Duke, Phillip'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1080%2F00387016809438140\"}'],\n", - " 'title': ['Ascorbyl EPR Doublet Signal in Normal Mouse Liver Oxygenated Homogenates']},\n", - " {'bibcode': '2013ToxIH..29..761T',\n", - " 'abstract': 'Schistosomiasis is one of the major human parasitic diseases in many developing countries and is one of the causes of morbidity and mortality in the human population. The present work has been planned to study the histopathological and immunohistochemical expression of P53 and CD68 in mouse liver tissues experimentally infected with Schistosoma mansoni, in addition to the ameliorating role of silymarin. A total of 50 adult male mice were divided into 5 groups (10 animals each). Groups 1 and 2 were the control and silymarin groups, respectively, while group 3 was the infected group in which the mice were infected with S. mansoni live cercariae for 6 weeks. Groups 4 and 5 were the cotreated and posttreated groups, respectively, in which mice were infected with cercariae of S. mansoni and treated with silymarin during and after Schistosoma infection, respectively. The major histopathological lesions were variable numbers of perioval granulomas, diffuse infiltration of inflammatory cells, mainly eosinophils and small mononuclear cells, and fibrosis of portal areas and interlobular septa. Treatment with silymarin led to a significant reduction in granuloma area in all treated infected mice compared with nontreated infected mice. Immunohistochemical observations of the liver tissues showed a significant increase in the apoptotic proteins P53 and CD68 after the infection with the cercariae of Schistosoma, compared with the control group. The expression of the cytoplasmic P53 and CD68 was very low in the control liver sections. A significant decrease in the expression of the cytoplasmic P53 and CD68 was observed after silymarin treatment.',\n", - " 'author': ['Tousson, Ehab',\n", - " 'Beltagy, Doha M.',\n", - " 'Gazia, Maha Abo',\n", - " 'Al-Behbehani, Bahija'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1177%2F0748233712442733\"}'],\n", - " 'title': ['Expressions of P53 and CD68 in mouse liver with Schistosoma mansoni infection and the protective role of silymarin']},\n", - " {'bibcode': '2007Natur.450.1086H',\n", - " 'abstract': 'Regulation of circadian physiology relies on the interplay of interconnected transcriptional-translational feedback loops. The CLOCK-BMAL1 complex activates clock-controlled genes, including cryptochromes (Crys), the products of which act as repressors by interacting directly with CLOCK-BMAL1. We have demonstrated that CLOCK possesses intrinsic histone acetyltransferase activity and that this enzymatic function contributes to chromatin-remodelling events implicated in circadian control of gene expression. Here we show that CLOCK also acetylates a non-histone substrate: its own partner, BMAL1, is specifically acetylated on a unique, highly conserved Lys537 residue. BMAL1 undergoes rhythmic acetylation in mouse liver, with a timing that parallels the downregulation of circadian transcription of clock-controlled genes. BMAL1 acetylation facilitates recruitment of CRY1 to CLOCK-BMAL1, thereby promoting transcriptional repression. Importantly, ectopic expression of a K537R-mutated BMAL1 is not able to rescue circadian rhythmicity in a cellular model of peripheral clock. These findings reveal that the enzymatic interplay between two clock core components is crucial for the circadian machinery.',\n", - " 'author': ['Hirayama, Jun',\n", - " 'Sahar, Saurabh',\n", - " 'Grimaldi, Benedetto',\n", - " 'Tamaru, Teruya',\n", - " 'Takamatsu, Ken',\n", - " 'Nakahata, Yasukazu',\n", - " 'Sassone-Corsi, Paolo'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature06394\"}'],\n", - " 'title': ['CLOCK-mediated acetylation of BMAL1 controls circadian function']},\n", - " {'bibcode': '2021iSci...24j3233S',\n", - " 'author': ['Su, Qi',\n", - " 'Kim, Sun Y.',\n", - " 'Adewale, Funmi',\n", - " 'Zhou, Ye',\n", - " 'Aldler, Christina',\n", - " 'Ni, Min',\n", - " 'Wei, Yi',\n", - " 'Burczynski, Michael E.',\n", - " 'Atwal, Gurinder S.',\n", - " 'Sleeman, Mark W.',\n", - " 'Murphy, Andrew J.',\n", - " 'Xin, Yurong',\n", - " 'Cheng, Xiping'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.isci.2021.103233\"}'],\n", - " 'title': ['Single-cell RNA transcriptome landscape of hepatocytes and non-parenchymal cells in healthy and NAFLD mouse liver']},\n", - " {'bibcode': '2014PLoSO...998155F',\n", - " 'author': ['Farah, Benjamin L.',\n", - " 'Sinha, Rohit A.',\n", - " 'Wu, Yajun',\n", - " 'Singh, Brijesh K.',\n", - " 'Zhou, Jin',\n", - " 'Bay, Boon-Huat',\n", - " 'Yen, Paul M.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0098155\"}'],\n", - " 'title': ['β-Adrenergic Agonist and Antagonist Regulation of Autophagy in HepG2 Cells, Primary Mouse Hepatocytes, and Mouse Liver']},\n", - " {'bibcode': '2015Chmsp.139..318Q',\n", - " 'author': ['Qin, Guohua', 'Wu, Meiqiong', 'Sang, Nan'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.chemosphere.2015.06.052\"}'],\n", - " 'title': ['Sulfur dioxide and benzo(a)pyrene trigger apoptotic and anti-apoptotic signals at different post-exposure times in mouse liver']},\n", - " {'bibcode': '2018SciA....4.5508W',\n", - " 'author': ['Wang, Guangchuan',\n", - " 'Chow, Ryan D.',\n", - " 'Ye, Lupeng',\n", - " 'Guzman, Christopher D.',\n", - " 'Dai, Xiaoyun',\n", - " 'Dong, Matthew B.',\n", - " 'Zhang, Feng',\n", - " 'Sharp, Phillip A.',\n", - " 'Platt, Randall J.',\n", - " 'Chen, Sidi'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fsciadv.aao5508\"}'],\n", - " 'title': ['Mapping a functional cancer genome atlas of tumor suppressors in mouse liver using AAV-CRISPR-mediated direct in vivo screening']},\n", - " {'bibcode': '2009PNAS..10613765S',\n", - " 'abstract': 'Lipid homeostasis in vertebrates is regulated by 3 sterol regulatory element binding protein (SREBP) isoforms. Here, we identify targets of SREBP-1 in mammalian liver using chromatin immunoprecipitation-high-throughput DNA sequencing. Antisera to SREBP-1 were used with liver chromatin from mice fed a high-carbohydrate diet after a fast, which leads to superinduction of hepatic SREBP-1c expression. SREBP-1-DNA complexes were subjected to massive parallel DNA sequencing using the Illumina Genome Analyzer II, resulting in 5.7 million sequence reads. Mapping these reads to the mouse reference genome identified 426 peaks of SREBP-1 binding vs. a control antibody. These binding peaks show a striking enrichment in proximal promoter regions, with 52% located within 1 kb upstream of a transcription start site. A previously undescribed sequence motif (5\\'-ACTACANNTCCC-3\\') was present in 76% of the total peaks, and we show that it is a functional SREBP-1 response element. Our analysis also reveals that an Sp1 consensus site is present as a \"coregulatory\" motif in 50% of the SREBP-1 binding peaks, consistent with previous functional studies. SREBP-1 bound not only to many well-characterized SREBP-1 target genes but to several other previously unknown targets in lipid and carbohydrate metabolism as well as many putative target genes in other diverse biological pathways.',\n", - " 'author': ['Seo, Young-Kyo',\n", - " 'Chong, Hansook Kim',\n", - " 'Infante, Aniello M.',\n", - " 'Im, Seung-Soon',\n", - " 'Xie, Xiaohui',\n", - " 'Osborne, Timothy F.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/106/33/13765\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0904246106\"}'],\n", - " 'title': ['Genome-wide analysis of SREBP-1 binding in mouse liver chromatin reveals a preference for promoter proximal binding to a new motif']},\n", - " {'bibcode': '1998EnvMM..32..269M',\n", - " 'author': ['Morita, Takeshi', 'Hayashi, Makoto'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2F%28SICI%291098-2280%281998%2932%3A3%3C269%3A%3AAID-EM10%3E3.0.CO%3B2-8\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2F%28SICI%291098-2280%281998%2932%3A3%3C269%3A%3AAID-EM10%3E3.0.CO2-8\"}'],\n", - " 'title': ['1,4-Dioxane is not mutagenic in five in vitro assays and mouse peripheral blood micronucleus assay, but is in mouse liver micronucleus assay']},\n", - " {'bibcode': '1965Natur.206.1262P',\n", - " 'abstract': \"PREVIOUS in vivo experiments in man have shown that the formation of water-soluble conjugates of aldosterone is a very important part of its metabolism1. These investigators have also demonstrated the presence of a urinary conjugate of aldosterone which is split by mild acid hydrolysis and which has been designated the `3-oxo-conjugate'1. In addition, the discovery of urinary tetrahydro aldosterone and glucuronide conjugates of this compound reveals that glucuronides of aldosterone are of great importance in the metabolism of this compound2-4.\",\n", - " 'author': ['Panagiotis, N. M.', 'Berliner, D. L.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F2061262a0\"}'],\n", - " 'title': ['Conjugation of Aldosterone by Bovine and Mouse Liver and Kidney']},\n", - " {'bibcode': '2009AcAC..652..324W',\n", - " 'abstract': 'Capillary column plays an important role in nano-flow liquid chromatography coupled with tandem mass spectrometry for dealing with the high dynamic range and complexity of protein samples in shotgun proteome analysis. In this study, the integrated monolithic frit into the particulate capillary (IMFPC) column was prepared. By comparing the prepared IMFPC column with conventionally fritless capillary column, smaller size of packing materials could be easily packed into the capillary to achieve higher average peak capacity and proteome coverage. As the monolithic emitter was integrated onto this type of column, the void volume between packing particles and electrospray emitter was eliminated and the electrospray quality was improved. The prepared IMFPC column was applied to proteome analysis of mouse liver extracts, and it was observed that the number of identified proteins and peptides increased 14.9 and 12.9% as well as the peak capacity increased 11.6% by using IMFPC column over conventionally fritless capillary column.',\n", - " 'author': ['Wang, Fangjun',\n", - " 'Dong, Jing',\n", - " 'Ye, Mingliang',\n", - " \"Wu, Ren'an\",\n", - " 'Zou, Hanfa'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.aca.2009.06.066\"}'],\n", - " 'title': ['Integration of monolithic frit into the particulate capillary (IMFPC) column in shotgun proteome analysis']},\n", - " {'bibcode': '2023Heliy...921011T',\n", - " 'abstract': 'Aging is associated with gradual changes in liver structure, altered metabolites and other physiological/pathological functions in hepatic cells. However, its characterized phenotypes based on altered metabolites and the underlying biological mechanism are unclear. Advancements in high-throughput omics technology provide new opportunities to understand the pathological process of aging. Here, in our present study, both metabolomics and phosphoproteomics were applied to identify the altered metabolites and phosphorylated proteins in liver of young (the WTY group) and naturally aged (the WTA group) mice, to find novel biomarkers and pathways, and uncover the biological mechanism. Analysis showed that the body weights, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased in the WTA group. The grips decreased with age, while the triglyceride (TG) and cholesterol (TC) did not change significantly. The increase of fibrosis, accumulation of inflammatory cells, hepatocytes degeneration, the deposition of lipid droplets and glycogen, the damaged mitochondria, and deduction of endoplasmic reticulum were observed in the aging liver under optical and electron microscopes. In addition, a network of metabolites and phosphorylated proteomes of the aging liver was established. Metabolomics detected 970 metabolites in the positive ion mode and 778 metabolites in the negative ion mode. A total of 150 pathways were pooled. Phosphoproteomics identified 2618 proteins which contained 16621 phosphosites. A total of 164 pathways were detected. 65 common pathways were detected in two omics. Phosphorylated protein heat shock protein HSP 90-alpha (HSP90A) and v-raf murine viral oncogene homolog B1(BRAF), related to cancer pathway, were significantly upregulated in aged mice liver. Western blot verified that protein expression of MEK and ERK, downstream of BRAF pathway were elevated in the liver of aging mice. However, the protein expression of BRAF was not a significant difference. Overall, these findings revealed a close link between aging and cancer and contributed to our understanding of the multi-omics changes in natural aging.',\n", - " 'author': ['Tang, Cong-min',\n", - " 'Zhang, Zhen',\n", - " 'Sun, Yan',\n", - " 'Ding, Wen-jing',\n", - " 'Yang, Xue-chun',\n", - " 'Song, Yi-ping',\n", - " 'Ling, Ming-ying',\n", - " 'Li, Xue-hui',\n", - " 'Yan, Rong',\n", - " 'Zheng, Yu-jing',\n", - " 'Yu, Na',\n", - " 'Zhang, Wen-hua',\n", - " 'Wang, Yong',\n", - " 'Wang, Shao-peng',\n", - " 'Gao, Hai-qing',\n", - " 'Zhao, Chuan-li',\n", - " 'Xing, Yan-qiu'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.heliyon.2023.e21011\"}'],\n", - " 'title': ['Multi-omics reveals aging-related pathway in natural aging mouse liver']},\n", - " {'bibcode': '2020AcAC.1102....1W',\n", - " 'abstract': 'A microfluidic platform based on the integration of denaturation and online immobilized enzyme reactor (IMER) digestion for protein pretreatment was first developed on a glass chip. The design of three inlet channels and two groups of snake channel in glass chip can allow the protein solution, the reducing reagent and the alkylating agent to be simultaneously injected into the chip channel and ensured the reaction solution on-line efficient mixing and sufficient reacting. By thiol-ene click chemistry, the capillary-based and glass chip-based trypsin IMER on the surface of poly(trimethylolpropane trimethacrylate) monolith were fabricated. The wide range of flow rate tolerance (0.8-5.0 μL/min), and the acceptable reproducibility (RSD% = 3.1%, n = 5) and stability (13.8% decrease of enzyme activity in 2 months) indicated the feasibility of using IMER for online digestion of proteins. Compared with the solution denaturation-offline IMER digestion, the integrated microfluidic platform of chip denaturation-chip IMER and chip denaturation-online IMER have comparable protein identification ability for mouse liver protein with a similar number of protein (798 or 826 vs. 843) and unique peptides (3923 or 4593 vs. 3916). More importantly, the easy and fast digestion of protein samples and possible combination with MS revealed that this microfluidic platform can be a potential method for rapid proteomics analysis.',\n", - " 'author': ['Wei, Zehui',\n", - " 'Fan, Peiru',\n", - " 'Jiao, Yajie',\n", - " 'Wang, Yang',\n", - " 'Huang, Yanping',\n", - " 'Liu, Zhaosheng'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.aca.2020.01.025\"}'],\n", - " 'title': ['Integrated microfluidic chip for on-line proteome analysis with combination of denaturing and rapid digestion of protein']},\n", - " {'bibcode': '2012Natur.485..465Z',\n", - " 'abstract': 'An outstanding question is how cells control the number and size of membrane organelles. The small GTPase Rab5 has been proposed to be a master regulator of endosome biogenesis. Here, to test this hypothesis, we developed a mathematical model of endosome dependency on Rab5 and validated it by titrating down all three Rab5 isoforms in adult mouse liver using state-of-the-art RNA interference technology. Unexpectedly, the endocytic system was resilient to depletion of Rab5 and collapsed only when Rab5 decreased to a critical level. Loss of Rab5 below this threshold caused a marked reduction in the number of early endosomes, late endosomes and lysosomes, associated with a block of low-density lipoprotein endocytosis. Loss of endosomes caused failure to deliver apical proteins to the bile canaliculi, suggesting a requirement for polarized cargo sorting. Our results demonstrate for the first time, to our knowledge, the role of Rab5 as an endosome organizer in vivo and reveal the resilience mechanisms of the endocytic system.',\n", - " 'author': ['Zeigerer, Anja',\n", - " 'Gilleron, Jerome',\n", - " 'Bogorad, Roman L.',\n", - " 'Marsico, Giovanni',\n", - " 'Nonaka, Hidenori',\n", - " 'Seifert, Sarah',\n", - " 'Epstein-Barash, Hila',\n", - " 'Kuchimanchi, Satya',\n", - " 'Peng, Chang Geng',\n", - " 'Ruda, Vera M.',\n", - " 'Conte-Zerial, Perla Del',\n", - " 'Hengstler, Jan G.',\n", - " 'Kalaidzidis, Yannis',\n", - " 'Koteliansky, Victor',\n", - " 'Zerial, Marino'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature11133\"}'],\n", - " 'title': ['Rab5 is necessary for the biogenesis of the endolysosomal system in vivo']},\n", - " {'bibcode': '1978Sci...200.1391L',\n", - " 'abstract': \"Δ 6-Tetrahydrocannabinol-C-4'-glucuronide was found in the livers of mice that had been administered Δ 6-tetrahydrocannabinol. Thus, C-glucuronidation of a compound that contains a free hydroxyl group has been demonstrated in vivo.\",\n", - " 'author': ['Levy, Shlomo', 'Yagen, Boris', 'Mechoulam, Raphael'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.200.4348.1391\"}'],\n", - " 'title': ['Identification of a C-Glucuronide of Δ 6-Tetrahydrocannabinol as a Mouse Liver Conjugate in vivo']},\n", - " {'bibcode': '2014GeneE..36...54S',\n", - " 'author': ['Sakurai, Mikiya',\n", - " 'Watanabe, Takashi',\n", - " 'Suzuki, Takayoshi',\n", - " 'Furihata, Chie'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.3123%2Fjemsge.2014.005\"}'],\n", - " 'title': ['Time-course Comparison of Gene Expression Profiles Induced by the Genotoxic Hepatocarcinogen, Chrysene, in the Mouse Liver']},\n", - " {'bibcode': '2014PLoSO...9j9479P',\n", - " 'author': ['Park, Hye Min',\n", - " 'Shon, Jong Cheol',\n", - " 'Lee, Mee Youn',\n", - " 'Liu, Kwang-Hyeon',\n", - " 'Kim, Jeong Kee',\n", - " 'Lee, Sang Jun',\n", - " 'Lee, Choong Hwan'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0109479\"}'],\n", - " 'title': ['Mass Spectrometry-Based Metabolite Profiling in the Mouse Liver following Exposure to Ultraviolet B Radiation']},\n", - " {'bibcode': '2021NatSR..1121786K',\n", - " 'abstract': 'Spaceflight induces hepatic damage, partially owing to oxidative stress caused by the space environment such as microgravity and space radiation. We examined the roles of anti-oxidative sulfur-containing compounds on hepatic damage after spaceflight. We analyzed the livers of mice on board the International Space Station for 30 days. During spaceflight, half of the mice were exposed to artificial earth gravity (1 g) using centrifugation cages. Sulfur-metabolomics of the livers of mice after spaceflight revealed a decrease in sulfur antioxidants (ergothioneine, glutathione, cysteine, taurine, thiamine, etc.) and their intermediates (cysteine sulfonic acid, hercynine, N-acethylserine, serine, etc.) compared to the controls on the ground. Furthermore, RNA-sequencing showed upregulation of gene sets related to oxidative stress and sulfur metabolism, and downregulation of gene sets related to glutathione reducibility in the livers of mice after spaceflight, compared to controls on the ground. These changes were partially mitigated by exposure to 1 g centrifugation. For the first time, we observed a decrease in sulfur antioxidants based on a comprehensive analysis of the livers of mice after spaceflight. Our data suggest that a decrease in sulfur-containing compounds owing to both microgravity and other spaceflight environments (radiation and stressors) contributes to liver damage after spaceflight.',\n", - " 'author': ['Kurosawa, Ryo',\n", - " 'Sugimoto, Ryota',\n", - " 'Imai, Hiroe',\n", - " 'Atsuji, Kohei',\n", - " 'Yamada, Koji',\n", - " 'Kawano, Yusuke',\n", - " 'Ohtsu, Iwao',\n", - " 'Suzuki, Kengo'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-021-01129-1\"}'],\n", - " 'title': ['Impact of spaceflight and artificial gravity on sulfur metabolism in mouse liver: sulfur metabolomic and transcriptomic analysis']},\n", - " {'bibcode': '1985PNAS...82.8634F',\n", - " 'abstract': 'Molecular association between major histocompatibility complex (MHC) antigens and cellular proteins are thought to be involved in various immunological and nonimmunological functions of MHC antigens, including hormone signaling. The existence of physical interactions between insulin receptors and MHC class I antigens was investigated in liver plasma membranes from congenic H-2k mice. Insulin receptors were specifically labeled with a 125I-labeled photoreactive insulin analogue, and cellular proteins were solubilized and incubated with various monoclonal antibodies. Immunoprecipitates were analyzed by polyacrylamide gel electrophoresis followed by autoradiography. Antibodies reacting with distinct epitopes on H-2k class I antigens were all able to precipitate up to 25% of the labeled insulin receptors in H-2k mouse liver membranes, whereas no insulin receptors were precipitated in H-2b mouse liver membranes. Sequential immunoprecipitations showed that insulin receptors and H-2 antigens were coprecipitated and that no cross-reactivity occurred. The specificity of the interaction between insulin receptors and H-2 antigens was demonstrated after double labeling of membrane proteins by photoreactive insulin and lactoperoxidase-catalyzed iodination. These results thus show that, in mouse liver membranes, insulin receptors are physically associated to class I antigens of the MHC.',\n", - " 'author': ['Fehlmann, Max',\n", - " 'Peyron, Jean-Francois',\n", - " 'Samson, Michael',\n", - " 'van Obberghen, Emmanuel',\n", - " 'Brandenburg, Dietrich',\n", - " 'Brossette, Nicole'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/82/24/8634\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/82/24/8634\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/82/24/8634\"}'],\n", - " 'title': ['Molecular association between major histocompatibility complex class I antigens and insulin receptors in mouse liver membranes.']},\n", - " {'bibcode': '2012PLoSO...751656S',\n", - " 'author': ['Sekiguchi, Satoshi',\n", - " 'Kimura, Kiminori',\n", - " 'Chiyo, Tomoko',\n", - " 'Ohtsuki, Takahiro',\n", - " 'Tobita, Yoshimi',\n", - " 'Tokunaga, Yuko',\n", - " 'Yasui, Fumihiko',\n", - " 'Tsukiyama-Kohara, Kyoko',\n", - " 'Wakita, Takaji',\n", - " 'Tanaka, Toshiyuki',\n", - " 'Miyasaka, Masayuki',\n", - " 'Mizuno, Kyosuke',\n", - " 'Hayashi, Yukiko',\n", - " 'Hishima, Tsunekazu',\n", - " 'Matsushima, Kouji',\n", - " 'Kohara, Michinori'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0051656\"}'],\n", - " 'title': ['Immunization with a Recombinant Vaccinia Virus That Encodes Nonstructural Proteins of the Hepatitis C Virus Suppresses Viral Protein Levels in Mouse Liver']},\n", - " {'bibcode': '2014PLoSO...988584R',\n", - " 'author': ['Renaud, Helen J.',\n", - " 'Cui, Julia Y.',\n", - " 'Lu, Hong',\n", - " 'Klaassen, Curtis D.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0088584\"}'],\n", - " 'title': ['Effect of Diet on Expression of Genes Involved in Lipid Metabolism, Oxidative Stress, and Inflammation in Mouse Liver-Insights into Mechanisms of Hepatic Steatosis']},\n", - " {'bibcode': '2018PNAS..115.9080C',\n", - " 'abstract': 'Shortwave infrared (SWIR) fluorescence imaging is a tool for visualizing biological processes deep within tissue or living animals. Our study shows that the contrast in a SWIR fluorescence image is primarily mediated by the absorptivity of the tissue, and can therefore be tuned through deliberate selection of imaging wavelength. We show, for example, that, in 3D tissue phantoms and in brain vasculature in vivo in mice, imaging at SWIR wavelengths of the highest water absorptivity results in the greatest fluorescence contrast. We further demonstrate, in microscopy of ex vivo mouse liver tissue, that imaging at wavelengths of high tissue absorptivity can also increase imaging penetration depth, and use a theoretical contrast model to explain this effect.',\n", - " 'author': ['Carr, Jessica A.',\n", - " 'Aellen, Marianne',\n", - " 'Franke, Daniel',\n", - " 'So, Peter T. C.',\n", - " 'Bruns, Oliver T.',\n", - " 'Bawendi, Moungi G.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1803210115\"}'],\n", - " 'title': ['Absorption by water increases fluorescence image contrast of biological tissue in the shortwave infrared']},\n", - " {'bibcode': '2007PNAS..10412982R',\n", - " 'abstract': 'Achieving efficient in vivo delivery of siRNA to the appropriate target cell would be a major advance in the use of RNAi in gene function studies and as a therapeutic modality. Hepatocytes, the key parenchymal cells of the liver, are a particularly attractive target cell type for siRNA delivery given their central role in several infectious and metabolic disorders. We have developed a vehicle for the delivery of siRNA to hepatocytes both in vitro and in vivo, which we have named siRNA Dynamic PolyConjugates. Key features of the Dynamic PolyConjugate technology include a membrane-active polymer, the ability to reversibly mask the activity of this polymer until it reaches the acidic environment of endosomes, and the ability to target this modified polymer and its siRNA cargo specifically to hepatocytes in vivo after simple, low-pressure i.v. injection. Using this delivery technology, we demonstrate effective knockdown of two endogenous genes in mouse liver: apolipoprotein B (apoB) and peroxisome proliferator-activated receptor alpha (ppara). Knockdown of apoB resulted in clear phenotypic changes that included a significant reduction in serum cholesterol and increased fat accumulation in the liver, consistent with the known functions of apoB. Knockdown of ppara also resulted in a phenotype consistent with its known function, although with less penetrance than observed in apoB knockdown mice. Analyses of serum liver enzyme and cytokine levels in treated mice indicated that the siRNA Dynamic PolyConjugate was nontoxic and well tolerated.',\n", - " 'author': ['Rozema, David B.',\n", - " 'Lewis, David L.',\n", - " 'Wakefield, Darren H.',\n", - " 'Wong, So C.',\n", - " 'Klein, Jason J.',\n", - " 'Roesch, Paula L.',\n", - " 'Bertin, Stephanie L.',\n", - " 'Reppen, Tom W.',\n", - " 'Chu, Qili',\n", - " 'Blokhin, Andrei V.',\n", - " 'Hagstrom, James E.',\n", - " 'Wolff, Jon A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/104/32/12982\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0703778104\"}'],\n", - " 'title': ['Dynamic PolyConjugates for targeted in vivo delivery of siRNA to hepatocytes']},\n", - " {'bibcode': '1986PNAS...83...33R',\n", - " 'abstract': 'Species- and strain-specific spontaneously occurring tumors have been observed in rodents maintained under normal laboratory conditions. Elucidation of the molecular mechanisms associated with the development of these spontaneous tumors may provide a better understanding of tumor development associated with exposure to chemical carcinogens. In view of the high frequencies of oncogene activation shown in rodent tumors induced by known chemical carcinogens, we have investigated oncogene activation in spontaneous tumors of the B6C3F1 mouse and Fischer 344/N rat by DNA transfection techniques. A marked difference in the presence of activated oncogenes in spontaneous rat tumors versus spontaneous mouse liver tumors was observed in this study. All rat tumors tested failed to yield activated oncogenes (0/29), whereas 30% (3/10) of mouse hepatocellular adenomas and 77% (10/13) of hepatocellular carcinomas scored positive by DNA transfection. These transforming genes were identified as an activated Ha-ras gene in all the adenoma transfectants and in 8 of the 10 carcinoma transfectants. The two remaining hepatocellular carcinomas contained transforming genes that appear not to be members of the known ras gene family. The B6C3F1 mouse liver system might provide a very sensitive assay not only for assessing the potential of a chemical to activate a cellular proto-oncogene, but also for detecting various classes of proto-oncogenes that are susceptible to mutational activation.',\n", - " 'author': ['Reynolds, Steven H.',\n", - " 'Stowers, Shari J.',\n", - " 'Maronpot, Robert R.',\n", - " 'Anderson, Marshall W.',\n", - " 'Aaronson, Stuart A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/83/1/33\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/83/1/33\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/83/1/33\"}'],\n", - " 'title': ['Detection and identification of activated oncogenes in spontaneously occurring benign and malignant hepatocellular tumors of the B6C3F1 mouse.']},\n", - " {'bibcode': '1985ER.....37..320C',\n", - " 'author': ['Csallany, A.', 'Manwaring, J.', 'Menken, B.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2F0013-9351%2885%2990112-4\"}'],\n", - " 'title': ['Ozone-related fluorescent compounds in mouse liver and lung']},\n", - " {'bibcode': '2015PLoSO..1040619K',\n", - " 'author': ['Kim, Sun-Yee',\n", - " 'Sim, Choon Kiat',\n", - " 'Tang, Hui',\n", - " 'Han, Weiping',\n", - " 'Zhang, Kangling',\n", - " 'Xu, Feng'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0140619\"}'],\n", - " 'title': ['Acetylome Analysis Identifies SIRT1 Targets in mRNA-Processing and Chromatin-Remodeling in Mouse Liver']},\n", - " {'bibcode': '2009PLoSO...4.7212R',\n", - " 'author': ['Rodriguez, Alejandra',\n", - " 'Luukkaala, Tiina',\n", - " 'Fleming, Robert E.',\n", - " 'Britton, Robert S.',\n", - " 'Bacon, Bruce R.',\n", - " 'Parkkila, Seppo'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0007212\"}'],\n", - " 'title': ['Global Transcriptional Response to Hfe Deficiency and Dietary Iron Overload in Mouse Liver and Duodenum']},\n", - " {'bibcode': '2015Ana...140.7868X',\n", - " 'author': ['Xu, Leilei',\n", - " 'Wang, Fang',\n", - " 'Xu, Ying',\n", - " 'Wang, Yi',\n", - " 'Zhang, Cuiping',\n", - " 'Qin, Xue',\n", - " 'Yu, Hongxiu',\n", - " 'Yang, Pengyuan'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1039%2FC5AN01832C\"}'],\n", - " 'title': ['An MRM-based workflow for absolute quantitation of lysine-acetylated metabolic enzymes in mouse liver']},\n", - " {'bibcode': '2017NatSR...737541G',\n", - " 'abstract': 'Dysfunction of cell-cell tight junction (TJ) adhesions is a major feature in the pathogenesis of various diseases. Liver TJs preserve cellular polarity by delimiting functional bile-canalicular structures, forming the blood-biliary barrier. In acetaminophen-hepatotoxicity, the mechanism by which tissue cohesion and polarity are affected remains unclear. Here, we demonstrate that acetaminophen, even at low-dose, disrupts the integrity of TJ and cell-matrix adhesions, with indicators of cellular stress with liver injury in the human hepatic HepaRG cell line, and primary hepatocytes. In mouse liver, at human-equivalence (therapeutic) doses, dose-dependent loss of intercellular hepatic TJ-associated ZO-1 protein expression was evident with progressive clinical signs of liver injury. Temporal, dose-dependent and specific disruption of the TJ-associated ZO-1 and cytoskeletal-F-actin proteins, correlated with modulation of hepatic ultrastructure. Real-time impedance biosensing verified in vitro early, dose-dependent quantitative decreases in TJ and cell-substrate adhesions. Whereas treatment with NAPQI, the reactive metabolite of acetaminophen, or the PKCα-activator and TJ-disruptor phorbol-12-myristate-13-acetate, similarly reduced TJ integrity, which may implicate oxidative stress and the PKC pathway in TJ destabilization. These findings are relevant to the clinical presentation of acetaminophen-hepatotoxicity and may inform future mechanistic studies to identify specific molecular targets and pathways that may be altered in acetaminophen-induced hepatic depolarization.',\n", - " 'author': ['Gamal, Wesam',\n", - " 'Treskes, Philipp',\n", - " 'Samuel, Kay',\n", - " 'Sullivan, Gareth J.',\n", - " 'Siller, Richard',\n", - " 'Srsen, Vlastimil',\n", - " 'Morgan, Katie',\n", - " 'Bryans, Anna',\n", - " 'Kozlowska, Ada',\n", - " 'Koulovasilopoulos, Andreas',\n", - " 'Underwood, Ian',\n", - " 'Smith, Stewart',\n", - " 'Del-Pozo, Jorge',\n", - " 'Moss, Sharon',\n", - " 'Thompson, Alexandra Inés',\n", - " 'Henderson, Neil C.',\n", - " 'Hayes, Peter C.',\n", - " 'Plevris, John N.',\n", - " 'Bagnaninchi, Pierre-Olivier',\n", - " 'Nelson, Leonard J.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep37541\"}'],\n", - " 'title': ['Low-dose acetaminophen induces early disruption of cell-cell tight junctions in human hepatic cells and mouse liver']},\n", - " {'bibcode': '2015APS..MARJ26001S',\n", - " 'abstract': 'Our lab at MIT has been interested in how the 1D and 2D electronic structures of carbon nanotubes and graphene respectively can be utilized to advance new concepts in molecular detection. We introduce CoPhMoRe or corona phase molecular recognition as a method of discovering synthetic antibodies, or nanotube-templated recognition sites from a heteropolymer library. We show that certain synthetic heteropolymers, once constrained onto a single-walled carbon nanotube by chemical adsorption, also form a new corona phase that exhibits highly selective recognition for specific molecules. To prove the generality of this phenomenon, we report three examples of heteropolymers-nanotube recognition complexes for riboflavin, L-thyroxine and estradiol. The platform opens new opportunities to create synthetic recognition sites for molecular detection. We have also extended this molecular recognition technique to neurotransmitters, producing the first fluorescent sensor for dopamine. Another area of advancement in biosensor development is the use of near infrared fluorescent carbon nanotube sensors for in-vivo detection. Here, we show that PEG-ligated d(AAAT)7 DNA wrapped SWNT are selective for nitric oxide, a vasodilator of blood vessels, and can be tail vein injected into mice and localized within the viable mouse liver. We use an SJL mouse model to study liver inflammation in vivo using the spatially and spectrally resolved nIR signature of the localized SWNT sensors.',\n", - " 'author': ['Strano, Michael'],\n", - " 'title': ['Corona Phase Molecular Recognition (CoPhMoRe) to Enable New Nanosensor Interfaces']},\n", - " {'bibcode': '1984PNAS...81.1327D',\n", - " 'abstract': 'N-acetyl-p-benzoquinone imine (NAPQI) has been proposed as the toxic metabolite of acetaminophen for the past 10 years, although it has never been detected as an enzymatic oxidation product of acetaminophen. We report (i) direct detection of NAPQI formed as an oxidation product of acetaminophen by cytochrome P-450 and cumene hydroperoxide and (ii) indirect evidence that is compelling for NAPQI formation from acetaminophen by cytochrome P-450, NADPH, and NADPH-cytochrome P-450 reductase. Evidence is provided for the rapid reduction of NAPQI back to acetaminophen by NADPH and NADPH-cytochrome P-450 reductase such that steady-state levels of NAPQI were below our detection limits of 6.7 X 10(-8) M. In mouse liver microsomal incubations, radiolabeled analogs of both NAPQI and acetaminophen bound covalently to microsomal protein with the loss of approximately equal to 20% of the acetyl group as acetamide. The binding in each case was decreased by glutathione with concomitant formation of 3-S-glutathionylacetaminophen. The binding also was decreased by L-ascorbic acid, NADPH, and NADH with reduction of NAPQI to acetaminophen. Results of partitioning experiments indicate that NAPQI is a major metabolite of acetaminophen, a considerable fraction of which is rapidly reduced back to acetaminophen.',\n", - " 'author': ['Dahlin, David C.',\n", - " 'Miwa, Gerald T.',\n", - " 'Lu, Anthony Y. H.',\n", - " 'Nelson, Sidney D.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/81/5/1327\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/81/5/1327\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/81/5/1327\"}'],\n", - " 'title': ['N-acetyl-p-benzoquinone imine: a cytochrome P-450-mediated oxidation product of acetaminophen.']},\n", - " {'bibcode': '2017AIPC.1890c0006L',\n", - " 'abstract': 'The insulin resistance models of mouse liver epithelial and rat myoblasts cells were induced by three kinds of inducers: dexamethasone, high insulin and high glucose. The purpose is to select the optimal insulin resistance model, to provide a simple and reliable TR cell model for the study of the pathogenesis of TR and the improvement of TR drugs and functional foods. The MTT method is used for toxicity screening of three compounds, selecting security and suitable concentration. We performed a Glucose oxidase peroxidase (GOD-POD) method involving FL83B and L6 cell with dexamethasone, high insulin and high glucose-induced insulin resistance. Results suggested that FL83B cells with dexamethasone-induced (0.25uM) were established insulin resistance and L6 cells with high-glucose (30mM) and dexamethasone-induced (0.25uM) were established insulin resistance.',\n", - " 'author': ['Liu, Lanlan',\n", - " 'Han, Jizhong',\n", - " 'Li, Haoran',\n", - " 'Liu, Mengmeng',\n", - " 'Zeng, Bin'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1063%2F1.5005194\"}'],\n", - " 'title': ['The establishment of insulin resistance model in FL83B and L6 cell']},\n", - " {'bibcode': '1981PNAS...78.2403C',\n", - " 'abstract': 'Laminin, a basement membrane glycoprotein isolated from cultures of mouse endodermal cells and rat yolk sac carcinoma cells, promoted the attachment of liver cells obtained from regenerating mouse liver. Cells from normal mouse liver attached readily to dishes coated with fibronectin but attached poorly to surfaces coated with laminin. Both proteins efficiently promoted the attachment of cells from livers undergoing regeneration. After regeneration, the attachment to laminin returned to the low levels found in animals not subjected to partial hepatectomy but attachment to fibronectin remained high. Immunofluorescent staining of sections of normal liver with antilaminin revealed the presence of laminin in or adjacent to the walls of the bile ducts and blood vessels. After induction of regeneration by partial hepatectomy, increased amounts of laminin appeared in the sinusoidal areas. After carbon tetrachloride poisoning, staining for laminin was especially pronounced in the necrotic and postnecrotic areas around the central veins. This additional expression of laminin was transient. It reached a maximum around 5-6 days after the injury and then gradually disappeared. These findings show that laminin is an adhesive protein. The increase of laminin in regenerating liver and the adhesiveness of cells from such livers to laminin suggest a role for laminin in the maintenance of a proper tissue organization during liver regeneration.',\n", - " 'author': ['Carlsson, Roland',\n", - " 'Engvall, Eva',\n", - " 'Freeman, Aaron',\n", - " 'Ruoslahti, Erkki'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/78/4/2403\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/78/4/2403\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/78/4/2403\"}'],\n", - " 'title': ['Laminin and Fibronectin in Cell Adhesion: Enhanced Adhesion of Cells from Regenerating Liver to Laminin']},\n", - " {'bibcode': '2008SPIE.6860E..1YL',\n", - " 'abstract': 'Conventional hepatic research relies heavily on histological images for obtaining morphological information of the liver. However, static histological images can not provide real-time dynamic information of in vivo physiological processes such as cellular motion or damage. For a long time, panadol has been used in pain relief. However, Panadol may have unwanted side effects and detailed information of the effects of Panadol on hepatic metabolism is unknown. In this work, we developed a high resolution intravital hepatic imaging chamber to study the effects of Panadol on liver. We expect this methodology to be useful in revealing the detailed metabolism of liver after using Panadol and this approach allows us to achieve a better understanding of hepatic processes. In our approach, we use multiphoton fluorescence (MPF) microscopy to observe the side effect of liver on using Panadol inside the in vivo mouse animal model.',\n", - " 'author': ['Li, Feng Chieh',\n", - " 'Liang, Huei, Jr.',\n", - " 'Yang, Shu-Mei',\n", - " 'Lee, Hsuan-Shu',\n", - " 'Dong, Chen-Yuan'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1117%2F12.763367\"}'],\n", - " 'title': ['Investigating the effects of Panadol on mouse liver by in vivo multiphoton microscopy']},\n", - " {'bibcode': '1998JTEHA..53...19C',\n", - " 'author': ['Carlson, Gary P.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1080%2F009841098159448\"}'],\n", - " 'title': ['Metabolism of Styrene Oxide to Styrene Glycol by Mouse Liver and Lung']},\n", - " {'bibcode': '1978PNAS...75.3322H',\n", - " 'abstract': 'Papain solubilized H-2a histocompatibility antigens (H-2Kk plus H-2Dd) have been purified by a large-scale procedure that can routinely provide 2-3 mg of heavy chain from 1 kg of mouse liver. The heavy chains were homogeneous by sodium dodecyl sulfate electrophoresis. Disc gel electrophoresis resolved two protein bands that were identified as H-2Dd and H-2Kd by immune complex formation and autoradiography. Comparative amino acid composition and NH2-terminal sequence analyses of unfractionated H-2a, H-2Kk, and HLA suggested close structural relationships. However, the following observations suggest that papain cleaves these membrane bound antigens at different positions with respect to the COOH terminus: the molecular weight of the peptide portion of papain solubilized HLA is smaller than that of H-2 (30,000 versus 33,700); the COOH-terminal sequences are different; and, finally, papain-solubilized H-2 contains a free cysteine residue in addition to the two disulfide bridges that are present in both H-2 and HLA.',\n", - " 'author': ['Henriksen, Ole', 'Robinson, Elizabeth A.', 'Appella, Ettore'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/75/7/3322\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/75/7/3322\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/75/7/3322\"}'],\n", - " 'title': ['Structural characterization of H-2 antigens purified from mouse liver.']},\n", - " {'bibcode': '1968Natur.217..180C',\n", - " 'abstract': 'I HAVE studied the chromosomal aberrations which are induced in mouse hepatocytes by single and fractionated doses of X-rays given at various times before or after surgical partial hepatectomy. The data presented here show that the different phases of the cell cycle possibly differ not only in their sensitivity to chromosomal damage by radiation but also in their ability to recover from such damage.',\n", - " 'author': ['Coggle, J. E.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F217180a0\"}'],\n", - " 'title': ['Effect of Cell Cycle on Recovery from Radiation Damage in the Mouse Liver']},\n", - " {'bibcode': '1982NYASA.389..467T',\n", - " 'author': ['Tatsuta, Emiko',\n", - " 'Shirahama, Tsuranobu',\n", - " 'Sipe, Jean D.',\n", - " 'Skinner, Martha',\n", - " 'Cohen, Alan S.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1111%2Fj.1749-6632.1982.tb22176.x\"}'],\n", - " 'title': ['Kinetics of Sap and Saa Production by Cultured Mouse Liver Cells']},\n", - " {'bibcode': '2020AcSpA.22817719C',\n", - " 'abstract': \"Mad honey (MH) is obtained from Rhododendron plants, which are extensively grown in some regions of the world such as Europe, North America, Tropical Asia and Turkey. Although it has been known that MH induces adverse effects in the body due to grayanotoxin (GTX) in it, it is widely used for some medical purposes by the public. In this study, the effects of MH (25, 50 and 75 mg/kg) and GTX-III (0.01 mg/kg), which is the pure form of the most toxic type of the GTXs in MH, were investigated on the mouse liver at molecular level via Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) spectroscopy. The results showed that 25 and 50 mg/kg of MH didn't cause any significant alterations in the liver tissue except a decrease in the glycogen amount. However, significant differences were observed between 75 mg/kg MH and GTX-III treated groups and control group. For example, the amounts of saturated lipids, nucleic acids and proteins increased in the 75 mg/kg MH and GTX-III treated groups. A decrease in the ratios of unsaturated/saturated lipid, CH2/lipid and carbonyl/lipid and an increase in the ratio of CH3/lipid were observed after the administration of 75 mg/kg MH and GTX-III, all of which may be a consequence of lipid peroxidation. Moreover, 75 mg/kg MH and GTX-III caused a decrease in the membrane order, an increase in the membrane fluidity and some important changes on the secondary structure of proteins indicating protein denaturation. In addition, Hierarchical Cluster Analysis (HCA) and Principal Component Analysis (PCA) confirmed these findings. These results revealed that MH induces significant dose-dependent toxic effects in the structure and function of the liver tissue. This study also showed that ATR-FTIR spectroscopy provides a rapid and sensitive monitoring of the changes induced by a toxic compound on biological tissues at molecular level.\",\n", - " 'author': ['Cakmak-Arslan, Gulgun',\n", - " 'Haksoy, Humeyra',\n", - " 'Goc-Rasgele, Pinar',\n", - " 'Kekecoglu, Meral'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.saa.2019.117719\"}'],\n", - " 'title': ['Determination of the dose-dependent toxic effects of mad honey on mouse liver using ATR-FTIR spectroscopy']},\n", - " {'bibcode': '2017NatSR...7.2965L',\n", - " 'abstract': 'Imaging the size distribution of metal nanoparticles (NPs) in a tissue has important implications in terms of evaluating NP toxicity. Microscopy techniques used to image tissue NPs are limited by complicated sample preparation or poor resolution. In this study, we developed a laser ablation (LA) system coupled to single-particle inductively coupled plasma mass spectrometry (SP-ICP-MS) for quantitative imaging of gold (G)NPs in tissue samples. In this system, GNPs were ablated but did not disintegrate and integrate under optimised operation conditions, which were verified by characterising LA particles by scanning electron microscopy. The feasibility of imaging size distributions in tissue was validated using reference GNPs 60 and 80 nm in size on matrix-matched kidney. A transport efficiency of 6.07% was obtained by LA-SP-ICP-MS under optimal conditions. We used this system to image 80-nm GNPs in mouse liver and the size distribution thus obtained was in accordance with that determined by nebuliser SP-ICP-MS. The images revealed that 80-nm GNPs mainly accumulate in the liver and did not obviously aggregate. Our results demonstrate that LA-SP-ICP-MS is an effective tool for evaluating the size distribution of metal NPs in tissue.',\n", - " 'author': ['Li, Qing',\n", - " 'Wang, Zheng',\n", - " 'Mo, Jiamei',\n", - " 'Zhang, Guoxia',\n", - " 'Chen, Yirui',\n", - " 'Huang, Chuchu'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-017-03275-x\"}'],\n", - " 'title': ['Imaging gold nanoparticles in mouse liver by laser ablation inductively coupled plasma mass spectrometry']},\n", - " {'bibcode': '2019NatSR...9.6913S',\n", - " 'abstract': 'To-date, most proteomic studies aimed at discovering tissue-based cancer biomarkers have compared the quantity of selected proteins between case and control groups. However, proteins generally function in association with other proteins to form modules localized in particular subcellular compartments in specialized cell types and tissues. Sub-cellular mislocalization of proteins has in fact been detected as a key feature in a variety of cancer cells. Here, we describe a strategy for tissue-biomarker detection based on a mitochondrial fold enrichment (mtFE) score, which is sensitive to protein abundance changes as well as changes in subcellular distribution between mitochondria and cytosol. The mtFE score integrates protein abundance data from total cellular lysates and mitochondria-enriched fractions, and provides novel information for the classification of cancer samples that is not necessarily apparent from conventional abundance measurements alone. We apply this new strategy to a panel of wild-type and mutant mice with a liver-specific gene deletion of Liver receptor homolog 1 (Lrh-1hep-/-), with both lines containing control individuals as well as individuals with liver cancer induced by diethylnitrosamine (DEN). Lrh-1 gene deletion attenuates cancer cell metabolism in hepatocytes through mitochondrial glutamine processing. We show that proteome changes based on mtFE scores outperform protein abundance measurements in discriminating DEN-induced liver cancer from healthy liver tissue, and are uniquely robust against genetic perturbation. We validate the capacity of selected proteins with informative mtFE scores to indicate hepatic malignant changes in two independent mouse models of hepatocellular carcinoma (HCC), thus demonstrating the robustness of this new approach to biomarker research. Overall, the method provides a novel, sensitive approach to cancer biomarker discovery that considers contextual information of tested proteins.',\n", - " 'author': ['Sajic, Tatjana',\n", - " 'Ciuffa, Rodolfo',\n", - " 'Lemos, Vera',\n", - " 'Xu, Pan',\n", - " 'Leone, Valentina',\n", - " 'Li, Chen',\n", - " 'Williams, Evan G.',\n", - " 'Makris, Georgios',\n", - " 'Banaei-Esfahani, Amir',\n", - " 'Heikenwalder, Mathias',\n", - " 'Schoonjans, Kristina',\n", - " 'Aebersold, Ruedi'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-019-43091-z\"}'],\n", - " 'title': ['A new class of protein biomarkers based on subcellular distribution: application to a mouse liver cancer model']},\n", - " {'bibcode': '2013TxEC...95..495S',\n", - " 'author': ['Syama, S.',\n", - " 'Reshma, S. C.',\n", - " 'Sreekanth, P. J.',\n", - " 'Varma, H. K.',\n", - " 'Mohanan, P. V.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1080%2F02772248.2013.789606\"}'],\n", - " 'title': ['Effect of Zinc Oxide nanoparticles on cellular oxidative stress and antioxidant defense mechanisms in mouse liver']},\n", - " {'bibcode': '1985Natur.316..552B',\n", - " 'abstract': \"In mammals, several well-defined metabolic changes occur during infection, many of which are attributable to products of the reticuloendothelial system1-3. Among these changes, a hypertrigly-ceridaemic state is frequently evident4-9, resulting from defective triglyceride clearance, caused by systemic suppression of the enzyme lipoprotein lipase (LPL)9. We have found previously that macrophages secrete the hormone cachectin, which specifically suppresses LPL activity in cultured adipocytes (3T3-L1 cells)10-17. When originally purified from RAW 264.7 (mouse macrophage) cells, cachectin was shown to have a pI of 4.7, a subunit size of relative molecular mass (Mr) 17,000 and to form non-covalent multimers17. A receptor for cachectin was identified on non-tumorigenic cultured cells and on normal mouse liver membranes17. A new high-yield purification technique has enabled us to determine further details of the structure of mouse cachectin. We now report that a high degree of homology exists between the N-terminal sequence of mouse cachectin and the N-terminal sequence recently determined for human tumour necrosis factor (TNF)18,19. Purified cachectin also possesses potent TNF activity in vitro. These findings suggest that the `cachectin' and `TNF' activities of murine macrophage conditioned medium are attributable to a single protein, which modulates the metabolic activities of normal as well as neoplastic cells through interaction with specific high-affinity receptors.\",\n", - " 'author': ['Beutler, B.',\n", - " 'Greenwald, D.',\n", - " 'Hulmes, J. D.',\n", - " 'Chang, M.',\n", - " 'Pan, Y. -C. E.',\n", - " 'Mathison, J.',\n", - " 'Ulevitch, R.',\n", - " 'Cerami, A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F316552a0\"}'],\n", - " 'title': ['Identity of tumour necrosis factor and the macrophage-secreted factor cachectin']},\n", - " {'bibcode': '2009PLoSO...4.6787Z',\n", - " 'author': ['Zeng, Jia', 'Parvanova, Iana Angelova', 'Howard, Jonathan C.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0006787\"}'],\n", - " 'title': ['A Dedicated Promoter Drives Constitutive Expression of the Cell-Autonomous Immune Resistance GTPase, Irga6 (IIGP1) in Mouse Liver']},\n", - " {'bibcode': '2017PLoSO..1282671Y',\n", - " 'author': ['Yi, Lan',\n", - " 'Hu, Nan',\n", - " 'Yin, Jie',\n", - " 'Sun, Jing',\n", - " 'Mu, Hongxiang',\n", - " 'Dai, Keren',\n", - " 'Ding, Dexin'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0182671\"}'],\n", - " 'title': ['Up-regulation of calreticulin in mouse liver tissues after long-term irradiation with low-dose-rate gamma rays']},\n", - " {'bibcode': '2011PLoSO...621229S',\n", - " 'author': ['Sueyoshi, Tatsuya',\n", - " 'Green, William D.',\n", - " 'Vinal, Kellie',\n", - " 'Woodrum, Tyler S.',\n", - " 'Moore, Rick',\n", - " 'Negishi, Masahiko'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0021229\"}'],\n", - " 'title': ['Garlic Extract Diallyl Sulfide (DAS) Activates Nuclear Receptor CAR to Induce the Sult1e1 Gene in Mouse Liver']},\n", - " {'bibcode': '1997HETox..16....3G',\n", - " 'abstract': 'B6C3F1 mice exposed to high dose levels of methylene chloride by inhalation for 2 years had an elevated incidence of liver and lung tumours. These tumours were not increased in rats or hamsters exposed under the same or similar conditions. This paper gives an overview of research conducted over the last 10 years into the mechanism of action of methylene chloride as a mouse carcinogen and into the relevance of the mouse data to humans exposed to this chemical. Data are presented on the comparative metabolism and pharmacokinetics of methylene chloride in mice, rats, hamsters and humans, on the toxicity of methylene chloride to the target organs in the mouse, and on the genotoxicity of methylene chloride in vitro and in vivo. The enzyme which activates methylene chloride to its carcinogenic form has been isolated, sequenced, and cloned, and its distribution studied within cells, organs and between species. Evidence has been obtained to show that methylene chloride caused cancer in mice as a result of interactions between metabolites of the glutathione S-transferase pathway and DNA. Damage to mouse lung Clara cells and increased cell division are believed to have influenced the development of the lung tumours. The species specificity was a direct consequence of the very high activity and specific cellular and nuclear localisation of a theta class glutathione S-transferase enzyme which was unique to the mouse. Consequently, DNA damage was not detectable in rats in vivo, or in hamster and human hepatocytes exposed to cytotoxic dose levels of methylene chloride in vitro. These results provide evidence that the mouse is unique in its response to methylene chloride and that it is an inappropriate model for human health assessment.',\n", - " 'author': ['Green, Trevor'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1177%2F0960327197016001021\"}'],\n", - " 'title': ['Methylene chloride induced mouse liver and lung tumours: An overview of the role of mechanistic studies in human safety assessment']},\n", - " {'bibcode': '2013PNAS..110.6601R',\n", - " 'abstract': 'Large-scale proteomic approaches have identified numerous mitochondrial acetylated proteins; however in most cases, their regulation by acetyltransferases and deacetylases remains unclear. Sirtuin 3 (SIRT3) is an NAD+-dependent mitochondrial protein deacetylase that has been shown to regulate a limited number of enzymes in key metabolic pathways. Here, we use a rigorous label-free quantitative MS approach (called MS1 Filtering) to analyze changes in lysine acetylation from mouse liver mitochondria in the absence of SIRT3. Among 483 proteins, a total of 2,187 unique sites of lysine acetylation were identified after affinity enrichment. MS1 Filtering revealed that lysine acetylation of 283 sites in 136 proteins was significantly increased in the absence of SIRT3 (at least twofold). A subset of these sites was independently validated using selected reaction monitoring MS. These data show that SIRT3 regulates acetylation on multiple proteins, often at multiple sites, across several metabolic pathways including fatty acid oxidation, ketogenesis, amino acid catabolism, and the urea and tricarboxylic acid cycles, as well as mitochondrial regulatory proteins. The widespread modification of key metabolic pathways greatly expands the number of known substrates and sites that are targeted by SIRT3 and establishes SIRT3 as a global regulator of mitochondrial protein acetylation with the capability of coordinating cellular responses to nutrient status and energy homeostasis.',\n", - " 'author': ['Rardin, Matthew J.',\n", - " 'Newman, John C.',\n", - " 'Held, Jason M.',\n", - " 'Cusack, Michael P.',\n", - " 'Sorensen, Dylan J.',\n", - " 'Li, Biao',\n", - " 'Schilling, Birgit',\n", - " 'Mooney, Sean D.',\n", - " 'Kahn, C. Ronald',\n", - " 'Verdin, Eric',\n", - " 'Gibson, Bradford W.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/110/16/6601\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1302961110\"}'],\n", - " 'title': ['Label-free quantitative proteomics of the lysine acetylome in mitochondria identifies substrates of SIRT3 in metabolic pathways']},\n", - " {'bibcode': '2016NatCo...712917M',\n", - " 'abstract': 'Although protein ADP-ribosylation is involved in diverse biological processes, it has remained a challenge to identify ADP-ribose acceptor sites. Here, we present an experimental workflow for sensitive and unbiased analysis of endogenous ADP-ribosylation sites, capable of detecting more than 900 modification sites in mammalian cells and mouse liver. In cells, we demonstrate that Lys residues, besides Glu, Asp and Arg residues, are the dominant in vivo targets of ADP-ribosylation during oxidative stress. In normal liver tissue, we find Arg residues to be the predominant modification site. The cellular distribution and biological processes that involve ADP-ribosylated proteins are different in cultured cells and liver tissue, in the latter of which the majority of sites were found to be in cytosolic and mitochondrial protein networks primarily associated with metabolism. Collectively, we describe a robust methodology for the assessment of the role of ADP-ribosylation and ADP-ribosyltransferases in physiological and pathological states.',\n", - " 'author': ['Martello, Rita',\n", - " 'Leutert, Mario',\n", - " 'Jungmichel, Stephanie',\n", - " 'Bilan, Vera',\n", - " 'Larsen, Sara C.',\n", - " 'Young, Clifford',\n", - " 'Hottiger, Michael O.',\n", - " 'Nielsen, Michael L.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fncomms12917\"}'],\n", - " 'title': ['Proteome-wide identification of the endogenous ADP-ribosylome of mammalian cells and tissue']},\n", - " {'bibcode': '2010PNAS..107.4890K',\n", - " 'abstract': 'Cisplatin is one of the most commonly used anticancer drugs. It kills cancer cells by damaging their DNA, and hence cellular DNA repair capacity is an important determinant of its efficacy. Here, we investigated the repair of cisplatin-induced DNA damage in mouse liver and testis tissue extracts prepared at regular intervals over the course of a day. We find that the XPA protein, which plays an essential role in repair of cisplatin damage by nucleotide excision repair, exhibits circadian oscillation in the liver but not in testis. Consequently, removal of cisplatin adducts in liver extracts, but not in testis extracts, exhibits a circadian pattern with zenith at ∼5 pm and nadir at ∼5 am. Furthermore, we find that the circadian oscillation of XPA is achieved both by regulation of transcription by the core circadian clock proteins including cryptochrome and by regulation at the posttranslational level by the HERC2 ubiquitin ligase. These findings may be used as a guide for timing of cisplatin chemotherapy.',\n", - " 'author': ['Kang, Tae-Hong',\n", - " 'Lindsey-Boltz, Laura A.',\n", - " 'Reardon, Joyce T.',\n", - " 'Sancar, Aziz'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/107/11/4890\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0915085107\"}'],\n", - " 'title': ['Circadian control of XPA and excision repair of cisplatin-DNA damage by cryptochrome and HERC2 ubiquitin ligase']},\n", - " {'bibcode': '2008PNAS..105...94K',\n", - " 'abstract': 'The ability to store fat in the form of cytoplasmic triglyceride droplets is conserved from Saccharomyces cerevisiae to humans. Although much is known regarding the composition and catabolism of lipid droplets, the molecular components necessary for the biogenesis of lipid droplets have remained obscure. Here we report the characterization of a conserved gene family important for lipid droplet formation named fat-inducing transcript (FIT). FIT1 and FIT2 are endoplasmic reticulum resident membrane proteins that induce lipid droplet accumulation in cell culture and when expressed in mouse liver. shRNA silencing of FIT2 in 3T3-LI adipocytes prevents accumulation of lipid droplets, and depletion of FIT2 in zebrafish blocks diet-induced accumulation of lipid droplets in the intestine and liver, highlighting an important role for FIT2 in lipid droplet formation in vivo. Together these studies identify and characterize a conserved gene family that is important in the fundamental process of storing fat.',\n", - " 'author': ['Kadereit, Bert',\n", - " 'Kumar, Pradeep',\n", - " 'Wang, Wen-Jun',\n", - " 'Miranda, Diego',\n", - " 'Snapp, Erik L.',\n", - " 'Severina, Nadia',\n", - " 'Torregroza, Ingrid',\n", - " 'Evans, Todd',\n", - " 'Silver, David L.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/105/1/94\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/105/1/94.full.pdf\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0708579105\"}'],\n", - " 'title': ['Evolutionarily conserved gene family important for fat storage']},\n", - " {'bibcode': '2022ScTEn.812o1509S',\n", - " 'author': ['Sun, Sujie',\n", - " 'Wang, Jianshe',\n", - " 'Yao, Jingzhi',\n", - " 'Guo, Hua',\n", - " 'Dai, Jiayin'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.scitotenv.2021.151509\"}'],\n", - " 'title': ['Transcriptome analysis of 3D primary mouse liver spheroids shows that long-term exposure to hexafluoropropylene oxide trimer acid disrupts hepatic bile acid metabolism']},\n", - " {'bibcode': '1974PNAS...71.1677C',\n", - " 'abstract': 'A method is described for the colonial growth, in semi-solid medium, of erythropoietin-responsive erythroid cell precursors. The erythroid cell precursors were isolated by immune hemolysis from fetal mouse liver. Both the number of precursor cells triggered to proliferate and differentiate, and the size of the erythropoietic colonies formed, are directly dependent upon the concentration of erythropoietin included in the culture.',\n", - " 'author': ['Cooper, Marvin C.',\n", - " 'Levy, Joseph',\n", - " 'Cantor, Linda N.',\n", - " 'Marks, Paul A.',\n", - " 'Rifkind, Richard A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/71/5/1677\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/71/5/1677\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/71/5/1677\"}'],\n", - " 'title': ['The Effect of Erythropoietin on Colonial Growth of Erythroid Precursor Cells In Vitro']},\n", - " {'bibcode': '1966PNAS...56.1759C',\n", - " 'author': ['Commerford, S. L.', 'Delihas, N.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/56/6/1759\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/56/6/1759\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.56.6.1759\"}'],\n", - " 'title': ['Examination of The Nucleohistone from Mouse Liver and Intestine for RNA Covalently Linked to Histone']},\n", - " {'bibcode': '2013PLoSO...884383U',\n", - " 'author': ['Underkoffler, Lara A.',\n", - " 'Carr, Erikka',\n", - " 'Nelson, Anthony',\n", - " 'Ryan, Matthew J.',\n", - " 'Schultz, Reiner',\n", - " 'Loomes, Kathleen M.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0084383\"}'],\n", - " 'title': ['Microarray Data Reveal Relationship between Jag1 and Ddr1 in Mouse Liver']},\n", - " {'bibcode': '2021NatSR..11.1733D',\n", - " 'abstract': 'The acute liver injury (ALI) and hepatic fibrosis caused by the co-treatment of lipopolysaccharide (LPS)/D-galactosamine (D-GalN) have been extensively studied. However, whether LPS/D-GalN are genotoxic has been left unknown. In this study, male mice were divided into eight groups with eight animals in each group. For acute challenge of LPS/D-GalN, the mice in each group received a combination of LPS/D-GalN via intraperitoneal injection at the dose of 25 μg/kg/250 mg/kg, 25 μg/kg/500 mg/kg, or 50 μg/kg/500 mg/kg body weight. An additional group for chronic administration of test compounds was conducted by i.p. injection of LPS/D-GalN (10 μg/kg/100 mg/kg) every other day for 8 weeks. Saline solution (0.9%) and cyclophosphamide (CTX) (50 mg/kg body weight) given by i.p. injection was used as the negative and positive control, respectively. The results of single cell gel electrophoresis (SCGE) assay indicated that acute exposure of the mice to LPS/D-GalN caused severe DNA damage in hepatic cells, but not in the brain, sperm or bone marrow cells, which evidenced the genotoxicity of LPS/D-GalN administrated in combination. Interestingly, the chronic administration of LPS/D-GalN triggered significant genotoxic effects not only in hepatic but also in brain cells, with negative results in sperm and bone marrow cells. Histopathological examination in the liver and brain tissues revealed changes consistent with the SCGE results. The present study indicates genotoxic potential of LPS/D-GalN co-administered in mice, which may serve as an in vivo experimental model for relevant genotoxic study.',\n", - " 'author': ['Dong, Wenjing', 'Song, Erqun', 'Song, Yang'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-021-81383-5\"}'],\n", - " 'title': ['Co-administration of lipopolysaccharide and D-galactosamine induces genotoxicity in mouse liver']},\n", - " {'bibcode': '2011PhDT.......242L',\n", - " 'abstract': \"Currently, few studies are available that have explored the role of carbon nanoparticles in liver toxicity. The susceptibility of the liver to nanoparticles rises from the inhalation exposure route often encountered during manufacturing and occupational exposure. Persons occupying these types of environmental setting are exposed to airborne nanoparticles less than 100nm, which have unobstructed access to most area of the lungs due to their size. Several reports have shown that single walled carbon nanotubes (SWCNTs) induce oxidative stress and pose the greatest cytotoxicity potential do to their size. Also, studies in mice indicate nanoparticles tend to accumulate in organs such as the spleen, kidney and liver, which is a major concern due to a lack of knowledge as to their fate. Single Wall Carbon Nanotubes (SWCNT's) are able to more easily penetrate through the cell membrane and display higher cell toxicity than Multi walled carbon nanotubes (MWCTs), opening the possibility for crossing various biological barriers within the body. Therefore effective occupational and environmental health risk assessments are significant in controlling the manufacture process of carbon nanotubes (CNTs). The present study was undertaken to determine the toxicity exhibited by SWCNT in mouse liver tissue as a model system. Mouse exposure during inhalation with and without SWCNT and reactive oxygen species (ROS) products were measured by change in fluorescence using dichloro fluorescein (DCF). The result showed no increase ROS on exposure of SWCNT in a dose and time dependent manner. Also, there is no reduction levels of glutathione (GSH) and super oxide dismutase (SOD), the antioxidant protective mechanism present in mouse liver cells upon SWCNT exposure. Lipid Peroxidation (LPO) and Lactate Dehydrogenase (LDH) assays indicated no tissue or protein damage. Additionally, Caspases --8 and --3 assays were conducted in order to understand the apoptotic signaling pathways initiated by oxidative stress. PEPCK and Hexokinase activity in mouse liver measured no hepatic glucokinase activity within the sensitivity of the assays. Based on the assays performed, the liver tolerated the SWCNT's 5mug dosage for 7 days, with no acute toxic effect. Although current tests and procedures may be appropriate to detect many risks associated with the use of these nanoparticles, it cannot be assumed that these assays will detect all potential risks. Given their limitations, specific emphasis should be on investigation in term of distribution in vivo both at the organ and cellular level using proteomics.\",\n", - " 'author': ['Lyons, Lyndon L.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:3569128\"}'],\n", - " 'title': ['Study of in vivo exposure of single-walled carbon nanotubes in mouse liver']},\n", - " {'bibcode': '2012JBO....17l6012W',\n", - " 'abstract': 'Liver cancer is one of the most common malignant tumors worldwide. In order to enable the noninvasive detection of small liver tumors in mice, we present a parallel iterative shrinkage (PIS) algorithm for dual-modality tomography. It takes advantage of microcomputed tomography and multiview bioluminescence imaging, providing anatomical structure and bioluminescence intensity information to reconstruct the size and location of tumors. By incorporating prior knowledge of signal sparsity, we associate some mathematical strategies including specific smooth convex approximation, an iterative shrinkage operator, and affine subspace with the PIS method, which guarantees the accuracy, efficiency, and reliability for three-dimensional reconstruction. Then an in vivo experiment on the bead-implanted mouse has been performed to validate the feasibility of this method. The findings indicate that a tiny lesion less than 3 mm in diameter can be localized with a position bias no more than 1 mm the computational efficiency is one to three orders of magnitude faster than the existing algorithms; this approach is robust to the different regularization parameters and the lp norms. Finally, we have applied this algorithm to another in vivo experiment on an HCCLM3 orthotopic xenograft mouse model, which suggests the PIS method holds the promise for practical applications of whole-body cancer detection.',\n", - " 'author': ['Wu, Ping',\n", - " 'Liu, Kai',\n", - " 'Zhang, Qian',\n", - " 'Xue, Zhenwen',\n", - " 'Li, Yongbao',\n", - " 'Ning, Nannan',\n", - " 'Yang, Xin',\n", - " 'Li, Xingde',\n", - " 'Tian, Jie'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1117%2F1.JBO.17.12.126012\"}'],\n", - " 'title': ['Detection of mouse liver cancer via a parallel iterative shrinkage method in hybrid optical/microcomputed tomography imaging']},\n", - " {'bibcode': '1981RadEf..56..187W',\n", - " 'author': ['Wilson, D. J.', 'Bentley, K. W.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1080%2F00337578108229889\"}'],\n", - " 'title': ['The use of neutron-induced autoradiography to determine the range of fission fragments in tissue and the plutonium burden of mouse liver']},\n", - " {'bibcode': '2017NatSR...745049T',\n", - " 'abstract': 'The transglutaminase (TG) family comprises eight isozymes that form the isopeptide bonds between glutamine and lysine residues and contribute to the fibrotic diseases via crosslinking-mediated stabilization of ECM and the activation of TGF-β in several tissues. However, despite a growing body of evidence implicating TG2 as a key enzyme in fibrosis, the causative role of TG2 and the involvement of the other isozymes have not yet been fully elucidated. Therefore, here we clarified the distributions of TG isozymes and their in situ activities and identified the isozyme-specific possible substrates for both TG1 and TG2 using their substrate peptides in mouse fibrotic liver. We found that TG1 activity was markedly enhanced intracellularly over a widespread area, whereas TG2 activity increased in the extracellular space. In total, 43 and 42 possible substrates were identified for TG1 and TG2, respectively, as involved in chromatin organization and cellular component morphogenesis. These included keratin 18, a biomarker for hepatic injury, which was accumulated in the fibrotic liver and showed the partly similar distribution with TG1 activity. These findings suggest that TG1 activity may be involved in the functional modification of intracellular proteins, whereas TG2 activity contributes to the stabilization of extracellular proteins during liver fibrosis.',\n", - " 'author': ['Tatsukawa, Hideki',\n", - " 'Tani, Yuji',\n", - " 'Otsu, Risa',\n", - " 'Nakagawa, Haruka',\n", - " 'Hitomi, Kiyotaka'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep45049\"}'],\n", - " 'title': ['Global identification and analysis of isozyme-specific possible substrates crosslinked by transglutaminases using substrate peptides in mouse liver fibrosis']},\n", - " {'bibcode': '2004RCMS...18.2522O',\n", - " 'author': ['Ong, Eng Shi',\n", - " 'Len, Shea Mei',\n", - " 'Lee, Audrey Chee Huay',\n", - " 'Chui, Paul',\n", - " 'Chooi, Kum Fai'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Frcm.1654\"}'],\n", - " 'title': ['Proteomic analysis of mouse liver for the evaluation of effects ofScutellariae radix by liquid chromatography with tandem mass spectrometry']},\n", - " {'bibcode': '2022Chmsp.299m4431P',\n", - " 'author': ['Pham, Thanh Minh',\n", - " 'Duong, Van Dong',\n", - " 'Doan, Van-Dat',\n", - " 'Vo, Van Thanh',\n", - " 'Le, Van Thuan'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.chemosphere.2022.134431\"}'],\n", - " 'title': ['Design synthesis of Y-90 glass microspheres and study of their therapeutic effects on mouse liver cancer cell line Hep3B']},\n", - " {'bibcode': '1999EnvMM..33..320B',\n", - " 'author': ['Buettner, Victoria L.',\n", - " 'Hill, Kathleen A.',\n", - " 'Halangoda, Asanga',\n", - " 'Sommer, Steve S.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2F%28SICI%291098-2280%281999%2933%3A4%3C320%3A%3AAID-EM9%3E3.0.CO%3B2-S\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2F%28SICI%291098-2280%281999%2933%3A4%3C320%3A%3AAID-EM9%3E3.0.CO2-S\"}'],\n", - " 'title': ['Tandem-base mutations occur in mouse liver and adipose tissue preferentially as G:C to T:A transversions and accumulate with age']},\n", - " {'bibcode': '2011JRadR..52..249V',\n", - " 'author': ['Vares, Guillaume',\n", - " 'Uehara, Yoshihiko',\n", - " 'Ono, Tetsuya',\n", - " 'Nakajima, Tetsuo',\n", - " 'Wang, Bing',\n", - " 'Taki, Keiko',\n", - " 'Matsumoto, Tsuneya',\n", - " 'Oghiso, Yoichi',\n", - " 'Tanaka, Kimio',\n", - " 'Ichinohe, Kazuaki',\n", - " 'Nakamura, Shingo',\n", - " 'Tanaka, Satoshi',\n", - " 'Nenoi, Mitsuru'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1269%2Fjrr.10110\"}'],\n", - " 'title': ['Transcription Factor-recognition Sequences Potentially Involved in Modulation of Gene Expression after Exposure to Low-dose-rate γ-rays in the Mouse Liver']},\n", - " {'bibcode': '1961Natur.190..372L',\n", - " 'abstract': 'Ohno and Hauschka1 showed that in female mice one chromosome of mammary carcinoma cells and of normal diploid cells of the ovary, mammary gland and liver was heteropyknotic. They interpreted this chromosome as an X-chromosome and suggested that the so-called sex chromatin was composed of one heteropyknotic X-chromosome. They left open the question whether the heteropyknosis was shown by the paternal X-chromosome only, or the chromosome from either parent indifferently.',\n", - " 'author': ['Lyon, Mary F.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F190372a0\"}'],\n", - " 'title': ['Gene Action in the X-chromosome of the Mouse (Mus musculus L.)']},\n", - " {'bibcode': '2015Nanos...7.3100C',\n", - " 'abstract': 'Highly selective and efficient capture of glycosylated proteins and peptides from complex biological samples is of profound significance for the discovery of disease biomarkers in biological systems. Recently, hydrophilic interaction liquid chromatography (HILIC)-based functional materials have been extensively utilized for glycopeptide enrichment. However, the low amount of immobilized hydrophilic groups on the affinity material has limited its specificity, detection sensitivity and binding capacity in the capture of glycopeptides. Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). The thick polymer shell endows the nanoparticles with excellent hydrophilic property and several functional groups on the polymer chains. The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g-1), high enrichment recovery (above 73.6%) and rapid magnetic separation. Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples.Highly selective and efficient capture of glycosylated proteins and peptides from complex biological samples is of profound significance for the discovery of disease biomarkers in biological systems. Recently, hydrophilic interaction liquid chromatography (HILIC)-based functional materials have been extensively utilized for glycopeptide enrichment. However, the low amount of immobilized hydrophilic groups on the affinity material has limited its specificity, detection sensitivity and binding capacity in the capture of glycopeptides. Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). The thick polymer shell endows the nanoparticles with excellent hydrophilic property and several functional groups on the polymer chains. The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g-1), high enrichment recovery (above 73.6%) and rapid magnetic separation. Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples.

Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr05955g',\n", - " 'author': ['Chen, Yajing',\n", - " 'Xiong, Zhichao',\n", - " 'Zhang, Lingyi',\n", - " 'Zhao, Jiaying',\n", - " 'Zhang, Quanqing',\n", - " 'Peng, Li',\n", - " 'Zhang, Weibing',\n", - " 'Ye, Mingliang',\n", - " 'Zou, Hanfa'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1039%2Fc4nr05955g\"}'],\n", - " 'title': ['Facile synthesis of zwitterionic polymer-coated core-shell magnetic nanoparticles for highly specific capture of N-linked glycopeptides']},\n", - " {'bibcode': '2007GeneE..29..115W',\n", - " 'author': ['Watanabe, Takashi',\n", - " 'Tobe, Kaori',\n", - " 'Nakachi, Yutaka',\n", - " 'Kondoh, Yasumitsu',\n", - " 'Nakajima, Madoka',\n", - " 'Hamada, Shuichi',\n", - " 'Namiki, Chiaki',\n", - " 'Suzuki, Takayoshi',\n", - " 'Maeda, Satoru',\n", - " 'Tadakuma, Ayami',\n", - " 'Sakurai, Mikiya',\n", - " 'Arai, Yuko',\n", - " 'Hyogo, Atsushi',\n", - " 'Hoshino, Masako',\n", - " 'Tashiro, Tomoko',\n", - " 'Ito, Hisashi',\n", - " 'Inazumi, Hiroshige',\n", - " 'Sakaki, Yoshiyuki',\n", - " 'Tashiro, Hideo',\n", - " 'Furihata, Chie'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.3123%2Fjemsge.29.115\"}'],\n", - " 'title': ['Differential Gene Expression Induced by Two Genotoxic N-nitroso Carcinogens, Phenobarbital and Ethanol in Mouse Liver Examined with Oligonucleotide Microarray and Quantitative Real-time PCR']},\n", - " {'bibcode': '2014PLoSO...997568B',\n", - " 'author': ['Börsch-Haubold, Angelika G.',\n", - " 'Montero, Inka',\n", - " 'Konrad, Kathryn',\n", - " 'Haubold, Bernhard'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0097568\"}'],\n", - " 'title': ['Genome-Wide Quantitative Analysis of Histone H3 Lysine 4 Trimethylation in Wild House Mouse Liver: Environmental Change Causes Epigenetic Plasticity']},\n", - " {'bibcode': '2013IJMSp.354..281M',\n", - " 'author': ['M-M, Pornwilard',\n", - " 'Merle, Uta',\n", - " 'Weiskirchen, Ralf',\n", - " 'Becker, J. Sabine'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.ijms.2013.07.006\"}'],\n", - " 'title': [\"Bioimaging of copper deposition in Wilson's diseases mouse liver by laser ablation inductively coupled plasma mass spectrometry imaging (LA-ICP-MSI)\"]},\n", - " {'bibcode': '1997PNAS...94.4686K',\n", - " 'abstract': 'Although recombinant adenovirus vectors offer a very efficient means by which to transfer genetic information into cells in vivo, antigen-dependent immunity limits the duration of gene expression and prevents retreatment. Recombinant murine CTLA4Ig and anti-CD40 ligand antibody block costimulatory interactions between T cells and antigen presenting cells. We previously reported that murine CTLA4Ig prolongs adenoviral-mediated gene transfer, but does not allow for secondary expression after readministration of the vector. In studies described here, when anti-CD40 ligand and recombinant murine CTLA4Ig were coadministered around the time of primary vector administration (i) prolonged adenovirus-mediated gene expression (length of experiment up to 1 year) from the livers of >90% of treated mice was observed, and (ii) secondary adenovirus-mediated gene transfer was achieved in >50% of the mice even after the immunosuppressive effects of these agents were no longer present. Nearly two-thirds of these mice had persistent secondary gene expression lasting for at least 200-300 days. Neither agent alone allowed transduction after secondary vector administration. Treated mice had decreased immune responses to the vector as shown by markedly decreased production of neutralizing antibodies, diminished spleen proliferation responses and IFN-γ production in vitro, and reduced T cell infiltrates in the liver. These results suggest that it may be possible to obtain persistence as well as secondary adenoviral-mediated gene transfer with transient immunosuppressive therapies.',\n", - " 'author': ['Kay, Mark A.',\n", - " 'Meuse, Leonard',\n", - " 'Gown, Allen M.',\n", - " 'Linsley, Peter',\n", - " 'Hollenbaugh, Diane',\n", - " 'Aruffo, Alejandro',\n", - " 'Ochs, Hans D.',\n", - " 'Wilson, Christopher B.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/94/9/4686\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/94/9/4686\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/94/9/4686\"}'],\n", - " 'title': ['Transient Immunomodulation with Anti-CD40 Ligand Antibody and CTLA4Ig Enhances Persistence and Secondary Adenovirus-Mediated Gene Transfer into Mouse Liver']},\n", - " {'bibcode': '2001SPIE.4158...49H',\n", - " 'abstract': 'Owing to their low losses in the 2-12 micrometers region, the Te- As-Se glass fibers are used for infrared light transportation as well as sensing element based on evanescent wave absorption mechanism. The efficiency of the system is improved by tapering the fiber diameter in the sensing zone. With this kind of sensor, infrared spectra of biological tissue have been obtained. Spectra of mouse liver have been especially recorded in order to detect spectral differences between the healthy and the tumoral states of mouse liver.',\n", - " 'author': ['Hocde, Sandrine',\n", - " 'Loreal, O.',\n", - " 'Sire, O.',\n", - " 'Turlin, B.',\n", - " 'Boussard-Pledel, Catherine',\n", - " 'Le Coq, D.',\n", - " 'Bureau, B.',\n", - " 'Fonteneau, Gilles',\n", - " 'Pigeon, C.',\n", - " 'Leroyer, P.',\n", - " 'Lucas, Jacques'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1117%2F12.413808\"}'],\n", - " 'title': ['Biological tissue infrared analysis by chalcogenide glass optical fiber spectroscopy']},\n", - " {'bibcode': '1978RadR...76..180B',\n", - " 'author': ['Bhattacharyya, Maryka H.',\n", - " 'Peterson, David P.',\n", - " 'Lindenbaum, Arthur'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.2307%2F3574937\"}'],\n", - " 'title': ['Action of DTPA on Hepatic Plutonium: II. DTPA-Induced Removal of Monomeric Plutonium from Mouse Liver Parenchymal Cells']},\n", - " {'bibcode': '2018Ana...143.2416M',\n", - " 'author': ['Mohammadi, Saeedeh', 'Parastar, Hadi'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1039%2FC7AN02059G\"}'],\n", - " 'title': ['Quantitative analysis of multiple high-resolution mass spectrometry images using chemometric methods: quantitation of chlordecone in mouse liver']},\n", - " {'bibcode': '2010PLoSO...515316B',\n", - " 'author': ['Bur, Isabelle M.',\n", - " 'Zouaoui, Sonia',\n", - " 'Fontanaud, Pierre',\n", - " 'Coutry, Nathalie',\n", - " 'Molino, François',\n", - " 'Martin, Agnès O.',\n", - " 'Mollard, Patrice',\n", - " 'Bonnefont, Xavier'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0015316\"}'],\n", - " 'title': ['The Comparison between Circadian Oscillators in Mouse Liver and Pituitary Gland Reveals Different Integration of Feeding and Light Schedules']},\n", - " {'bibcode': '2022NatCo..13.3279U',\n", - " 'abstract': 'Invariant NKT (iNKT) cells comprise a heterogeneous group of non-circulating, tissue-resident T lymphocytes that recognize glycolipids, including alpha-galactosylceramide (αGalCer), in the context of CD1d, but whether peripheral iNKT cell subsets are terminally differentiated remains unclear. Here we show that mouse and human liver-resident αGalCer/CD1d-binding iNKTs largely correspond to a novel Zbtb16+Tbx21+Gata3+MaflowRorc- subset that exhibits profound transcriptional, phenotypic and functional plasticity. Repetitive in vivo encounters of these liver iNKT (LiNKT) cells with intravenously delivered αGalCer/CD1d-coated nanoparticles (NP) trigger their differentiation into immunoregulatory, IL-10+IL-21-producing Zbtb16highMafhighTbx21+Gata3+Rorc- cells, termed LiNKTR1, expressing a T regulatory type 1 (TR1)-like transcriptional signature. This response is LiNKT-specific, since neither lung nor splenic tissue-resident iNKT cells from αGalCer/CD1d-NP-treated mice produce IL-10 or IL-21. Additionally, these LiNKTR1 cells suppress autoantigen presentation, and recognize CD1d expressed on conventional B cells to induce IL-10+IL-35-producing regulatory B (Breg) cells, leading to the suppression of liver and pancreas autoimmunity. Our results thus suggest that LiNKT cells are plastic for further functional diversification, with such plasticity potentially targetable for suppressing tissue-specific inflammatory phenomena.',\n", - " 'author': ['Umeshappa, Channakeshava Sokke',\n", - " 'Solé, Patricia',\n", - " 'Yamanouchi, Jun',\n", - " 'Mohapatra, Saswat',\n", - " 'Surewaard, Bas G. J.',\n", - " 'Garnica, Josep',\n", - " 'Singha, Santiswarup',\n", - " 'Mondal, Debajyoti',\n", - " 'Cortés-Vicente, Elena',\n", - " \"D'Mello, Charlotte\",\n", - " 'Mason, Andrew',\n", - " 'Kubes, Paul',\n", - " 'Serra, Pau',\n", - " 'Yang, Yang',\n", - " 'Santamaria, Pere'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41467-022-30759-w\"}'],\n", - " 'title': ['Re-programming mouse liver-resident invariant natural killer T cells for suppressing hepatic and diabetogenic autoimmunity']},\n", - " {'bibcode': '2021NatCo..12.4110Z',\n", - " 'abstract': 'We hypothesized that the highly controlled pattern of gene expression that is essential for liver regeneration is encoded by an epigenetic code set in quiescent hepatocytes. Here we report that epigenetic and transcriptomic profiling of quiescent and regenerating mouse livers define chromatin states that dictate gene expression and transposon repression. We integrate ATACseq and DNA methylation profiling with ChIPseq for the histone marks H3K4me3, H3K27me3 and H3K9me3 and the histone variant H2AZ to identify 6 chromatin states with distinct functional characteristics. We show that genes involved in proliferation reside in active states, but are marked with H3K27me3 and silenced in quiescent livers. We find that during regeneration, H3K27me3 is depleted from their promoters, facilitating their dynamic expression. These findings demonstrate that hepatic chromatin states in quiescent livers predict gene expression and that pro-regenerative genes are maintained in active chromatin states, but are restrained by H3K27me3, permitting a rapid and synchronized response during regeneration.',\n", - " 'author': ['Zhang, Chi',\n", - " 'Macchi, Filippo',\n", - " 'Magnani, Elena',\n", - " 'Sadler, Kirsten C.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41467-021-24466-1\"}'],\n", - " 'title': ['Chromatin states shaped by an epigenetic code confer regenerative potential to the mouse liver']},\n", - " {'bibcode': '1973Natur.245..146F',\n", - " 'abstract': 'INTERFERON exhibits a marked antitumour effect in mice inoculated with allogeneic or syngeneic transplantahle tumours1-3, but comparable interferon preparations did not affect the growth or development of newborn mice4. It is important from both a theoretical and a practical point of view to determine whether interferon can inhibit normal cell division in the animal. It has been shown that interferon preparations inhibited the multiplication of normal adult allogeneic spleen cells and syngeneic bone marrow cells injected into heavily X-irradiated mice5. Jahiel and his co-workers demonstrated that three interferon inducers, Newcastle disease virus (NDV), polyinosinicpolycytidylic acid and statolon, inhibited the mitbtic response of liver cells after partial hepatectomy6, but that administration of interferon itself did not inhibit this response7. Now that potent and relatively purified mouse interferon preparations are available, we have used this experimental system, and report here a marked inhibition by interferon of liver regeneration after partial hepatectomy.',\n", - " 'author': ['Frayssinet, C.', 'Gresser, I.', 'Tovey, M.', 'Lindahl, P.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F245146b0\"}'],\n", - " 'title': ['Inhibitory Effect of Potent Interferon Preparations on the Regeneration of Mouse Liver after Partial Hepatectomy']},\n", - " {'bibcode': '2017PNAS..114..292Y',\n", - " 'abstract': 'Isocitrate dehydrogenase 1 (IDH1) is abundant in liver. Although it was reported that IDH1 participates in lipid biosynthesis, we show here that IDH1 is instead critical for hepatic amino acid (AA) utilization. IDH1 catalyzes the generation of cytosolic α-ketoglutarate, which can be converted to glutamate in the liver via transamination. Both IDH1-null liver and IDH1-deficient HepG2 cells show defects in AA utilization. Because IDH1 mutations occur in various tumors and AA metabolism is critical for tumor cell growth, our elucidation of the functions of wild-type IDH1 in AA utilization should advance our understanding of how mutant IDH promotes malignancy.',\n", - " 'author': ['Ye, Jing',\n", - " 'Gu, Yu',\n", - " 'Zhang, Feng',\n", - " 'Zhao, Yuanlin',\n", - " 'Yuan, Yuan',\n", - " 'Hao, Zhenyue',\n", - " 'Sheng, Yi',\n", - " 'Li, Wanda Y.',\n", - " 'Wakeham, Andrew',\n", - " 'Cairns, Rob A.',\n", - " 'Mak, Tak W.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1618605114\"}'],\n", - " 'title': ['IDH1 deficiency attenuates gluconeogenesis in mouse liver by impairing amino acid utilization']},\n", - " {'bibcode': '1976BuECT..15..762P',\n", - " 'author': ['Pawar, Sitaram S.', 'Mungikar, Avinash M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1007%2FBF01685630\"}'],\n", - " 'title': ['Dioxane-induced changes in mouse liver microsomal mixed function oxidase system']},\n", - " {'bibcode': '1980PNAS...77.6597D',\n", - " 'abstract': 'The objective of this study was to determine if prostaglandins alter the fluidity of hepatic membranes and if this, in turn, modifies their ability to bind prolactin. Liver homogenates of adult C3H female mice incubated with 1-1000 nM prostaglandin A1, A2, B2, F1 alpha, 6-keto-F1 alpha, E1, E2, I2, or thromboxane B2 provided the 100,000 X g membrane pellets for subsequent ovine prolactin binding and membrane fluidity studies. Only membrane preparations treated with prostaglandin I2 showed an increase in specific binding of ovine prolactin. The effect (40-50%) was maximal at 100 nM prostaglandin I2 after 30 min of incubation and was due to an increase in the number of receptor sites. Under the same conditions, prostaglandin I2 induced a 17% decrease in membrane microviscosity. These data suggest that specific prostaglandins may modulate the number of prolactin receptors in vivo by modifying the fluidity of the lipid bilayer and the subsequent ease with which receptors can assume active configurations within the matrix.',\n", - " 'author': ['Dave, J. R.', 'Knazek, R. A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/77/11/6597\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/77/11/6597\"}'],\n", - " 'title': ['Prostaglandin I2 modifies Both Prolactin Binding Capacity and Fluidity of Mouse Liver Membranes']},\n", - " {'bibcode': '2015NatSR...517186F',\n", - " 'abstract': 'In the interphase nucleus, chromatin is organized into three-dimensional conformation to coordinate genome functions. The lamina-chromatin association is important to facilitate higher-order chromatin in mammalian cells, but its biological significances and molecular mechanisms remain poorly understood. One obstacle is that the list of lamina-associated proteins remains limited, presumably due to the inherent insolubility of lamina proteins. In this report, we identified 182 proteins associated with lamin B1 (a constitutive component of lamina) in mouse hepatocytes, by adopting virus-based proximity-dependent biotin identification. These proteins are functionally related to biological processes such as chromatin organization. As an example, we validated the association between lamin B1 and core histone macroH2A1, a histone associated with repressive chromatin. Furthermore, we mapped Lamina-associated domains (LADs) in mouse liver cells and found that boundaries of LADs are enriched for macroH2A. More interestingly, knocking-down of macroH2A1 resulted in the release of heterochromatin foci marked by histone lysine 9 trimethylation (H3K9me3) and the decondensation of global chromatin structure. However, down-regulation of lamin B1 led to redistribution of macroH2A1. Taken together, our data indicated that macroH2A1 is associated with lamina and is required to maintain chromatin architecture in mouse liver cells.',\n", - " 'author': ['Fu, Yuhua',\n", - " 'Lv, Pin',\n", - " 'Yan, Guoquan',\n", - " 'Fan, Hui',\n", - " 'Cheng, Lu',\n", - " 'Zhang, Feng',\n", - " 'Dang, Yongjun',\n", - " 'Wu, Hao',\n", - " 'Wen, Bo'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep17186\"}'],\n", - " 'title': ['MacroH2A1 associates with nuclear lamina and maintains chromatin architecture in mouse liver cells']},\n", - " {'bibcode': '2003PNAS..10011881W',\n", - " 'abstract': 'The appearance of bipotential oval cells in chronic liver injury suggests the existence of hepatocyte progenitor/stem cells. To study the origin and properties of this cell population, oval cell proliferation was induced in adult mouse liver by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) and a method for their isolation was developed. Transplantation into fumarylacetoacetate hydrolase (Fah) deficient mice was used to determine their capacity for liver repopulation. In competitive repopulation experiments, hepatic oval cells were at least as efficient as mature hepatocytes in repopulating the liver. In mice with chimeric livers, the oval cells were not derived from hepatocytes but from liver nonparenchymal cells. This finding supports a model in which intrahepatic progenitors differentiate into hepatocytes irreversibly. To determine whether oval cells originated from stem cells residing in the bone marrow, bone marrow transplanted wild-type mice were treated with DDC for 8 months and oval cells were then serially transferred into Fah mutants. The liver repopulating cells in these secondary transplant recipients lacked the genetic markers of the original bone marrow donor. We conclude that hepatic oval cells do not originate in bone marrow but in the liver itself, and that they have valuable properties for therapeutic liver repopulation.',\n", - " 'author': ['Wang, Xin',\n", - " 'Foster, Mark',\n", - " 'Al-Dhalimy, Muhsen',\n", - " 'Lagasse, Eric',\n", - " 'Finegold, Milton',\n", - " 'Grompe, Markus'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/100/suppl_1/11881\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1734199100\"}'],\n", - " 'title': ['The origin and liver repopulating capacity of murine oval cells']},\n", - " {'bibcode': '1999PNAS...9614511F',\n", - " 'abstract': 'The importance of glucokinase (GK; EC 2.7.1.12) in glucose homeostasis has been demonstrated by the association of GK mutations with diabetes mellitus in humans and by alterations in glucose metabolism in transgenic and gene knockout mice. Liver GK activity in humans and rodents is allosterically inhibited by GK regulatory protein (GKRP). To further understand the role of GKRP in GK regulation, the mouse GKRP gene was inactivated. With the knockout of the GKRP gene, there was a parallel loss of GK protein and activity in mutant mouse liver. The loss was primarily because of posttranscriptional regulation of GK, indicating a positive regulatory role for GKRP in maintaining GK levels and activity. As in rat hepatocytes, both GK and GKRP were localized in the nuclei of mouse hepatocytes cultured in low-glucose-containing medium. In the presence of fructose or high concentrations of glucose, conditions known to relieve GK inhibition by GKRP in vitro, only GK was translocated into the cytoplasm. In the GKRP-mutant hepatocytes, GK was not found in the nucleus under any tested conditions. We propose that GKRP functions as an anchor to sequester and inhibit GK in the hepatocyte nucleus, where it is protected from degradation. This ensures that glucose phosphorylation is minimal when the liver is in the fasting, glucose-producing phase. This also enables the hepatocytes to rapidly mobilize GK into the cytoplasm to phosphorylate and store or metabolize glucose after the ingestion of dietary glucose. In GKRP-mutant mice, the disruption of this regulation and the subsequent decrease in GK activity leads to altered glucose metabolism and impaired glycemic control.',\n", - " 'author': ['Farrelly, Dennis',\n", - " 'Brown, Karen S.',\n", - " 'Tieman, Aaron',\n", - " 'Ren, Jianming',\n", - " 'Lira, Sergio A.',\n", - " 'Hagan, Deborah',\n", - " 'Gregg, Richard',\n", - " 'Mookhtiar, Kasim A.',\n", - " 'Hariharan, Narayanan'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/96/25/14511\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/96/25/14511\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/96/25/14511\"}'],\n", - " 'title': ['Mice Mutant for Glucokinase Regulatory Protein Exhibit Decreased Liver Glucokinase: A Sequestration Mechanism in Metabolic Regulation']},\n", - " {'bibcode': '1989PNAS...86.6474B',\n", - " 'abstract': 'We have isolated a cDNA clone of the murine homologue of the human retinoblastoma (Rb) susceptibility gene. DNA sequence analysis reveals a high degree of conservation with the human Rb sequence, both in the coding and in the noncoding regions. The predicted amino acid sequence of the mouse Rb protein shows 91% identity to that of the human protein. Both proteins were found to contain a peptide sequence reminiscent of a leucine-repeat motif (\"leucine-zipper\") that is also found in the myc, fos, and jun oncogenes. Synthetic peptide antiserum directed against a portion of the mouse Rb protein detects three proteins of 104-110 kDa in cells that were transiently transfected with a mouse Rb gene expression construct. In the mouse embryo the expression of Rb mRNA was ubiquitous, with maximal expression being observed around 13 days of gestation. In the embryo, the highest level of expression was observed in liver and brain. In contrast, the Rb gene was found to be expressed at a very low level in adult mouse liver with high levels being found in lung, thymus, and spleen. A shorter Rb transcript was detected in mouse testes.',\n", - " 'author': ['Bernards, Rene',\n", - " 'Schackleford, Gregory M.',\n", - " 'Gerber, Monica R.',\n", - " 'Horowitz, Jonathan M.',\n", - " 'Friend, Stephen H.',\n", - " 'Schartl, Manfred',\n", - " 'Bogenmann, Emil',\n", - " 'Rapaport, Joyce M.',\n", - " 'McGee, Terry',\n", - " 'Dryja, Thaddeus P.',\n", - " 'Weinberg, Robert A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/86/17/6474\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/86/17/6474\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/86/17/6474\"}'],\n", - " 'title': ['Structure and expression of the murine retinoblastoma gene and characterization of its encoded protein.']},\n", - " {'bibcode': '2010PNAS..107.4383S',\n", - " 'abstract': 'Autophagy is a catabolic process by which cells remove long-lived proteins and damaged organelles for recycling. Viral infections may also induce autophagic response. Here we show that hepatitis B virus (HBV), a pathogen that chronically infects ≈350 million people globally, can enhance autophagic response in cell cultures, mouse liver, and during natural infection. This enhancement of the autophagic response is not coupled by an increase of autophagic protein degradation and is dependent on the viral X protein, which binds to and enhances the enzymatic activity of phosphatidylinositol 3-kinase class III, an enzyme critical for the initiation of autophagy. Further analysis indicates that autophagy enhances HBV DNA replication, with minimal involvement of late autophagic vacuoles in this process. Our studies thus demonstrate that a DNA virus can use autophagy to enhance its own replication and indicate the possibility of targeting the autophagic pathway for the treatment of HBV patients.',\n", - " 'author': ['Donna, Sir',\n", - " 'Tian, Yongjun',\n", - " 'Chen, Wen-ling',\n", - " 'Ann, David K.',\n", - " 'Yen, Tien-Sze Benedict',\n", - " 'Ou, Jing-hsiung James'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0911373107\"}'],\n", - " 'title': ['The early autophagic pathway is activated by hepatitis B virus and required for viral DNA replication']},\n", - " {'bibcode': '1985PNAS...82.5246J',\n", - " 'abstract': 'We have developed a 1H NMR technique to selectively edit the spectrum of perfused liver for specific resonances of metabolites that occur in low concentration. The method employs selective DANTE pulses, which avoid exciting the water signal and at the same time control the J modulation effect in the homonuclear spin-echo experiment. By difference spectroscopy, we have suppressed the background signals from lipids and water and have resolved the CH3 resonance of lactate at 1.33 ppm. Moreover, the technique is highly selective and allows us to select the CH3 resonance of alanine at 1.47 ppm in the presence of the CH3 resonance of lactate at 1.33 ppm, even though the latter was much larger before editing. We have applied this technique to study the metabolic effect of ethanol in perfused mouse liver and have observed that the rate of formation of lactate from pyruvate is increased by a factor of 2.8 when ethanol is added.',\n", - " 'author': ['Jue, T.',\n", - " 'Arias-Mendoza, F.',\n", - " 'Gonnella, N. C.',\n", - " 'Shulman, G. I.',\n", - " 'Shulman, R. G.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/82/16/5246\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/82/16/5246\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/82/16/5246\"}'],\n", - " 'title': ['A 1H NMR Technique for Observing Metabolite Signals in the Spectrum of Perfused Liver']},\n", - " {'bibcode': '2014MicST..25..303R',\n", - " 'abstract': \"Gravity supports all the life activities present on earth. Microgravity environments have effect on the biological functions and physiological status of an individual. The present study was undertaken to investigate the effect of simulated microgravity on important regulatory enzymes of carbohydrate metabolism in liver using HLS mice model. Following hind limb unloading of mice for 11 days the animal's average body weights were found to be not different, while the liver weights were decreased and found to be significantly different ( p < 0.05) from control mice. Further, in liver the specific activity of hexokinase enzyme was reduced ( p < 0.02) and the phosphoenolpyruvate carboxykinase activity was significantly increased in simulated microgravity subjected mice compared to control ( p < 0.003). Immunoblot analysis show decreased phosphofructokinase-2 activity in HLS mice compared to control. Liver lactate dehydrogenase activity significantly reduced in simulated microgravity subjected mice ( p < 0.005). Thus in our study the rodents have adapted to simulated microgravity conditions, with decreased glycolysis and increased gluconeogenesis in liver and reciprocally regulated.\",\n", - " 'author': ['Ramirez, Joaquin',\n", - " 'Periyakaruppan, Adaikkappan',\n", - " 'Sarkar, Shubhashish',\n", - " 'Ramesh, Govindarajan T.',\n", - " 'Sharma, S. Chidananda'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1007%2Fs12217-013-9356-7\"}'],\n", - " 'title': ['Effect of Simulated Microgravity on the Activity of Regulatory Enzymes of Glycolysis and Gluconeogenesis in Mice Liver']},\n", - " {'bibcode': '1990PNAS...87.5288T',\n", - " 'abstract': 'Accelerator mass spectrometry (AMS) is used to determine the amount of carcinogen covalently bound to mouse liver DNA (DNA adduct) following very low-level exposure to a 14C-labeled carcinogen. AMS is a highly sensitive method for counting long-lived but rare cosmogenic isotopes. While AMS is a tool of importance in the earth sciences, it has not been applied in biomedical research. The ability of AMS to assay rare isotope concentrations (10Be, 14C, 26Al, 41Ca, and 129I) in microgram amounts suggests that extension to the biomedical sciences is a natural and potentially powerful application of the technology. In this study, the relationship between exposure to low levels of 2-amino-3,8-dimethyl[2-14C]imidazo[4,5-f]quinoxaline and formation of DNA adducts is examined to establish the dynamic range of the technique and the potential sensitivity for biological measurements, as well as to evaluate the relationship between DNA adducts and low-dose carcinogen exposure. Instrument reproducibility in this study is 2%; sensitivity is 1 adduct per 10(11) nucleotides. Formation of adducts is linearly dependent on dose down to an exposure of 500 ng per kg of body weight. With the present measurements, we demonstrate at least 1 order of magnitude improvement over the best adduct detection sensitivity reported to date and 3-5 orders of magnitude improvement over other methods used for adduct measurement. An additional improvement of 2 orders of magnitude in sensitivity is suggested by preliminary experiments to develop bacterial hosts depleted in radiocarbon. Expanded applications involving human subjects, including clinical applications, are now expected because of the great detection sensitivity and small sample size requirements of AMS.',\n", - " 'author': ['Turteltaub, K. W.',\n", - " 'Felton, J. S.',\n", - " 'Gledhill, B. L.',\n", - " 'Vogel, J. S.',\n", - " 'Southon, J. R.',\n", - " 'Caffee, M. W.',\n", - " 'Finkel, R. C.',\n", - " 'Nelson, D. E.',\n", - " 'Proctor, I. D.',\n", - " 'Davis, J. C.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/87/14/5288\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/87/14/5288\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/87/14/5288\"}'],\n", - " 'title': ['Accelerator mass spectrometry in biomedical dosimetry: relationship between low-level exposure and covalent binding of heterocyclic amine carcinogens to DNA.']},\n", - " {'bibcode': '1991PNAS...88.9543B',\n", - " 'abstract': 'Indole-3-carbinol (I3C) is a secondary plant metabolite produced in vegetables of the Brassica genus, including cabbage, cauliflower, and brussels sprouts. I3C is both an anti-initiator and a promoter of carcinogenesis. Consumption of I3C by humans and rodents can lead to marked increases in activities of cytochrome P-450-dependent monooxygenases and in a variety of phase II drug-metabolizing enzymes. We have reported previously that the enzyme-inducing activity of I3C is mediated through a mechanism requiring exposure of the compound to the low-pH environment of the stomach. We report here the aromatic hydrocarbon responsiveness-receptor Kd values (22 nM-90 nM), determined with C57BL/6J mouse liver cytosol and the in vitro- and in vivo-molar yields (0.1-6%) of the major acid condensation products of I3C. We also show that indolo[3,2-b]carbazole (ICZ) is produced from I3C in yields on the order of 0.01% in vitro and, after oral intubation, in vivo. ICZ has a Kd of 190 pM for aromatic hydrocarbon responsiveness-receptor binding and an EC50 of 269 nM for induction of cytochrome P4501A1, as measured by ethoxyresorufin O-deethylase activity in murine hepatoma Hepa 1c1c7 cells. The binding affinity of ICZ is only a factor of 3.7 x 10(-2) lower than that of the highly toxic environmental contaminant and cancer promoter 2,3,7,8-tetrachlorodibenzo-p-dioxin. ICZ and related condensation products appear responsible for the enzyme-inducing effects of dietary I3C.',\n", - " 'author': ['Bjeldanes, Leonard F.',\n", - " 'Kim, Jin-Young',\n", - " 'Grose, Karl R.',\n", - " 'Bartholomew, James C.',\n", - " 'Bradfield, Christopher A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/88/21/9543\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/88/21/9543\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/88/21/9543\"}'],\n", - " 'title': ['Aromatic hydrocarbon responsiveness-receptor agonists generated from indole-3-carbinol in vitro and in vivo: comparisons with 2,3,7,8-tetrachlorodibenzo-p-dioxin.']},\n", - " {'bibcode': '1996PNAS...93.9565N',\n", - " 'abstract': 'The gap junctional protein connexin32 is expressed in hepatocytes, exocrine pancreatic cells, Schwann cells, and other cell types. We have inactivated the connexin32 gene by homologous recombination in the mouse genome and have generated homozygous connexin32-deficient mice that were viable and fertile but weighed on the average approximately 17% less than wild-type controls. Electrical stimulation of sympathetic nerves in connexin32-deficient liver triggered a 78% lower amount of glucose mobilization from glycogen stores, when compared with wild-type liver. Thus, connexin32-containing gap junctions are essential in mouse liver for maximal intercellular propagation of the noradrenaline signal from the periportal (upstream) area, where it is received from sympathetic nerve endings, to perivenous (downstream) hepatocytes. In connexin32-defective liver, the amount of connexin26 protein expressed was found to be lower than in wild-type liver, and the total area of gap junction plaques was approximately 1000-fold smaller than in wild-type liver. In contrast to patients with connexin32 defects suffering from X chromosome-linked Charcot-Marie-Tooth disease (CMTX) due to demyelination in Schwann cells of peripheral nerves, connexin32-deficient mice did not show neurological abnormalities when analyzed at 3 months of age. It is possible, however, that they may develop neurodegenerative symptoms at older age.',\n", - " 'author': ['Nelles, Eric',\n", - " 'Butzler, Christoph',\n", - " 'Jung, Dirk',\n", - " 'Temme, Achim',\n", - " 'Gabriel, Heinz-Dieter',\n", - " 'Dahl, Ursula',\n", - " 'Traub, Otto',\n", - " 'Stumpel, Frank',\n", - " 'Jungermann, Kurt',\n", - " 'Zielasek, Jurgen',\n", - " 'Toyka, Klaus V.',\n", - " 'Dermietzel, Rolf',\n", - " 'Willecke, Klaus'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/93/18/9565\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/93/18/9565\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/93/18/9565\"}'],\n", - " 'title': ['Defective propagation of signals generated by sympathetic nerve stimulation in the liver of connexin32-deficient mice.']},\n", - " {'bibcode': '2008JRadR..49..445K',\n", - " 'author': ['Koike, Manabu',\n", - " 'Mashino, Minako',\n", - " 'Sugasawa, Jun',\n", - " 'Koike, Aki'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1269%2Fjrr.08010\"}'],\n", - " 'title': ['Histone H2AX Phosphorylation Independent of ATM after X-irradiation in Mouse Liver and Kidney in situ']},\n", - " {'bibcode': '1964Natur.201..393S',\n", - " 'abstract': 'DURING starvation, glycogenolysis is associated with the release of the enzymes phosphorylase and glycogen synthetase from insoluble granules into the cytoplasm. This event is accompanied by a decrease in the activity of glycogen synthetase and a transient increase in phosphorylase activity. The phenomena can be prevented by the prior administration of the glucocorticoid, cortisol. Moreover, once the alterations have occurred, they can be reversed by glycogenesis produced by either cortisol injection or glucose feeding, DOCA was ineffective.',\n", - " 'author': ['Sie, Hsien-Gieh', 'Hablanian, Ann', 'Fishman, William H.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F201393a0\"}'],\n", - " 'title': ['Solubilization of Mouse Liver Glycogen Synthetase and Phosphorylase during Starvation Glycogenolysis and its Reversal by Cortisol']},\n", - " {'bibcode': '2017NatSR...7.2343L',\n", - " 'abstract': 'Liver granulomatous inflammation and fibrosis were the primary pathological changes observed during Schistosoma japonicum (S. japonicum) infection. In the present study, the characteristics of IL-9 were investigated in the liver of S. japonicum infection C57BL/6 mice. Immunofluorescence, qRT-PCR, and ELISA results demonstrated that the expression of IL-9 significantly increased after infection (P < 0.01). FACS results indicated that the peak of IL-9+ Th9 cells in the liver mononuclear cells appeared at the early phase of infection (week 5), except that Th9 cells, CD8+ Tc cells, NKT and γδT cells could secrete IL-9 in this model. Although IL-9 neutralization has a limited effect on liver granulomatous inflammation, it could decrease the level of fibrosis-associated factor, PC-III, in the serum of infected mice (P < 0.05). Taken together, our results indicated that IL-9 was an important type of cytokine involved in the progression of S. japonicum infection-induced hepatic damage.',\n", - " 'author': ['Li, Lu',\n", - " 'Xie, Hongyan',\n", - " 'Wang, Mei',\n", - " 'Qu, Jiale',\n", - " 'Cha, Hefei',\n", - " 'Yang, Quan',\n", - " 'Feng, Yuanfa',\n", - " 'Qi, Yanwei',\n", - " 'Qiu, Huaina',\n", - " 'Dong, Nuo',\n", - " 'Huang, Jun'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-017-02422-8\"}'],\n", - " 'title': ['Characteristics of IL-9 induced by Schistosoma japonicum infection in C57BL/6 mouse liver']},\n", - " {'bibcode': '1974Natur.249..269T',\n", - " 'abstract': \"ALPHA foetoprotein (αFP) is an α-globulin present in foetal and early postnatal sera of various animal species. It is not normally detectable in adult serum by the immunodiffusion test, but in several pathological conditions, particularly primary hepatomas, the level of αFP increases to a significant level. The potential use of this phenomenon in early diagnosis of hepatomas has been explored. These and related studies on αFP and other `foetal-tumour antigens' have been reviewed recently1-5.\",\n", - " 'author': ['Tamaoki, T.', 'Thomas, K.', 'Schindler, I.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F249269b0\"}'],\n", - " 'title': ['Cell-free studies of developmental changes in synthesis of α-foetoprotein and albumin in the mouse liver']},\n", - " {'bibcode': '2014NYASA1315...37H',\n", - " 'author': ['Huster, Dominik'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1111%2Fnyas.12337\"}'],\n", - " 'title': [\"Structural and metabolic changes inAtp7b-/-mouse liver and potential for new interventions in Wilson's disease\"]},\n", - " {'bibcode': '1965PNAS...53..622W',\n", - " 'author': ['Williams, Curtis A.', 'Ganoza, Clélia M.', 'Lipmann, Fritz'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/53/3/622\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/53/3/622\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.53.3.622\"}'],\n", - " 'title': ['Effect of Bacterial Infection on the Synthesis of Serum Proteins by a Mouse Liver Cell-Free System']},\n", - " {'bibcode': '1958Natur.181..773A',\n", - " 'abstract': 'RECENT studies have shown that sodium salicylate and acetyl-salicylic acid increase oxygen consumption in rats, rabbits and man1-3. Sproull has shown that both sodium salicylate and 2 : 4-dinitrophenol stimulate metabolism in mouse-liver slices4, but has recently found a difference between the slopes of the concentration-response curves for the two compounds5. Reid has also directed attention to these similarities, and has shown that both compounds inhibit the growth of wheat coleoptiles6. Cochran3 suggested that the stimulation of respiration by salicylate may be of fundamental importance in the therapeutic action of the drug.',\n", - " 'author': ['Adams, S. S.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F181773b0\"}'],\n", - " 'title': ['A Possible Basis for the Anti-inflammatory Activity of Salicylates and other Non-Hormonal Anti-Rheumatic Drugs']},\n", - " {'bibcode': '2021NatNa..16..466H',\n", - " 'abstract': 'Relaxin is an antifibrotic peptide hormone previously assumed to directly reverse the activation of hepatic stellate cells for liver fibrosis resolution. Using nanoparticle-mediated delivery, here we show that, although relaxin gene therapy reduces liver fibrosis in vivo, in vitro treatment fails to induce quiescence of the activated hepatic stellate cells. We show that hepatic macrophages express the primary relaxin receptor, and that, on relaxin binding, they switch from the profibrogenic to the pro-resolution phenotype. The latter releases exosomes that promote the relaxin-mediated quiescence of activated hepatic stellate cells through miR-30a-5p. Building on these results, we developed lipid nanoparticles that preferentially target activated hepatic stellate cells in the fibrotic liver and encapsulate the relaxin gene and miR-30a-5p mimic. The combinatorial gene therapy achieves synergistic antifibrosis effects in models of mouse liver fibrosis. Collectively, our findings highlight the key role that macrophages play in the relaxin-primed alleviation of liver fibrosis and demonstrate a proof-of-concept approach to devise antifibrotic strategies through the complementary application of nanotechnology and basic science.',\n", - " 'author': ['Hu, Mengying',\n", - " 'Wang, Ying',\n", - " 'Liu, Zhengsheng',\n", - " 'Yu, Zhuo',\n", - " 'Guan, Kaiyun',\n", - " 'Liu, Mengrui',\n", - " 'Wang, Menglin',\n", - " 'Tan, Jun',\n", - " 'Huang, Leaf'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41565-020-00836-6\"}'],\n", - " 'title': ['Hepatic macrophages act as a central hub for relaxin-mediated alleviation of liver fibrosis']},\n", - " {'bibcode': '2014NatSR...4E5782K',\n", - " 'abstract': \"Circadian clocks are endogenous oscillators driving daily rhythms in physiology. The cell-autonomous clock is governed by an interlocked network of transcriptional feedback loops. Hundreds of clock-controlled genes (CCGs) regulate tissue specific functions. Transcriptome studies reveal that different organs (e.g. liver, heart, adrenal gland) feature substantially varying sets of CCGs with different peak phase distributions. To study the phase variability of CCGs in mammalian peripheral tissues, we develop a core clock model for mouse liver and adrenal gland based on expression profiles and known cis-regulatory sites. `Modulation factors' associated with E-boxes, ROR-elements, and D-boxes can explain variable rhythms of CCGs, which is demonstrated for differential regulation of cytochromes P450 and 12 h harmonics. By varying model parameters we explore how tissue-specific peak phase distributions can be generated. The central role of E-boxes and ROR-elements is confirmed by analysing ChIP-seq data of BMAL1 and REV-ERB transcription factors.\",\n", - " 'author': ['Korenčič, Anja',\n", - " 'Košir, Rok',\n", - " 'Bordyugov, Grigory',\n", - " 'Lehmann, Robert',\n", - " 'Rozman, Damjana',\n", - " 'Herzel, Hanspeter'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep05782\"}'],\n", - " 'title': ['Timing of circadian genes in mammalian tissues']},\n", - " {'bibcode': '2017NatSR...716108G',\n", - " 'abstract': 'Hepatocytes perform most of the functions of the liver and are considered terminally differentiated cells. Recently, it has been suggested that hepatocytes might have the potential to transdifferentiate or dedifferentiate under physiological or pathological conditions in vivo. Epithelial-mesenchymal transition of hepatocytes in liver fibrosis has also been proposed. However, these findings have not been fully confirmed. In this study, hepatocytes were genetically labelled for cell fate tracing using lacZ via the tamoxifen-induced CreERT/loxP system. After induction with tamoxifen, alb + cells were permanently marked by lacZ expression, and all progeny lacZ + cells were derived from a single source with no interference. We did not observe transdifferentiation or dedifferentiation of hepatocytes into cholangiocytes or hepatic progenitor cells under conditions of liver homeostasis or following a 2/3 partial hepatectomy. Meanwhile, lacZ/OPN-positive cells were observed in livers of 3,5-diethoxycarbonyl-1,4-dihydrocollidine-fed mice, and lacZ/alpha-smooth muscle actin-positive cells were detected in carbon tetrachloride-induced chronic liver injury models. These results suggested that some existing differentiated alb + cells might have the potential of transdifferentiation/dedifferentiation or epithelial-to-mesenchymal transition in vivo in some liver injury models, but the proportion of these alb + cells in liver was very low, and their significance and actual function during the pathological process remains to be elucidated.',\n", - " 'author': ['Gu, Xiaowen',\n", - " 'Huang, Danyi',\n", - " 'Ci, Lei',\n", - " 'Shi, Jiahao',\n", - " 'Zhang, Mengjie',\n", - " 'Yang, Hua',\n", - " 'Wang, Zhugang',\n", - " 'Sheng, Zhejin',\n", - " 'Sun, Ruilin',\n", - " 'Fei, Jian'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-017-15973-7\"}'],\n", - " 'title': ['Fate tracing of hepatocytes in mouse liver']},\n", - " {'bibcode': '1980Sci...209.1128N',\n", - " 'abstract': \"A 15.8-kilobase pair fragment of BALB/c mouse liver DNA, cloned in the Charon 4Aλ phage vector system, was shown to contain the μ heavy chain constant region (CHμ ) gene for the mouse immunoglobulin M. In addition, this fragment of DNA contains at least two J genes, used to code for the carboxyl terminal portion of heavy chain variable regions. These genes are located in genomic DNA about eight kilobase pairs to the 5' side of the CHμ gene. The complete nucleotide sequence of a 1120-base pair stretch of DNA that includes the two J genes has been determined.\",\n", - " 'author': ['Newell, Nanette',\n", - " 'Richards, Julia E.',\n", - " 'Tucker, Philip W.',\n", - " 'Blattner, Frederick R.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.6250219\"}'],\n", - " 'title': ['J Genes for Heavy Chain Immunoglobulins of Mouse']},\n", - " {'bibcode': '2011EnTox..26..443H',\n", - " 'author': ['Huang, Pu', 'Zheng, Qun', 'Xu, Li-Hong'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Ftox.20570\"}'],\n", - " 'title': ['The apoptotic effect of oral administration of microcystin-RR on mice liver']},\n", - " {'bibcode': '1983Sci...219...63W',\n", - " 'abstract': 'The mouse liver microsomal mixed-function oxidase system converts several phosphorothiolate pesticides with S-ethyl, S-propyl, or S-butyl groups to more potent inhibitors of acetylcholinesterase. This activation is stereospecific for the chiral isomers of O-(4-bromo-2-chlorophenyl) O-ethyl S-propyl phosphorothiolate (profenofos insecticide); the more toxic (-) isomer becomes a 34-fold better inhibitor of acetylcholinesterase in vitro, whereas the less toxic (+) isomer is deactivated by a factor of 2. Prior treatment of the microsomes with piperonyl butoxide or another mixed-function oxidase inhibitor markedly decreases the activation. Piperonyl butoxide also protects against brain acetylcholinesterase inhibition and cholinergic symptoms in chicks resulting from (-)-profenofos administration, thus establishing the importance of the oxidative bioactivation of S-alkyl phosphorothiolate pesticides in vivo.',\n", - " 'author': ['Wing, Keith D.', 'Glickman, Andrew H.', 'Casida, John E.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.6849116\"}'],\n", - " 'title': ['Oxidative Bioactivation of S-Alkyl Phosphorothiolate Pesticides: Stereospecificity of Profenofos Insecticide Activation']},\n", - " {'bibcode': '2016NatSR...631331K',\n", - " 'abstract': 'Accumulating evidence suggests a role of bisphenol A (BPA) in metabolic disorders. However, the underlying mechanism is still unclear. Using a mouse BPA exposure model, we investigated the effects of long-term BPA exposure on lipid metabolism and the underlying mechanisms. The male mice exposed to BPA (0.5\\u2009μg BPA /kg/day, a human relevant dose) for 10 months exhibited significant hepatic accumulation of triglycerides and cholesterol. The liver cells from the BPA-exposed mice showed significantly increased expression levels of the genes related to lipid synthesis. These liver cells showed decreased DNA methylation levels of Srebf1 and Srebf2, and increased expression levels of Srebf1 and Srebf2 that may upregulate the genes related to lipid synthesis. The expression levels of DNA methyltransferases were decreased in BPA-exposed mouse liver. Hepa1-6 cell line treated with BPA showed decreased expression levels of DNA methyltransferases and increased expression levels of genes involved in lipid synthesis. DNA methyltransferase knockdown in Hepa1-6 led to hypo-methylation and increased expression levels of genes involved in lipid synthesis. Our results suggest that long-term BPA exposure could induce hepatic lipid accumulation, which may be due to the epigenetic reprogramming of the genes involved in lipid metabolism, such as the alterations of DNA methylation patterns.',\n", - " 'author': ['Ke, Zhang-Hong',\n", - " 'Pan, Jie-Xue',\n", - " 'Jin, Lu-Yang',\n", - " 'Xu, Hai-Yan',\n", - " 'Yu, Tian-Tian',\n", - " 'Ullah, Kamran',\n", - " 'Rahman, Tanzil Ur',\n", - " 'Ren, Jun',\n", - " 'Cheng, Yi',\n", - " 'Dong, Xin-Yan',\n", - " 'Sheng, Jian-Zhong',\n", - " 'Huang, He-Feng'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep31331\"}'],\n", - " 'title': ['Bisphenol A Exposure May Induce Hepatic Lipid Accumulation via Reprogramming the DNA Methylation Patterns of Genes Involved in Lipid Metabolism']},\n", - " {'bibcode': '1983Natur.305..427L',\n", - " 'abstract': 'A major event of nervous system development1 is the migration of granule cell neurones, during the early postnatal development of the cerebellar cortex, from their germinating zone in the external granular layer to then final location in the internal granular layer. During migration, many granule cells are seen in direct cell-surface contact with processes of Bergmann glia, a subclass of astrocytes2. In the neurological mutant mouse weaver, however, migration of granule cells is impaired, probably due to a deficit in cell-cell interactions3-5. To gain insight into the cellular and molecular mechanisms involved in granule cell migration, we have used a modification of an in vitro assay system, previously described by Moonen et al.6, which displays migratory behaviour in small tissue explants during several days of suspension culture. The aim of this study was to investigate the process of granule cell migration by using antibodies directed against cell-surface components of developing neural cells. We report here that migration of 3H-thymidine-labelled granule cell neurones can be modified by Fab fragments of both mono- and polyclonal L1 antibodies, but not by Fab fragments of polyclonal antibodies prepared against mouse liver membranes, which also react with cerebellar cell surfaces.',\n", - " 'author': ['Lindner, J.', 'Rathjen, F. G.', 'Schachner, M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F305427a0\"}'],\n", - " 'title': ['L1 mono- and polyclonal antibodies modify cell migration in early postnatal mouse cerebellum']},\n", - " {'bibcode': '2014PLoSO...9j8855W',\n", - " 'author': ['Wang, Chengfen',\n", - " 'Chen, Kan',\n", - " 'Xia, Yujing',\n", - " 'Dai, Weiqi',\n", - " 'Wang, Fan',\n", - " 'Shen, Miao',\n", - " 'Cheng, Ping',\n", - " 'Wang, Junshan',\n", - " 'Lu, Jie',\n", - " 'Zhang, Yan',\n", - " 'Yang, Jing',\n", - " 'Zhu, Rong',\n", - " 'Zhang, Huawei',\n", - " 'Li, Jingjing',\n", - " 'Zheng, Yuanyuan',\n", - " 'Zhou, Yingqun',\n", - " 'Guo, Chuanyong'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0108855\"}'],\n", - " 'title': ['N-Acetylcysteine Attenuates Ischemia-Reperfusion-Induced Apoptosis and Autophagy in Mouse Liver via Regulation of the ROS/JNK/Bcl-2 Pathway']},\n", - " {'bibcode': '2020NatSR..1015473G',\n", - " 'abstract': 'Due to breakthroughs in RNAi and genome editing methods in the past decade, it is now easier than ever to study fine details of protein synthesis in animal models. However, most of our understanding of translation comes from unicellular organisms and cultured mammalian cells. In this study, we demonstrate the feasibility of perturbing protein synthesis in a mouse liver by targeting translation elongation factor 2 (eEF2) with RNAi. We were able to achieve over 90% knockdown efficacy and maintain it for 2 weeks effectively slowing down the rate of translation elongation. As the total protein yield declined, both proteomics and ribosome profiling assays showed robust translational upregulation of ribosomal proteins relative to other proteins. Although all these genes bear the TOP regulatory motif, the branch of the mTOR pathway responsible for translation regulation was not activated. Paradoxically, coordinated translational upregulation of ribosomal proteins only occurred in the liver but not in murine cell culture. Thus, the upregulation of ribosomal transcripts likely occurred via passive mTOR-independent mechanisms. Impaired elongation sequesters ribosomes on mRNA and creates a shortage of free ribosomes. This leads to preferential translation of transcripts with high initiation rates such as ribosomal proteins. Furthermore, severe eEF2 shortage reduces the negative impact of positively charged amino acids frequent in ribosomal proteins on ribosome progression.',\n", - " 'author': ['Gerashchenko, Maxim V.',\n", - " 'Nesterchuk, Mikhail V.',\n", - " 'Smekalova, Elena M.',\n", - " 'Paulo, Joao A.',\n", - " 'Kowalski, Piotr S.',\n", - " 'Akulich, Kseniya A.',\n", - " 'Bogorad, Roman',\n", - " 'Dmitriev, Sergey E.',\n", - " 'Gygi, Steven',\n", - " 'Zatsepin, Timofei',\n", - " 'Anderson, Daniel G.',\n", - " 'Gladyshev, Vadim N.',\n", - " 'Koteliansky, Victor E.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-020-72399-4\"}'],\n", - " 'title': ['Translation elongation factor 2 depletion by siRNA in mouse liver leads to mTOR-independent translational upregulation of ribosomal protein genes']},\n", - " {'bibcode': '2021NatCo..12.2121L',\n", - " 'abstract': 'Prime editors (PEs) mediate genome modification without utilizing double-stranded DNA breaks or exogenous donor DNA as a template. PEs facilitate nucleotide substitutions or local insertions or deletions within the genome based on the template sequence encoded within the prime editing guide RNA (pegRNA). However, the efficacy of prime editing in adult mice has not been established. Here we report an NLS-optimized SpCas9-based prime editor that improves genome editing efficiency in both fluorescent reporter cells and at endogenous loci in cultured cell lines. Using this genome modification system, we could also seed tumor formation through somatic cell editing in the adult mouse. Finally, we successfully utilize dual adeno-associated virus (AAVs) for the delivery of a split-intein prime editor and demonstrate that this system enables the correction of a pathogenic mutation in the mouse liver. Our findings further establish the broad potential of this genome editing technology for the directed installation of sequence modifications in vivo, with important implications for disease modeling and correction.',\n", - " 'author': ['Liu, Pengpeng',\n", - " 'Liang, Shun-Qing',\n", - " 'Zheng, Chunwei',\n", - " 'Mintzer, Esther',\n", - " 'Zhao, Yan G.',\n", - " 'Ponnienselvan, Karthikeyan',\n", - " 'Mir, Aamir',\n", - " 'Sontheimer, Erik J.',\n", - " 'Gao, Guangping',\n", - " 'Flotte, Terence R.',\n", - " 'Wolfe, Scot A.',\n", - " 'Xue, Wen'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41467-021-22295-w\"}'],\n", - " 'title': ['Improved prime editors enable pathogenic allele correction and cancer modelling in adult mice']},\n", - " {'bibcode': '2016PLoSO..1165963C',\n", - " 'abstract': 'Fluorescence microscopic imaging in centimeter-deep tissue has been highly sought-after for many years because much interesting in vivo micro-information, such as microcirculation, tumor angiogenesis, and metastasis, may deeply locate in tissue. In this study, for the first time this goal has been achieved in 3-centimeter deep tissue with high signal-to-noise ratio (SNR) and picomole sensitivity under radiation safety thresholds. These results are demonstrated not only in tissue-mimic phantoms but also in actual tissues, such as porcine muscle, ex vivo mouse liver, ex vivo spleen, and in vivo mouse tissue. These results are achieved based on three unique technologies: excellent near infrared ultrasound-switchable fluorescence (USF) contrast agents, a sensitive USF imaging system, and an effective correlation method. Multiplex USF fluorescence imaging is also achieved. It is useful to simultaneously image multiple targets and observe their interactions. This work opens the door for future studies of centimeter-deep tissue fluorescence microscopic imaging.',\n", - " 'author': ['Cheng, Bingbing',\n", - " 'Bandi, Venugopal',\n", - " 'Wei, Ming-Yuan',\n", - " 'Pei, Yanbo',\n", - " \"D'Souza, Francis\",\n", - " 'Nguyen, Kytai T.',\n", - " 'Hong, Yi',\n", - " 'Yuan, Baohong'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"preprint\", \"url\": \"http://arxiv.org/abs/1510.02112\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0165963\"}'],\n", - " 'title': ['High-Resolution Ultrasound-Switchable Fluorescence Imaging in Centimeter-Deep Tissue Phantoms with High Signal-To-Noise Ratio and High Sensitivity via Novel Contrast Agents']},\n", - " {'bibcode': '2009ChPhC..33..986Z',\n", - " 'abstract': 'Neovascularization is correlative with many processes of diseases, especially for tumor growth, invasion, and metastasis. What is more, these tumor microvessels are totally different from normal vessels in morphology. Therefore, observation of the morphologic distribution of microvessels is one of the key points for many researchers in the field. Using diffraction enhanced imaging (DEI), we observed the mirocvessles with diameter of about 40 μm in mouse liver. Moreover, the refraction image obtained from DEI shows higher image contrast and exhibits potential use for medical applications.',\n", - " 'author': ['Zhang, Xi',\n", - " 'Yuan, Qing-Xi',\n", - " 'Yang, Xin-Rong',\n", - " 'Li, Hai-Qing',\n", - " 'Chen, Yu',\n", - " 'Chen, Shao-Liang',\n", - " 'Zhu, Pei-Ping',\n", - " 'Huang, Wan-Xia'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1088%2F1674-1137%2F33%2F11%2F011\"}'],\n", - " 'title': ['PROCEEDINGS ON SYNCHROTRON RADIATION: Medical application of diffraction enhanced imaging in mouse liver blood vessels']},\n", - " {'bibcode': '2021FrCh....9..669G',\n", - " 'abstract': 'Acetaminophen (N-acetyl-p-aminophenol; APAP) is a mild analgesic and antipyretic used commonly worldwide. Although APAP is considered a safe and effective over-the-counter medication, it is also the leading cause of drug-induced acute liver failure. Its hepatotoxicity has been linked to the covalent binding of its reactive metabolite, N-acetyl p-benzoquinone imine (NAPQI), to proteins. The aim of this in vivo study was to identify APAP-protein targets in both rat and mouse liver, and to compare the results from both species, using bottom-up proteomics and targeted multiple reaction monitoring (MRM) experiments. Livers from rats and mice, treated with APAP, were homogenized and digested by trypsin. Digests were then fractionated by mixed-mode solid-phase extraction prior to liquid chromatography-tandem mass spectrometry (LC-MS/MS) using scheduled multiple reaction monitoring (MRM) acquisition. The targeted assays were optimized based on high-resolution MS/MS data from information-dependent acquisition (IDA) using control liver homogenates treated with a custom alkylating reagent forming a positional isomer of the APAP modification on all cysteine residues, in order to build an in-house modified peptide database for targeted analysis. A list of putative in vivo targets of APAP were screened from previous in vitro studies, data-dependent high-resolution MS/MS analyses of liver digests, as well as selected proteins from the target protein database (TPDB), an online resource which references previous reports of proteins found to be modified by acetaminophen. Multiple protein targets of APAP in each species were found, while confirming modification sites. Several proteins were found to be modified in both species, including ATP-citrate synthase, betaine-homocysteine S-methyltransferase 1, cytochrome P450 2C6/29, mitochondrial glutamine amidotransferase-like protein/ES1 protein homolog, glutamine synthetase, microsomal glutathione S-transferase 1, mitochondrial-processing peptidase, methanethiol oxidase, protein/nucleic acid deglycase DJ-1, triosephosphate isomerase and thioredoxin. The targeted method afforded better reproducibility for analysing these low-abundant modified peptides in highly complex samples compared to traditional data-dependent experiments.',\n", - " 'author': ['Geib, Timon',\n", - " 'Moghaddam, Ghazaleh',\n", - " 'Supinski, Aimee',\n", - " 'Golizeh, Makan',\n", - " 'Sleno, Lekha'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.3389%2Ffchem.2021.736788\"}'],\n", - " 'title': ['Protein Targets of Acetaminophen Covalent Binding in Rat and Mouse Liver Studied by LC-MS/MS']},\n", - " {'bibcode': '1995PNAS...92.1302Y',\n", - " 'abstract': \"Mouse Slp, a duplicate of the fourth complement component (C4) gene, exhibits EDTA-independent complement activity with a hepatic expression that is male specific. To provide an underlying mechanism for the male-specific expression, we have analyzed the promoter activity of the various 5'-flanking sequences and CpG demethylation of the Slp gene. Transient transfections using HepG2 cells indicate that the element TTCCGGGC (nt -124 to -117) regulates the promoter activity. Moreover, CpG at position -121 of this regulatory element is demethylated to a much higher degree in males than in females. This sexually dimorphic DNA demethylation is consistent with the male-specific expression of the Slp gene in DBA/2 males. The regulatory element binds to the different TTCCGGGC-specific nuclear proteins depending on the methylation of the CpG site. In contrast, the corresponding CpG at position -119 of the C4 gene, which is expressed in both males and females, is demethylated at equal and high levels in both sexes. We therefore propose that the DNA demethylation and methylation-sensitive transcription factors may be a part of the regulatory mechanism for the male-specific expression of the Slp gene.\",\n", - " 'author': ['Yokomori, Norihiko', 'Moore, Rickie', 'Negishi, Masahiko'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/92/5/1302\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/92/5/1302\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/92/5/1302\"}'],\n", - " 'title': ['Sexually dimorphic DNA demethylation in the promoter of the Slp (sex-limited protein) gene in mouse liver.']},\n", - " {'bibcode': '2008PNAS..10515172L',\n", - " 'abstract': 'Mammals have circadian clocks in peripheral tissues, but there is no direct evidence of their physiological importance. Unlike the suprachiasmatic nucleus clock that is set by light and drives rest-activity and fasting-feeding cycles, peripheral clocks are set by daily feeding, suggesting that at least some contribute metabolic regulation. The liver plays a well known role in glucose homeostasis, and we report here that mice with a liver-specific deletion of Bmal1, an essential clock component, exhibited hypoglycemia restricted to the fasting phase of the daily feeding cycle, exaggerated glucose clearance, and loss of rhythmic expression of hepatic glucose regulatory genes. We conclude that the liver clock is important for buffering circulating glucose in a time-of-day-dependent manner. Our findings suggest that the liver clock contributes to homeostasis by driving a daily rhythm of hepatic glucose export that counterbalances the daily cycle of glucose ingestion resulting from the fasting-feeding cycle.',\n", - " 'author': ['Lamia, Katja A.', 'Storch, Kai-Florian', 'Weitz, Charles J.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/105/39/15172\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/105/39/15172.full.pdf\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0806717105\"}'],\n", - " 'title': ['From the Cover: Physiological significance of a peripheral tissue circadian clock']},\n", - " {'bibcode': '2020AIPA...10k5009F',\n", - " 'abstract': 'X-ray computed tomography (X-CT) is often used to examine organs, but the reconstructed images can only be used for structural identification. Whether the organs are healthy or not requires a professional doctor to examine the reconstructed image and judge from his or her own experience. The purpose of this paper is to identify the cirrhotic mouse liver and normal mouse liver with hyperspectral x-ray CT (HXCT) and machine learning. HXCT is proposed to reconstruct the x-ray absorption spectrum (XAS) characteristics of a single pixel in the reconstructed mouse liver images. HXCT uses a cadmium telluride photon counter as the x-ray detector, which can improve the spectral resolution and separate spectral lines. Filtered back-projection and algebra reconstruction technique reconstruction algorithms are used for image and XAS reconstruction. In the machine learning model, principal component analysis is utilized to reduce the dimensionality of XAS. Besides, the neural network algorithm Artificial Neural Network (ANN) is used to train and identify the reconstructed XAS of two different kinds of livers. These two different mouse livers can be well recognized since the accuracy goes to almost 100% based on ANN. It is feasible to employ the machine learning algorithm to identify the XAS of different mouse livers.',\n", - " 'author': ['Fang, Zheng', 'Zhong, Shuo', 'Hu, Weifeng', 'Cheng, Siyuan'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1063%2F5.0010463\"}'],\n", - " 'title': ['Mouse livers machine learning identification based on hyperspectral x-ray computed tomography reconstructed x-ray absorption spectra']},\n", - " {'bibcode': '2013MiMic..19.1290K',\n", - " 'abstract': 'The use of nanoparticles for the diagnosis and treatment of cancer requires the complete characterization of their toxicity, including accurately locating them within biological tissues. Owing to their size, traditional light microscopy techniques are unable to resolve them. Transmission electron microscopy provides the necessary spatial resolution to image individual nanoparticles in tissue, but is severely limited by the very small analysis volume, usually on the order of tens of cubic microns. In this work, we developed a scanning transmission electron microscopy (STEM) approach to analyze large volumes of tissue for the presence of polyethylene glycol-coated Raman-active-silica-gold-nanoparticles (PEG-R-Si-Au-NPs). This approach utilizes the simultaneous bright and dark field imaging capabilities of STEM along with careful control of the image contrast settings to readily identify PEG-R-Si-Au-NPs in mouse liver tissue without the need for additional time-consuming analytical characterization. We utilized this technique to analyze 243,000 μm3 of mouse liver tissue for the presence of PEG-R-Si-Au-NPs. Nanoparticles injected into the mice intravenously via the tail vein accumulated in the liver, whereas those injected intrarectally did not, indicating that they remain in the colon and do not pass through the colon wall into the systemic circulation.',\n", - " 'author': ['Kempen, Paul J.',\n", - " 'Thakor, Avnesh S.',\n", - " 'Zavaleta, Cristina',\n", - " 'Gambhir, Sanjiv S.',\n", - " 'Sinclair, Robert'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1017%2FS143192761300192X\"}'],\n", - " 'title': ['A Scanning Transmission Electron Microscopy Approach to Analyzing Large Volumes of Tissue to Detect Nanoparticles']},\n", - " {'bibcode': '1974BuECT..11..169S',\n", - " 'author': ['Settlemire, C. T.',\n", - " 'Huston, Anne S.',\n", - " 'Jacobs, Linda S.',\n", - " 'Havey, Jane C.',\n", - " 'Howland, John L.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1007%2FBF01684599\"}'],\n", - " 'title': ['Action of some insecticides on membranes of mouse liver mitochondria']},\n", - " {'bibcode': '1973BuECT..10..365P',\n", - " 'author': ['Payne, Nancy B.', 'Herzberg, Gene R.', 'Howland, John L.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1007%2FBF01721004\"}'],\n", - " 'title': ['Influence of some insecticides on the ATPase of mouse liver mitochondria']},\n", - " {'bibcode': '1953Natur.172..671N',\n", - " 'abstract': \"MANY workers have found that the multiplication of viruses occurs in definite cycles, each involving several stages, namely, adsorption and entry to host cell, a loss of part or all of the infectivity, a `lag' phase during which no new infective virus can be demonstrated, a period of intracellular rise in infectivity, and finally release of this virus followed by invasion of a fresh population of susceptible cells. We have studied the intracellular multiplication of ectromelia virus in mouse liver, using intravenous inoculation and assaying the infective titre of the liver at intervals. We have found that over a range of inocula from 106 to 1010 LD50 about 30 per cent of the inoculum is adsorbed to the liver in five minutes. Inocula of 109 LD50 infect practically all the liver cells within five minutes, as measured by a histological method1.\",\n", - " 'author': ['Nossal, G. J. V.', 'de Burgh, P. M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F172671a0\"}'],\n", - " 'title': ['Growth Cycle of Ectromelia Virus in Mouse Liver']},\n", - " {'bibcode': '1977JRadR..18..302S',\n", - " 'author': ['Saharan, B. R.', 'Singh, R. P.', 'Verma, A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1269%2Fjrr.18.302\"}'],\n", - " 'title': ['Toxicity of 2-Mercaptopropionylglycine (MPG) on Mouse Liver']},\n", - " {'bibcode': '1977JRadR..18..206S',\n", - " 'author': ['Saini, M. R.',\n", - " 'Saharan, B. R.',\n", - " 'Bhartiya, H. C.',\n", - " 'Devi, P. Uma'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1269%2Fjrr.18.206\"}'],\n", - " 'title': ['Radiation Protection of Mouse Liver by 2-Mercaptopropionylglycine']},\n", - " {'bibcode': '2016BpJ...110..138A',\n", - " 'author': ['Amin, Anowarul', 'Weston, Mary', 'Mindell, Joseph A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.bpj.2015.11.789\"}'],\n", - " 'title': ['Role of Counterions in Acidification in Mouse Liver Lysosomes']},\n", - " {'bibcode': '1970Natur.227..710L',\n", - " 'abstract': 'POLYPURINES have been isolated from subcellular fractions of mouse liver by a method which involves a limited nuclease digestion of the RNA, followed by chromatography of the digestion products on polystyrene columns1-3. These polypurines consist of clusters of adenylic acid and guanylic acid in which the A/G ratio is 2-10 the materials isolated from the rough endoplasmic reticulum have sedimentation coefficients of 3-5S, but a molecule containing twenty nucleotides can be obtained from the free polysomes4. The latter polymer is part of a rapidly labelled RNA species that sediments between the 32S subunit and 5S RNA when EDTA-treated polysomes are centrifuged on a sucrose density gradient. With longer times of labelling with 32P the polymer is also found in association with the 32S subunit. It seems likely that the adenine-rich polymer is found in close association with messenger-like RNA. These obssrvations prompted us to investigate the polypurine content of a better characterized mammalian messenger RNA. Such an RNA is the haemoglobin messenger RNA which has been isolated from rabbit reticulocytes5,6, and purified by polyacrylamide gel electrophoresis7. This species of RNA8 and a similar RNA from mouse reticulocytes9 have been demonstrated to initiate specific globin synthesis in vitro. We now describe the isolation of an adenine-rich polymer from purified messenger RNA obtained from rabbit reticulocyte polysomes and its relationship to the size of the ribosomes from which the messenger RNA is derived.',\n", - " 'author': ['Lim, L.', 'Canellakis, E. S.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F227710a0\"}'],\n", - " 'title': ['Adenine-rich Polymer associated with Rabbit Reticulocyte Messenger RNA']},\n", - " {'bibcode': '2017NatSR...741711K',\n", - " 'abstract': 'We have reported that an extract of Scutellaria baicalensis (ESB) has effects against obesity and hypertriglyceridemia in type 2 diabetic animal model (db/db mouse). In the present study, we tried to explain the pharmacological effects of ESB by integrating gene expression information from db/db mouse liver with that of ESB-treated HepG2 hepatocellular carcinoma cells. Using Connectivity Map (cmap) analysis, we found an inverse relationship in the pharmaceutical profiles based on gene expression between db/db mouse liver and ESB-treated HepG2 cells. This inverse relationship between the two data sets was also observed for pathway activities. Functional network analysis showed that biological functions associated with diabetes and lipid metabolism were commonly enriched in both data sets. We also observed a similarity in distribution of cmap enrichment scores between db/db mouse liver and human diabetic liver, whereas there was an inverse pattern of cmap enrichment scores in human diabetic liver compared with ESB-treated HepG2 cells. This relationship might explain the pharmacological activities of ESB against db/db mouse and possible effectiveness of ESB against human diabetes. We expect that our approach using in vitro cell lines could be applied in predicting the pharmacological effectiveness of herbal drugs in in vivo systems.',\n", - " 'author': ['Kim, Bu-Yeo',\n", - " 'Song, Kwang Hoon',\n", - " 'Lim, Chi-Yeon',\n", - " 'Cho, Su-In'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep41711\"}'],\n", - " 'title': ['Therapeutic properties of Scutellaria baicalensis in db/db mice evaluated using Connectivity Map and network pharmacology']},\n", - " {'bibcode': '2002EnvMM..40..283L',\n", - " 'abstract': 'Cis‑diamminedichloroplatinum (II) (cisplatin) is a well characterized antitumor drug used for the treatment of a variety of human cancers. The cytotoxicity of cisplatin is mainly mediated through the formation of DNA adducts, which are also believed to be responsible for the secondary malignancies produced by the drug. The aim of this study was to determine the in vivo mutagenic activity of cisplatin in the lacZ plasmid‑based transgenic mouse model. The mutant frequency (MF) and the spectrum of mutations induced by cisplatin in the mouse liver were analyzed and compared to controls. The mean MF in the lacZ gene was increased 2‑fold in mice treated with a single 6 mg/kg body weight dose of cisplatin and sacrificed after 17 and 28 days (P = 0.001 and P < 0.0001). Restriction analysis and sequencing of mutant DNA showed that cisplatin was able to induce both large deletions and point mutations. A specific profile of base substitution and frameshift mutations was identified in treated mice, consisting primarily of G:C→A:T transitions at GpG and ApG sites, the preferential DNA binding sites of cisplatin, and single basepair deletions/insertions. The present results provide the first evidence that cisplatin has mutagenic activity in vivo and induces a characteristic pattern of mutations in the mouse liver. This mutagenicity may be responsible for its tumorigenic activity. Environ. Mol. Mutagen. 40:283–291, 2002.',\n", - " 'author': ['Louro, Henriqueta', 'Silva, Maria J.', 'Boavida, Maria G.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Fem.10118\"}'],\n", - " 'title': ['Mutagenic activity of cisplatin in the lacZ plasmid‑based transgenic mouse model']},\n", - " {'bibcode': '2013PNAS..110.3339M',\n", - " 'abstract': 'The circadian clock is constituted by a complex molecular network that integrates a number of regulatory cues needed to maintain organismal homeostasis. To this effect, posttranslational modifications of clock proteins modulate circadian rhythms and are thought to convert physiological signals into changes in protein regulatory function. To explore reversible lysine acetylation that is dependent on the clock, we have characterized the circadian acetylome in WT and Clock-deficient (Clock-/-) mouse liver by quantitative mass spectrometry. Our analysis revealed that a number of mitochondrial proteins involved in metabolic pathways are heavily influenced by clock-driven acetylation. Pathways such as glycolysis/gluconeogenesis, citric acid cycle, amino acid metabolism, and fatty acid metabolism were found to be highly enriched hits. The significant number of metabolic pathways whose protein acetylation profile is altered in Clock-/- mice prompted us to link the acetylome to the circadian metabolome previously characterized in our laboratory. Changes in enzyme acetylation over the circadian cycle and the link to metabolite levels are discussed, revealing biological implications connecting the circadian clock to cellular metabolic state.',\n", - " 'author': ['Masri, Selma',\n", - " 'Patel, Vishal R.',\n", - " 'Eckel-Mahan, Kristin L.',\n", - " 'Peleg, Shahaf',\n", - " 'Forne, Ignasi',\n", - " 'Ladurner, Andreas G.',\n", - " 'Baldi, Pierre',\n", - " 'Imhof, Axel',\n", - " 'Sassone-Corsi, Paolo'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/110/9/3339\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1217632110\"}'],\n", - " 'title': ['From the Cover: Circadian acetylome reveals regulation of mitochondrial metabolic pathways']},\n", - " {'bibcode': '2015NatCo...6.7048G',\n", - " 'abstract': 'A bimodal switch model is widely used to describe transcriptional regulation by the thyroid hormone receptor (TR). In this model, the unliganded TR forms stable, chromatin-bound complexes with transcriptional co-repressors to repress transcription. Binding of hormone dissociates co-repressors and facilitates recruitment of co-activators to activate transcription. Here we show that in addition to hormone-independent TR occupancy, ChIP-seq against endogenous TR in mouse liver tissue demonstrates considerable hormone-induced TR recruitment to chromatin associated with chromatin remodelling and activated gene transcription. Genome-wide footprinting analysis using DNase-seq provides little evidence for TR footprints both in the absence and presence of hormone, suggesting that unliganded TR engagement with repressive complexes on chromatin is, similar to activating receptor complexes, a highly dynamic process. This dynamic and ligand-dependent interaction with chromatin is likely shared by all steroid hormone receptors regardless of their capacity to repress transcription in the absence of ligand.',\n", - " 'author': ['Grøntved, Lars',\n", - " 'Waterfall, Joshua J.',\n", - " 'Kim, Dong Wook',\n", - " 'Baek, Songjoon',\n", - " 'Sung, Myong-Hee',\n", - " 'Zhao, Li',\n", - " 'Park, Jeong Won',\n", - " 'Nielsen, Ronni',\n", - " 'Walker, Robert L.',\n", - " 'Zhu, Yuelin J.',\n", - " 'Meltzer, Paul S.',\n", - " 'Hager, Gordon L.',\n", - " 'Cheng, Sheue-Yann'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fncomms8048\"}'],\n", - " 'title': ['Transcriptional activation by the thyroid hormone receptor through ligand-dependent receptor recruitment and chromatin remodelling']},\n", - " {'bibcode': '2016NatSR...629423K',\n", - " 'abstract': \"Genetic ablation of C-terminus of Hsc70-interacting protein (CHIP) E3 ubiquitin-ligase impairs hepatic cytochrome P450 CYP2E1 degradation. Consequent CYP2E1 gain of function accelerates reactive O2 species (ROS) production, triggering oxidative/proteotoxic stress associated with sustained activation of c-Jun NH2-terminal kinase (JNK)-signaling cascades, pro-inflammatory effectors/cytokines, insulin resistance, progressive hepatocellular ballooning and microvesicular steatosis. Despite this, little evidence of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) was found in CHIP−/−-mice over the first 8-9-months of life. We herein document that this lack of tissue injury is largely due to the concurrent up-regulation and/or activation of the adiponectin-5'-AMP-activated protein kinase (AMPK)-forkhead box O (FOXO)-signaling axis stemming from at the least three synergistic features: Up-regulated expression of adipose tissue adiponectin and its hepatic adipoR1/adipoR2 receptors, stabilization of hepatic AMPKα1-isoform, identified herein for the first time as a CHIP-ubiquitination substrate (unlike its AMPKα2-isoform), as well as nuclear stabilization of FOXOs, well-known CHIP-ubiquitination targets. Such beneficial predominance of the adiponectin-AMPK-FOXO-signaling axis over the sustained JNK-elevation and injurious insulin resistance in CHIP−/−-livers apparently counteracts/delays rapid progression of the hepatic microvesicular steatosis to the characteristic macrovesicular steatosis observed in clinical NASH and/or rodent NASH-models.\",\n", - " 'author': ['Kim, Sung-Mi',\n", - " 'Grenert, James P.',\n", - " 'Patterson, Cam',\n", - " 'Correia, Maria Almira'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep29423\"}'],\n", - " 'title': ['CHIP−/−-Mouse Liver: Adiponectin-AMPK-FOXO-Activation Overrides CYP2E1-Elicited JNK1-Activation, Delaying Onset of NASH: Therapeutic Implications']},\n", - " {'bibcode': '2016NatSR...621783Z',\n", - " 'abstract': 'NG2-expressing cells are a population of periportal vascular stem/progenitors (MLpvNG2+ cells) that were isolated from healthy adult mouse liver by using a \"Percoll-Plate-Wait\" procedure. We demonstrated that isolated cells are able to restore liver function after transplantation into a cirrhotic liver and co-localized with the pericyte marker (immunohistochemistry: PDGFR-β) and CK19. Cells were positive for: stem cell (Sca-1, CD133, Dlk) and liver stem cell markers (EpCAM, CD14, CD24, CD49f); and negative for: hematopoietic (CD34, CD45) and endothelial markers (CD31, vWf, von Willebrand factor). Cells were transplanted (1 × 106 cells) in mice with diethylnitrosamine-induced cirrhosis at week 6. Cells showed increased hepatic associated gene expression of alpha-fetoprotein (AFP), Albumin (Alb), Glucose-6-phosphatase (G6Pc), SRY (sex determining region Y)-box 9 (Sox9), hepatic nuclear factors (HNF1a, HNF1β, HNF3β, HNF4α, HNF6, Epithelial cell adhesion molecule (EpCAM), Leucine-rich repeated-containing G-protein coupled receptor 5-positive (Lgr5) and Tyrosine aminotransferase (TAT). Cells showed decreased fibrogenesis, hepatic stellate cell infiltration, Kupffer cells and inflammatory cytokines. Liver function markers improved. In a cirrhotic liver environment, cells could differentiate into hepatic lineages. In addition, grafted MLpvNG2+ cells could mobilize endogenous stem/progenitors to participate in liver repair. These results suggest that MLpvNG2+ cells may be novel adult liver progenitors that participate in liver regeneration.',\n", - " 'author': ['Zhang, Hongyu',\n", - " 'Siegel, Christopher T.',\n", - " 'Shuai, Ling',\n", - " 'Lai, Jiejuan',\n", - " 'Zeng, Linli',\n", - " 'Zhang, Yujun',\n", - " 'Lai, Xiangdong',\n", - " 'Bie, Ping',\n", - " 'Bai, Lianhua'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep21783\"}'],\n", - " 'title': ['Repair of liver mediated by adult mouse liver neuro-glia antigen 2-positive progenitor cell transplantation in a mouse model of cirrhosis']},\n", - " {'bibcode': '2017NatCo...8..549A',\n", - " 'abstract': 'The histone deacetylase HDAC3 is a critical mediator of hepatic lipid metabolism, and liver-specific deletion of HDAC3 leads to fatty liver. To elucidate the underlying mechanism, here we report a method of cross-linking followed by mass spectrometry to define a high-confidence HDAC3 interactome in vivo that includes the canonical NCoR-HDAC3 complex as well as Prospero-related homeobox 1 protein (PROX1). HDAC3 and PROX1 co-localize extensively on the mouse liver genome, and are co-recruited by hepatocyte nuclear factor 4α (HNF4α). The HDAC3-PROX1 module controls the expression of a gene program regulating lipid homeostasis, and hepatic-specific ablation of either component increases triglyceride content in liver. These findings underscore the importance of specific combinations of transcription factors and coregulators in the fine tuning of organismal metabolism.',\n", - " 'author': ['Armour, Sean M.',\n", - " 'Remsberg, Jarrett R.',\n", - " 'Damle, Manashree',\n", - " 'Sidoli, Simone',\n", - " 'Ho, Wesley Y.',\n", - " 'Li, Zhenghui',\n", - " 'Garcia, Benjamin A.',\n", - " 'Lazar, Mitchell A.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41467-017-00772-5\"}'],\n", - " 'title': ['An HDAC3-PROX1 corepressor module acts on HNF4α to control hepatic triglycerides']},\n", - " {'bibcode': '2013PNAS..110.2324L',\n", - " 'abstract': 'In many organs, myofibroblasts play a major role in the scarring process in response to injury. In liver fibrogenesis, hepatic stellate cells (HSCs) are thought to transdifferentiate into myofibroblasts, but the origins of both HSCs and myofibroblasts remain elusive. In the developing liver, lung, and intestine, mesothelial cells (MCs) differentiate into specific mesenchymal cell types; however, the contribution of this differentiation to organ injury is unknown. In the present study, using mouse models, conditional cell lineage analysis has demonstrated that MCs expressing Wilms tumor 1 give rise to HSCs and myofibroblasts during liver fibrogenesis. Primary MCs, isolated from adult mouse liver using antibodies against glycoprotein M6a, undergo myofibroblastic transdifferentiation. Antagonism of TGF-β signaling suppresses transition of MCs to mesenchymal cells both in vitro and in vivo. These results indicate that MCs undergo mesothelial-mesenchymal transition and participate in liver injury via differentiation to HSCs and myofibroblasts.',\n", - " 'author': ['Li, Yuchang', 'Wang, Jiaohong', 'Asahina, Kinji'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/110/6/2324\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1214136110\"}'],\n", - " 'title': ['Mesothelial cells give rise to hepatic stellate cells and myofibroblasts via mesothelial-mesenchymal transition in liver injury']},\n", - " {'bibcode': '2016NatCo...712696D',\n", - " 'abstract': 'Although food availability is a potent synchronizer of the peripheral circadian clock in mammals, the underlying mechanisms are unclear. Here, we show that hepatic Bmal1, a core transcription activator of the molecular clock, is post-transcriptionally regulated by signals from insulin, an important hormone that is temporally controlled by feeding. Insulin promotes postprandial Akt-mediated Ser42-phosphorylation of Bmal1 to induce its dissociation from DNA, interaction with 14-3-3 protein and subsequently nuclear exclusion, which results in the suppression of Bmal1 transcriptional activity. Inverted feeding cycles not only shift the phase of daily insulin oscillation, but also elevate the amplitude due to food overconsumption. This enhanced and reversed insulin signalling initiates the reset of clock gene rhythms by altering Bmal1 nuclear accumulation in mouse liver. These results reveal the molecular mechanism of insulin signalling in regulating peripheral circadian rhythms.',\n", - " 'author': ['Dang, Fabin',\n", - " 'Sun, Xiujie',\n", - " 'Ma, Xiang',\n", - " 'Wu, Rong',\n", - " 'Zhang, Deyi',\n", - " 'Chen, Yaqiong',\n", - " 'Xu, Qian',\n", - " 'Wu, Yuting',\n", - " 'Liu, Yi'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fncomms12696\"}'],\n", - " 'title': ['Insulin post-transcriptionally modulates Bmal1 protein to affect the hepatic circadian clock']},\n", - " {'bibcode': '2007PNAS..10420507B',\n", - " 'abstract': 'We report the successful transplantation of human hepatocytes in immunodeficient, fumarylacetoacetate hydrolase-deficient (fah-/-) mice. Engraftment occurs over the entire liver acinus upon transplantation. A few weeks after transplantation, increasing concentrations of human proteins (e.g., human albumin and human C3a) can be measured in the blood of the recipient mouse. No fusion between mouse and human hepatocytes can be detected. Three months after transplantation, up to 20% of the mouse liver is repopulated by human hepatocytes, and sustained expression of lentiviral vector transduced gene can be observed. We further report the development of a hepatocyte transplantation method involving a transcutaneous, intrahepatic injection in neonatal mice. Human hepatocytes engraft over the entire injected lobe with an expansion pattern similar to those observed with intrasplenic transplantation.',\n", - " 'author': ['Bissig, Karl-Dimiter',\n", - " 'Le, Tam T.',\n", - " 'Woods, Niels-Bjarne',\n", - " 'Verma, Inder M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/104/51/20507\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0710528105\"}'],\n", - " 'title': ['Repopulation of adult and neonatal mice with human hepatocytes: A chimeric animal model']},\n", - " {'bibcode': '1976Natur.264..517A',\n", - " 'abstract': 'Digestion of mouse liver nuclei with DNase II leads to a novel cleavage pattern with a 100-nucleotide pair periodicity. From chromatin, this pattern or the standard 200-nucleotide pair repeat can be produced depending on the ionic conditions. The results are interpreted by assuming different conformational states of the nuclear material, including condensed and extended forms.',\n", - " 'author': ['Altenburger, Werner', 'Hörz, Wolfram', 'Zachau, Hans G.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F264517a0\"}'],\n", - " 'title': ['Nuclease cleavage of chromatin at 100-nucleotide pair intervals']},\n", - " {'bibcode': '2018PNAS..115E1916W',\n", - " 'abstract': 'Rhythms in gene expression propelled by the circadian clock and environmental signals are ubiquitous across cells and tissues. In particular, in mouse tissues, thousands of transcripts show oscillations with a period of 24 hours. Keys question are how such rhythms propagate and eventually exert functions, but also how these are generated. Here, we developed a mathematical model based on total RNA-seq to classify genes according to the respective contributions of transcriptional and posttranscriptional regulation toward mRNA expression profiles. We found that about one-third of rhythmically accumulating mRNA are under posttranscriptional regulation. Such regulation is only partially dependent on the circadian clock, showing that systemic pathways and feeding patterns contribute important posttranscriptional control of gene expression in liver.',\n", - " 'author': ['Wang, Jingkui',\n", - " 'Symul, Laura',\n", - " 'Yeung, Jake',\n", - " 'Gobet, Cédric',\n", - " 'Sobel, Jonathan',\n", - " 'Lück, Sarah',\n", - " 'Westermark, Pâl O.',\n", - " 'Molina, Nacho',\n", - " 'Naef, Felix'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1715225115\"}'],\n", - " 'title': ['Circadian clock-dependent and -independent posttranscriptional regulation underlies temporal mRNA accumulation in mouse liver']},\n", - " {'bibcode': '2013PLoSO...858843Z',\n", - " 'author': ['Zhou, Xiaoshan',\n", - " 'Kannisto, Kristina',\n", - " 'Curbo, Sophie',\n", - " 'von Döbeln, Ulrika',\n", - " 'Hultenby, Kjell',\n", - " 'Isetun, Sindra',\n", - " 'Gåfvels, Mats',\n", - " 'Karlsson, Anna'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0058843\"}'],\n", - " 'title': ['Thymidine Kinase 2 Deficiency-Induced mtDNA Depletion in Mouse Liver Leads to Defect β-Oxidation']},\n", - " {'bibcode': '2016ESPR...23.3809B',\n", - " 'author': ['Ben Saad, Hajer',\n", - " 'Kharrat, Nadia',\n", - " 'Krayem, Najeh',\n", - " 'Boudawara, Ons',\n", - " 'Boudawara, Tahia',\n", - " 'Zeghal, Najiba',\n", - " 'Ben Amara, Ibtissem'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1007%2Fs11356-015-5620-2\"}'],\n", - " 'title': ['Biological properties of Alsidium corallinum and its potential protective effects against damage caused by potassium bromate in the mouse liver']},\n", - " {'bibcode': '1992PNAS...8911867L',\n", - " 'abstract': 'The toxic effects of cantharidin from blister beetles and its analogs, including the herbicide endothall, are attributable to their high affinity and specificity for a cantharidin-binding protein (CBP). An ammonium sulfate precipitate of mouse liver cytosol was purified by five chromatographic steps to isolate CBP in 14% yield and > 99% purity as monitored by [3H]cantharidin-binding activity. The purification factor of 2230-fold corresponds to a CBP content of 0.045% of the liver cytosolic protein. CBP is a heterodimer consisting of a 61-kDa alpha subunit and a 39-kDa beta subunit. Amino acid sequences of four peptides from CBP-alpha and three peptides from CBP-beta are identical with deduced amino acid sequences for the A alpha regulatory and C beta catalytic subunits, respectively, of protein phosphatase 2A (PP2A). This assignment of CBP as PP2A-AC from structural evidence is supported by biochemical studies with selective substrates and inhibitors. CBP dephosphorylation of phosphorylase alpha is sensitive not only to okadaic acid, as with PP2A, but also to cantharidin and its analogs, consistent with their potency in blocking the radioligand binding site of CBP. Okadaic acid is a potent inhibitor of [3H]cantharidin binding to CBP. PP2A is present in many mammalian tissues and in plants and is involved in regulatory phosphorylation-dephosphorylation events which modulate multiple cellular functions. Inhibition of PP2A activity may account for the diverse effects and toxicity of cantharidin and its analogs, including the herbicide endothall, in mammals and possibly plants.',\n", - " 'author': ['Li, Yue-Ming', 'Casida, John E.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/89/24/11867\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/89/24/11867\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/89/24/11867\"}'],\n", - " 'title': ['Cantharidin-binding protein: identification as protein phosphatase 2A.']},\n", - " {'bibcode': '2000PNAS...9710144D',\n", - " 'abstract': 'IL-10-related T cell-derived inducible factor (IL-TIF or IL-21) is a new cytokine structurally related to IL-10 and originally identified in the mouse as a gene induced by IL-9 in T cells and mast cells. Here, we report the cloning of the human IL-TIF cDNA, which shares 79% amino acid identity with mouse IL-TIF and 25% identity with human IL-10. Recombinant human IL-TIF was found to activate signal transducer and activator of transcription factors-1 and -3 in several hepatoma cell lines. IL-TIF stimulation of HepG2 human hepatoma cells up-regulated the production of acute phase reactants such as serum amyloid A, α1-antichymotrypsin, and haptoglobin. Although IL-10 and IL-TIF have distinct activities, antibodies directed against the β chain of the IL-10 receptor blocked the induction of acute phase reactants by IL-TIF, indicating that this chain is a common component of the IL-10 and IL-TIF receptors. Similar acute phase reactant induction was observed in mouse liver upon IL-TIF injection, and IL-TIF expression was found to be rapidly increased after lipopolysaccharide (LPS) injection, suggesting that this cytokine contributes to the inflammatory response in vivo.',\n", - " 'author': ['Dumoutier, Laure',\n", - " 'Van Roost, Emiel',\n", - " 'Colau, Didier',\n", - " 'Renauld, Jean-Christophe'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/97/18/10144\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/97/18/10144\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/97/18/10144\"}'],\n", - " 'title': ['Human interleukin-10-related T cell-derived inducible factor: Molecular cloning and functional characterization as an hepatocyte-stimulating factor']},\n", - " {'bibcode': '1988PNAS...85.9576S',\n", - " 'abstract': 'Two mouse growth hormone-receptor primary translation products of Mr 95,900 and 31,800 were identified from in vitro-translated late pregnant mouse liver mRNA. RNA isolated from mouse liver was translated in a rabbit reticulocyte lysate system containing [35S]methionine, and the growth hormone receptor primary translation products were identified by immunoprecipitation with anti-mouse growth hormone receptor antiserum followed by sodium dodecyl sulfate/PAGE and fluorography. Detectable amounts of the Mr 95,900 and 31,800 proteins were not present in in vitro-translated nonpregnant mouse liver mRNA. This result is consistent with previous observations of the up-regulation of growth hormone receptors in the liver during pregnancy in the mouse. Northern (RNA) blot analysis of mouse liver and adipose tissue RNA with a rabbit growth hormone receptor cDNA probe revealed two hybridizing mRNAs of approximately 3.9 and 1.2 kilobases. These two RNAs were greatly up-regulated in liver, but not in adipose tissue, during pregnancy. The sizes of these mRNAs closely matched predictions of the sizes of the mRNAs coding for the proteins of Mr 95,900 and 31,800 made by in vitro translation of size-fractionated late-pregnant mouse liver poly(A)+RNA. These results suggest a mechanism for the generation of both the heterogeneous forms of the growth hormone receptor identified in mouse liver membrane preparations and the mouse serum growth hormone-binding protein.',\n", - " 'author': ['Smith, William C.',\n", - " 'Linzer, Daniel I. H.',\n", - " 'Talamantes, Frank'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/85/24/9576\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/85/24/9576\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/85/24/9576\"}'],\n", - " 'title': ['Detection of two growth hormone receptor mRNAs and primary translation products in the mouse.']},\n", - " {'bibcode': '2006Sci...313.1137O',\n", - " 'abstract': 'Endoplasmic reticulum (ER) stress is a key link between obesity, insulin resistance, and type 2 diabetes. Here, we provide evidence that this mechanistic link can be exploited for therapeutic purposes with orally active chemical chaperones. 4-Phenyl butyric acid and taurine-conjugated ursodeoxycholic acid alleviated ER stress in cells and whole animals. Treatment of obese and diabetic mice with these compounds resulted in normalization of hyperglycemia, restoration of systemic insulin sensitivity, resolution of fatty liver disease, and enhancement of insulin action in liver, muscle, and adipose tissues. Our results demonstrate that chemical chaperones enhance the adaptive capacity of the ER and act as potent antidiabetic modalities with potential application in the treatment of type 2 diabetes.',\n", - " 'author': ['Özcan, Umut',\n", - " 'Yilmaz, Erkan',\n", - " 'Özcan, Lale',\n", - " 'Furuhashi, Masato',\n", - " 'Vaillancourt, Eric',\n", - " 'Smith, Ross O.',\n", - " 'Görgün, Cem Z.',\n", - " 'Hotamisligil, Gökhan S.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.1128294\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.1128294\"}'],\n", - " 'title': ['Chemical Chaperones Reduce ER Stress and Restore Glucose Homeostasis in a Mouse Model of Type 2 Diabetes']},\n", - " {'bibcode': '1990PNAS...87.5061C',\n", - " 'abstract': 'To determine the importance of the third alpha-helix in bovine growth hormone (bGH) relative to growth-related biological activities, the following experimental approach was used: (i) mutagenesis of helix III of bGH to generate an idealized amphiphilic helix; (ii) in vitro expression analyses of the mutated bGH gene in cultured mouse L cells; (iii) mouse liver membrane binding studies of wild-type and mutated bGH; and (iv) expression of the mutated gene in the transgenic mouse. An altered bGH gene (pBGH10 delta 6-M8) was generated that encodes the following changes: glutamate-117 to leucine, glycine-119 to arginine, and alanine-122 to aspartate. The plasmid pBGH10 delta 6-M8 was shown to be expressed in, and its protein product secreted by, mouse L cells. The altered hormone possessed the same binding affinity to mouse liver membrane preparations as wild-type bGH. Transgenic mice containing the mutated bGH gene, however, showed a significant growth-suppressed phenotype. The degree of suppression was directly related to serum levels of the altered bGH molecule.',\n", - " 'author': ['Chen, Wen Y.',\n", - " 'Wight, David C.',\n", - " 'Wagner, Thomas E.',\n", - " 'Kopchick, John J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/87/13/5061\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/87/13/5061\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/87/13/5061\"}'],\n", - " 'title': ['Expression of a mutated bovine growth hormone gene suppresses growth of transgenic mice.']},\n", - " {'bibcode': '1960Natur.188.1116V',\n", - " 'abstract': 'IN papers dealing with methods of determining catalase activity in animal tissue, while dealing with the experimental conditions, usually little attention is paid to the condition of the animal. We have found the latter to be of utmost importance.',\n", - " 'author': ['van Senden, K. G.', 'de Jong, J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F1881116a0\"}'],\n", - " 'title': ['Catalase Activity of Mouse Liver and its Relation to the Condition of the Animal']},\n", - " {'bibcode': '1973JEZ...184..149K',\n", - " 'author': ['Kistler, Andreas', 'Weber, Rudolf'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Fjez.1401840202\"}'],\n", - " 'title': ['Enzyme patterns in mitochondria of mouse liver and heart muscle']},\n", - " {'bibcode': '1974RSPSB.187..363G',\n", - " 'abstract': 'Readmitting potassium to potassium-deprived mouse liver segments during intracellular microelectrode recording caused an increase in membrane potential and a gradual reduction in amplitude of electrotonic potentials set up by current pulses applied to another liver cell some distance away. Readmitting K in a high concentration (100 mM) caused a transient hyperpolarization followed by depolarization. The transient hyperpolarization was abolished by Strophanthin-G.',\n", - " 'author': ['Graf, J.', 'Petersen, O. H.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.jstor.org/stable/76409?origin=ads\"}'],\n", - " 'title': ['Electrogenic Sodium Pump in Mouse Liver Parenchymal Cells']},\n", - " {'bibcode': '1985ToxIH...1..311P',\n", - " 'abstract': 'Significant numbers of chemicals have been shown to be carcinogenic in mouse liver although they do not exhibit carcinogenic activity in other organs or tissues of mice or rats. This review focuses on the reasons for the unique susceptibility of the mouse liver to these carcinogens and the extent to which the carcinogenic activity of a chemical in mouse liver can be used to predict carcinogenicity in humans. Many of these mouse liver carcinogens lack genotoxic activity and, as such, have been proposed to be tumor promoters. Two mechanisms that may explain the action of nongenotoxic carcinogens in mouse liver are reviewed. These are: (1) direct action on precursor cancer cells, either to accelerate their growth or to prevent their death and (2) the selective growth advantage, resulting from regenerative hyperplasia of precursor cancer cells in response to the necrosis of normal cells produced by hepatotoxins. Estimating human health risks on the basis of mouse liver tumor data is believed to differ for nongenotoxic and genotoxic carcinogens in two fundamental ways. The first involves intraspecies extrapolation and the second involves low-dose extrapolation. In conclusion, although mouse liver tumor data are seen to be of value in estimating human health hazard, it is important to distinguish between genotoxic and nongenotoxic mechanisms in applying such data. Further study of the biochemical and molecular mechanisms of chemical carcinogens is necessary to determine the relationship between their activity in mouse liver and their activity in humans.',\n", - " 'author': ['Pereira, Michael A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1177%2F074823378500100421\"}'],\n", - " 'title': ['Mouse Liver Tumor Data: Assessment of Carcinogenic Activity']},\n", - " {'bibcode': '1981Natur.291..167G',\n", - " 'abstract': \"The intense interest in the metabolic fate of epoxidized xeno-biotics is due to several factors. For instance, epoxides are often intermediates in the lipophile to hydrophile conversions necessary for the excretion of olefinic and aromatic compounds by living systems1, and are widely encountered in man's diet from both natural and man-made sources. Some of these epoxidized compounds may alkylate proteins and nucleic acids and thus include some of the most potent cytotoxins, mutagens and carcinogens known2. In mammals, epoxides may rearrange, deoxygenate to olefins, react with glutathione to form conjugates, or be hydrolysed by water to yield 1,2-diols with or without enzymatic catalysis1,3,4,. The enzymes which catalyse the formation of diols are known as epoxide hydrolases (EC 3.3.2.3), and their subcellular distribution is the subject of this report. Early data showed that styrene oxide hydrolase activity was associated with the microsomal subcellular fraction5. Epoxide hydrolase activity was subsequently demonstrated on the nuclear6, Golgi apparatus and plasma membranes7, and in the cytosol of the cell8,9, leaving the mitochondria as the last major cellular organelle assumed to be devoid of epoxide hydrolase activity. We now report strong evidence for the occurrence of substantial epoxide hydrolase activity in the mitochondria.\",\n", - " 'author': ['Gill, Sarjeet S.', 'Hammock, Bruce D.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F291167a0\"}'],\n", - " 'title': ['Epoxide hydrolase activity in the mitochondrial fraction of mouse liver']},\n", - " {'bibcode': '1953Natur.171..748L',\n", - " 'abstract': 'IN a previous report1, there were presented findings which were unexpected if the entire polycarboxylic acid cycle were involved in carbon dioxide fixation by animals. At 5 and 15 min. after the injection of radioactive sodium bicarbonate (NaH14CO3) (obtained as Ba14CO3 from the Atomic Energy Commission, Oak Ridge, Tennessee) there appeared to be a more direct path of carbon to succinate than that previously postulated. In addition, the labelling in such acids as α-ketoglutarate, citrate and aconitate was not measurable. It was thought desirable to examine the path of carbon dioxide employing paper chromatography, because by this technique compounds retained by the silica gel (used in previous studies) which escaped examination would become detectable.',\n", - " 'author': ['Leeper, Lemuell C.',\n", - " 'Friedberg, Felix',\n", - " 'Marshall, Lawrence M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F171748b0\"}'],\n", - " 'title': ['Short-Term Carbon Dioxide Fixation in Mouse Liver']},\n", - " {'bibcode': '1982NYASA.386..417G',\n", - " 'author': ['Gee, Robert', 'Tolbert, N. E.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1111%2Fj.1749-6632.1982.tb21439.x\"}'],\n", - " 'title': ['Glycerol Phosphate Dehydrogenase in Rat and Mouse Liver Peroxisomes']},\n", - " {'bibcode': '1986Natur.319..507R',\n", - " 'abstract': 'The liver of the neonatal mouse continues to show haematopoietic activity for up to 2 weeks after birth1,2 and morphological analysis has shown that this activity becomes focused in discrete haematopoietic colonies by the end of the first week postnatal3. Furthermore, each colony contains cells of one haematopoietic lineage only, that is, erythroid, myeloid or pre-B-lymphoid cells. This pattern of differentiation suggests that each colony is derived from a single committed precursor cell, which, if true, would represent the first demonstration of non-mixed haematopoietic colonies in normal development and would provide a useful system for studying the factors affecting the clonal diversity of haematopoietic stem cells and their lineage-committed progeny. Here we have analysed the haematopoietic foci in the liver of neonatal mouse chimaeras, using a newly developed ubiquitous in situ cell marker system which clearly demonstrates the clonal origin of these colonies.',\n", - " 'author': ['Rossant, J.', 'Vijh, K. M.', 'Grossi, C. E.', 'Cooper, M. D.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F319507a0\"}'],\n", - " 'title': ['Clonal origin of haematopoietic colonies in the postnatal mouse liver']},\n", - " {'bibcode': '2021NatSR..1119720S',\n", - " 'abstract': 'Chinese herbal medicine is widely used because it has a good safety profile and few side effects. However, the risk of adverse drug reactions caused by herb-drug interactions (HDIs) is often overlooked. Therefore, the task of identifying possible HDIs and elucidating their mechanisms is of great significance for the prevention and treatment of HDI-related adverse reactions. Since extract from Dioscorea bulbifera L. rhizomes (DB) can cause various degrees of liver damage, it is speculated that HDIs may occur between DB extract and chemicals metabolized or excreted by the liver. Our study revealed that the cardiotoxicity of pirarubicin (THP) was increased by co-administration of DB, and the expression of P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (Mrp2) in the liver was inhibited by DB extract, which led to the accumulation of THP in heart tissue. In conclusion, there are risks of the co-administration of DB extract and THP. The mechanism of HDIs can be better revealed by targeting the efflux transporters.',\n", - " 'author': ['Sun, Li-rui', 'Guo, Qiu-shi', 'Zhou, Wei', 'Li, Min'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-021-99264-2\"}'],\n", - " 'title': ['Extract from Dioscorea bulbifera L. rhizomes aggravate pirarubicin-induced cardiotoxicity by inhibiting the expression of P-glycoprotein and multidrug resistance-associated protein 2 in the mouse liver']},\n", - " {'bibcode': '2014PLoSO...994962Z',\n", - " 'author': ['Zhang, Xiangrong',\n", - " 'Zhang, Ji',\n", - " 'Li, Wei',\n", - " 'Liu, Li',\n", - " 'Sun, Baoshan',\n", - " 'Guo, Zhenghong',\n", - " 'Shi, Caihong',\n", - " 'Zhao, Yuqing'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0094962\"}'],\n", - " 'title': ['In Vitro Metabolism of 20(R)-25-Methoxyl-Dammarane-3, 12, 20-Triol from Panax notoginseng in Human, Monkey, Dog, Rat, and Mouse Liver Microsomes']},\n", - " {'bibcode': '1968Natur.219..619H',\n", - " 'abstract': 'SEVERAL circadian rhythms of hepatic enzymes have been reported1-3, but it has not been possible to analyse the mechanism which determines the oscillation of enzyme activities, even though various factors-such as enzyme synthesis, rate of degradation, action of inhibitors, inactivation by steric alterations, and so on-have been considered4. Rapoport et al.5 have published a study of mouse liver tryptophan pyrrolase and its possible correlation with both substrate and corticosteroid oscillations. They found this enzyme activity rhythm to be corticosteroid-dependent, but could not detect an obvious relation between maxima of substrate, hormone, and enzyme activity. This report tries to identify the controlling factors for increase and decrease in rat liver tryptophan pyrrolase activity during a diurnal period.',\n", - " 'author': ['Hardeland, Rüdiger', 'Rensing, Ludger'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F219619a0\"}'],\n", - " 'title': ['Circadian Oscillation in Rat Liver Tryptophan Pyrrolase and its Analysis by Substrate and Hormone Induction']},\n", - " {'bibcode': '2014NatCo...5.3862S',\n", - " 'abstract': 'The liver has a unique regenerative capability, which involves extensive remodelling of cell-cell and cell-matrix contacts. Here we study the role of integrins in mouse liver regeneration using Cre/loxP-mediated gene deletion or intravenous delivery of β1-integrin siRNA formulated into nanoparticles that predominantly target hepatocytes. We show that although short-term loss of β1-integrin has no obvious consequences for normal livers, partial hepatectomy leads to severe liver necrosis and reduced hepatocyte proliferation. Mechanistically, loss of β1-integrin in hepatocytes impairs ligand-induced phosphorylation of the epidermal growth factor and hepatocyte growth factor receptors, thereby attenuating downstream receptor signalling in vitro and in vivo. These results identify a crucial role and novel mechanism of action of β1-integrins in liver regeneration and demonstrate that protein depletion by nanoparticle-based delivery of specific siRNA is a powerful strategy to study gene function in the regenerating liver.',\n", - " 'author': ['Speicher, Tobias',\n", - " 'Siegenthaler, Beat',\n", - " 'Bogorad, Roman L.',\n", - " 'Ruppert, Raphael',\n", - " 'Petzold, Tobias',\n", - " 'Padrissa-Altes, Susagna',\n", - " 'Bachofner, Marc',\n", - " 'Anderson, Daniel G.',\n", - " 'Koteliansky, Victor',\n", - " 'Fässler, Reinhard',\n", - " 'Werner, Sabine'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fncomms4862\"}'],\n", - " 'title': ['Knockdown and knockout of β1-integrin in hepatocytes impairs liver regeneration through inhibition of growth factor signalling']},\n", - " {'bibcode': '2014PLoSO...984925Z',\n", - " 'author': ['Zhang, Qinghao', 'Lei, Xiaohong', 'Lu, Hong'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0084925\"}'],\n", - " 'title': ['Alterations of Epigenetic Signatures in Hepatocyte Nuclear Factor 4α Deficient Mouse Liver Determined by Improved ChIP-qPCR and (h)MeDIP-qPCR Assays']},\n", - " {'bibcode': '2005PNAS..102.6843L',\n", - " 'abstract': 'Infection and inflammation produce systemic responses that include hypozincemia and hypoferremia. The latter involves regulation of the iron transporter ferroportin 1 by hepcidin. The mechanism of reduced plasma zinc is not known. Transcripts of the two zinc transporter gene families (ZnT and Zip) were screened for regulation in mouse liver after turpentine-induced inflammation and LPS administration. Zip14 mRNA was the transporter transcript most up-regulated by inflammation and LPS. IL-6 knockout (IL-6-/-) mice did not exhibit either hypozincemia or the induction of Zip14 with turpentine inflammation. However, in IL-6-/- mice, LPS produced a milder hypozincemic response but no Zip14 induction. Northern analysis showed Zip14 up-regulation was specific for the liver, with one major transcript. Immunohistochemistry, using an antibody to an extracellular Zip14 epitope, showed both LPS and turpentine increased abundance of Zip14 at the plasma membrane of hepatocytes. IL-6 produced increased expression of Zip14 in primary hepatocytes cultures and localization of the protein to the plasma membrane. Transfection of mZip14 cDNA into human embryonic kidney cells increased zinc uptake as measured by both a fluorescent probe for free Zn2+ and 65Zn accumulation, as well as by metallothionein mRNA induction, all indicating that Zip14 functions as a zinc importer. Zip14 was localized in plasma membrane of the transfected cells. These in vivo and in vitro experiments demonstrate that Zip14 expression is up-regulated through IL-6, and that this zinc transporter most likely plays a major role in the mechanism responsible for hypozincemia that accompanies the acute-phase response to inflammation and infection.',\n", - " 'author': ['Liuzzi, Juan P.',\n", - " 'Lichten, Louis A.',\n", - " 'Rivera, Seth',\n", - " 'Blanchard, Raymond K.',\n", - " 'Aydemir, Tolunay Beker',\n", - " 'Knutson, Mitchell D.',\n", - " 'Ganz, Tomas',\n", - " 'Cousins, Robert J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/102/19/6843\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0502257102\"}'],\n", - " 'title': ['Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response']},\n", - " {'bibcode': '2004PNAS..101.2458K',\n", - " 'abstract': 'Insulin-producing cells normally occur only in the pancreas and thymus. Surprisingly, we found widespread insulin mRNA and protein expression in different diabetic mouse and rat models, including streptozotocin-treated mice and rats, ob/ob mice, and mice fed high-fat diets. We detected in diabetic mice proinsulin- and insulin-positive cells in the liver, adipose tissue, spleen, bone marrow, and thymus; many cells also produced glucagon, somatostatin, and pancreatic polypeptide. By in situ nucleic acid hybridization, diabetic, but not nondiabetic, mouse liver exhibited insulin transcript-positive cells, indicating that insulin was synthesized by these cells. In transgenic mice that express GFP driven by the mouse insulin promoter, streptozotocin-induced diabetes led to the appearance of GFP-positive cells in liver, adipose tissue, and bone marrow; the fluorescent signals showed complete concordance with the presence of immunoreactive proinsulin. Hyperglycemia produced by glucose injections in nondiabetic mice led to the appearance of proinsulin- and insulin-positive cells within 3 days. Bone marrow transplantation experiments showed that most of the extrapancreatic proinsulin-producing cells originated from the bone marrow. Immunoreactive proinsulin- and insulin-positive cells were also detected in the liver, adipose tissue, and bone marrow of diabetic rats, indicating that extrapancreatic, extrathymic insulin production occurs in more than one species. These observations have implications for the regulation of insulin gene expression, modulation of self-tolerance by insulin gene expression, and strategies for the generation of insulin-producing cells for the treatment of diabetes.',\n", - " 'author': ['Kojima, Hideto',\n", - " 'Fujimiya, Mineko',\n", - " 'Matsumura, Kazuhiro',\n", - " 'Nakahara, Tamio',\n", - " 'Hara, Manami',\n", - " 'Chan, Lawrence'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/101/8/2458\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0308690100\"}'],\n", - " 'title': ['Extrapancreatic insulin-producing cells in multiple organs in diabetes']},\n", - " {'bibcode': '2014Natur.516..108S',\n", - " 'abstract': 'Lysosomal degradation of cytoplasmic components by autophagy is essential for cellular survival and homeostasis under nutrient-deprived conditions. Acute regulation of autophagy by nutrient-sensing kinases is well defined, but longer-term transcriptional regulation is relatively unknown. Here we show that the fed-state sensing nuclear receptor farnesoid X receptor (FXR) and the fasting transcriptional activator cAMP response element-binding protein (CREB) coordinately regulate the hepatic autophagy gene network. Pharmacological activation of FXR repressed many autophagy genes and inhibited autophagy even in fasted mice, and feeding-mediated inhibition of macroautophagy was attenuated in FXR-knockout mice. From mouse liver chromatin immunoprecipitation and high-throughput sequencing data, FXR and CREB binding peaks were detected at 178 and 112 genes, respectively, out of 230 autophagy-related genes, and 78 genes showed shared binding, mostly in their promoter regions. CREB promoted autophagic degradation of lipids, or lipophagy, under nutrient-deprived conditions, and FXR inhibited this response. Mechanistically, CREB upregulated autophagy genes, including Atg7, Ulk1 and Tfeb, by recruiting the coactivator CRTC2. After feeding or pharmacological activation, FXR trans-repressed these genes by disrupting the functional CREB-CRTC2 complex. This study identifies the new FXR-CREB axis as a key physiological switch regulating autophagy, resulting in sustained nutrient regulation of autophagy during feeding/fasting cycles.',\n", - " 'author': ['Seok, Sunmi',\n", - " 'Fu, Ting',\n", - " 'Choi, Sung-E.',\n", - " 'Li, Yang',\n", - " 'Zhu, Rong',\n", - " 'Kumar, Subodh',\n", - " 'Sun, Xiaoxiao',\n", - " 'Yoon, Gyesoon',\n", - " 'Kang, Yup',\n", - " 'Zhong, Wenxuan',\n", - " 'Ma, Jian',\n", - " 'Kemper, Byron',\n", - " 'Kemper, Jongsook Kim'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature13949\"}'],\n", - " 'title': ['Transcriptional regulation of autophagy by an FXR-CREB axis']},\n", - " {'bibcode': '1987PNAS...84.2668K',\n", - " 'abstract': \"Two species of glutamine tRNA were isolated from mouse liver and their nucleotide sequences were determined. The minor glutamine tRNA(tRNA(UmUGGln)) that possesses UmUG (where Um stands for 2'-O-methyluridine) as the anticodon sequence was found to have suppressor activity for the UAG termination codon of tobacco mosaic virus RNA in a rabbit reticulocyte in vitro translation system. The amount of this suppressor glutamine tRNA in mouse liver was 1-2% of the amount of the major glutamine tRNA(tRNA(CUGGln)) that has the CUG anticodon sequence, but it was markedly increased in NIH 3T3 cells infected with Moloney murine leukemia virus and in Ehrlich ascites cells. These results support the hypothesis that tRNA(UmUGGln) actually functions in vivo as a suppressor tRNA that recognizes the UAG termination codon located at the gag-pol gene junction of Moloney murine leukemia virus and results in the synthesis of the virus-encoded protease.\",\n", - " 'author': ['Kuchino, Yoshiyuki',\n", - " 'Beier, Hildburg',\n", - " 'Akita, Noriko',\n", - " 'Nishimura, Susumu'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/84/9/2668\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/84/9/2668\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/84/9/2668\"}'],\n", - " 'title': ['Natural UAG suppressor glutamine tRNA is elevated in mouse cells infected with Moloney murine leukemia virus.']},\n", - " {'bibcode': '1978PNAS...75.1217H',\n", - " 'abstract': 'Hybridization of mRNA to its corresponding cDNA was found to specifically inhibit translation of the mRNA in vitro. Using hybridization of globin cDNA to globin mRNA as a model system, we found that equivalent amounts of cDNA were required both for the saturation of the mRNA hybridization and for complete inhibition of globin synthesis. Also, the rate of inactivation of translation was identical to the rate of hybridization and followed the predicted kinetic form. This assay has been applied to the analysis of a set of abundant mRNAs in mouse liver. Hybridization of liver mRNA with total liver cDNA in slight excess to a low C0t value specifically inhibited translation of several major polypeptides. Melting of the hybrids prior to translation restored synthesis of these polypeptides. Moreover, we found that different liver mRNAs are inactivated with different kinetics; the results suggest that the mRNAs for the major urinary polypeptide and for albumin are the most abundant and second most abundant, respectively, in mouse liver. The general applications of this technique are discussed.',\n", - " 'author': ['Hastie, Nicholas D.', 'Held, William A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/75/3/1217\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/75/3/1217\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/75/3/1217\"}'],\n", - " 'title': ['Analysis of mRNA Populations by cDNA\\\\cdot mRNA Hybrid-Mediated Inhibition of Cell-Free Protein Synthesis']},\n", - " {'bibcode': '2010PLoSO...510585W',\n", - " 'author': ['Washburn, Michael L.',\n", - " 'Kovalev, Grigoriy I.',\n", - " 'Koroleva, Ekaterina',\n", - " 'Fu, Yang-Xin',\n", - " 'Su, Lishan'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0010585\"}'],\n", - " 'title': ['LIGHT Induces Distinct Signals to Clear an AAV-Expressed Persistent Antigen in the Mouse Liver and to Induce Liver Inflammation']},\n", - " {'bibcode': '1975PNAS...72.2644M',\n", - " 'abstract': 'When the content of cyclic AMP (cAMP) was compared in livers of a series of congenic mouse strains differing at the H-2 locus, significant variation in concentration of cAMP per unit wet weight was found among strains, and also for animals of a given strain with increasing age. For a given age, from 8 to 22 weeks, cAMP levels in liver of H-2a and H-2b genotype animals were significantly higher than that in liver of H-2k type animals. This difference was seen whether the H-2 gene was on the genetic background of strain C57BL/10, C3H, or A. Levels of cAMP in livers of H-2d animals were between those of H-2a and H-2k animals.',\n", - " 'author': ['Meruelo, Daniel', 'Edidin, Michael'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/72/7/2644\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/72/7/2644\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/72/7/2644\"}'],\n", - " 'title': [\"Association of mouse liver adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels with histocompatibility-2 genotype.\"]},\n", - " {'bibcode': '2015PLoSO..1022060C',\n", - " 'author': ['Chou, Chia-Hung',\n", - " 'Lai, Shou-Lun',\n", - " 'Ho, Cheng-Maw',\n", - " 'Lin, Wen-Hsi',\n", - " 'Chen, Chiung-Nien',\n", - " 'Lee, Po-Huang',\n", - " 'Peng, Fu-Chuo',\n", - " 'Kuo, Sung-Hsin',\n", - " 'Wu, Szu-Yuan',\n", - " 'Lai, Hong-Shiee'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0122060\"}'],\n", - " 'title': ['Lysophosphatidic Acid Alters the Expression Profiles of Angiogenic Factors, Cytokines, and Chemokines in Mouse Liver Sinusoidal Endothelial Cells']},\n", - " {'bibcode': '1969Sci...165..705B',\n", - " 'abstract': 'Deoxyribonucleic acid has been isolated from the microsomes of mouse liver homogenates under conditions designed to prevent or greatly reduce mitochondrial and nuclear contamination. The DNA rapidly incorporates tritiated thymidine, and this, together with its reannealing characteristics after thermal denaturation, shows that it is not mitochondrial or typically nuclear DNA.',\n", - " 'author': ['Bond, Howard E.',\n", - " 'Cooper, John A., II',\n", - " 'Courington, Doris P.',\n", - " 'Wood, Jeannie S.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.jstor.org/stable/1727894?origin=ads\"}'],\n", - " 'title': ['Microsome-Associated DNA']},\n", - " {'bibcode': '2001Natur.413..131Y',\n", - " 'abstract': 'Blood glucose levels are maintained by the balance between glucose uptake by peripheral tissues and glucose secretion by the liver. Gluconeogenesis is strongly stimulated during fasting and is aberrantly activated in diabetes mellitus. Here we show that the transcriptional coactivator PGC-1 is strongly induced in liver in fasting mice and in three mouse models of insulin action deficiency: streptozotocin-induced diabetes, ob/ob genotype and liver insulin-receptor knockout. PGC-1 is induced synergistically in primary liver cultures by cyclic AMP and glucocorticoids. Adenoviral-mediated expression of PGC-1 in hepatocytes in culture or in vivo strongly activates an entire programme of key gluconeogenic enzymes, including phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase, leading to increased glucose output. Full transcriptional activation of the PEPCK promoter requires coactivation of the glucocorticoid receptor and the liver-enriched transcription factor HNF-4α (hepatic nuclear factor-4α) by PGC-1. These results implicate PGC-1 as a key modulator of hepatic gluconeogenesis and as a central target of the insulin-cAMP axis in liver.',\n", - " 'author': ['Yoon, J. Cliff',\n", - " 'Puigserver, Pere',\n", - " 'Chen, Guoxun',\n", - " 'Donovan, Jerry',\n", - " 'Wu, Zhidan',\n", - " 'Rhee, James',\n", - " 'Adelmant, Guillaume',\n", - " 'Stafford, John',\n", - " 'Kahn, C. Ronald',\n", - " 'Granner, Daryl K.',\n", - " 'Newgard, Christopher B.',\n", - " 'Spiegelman, Bruce M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F35093050\"}'],\n", - " 'title': ['Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1']},\n", - " {'bibcode': '1974PNAS...71.4027T',\n", - " 'abstract': 'RNA preparations containing 70-80% mouse κ-chain mRNA have been prepared. The remainder consists of many RNA species, each of which represents a small fraction of the total RNA. The κ-chain mRNA preparation hybridizes with mouse liver DNA with bi-phasic kinetics, indicating that it consists of two fractions -\"unique\" and \"reiterated.\" Competition hybridization experiments show that the homology among the unique fractions from different mRNAs is the same as the homology among the amino acid sequences of the corresponding κ-chains. Hence, in addition to the C-region (constant-region) sequences, (most of) the V-region (variable-region) sequences are also derived from unique germ line genes. The reiterated fractions from different κ-chain mRNAs show essentially complete homology with each other. This fraction seems to consist mostly of sequences which do not code for amino-acid sequences of the secreted polypeptide chain, i.e., the \"external\" section of the mRNA molecule. It is concluded that the number of germ line genes is too small to account for the observed diversity of antibody molecules.',\n", - " 'author': ['Tonegawa, S.', 'Steinberg, C.', 'Dube, S.', 'Bernardini, A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/71/10/4027\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/71/10/4027\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/71/10/4027\"}'],\n", - " 'title': ['Evidence for Somatic Generation of Antibody Diversity']},\n", - " {'bibcode': '1980PNAS...77.6511D',\n", - " 'abstract': \"Double-stranded cDNA was synthesized from a mouse liver mRNA fraction enriched for metallothionein mRNA activity, ligated to restriction site linkers, inserted into pBR322, and used to transform Escherichia coli chi 1776. The sequence of the largest plasmid containing DNA that hybridized to metallothionein mRNA was determined and shown to contain a 380-base-pair insert that includes the entire coding region and 3' untranslated region of metallothionein-I. The metallothionein-I insert was nick-translated and used to screen both a mouse myeloma and a mouse embryo DNA library in bacteriophage lambda. A metallothionein-I genomic clone containing 13-15 kilobase pairs of mouse DNA was isolated from each library. Both contain a 3.8-kilobase-pair EcoRI fragment that hybridizes to the metallothionein-I probe. The location, size, and orientation of the metallothionein-I gene within the 3.8-kilobase-pair fragment were determined by heteroduplex and restriction mapping. The gene spans 1.1 kilobase pairs and contains at least two introns.\",\n", - " 'author': ['Durnam, Diane M.',\n", - " 'Perrin, Fabienne',\n", - " 'Gannon, Frank',\n", - " 'Palmiter, Richard D.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/77/11/6511\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/77/11/6511\"}'],\n", - " 'title': ['Isolation and characterization of the mouse metallothionein-I gene.']},\n", - " {'bibcode': '2015NatCo...6.8768B',\n", - " 'abstract': 'Although major genetic networks controlling early liver specification and morphogenesis are known, the mechanisms responsible for postnatal hepatic maturation are poorly understood. Here we employ global analyses of the mouse liver transcriptome to demonstrate that postnatal remodelling of the liver is accompanied by large-scale transcriptional and post-transcriptional transitions that are cell-type-specific and temporally coordinated. Combining detailed expression analyses with gain- and loss-of-function studies, we identify epithelial splicing regulatory protein 2 (ESRP2) as a conserved regulatory factor that controls the neonatal-to-adult switch of ~20% of splice isoforms in mouse and human hepatocytes. The normal shift in splicing coincides tightly with dramatic postnatal induction of ESRP2 in hepatocytes. We further demonstrate that forced expression of ESRP2 in immature mouse and human hepatocytes is sufficient to drive a reciprocal shift in splicing and causes various physiological abnormalities. These findings define a direct role for ESRP2 in the generation of conserved repertoires of adult splice isoforms that facilitate terminal differentiation and maturation of hepatocytes.',\n", - " 'author': ['Bhate, Amruta',\n", - " 'Parker, Darren J.',\n", - " 'Bebee, Thomas W.',\n", - " 'Ahn, Jaegyoon',\n", - " 'Arif, Waqar',\n", - " 'Rashan, Edrees H.',\n", - " 'Chorghade, Sandip',\n", - " 'Chau, Anthony',\n", - " 'Lee, Jae-Hyung',\n", - " 'Anakk, Sayeepriyadarshini',\n", - " 'Carstens, Russ P.',\n", - " 'Xiao, Xinshu',\n", - " 'Kalsotra, Auinash'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fncomms9768\"}'],\n", - " 'title': ['ESRP2 controls an adult splicing programme in hepatocytes to support postnatal liver maturation']},\n", - " {'bibcode': '1993PNAS...90.2965P',\n", - " 'abstract': 'Inductions of detoxication (phase 2) enzymes, such as glutathione transferases and NAD(P)H:(quinone-acceptor) oxidoreductase, are a major mechanism for protecting animals and their cells against the toxic and neoplastic effects of carcinogens. These inductions result from enhanced transcription, and they are evoked by diverse chemical agents: oxidizable diphenols and phenylenediamines; Michael reaction acceptors; organic isothiocyanates; other electrophiles--e.g., alkyl and aryl halides; metal ions--e.g., HgCl2 and CdCl2; trivalent arsenic derivatives; vicinal dimercaptans; organic hydroperoxides and hydrogen peroxide; and 1,2-dithiole-3-thiones. The molecular mechanisms of these inductions were analyzed with the help of a construct containing a 41-bp enhancer element derived from the 5\\' upstream region of the mouse liver glutathione transferase Ya subunit gene ligated to the 5\\' end of the isolated promoter region of this gene, and inserted into a plasmid containing a human growth hormone reporter gene. When this construct was transfected into Hep G2 human hepatoma cells, the concentrations of 28 compounds (from the above classes) required to double growth hormone production, and the concentrations required to double quinone reductase specific activities in Hepa 1c1c7 cells, spanned a range of four orders of magnitude but were closely linearly correlated. Six compounds tested were inactive in both systems. A 26-bp subregion of the above enhancer oligonucleotide (containing the two tandem \"AP-1-like\" sites but lacking the preceding ETS protein binding sequence) was considerably less responsive to the same inducers. We conclude that the 41-bp enhancer element mediates most, if not all, of the phase 2 enzyme inducer activity of all of these widely different classes of compounds.',\n", - " 'author': ['Prestera, Tory',\n", - " 'Holtzclaw, W. David',\n", - " 'Zhang, Yuesheng',\n", - " 'Talalay, Paul'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/90/7/2965\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/90/7/2965\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/90/7/2965\"}'],\n", - " 'title': ['Chemical and molecular regulation of enzymes that detoxify carcinogens.']},\n", - " {'bibcode': '1974Natur.252..495K',\n", - " 'abstract': 'α-FOETOPROTEIN (αFP) is a dominant serum protein in many mammalian species during embryonic and early postnatal life. It is hardly detectable in the adult body but is often found in an elevated quantity in the serum of individuals with hepatocarcinomas and teratocarcinomas1-5.',\n", - " 'author': ['Koga, K.', \"O'Keefe, D. W.\", 'Iio, T.', 'Tamaoki, T.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F252495a0\"}'],\n", - " 'title': ['Transcriptional control of α-foetoprotein synthesis in developing mouse liver']},\n", - " {'bibcode': '1968Natur.220...76L',\n", - " 'abstract': 'THERE are at least two endonucleases in mouse liver. One of these, probably identical to the enzyme in rat liver described by Curtis et al.1,2, at an optimum pH of 7, hydrolyses RNA and DNA denatured by heat, preferentially to native DNA (personal data). The other is an acid deoxyribonuclease (DNase), the partial purification and properties of which have been described elsewhere3. These properties are very similar to those of the acid DNases extracted from several organs of higher mammals4. Although these acid DNases are widely distributed, their role in the cell is still unknown. A relationship may exist between the activity of these enzymes and the replication of DNA5. We have investigated variations in acid DNase activity in mice of different ages. A nuclear fraction and a cytoplasmic fraction containing the mitochondria and lysosomes were isolated from liver cells. The nuclear activity is high at 24-48 h and decreases markedly during the first month of life, while the activity of the cyboplasmic fraction remains constant.',\n", - " 'author': ['Lesca, Pierre'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F220076a0\"}'],\n", - " 'title': ['Age Variations of Acid Deoxyribonuclease Activity in Mouse Liver Nuclei']},\n", - " {'bibcode': '1985JTEH...15..395C',\n", - " 'author': ['Charles, A. K.',\n", - " 'Rosenbaum, D. P.',\n", - " 'Ashok, L.',\n", - " 'Abraham, R.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1080%2F15287398509530667\"}'],\n", - " 'title': ['Uptake and disposition of mirex in hepatocytes and subcellular fractions in CD1 mouse liver']},\n", - " {'bibcode': '1998AcAC..372..241M',\n", - " 'abstract': 'A method for determining concentration of metallothionein (MT) isoforms in mouse liver was established by using capillary zone electrophoresis (CZE), and carbonic anhydrase was used as an internal standard. The cytosol fraction was heated at 100°C for 1 min, and the supernatant was applied directly to CZE after filtration. Both MT-1 and MT-2 isoforms were identified from the migration times of purified MT isoforms, and the peaks were definitely identified from the other peaks. In addition, carbonic anhydrase was adopted as an internal standard. Based on standard curves of purified MT isoforms, concentrations of MT isoforms in the liver were determined from the estimates of peak areas. In control mouse liver, MT-1 isoform was detected at 48.5±25.4 μg/g wet weight, and MT-2 isoform was 154.0±39.7 μg/g. Twenty-four hours after zinc injection, MT-1 increased to 773.7±374.3 μg/g, and MT-2 was 487.2±207.1 μg/g. The addition of ascorbic acid to the homogenizing medium resulted in the decrease of MT isoforms in mouse liver. From these findings, we concluded that CZE analysis using a polyacrylamide-coated tube at neutral pH makes quantitation of MT isoforms in mouse liver possible.',\n", - " 'author': ['Minami, Takeshi',\n", - " 'Tohno, Yoshiyuki',\n", - " 'Okazaki, Yuko',\n", - " 'Kubo, Kanenobu',\n", - " 'Otaki, Noriko',\n", - " 'Kimura, Masami'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2FS0003-2670%2898%2900337-7\"}'],\n", - " 'title': ['Quantitation of metallothionein isoforms in mouse liver on capillary zone electrophoresis']},\n", - " {'bibcode': '1961Natur.190..550C',\n", - " 'abstract': 'IN recent years, a number of reports have appeared concerning the antigenicity of mammalian and bacterial deoxyribonucleic acid. Evidence has been presented indicating that complement-fixing1 and precipitating2 antibodies may be produced by the injection of such preparations into experimental animals. In addition, serum from patients with systemic lupus erythematosus has been shown to react immunologically with highly purified deoxyribonucleic acid from a variety of sources3. The present communication concerns the production of antisera by the immunization of rabbits with deoxyribonucleic acid preparations isolated from mouse liver and from cells of the Ehrlich ascites tumour. The results obtained indicate that anti-tumour cell deoxyribonucleic acid serum has an inhibitory effect on the growth of the tumour in vivo.',\n", - " 'author': ['Colter, J. S.', 'Ellem, K. A. O.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F190550b0\"}'],\n", - " 'title': ['Antigenicity of Deoxyribonucleic Acids from Mouse Liver and from the Ehrlich Ascites Tumour']},\n", - " {'bibcode': '1967Natur.215..756A',\n", - " 'abstract': 'IT is well known that the renal tissue which remains after unilateral nephrectomy is effective in excretion and there is no increase of excreted metabolites in the blood serum a few hours after the operation. Changes in the other body functions (apart from the excretory function of the remaining kidney) after unilateral nephrectomy are still little known. A decrease in the dry weight of the liver1 and heart2 has been observed 1 month after unilateral nephrectomy in mice. This suggests that kidneys take part not only in the regulation of erythropoiesis by erythropoietin but also in the regulation of the growth of other tissues.',\n", - " 'author': ['Arasimowicz, C.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F215756a0\"}'],\n", - " 'title': ['Repression of DNA Synthesis in Mouse Liver Cells after Unilateral Nephrectomy']},\n", - " {'bibcode': '1983JESHB..18..393M',\n", - " 'author': ['Mostafa, M. H.',\n", - " 'El-Bassiouni, E. A.',\n", - " 'El-Sewedy, S. M.',\n", - " 'El-Zoghby, S. M.',\n", - " 'Ramadan, M.',\n", - " 'Abdel-Tawab, G. A.',\n", - " 'El-Sebae, A. H.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1080%2F03601238309372377\"}'],\n", - " 'title': ['Effect of some xenobiotics on kynurenine hydrolase and kynurenine aminotransferase of mouse liver']},\n", - " {'bibcode': '1967NYASA.145..533H',\n", - " 'author': ['Hampton, J. C.', 'Rosario, B.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1111%2Fj.1749-6632.1967.tb50257.x\"}'],\n", - " 'title': ['The Distribution of Colloidal Thorium Dioxide in Mouse Liver after Intravenous Injection']},\n", - " {'bibcode': '1993AcCrA..49C.116Z',\n", - " 'author': ['Zhao, Q.', 'Hayes, J.', 'Wolf, R.', 'Driessen, H.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1107%2FS010876737809666X\"}'],\n", - " 'title': ['Preliminary crystallographic studies of mouse liver glutathioneS-transferase Yb1']},\n", - " {'bibcode': '2018NatSR...812142H',\n", - " 'abstract': 'Fatty acid amide hydrolase (FAAH) is an important enzyme for lipid metabolism and an interesting pharmacological target, given its role in anandamide breakdown. The FAAH-/- genotype is the most widely used mouse model to investigate the effects of a complete pharmacological inhibition of this enzyme. In this paper, we explore, by means of label-free SWATH proteomics, the changes in protein expression occurring in the liver of FAAH-/- knockout (KO) mice. We identified several altered biological processes and pathways, like fatty acid synthesis and glycolysis, which explain the observed phenotype of this mouse. We also observed the alteration of other proteins, like carboxylesterases and S-methyltransferases, apparently not immediately related to FAAH, but known to have important biological roles. Our study, reporting more than 3000 quantified proteins, offers an in-depth analysis of the liver proteome of this model.',\n", - " 'author': ['Hamid, Zeeshan', 'Summa, Maria', 'Armirotti, Andrea'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-018-30553-z\"}'],\n", - " 'title': ['A Swath Label-Free Proteomics insight into the Faah-/- Mouse Liver']},\n", - " {'bibcode': '1977JChPh..66.2235C',\n", - " 'author': ['Chen, F. C.', 'Chu, B.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1063%2F1.434150\"}'],\n", - " 'title': ['Dynamics of mouse-liver DNA by single-clipped photon correlation']},\n", - " {'bibcode': '2010ChJOL..28.1180C',\n", - " 'abstract': 'Blooms of toxin-producing cyanobacteria have become increasingly common in the surface water of the world. In this study, we studied the dose- and time-dependent effects of a microcystin (MC) extract of cyanobacteria from Dianchi Lake in China on liver weight/body weight ratio and superoxide dismutase (SOD), lactate dehydrogenase (LDH) and glutathione peroxidase (GSH-Px) activities in mouse liver. We found that exposure to the cyanobacterial extract (CE) resulted in increase in liver weight/body weight ratio in a dose-dependent manner, and the mouse liver reached the maximum size at 1 h post-exposure (pe). SOD activity in mouse liver decreased in a dose-dependent manner, and time course study indicated that it decreased significantly at 1 and 2 h pe, and resumed at 3 h pe as compared to control. CE caused LDH activity in the livers of mice to decrease in a dose- and time-dependent manner except a small increase in 30 min pe mice. GSH-Px activity increased in a dose-dependent manner, and was higher than that in the control over the 3 h observation period. The present findings suggest that oxidative damage may be involved in the toxicity of microcystins on mouse.',\n", - " 'author': ['Chen, Jianzhong',\n", - " 'Liu, Zhili',\n", - " 'Zhou, Guoqing',\n", - " 'Han, Zhiping',\n", - " 'Zhang, Haiyang',\n", - " 'Zhang, Yixiang'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1007%2Fs00343-010-9911-7\"}'],\n", - " 'title': ['Effect of cyanobacteria extract on some associated enzymes in mouse liver in vivo']},\n", - " {'bibcode': '1954Natur.174..841C',\n", - " 'abstract': 'PREVIOUS work1 has shown that after intravenous injection of colloidal 3 : 4 benzpyrene the bulk of the carcinogen is held in the liver. Excretion takes place over approximately twenty-four hours, the hydrocarbon having undergone metabolic oxidation to one or other of two compounds labelled BpX1 or BpX2. These are oxidation products and have been characterized by physical methods and analogy with known derivatives of other polycyclic hydrocarbons as being: 8(OR1) - 9(OH) - 8,9 dihydro 3 : 4 benzpyrene and 8(OR1) - 9(OR2) - 8,9 dihydro benzpyrene respectively. The groups R1 and R2 are, at present, unidentified radicals. It has also been found1,2 that during metabolic oxidation the products derived from 3 : 4 benzpyrene are firmly bound within the tissues where they are formed.',\n", - " 'author': ['Calcutt, G.', 'Payne, S.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F174841a0\"}'],\n", - " 'title': ['Intracellular Sites of Metabolism of 3 : 4 Benzpyrene in Mouse Liver']},\n", - " {'bibcode': '1977PNAS...74.3879J',\n", - " 'abstract': 'Cells from CBA fetal mouse liver formed pure or mixed erythroid colonies in semisolid agarculture after stimulation by medium conditioned by pokeweed mitogen-stimulated mouse spleen cells. In general shape, the erythroid colonies resembled typical 7-day single or multiple (burst) colonies. However one-third to one-half contained, in addition to erythroid cells, macrophages and neutrophils and, less commonly, megakaryocytes or eosinophils. Culture of micro manipulated single colony-forming cells showed these erythroid colonies to be clones. Colony-forming cells declined in frequency with advancing fetal age, but low numbers were detectable in adult bone marrow. Assays of spleen conditioned medium in polycythemic mice failed to detect erythropoietin; the cloning system may detect a fetal type of erythropoietin-independent, erythropoietic cell since few were detected in adult marrow.',\n", - " 'author': ['Johnson, G. R.', 'Metcalf, D.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/74/9/3879\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/74/9/3879\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/74/9/3879\"}'],\n", - " 'title': ['Pure and mixed erythroid colony formation in vitro stimulated by spleen conditioned medium with no detectable erythropoietin.']},\n", - " {'bibcode': '2020FrP.....8..124M',\n", - " 'abstract': 'Ultrasound imaging is a well-established clinical imaging technique providing real-time, quantitative anatomical and physiological information in humans. The lack of ionising radiation and relative low purchase and maintenance costs results in it being one of the most frequently used clinical imaging techniques with increasing use for guiding interventional clinical procedures. Until 20 years ago, translation of clinical ultrasound practices to preclinical applications proved a significant technological challenge due to the smaller size (25g vs 70kg) and rapid conscious heart-rate (500-700bpm vs 60bpm) of the mouse requiring an increase in both spatial and temporal resolution of 10-20 fold in order to achieve diagnostic information comparable to that achieved clinically. Since 2000 (Foster et al 2000), these technological challenges have been overcome and commercial high frequency ultrasound scanners have enabled longitudinal studies of disease progression in small animal models to be undertaken. Adult, neonatal and embryonic rats, mice and zebrafish can now be scanned with resolutions down to 30 microns and with sufficient temporal resolution to enable cardiac abnormalities in all these species to be identified. In mice and rats, quantification of blood flow in cardiac chambers, renal, liver and uterine vessels and intra-mural tissue movements can be measured using the Doppler technique. Ultrasonic contrast microbubbles used routinely for clinical applications are now being further developed to include targeting mechanisms and drug-loading capabilities and the results in animal models bode well for translation for targeted drug delivery in humans.',\n", - " 'author': ['Moran, Carmel M.', 'Thomson, Adrian J. W.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.3389%2Ffphy.2020.00124\"}'],\n", - " 'title': ['Preclinical Ultrasound Imaging - a review of techniques and imaging applications']},\n", - " {'bibcode': '1992PNAS...89.5645F',\n", - " 'abstract': 'Pancreatic cancer is one of the most intractable and least understood of all human cancers. Pancreatic cancers is the fourth-leading cause of cancer-related mortality in the United States with less than 2% of the patients surviving for 5 yr. In an effort to help develop more effective treatment modalities for pancreatic cancer and improve detection, we report an animal model for individual human pancreatic-cancer patients. The model involves orthotopic transplantation of histologically intact pancreatic-cancer specimens to the nude-mouse pancreas, which can result in models that resemble the clinical picture including (i) extensive local tumor growth, (ii) extension of the locally growing human pancreatic cancer to the nude-mouse stomach and duodenum, (iii) metastases of the human pancreatic tumor to the nude-mouse liver and regional lymph nodes, and (iv) distant metastases of the human pancreatic tumor to the nude-mouse adrenal gland, diaphragm, and mediastinal lymph nodes. In a series of five patient cases, a 100% take rate has been demonstrated, and of 17 mice transplanted, 15 supported tumor growth. Immunohistochemical analysis of the antigenic phenotype of the transplanted human pancreatic tumors showed a similar pattern of expression of two different human tumor-associated antigens, such as tumor-associated glycoprotein 72 and carcinoembryonic antigen in the transplanted tumors when compared with the original surgical biopsy, suggesting similarity between the two. This model should, therefore, prove valuable for treatment evaluation of individual cancer patients, as well as for evaluation of experimental treatment modalities for this disease.',\n", - " 'author': ['Fu, Xinyu', 'Guadagni, Fiorella', 'Hoffman, Robert M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/89/12/5645\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/89/12/5645\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/89/12/5645\"}'],\n", - " 'title': ['A metastatic nude-mouse model of human pancreatic cancer constructed orthotopically with histologically intact patient specimens.']},\n", - " {'bibcode': '1971Sci...173..158H',\n", - " 'abstract': \"Under normal conditions of DNA renaturation, about 60 percent of mouse DNA fragments renature at a rate consistent with their being present only once per sperm. These nonrepeated sequences (also called single-copy or unique) may be used in RNA-DNA hybridization experiments to provide quantitative estimates of RNA diversity. About 10 percent of the mouse single-copy sequences are transcribed in mouse brain tissue. Estimates of about 3 percent were obtained for mouse liver and kidney RNA's. If only one of the complementary DNA strands is transcribed, this hybridization value implies that the equivalent of at least 300,000 different sequences of 1000 nucleotides are expressed in mouse brain tissue. It is suggested that the large amount of DNA in mammals is functionally important, and that a substantial proportion of the genome is expressed in the brain.\",\n", - " 'author': ['Hahn, William E.', 'Laird, Charles D.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.jstor.org/stable/1732216?origin=ads\"}'],\n", - " 'title': ['Transcription of Nonrepeated DNA in Mouse Brain']},\n", - " {'bibcode': '2015Natur.527..329H',\n", - " 'abstract': 'Ever since Stephen Paget’s 1889 hypothesis, metastatic organotropism has remained one of cancer’s greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.',\n", - " 'author': ['Hoshino, Ayuko',\n", - " 'Costa-Silva, Bruno',\n", - " 'Shen, Tang-Long',\n", - " 'Rodrigues, Goncalo',\n", - " 'Hashimoto, Ayako',\n", - " 'Tesic Mark, Milica',\n", - " 'Molina, Henrik',\n", - " 'Kohsaka, Shinji',\n", - " 'di Giannatale, Angela',\n", - " 'Ceder, Sophia',\n", - " 'Singh, Swarnima',\n", - " 'Williams, Caitlin',\n", - " 'Soplop, Nadine',\n", - " 'Uryu, Kunihiro',\n", - " 'Pharmer, Lindsay',\n", - " 'King, Tari',\n", - " 'Bojmar, Linda',\n", - " 'Davies, Alexander E.',\n", - " 'Ararso, Yonathan',\n", - " 'Zhang, Tuo',\n", - " 'Zhang, Haiying',\n", - " 'Hernandez, Jonathan',\n", - " 'Weiss, Joshua M.',\n", - " 'Dumont-Cole, Vanessa D.',\n", - " 'Kramer, Kimberly',\n", - " 'Wexler, Leonard H.',\n", - " 'Narendran, Aru',\n", - " 'Schwartz, Gary K.',\n", - " 'Healey, John H.',\n", - " 'Sandstrom, Per',\n", - " 'Jørgen Labori, Knut',\n", - " 'Kure, Elin H.',\n", - " 'Grandgenett, Paul M.',\n", - " 'Hollingsworth, Michael A.',\n", - " 'de Sousa, Maria',\n", - " 'Kaur, Sukhwinder',\n", - " 'Jain, Maneesh',\n", - " 'Mallya, Kavita',\n", - " 'Batra, Surinder K.',\n", - " 'Jarnagin, William R.',\n", - " 'Brady, Mary S.',\n", - " 'Fodstad, Oystein',\n", - " 'Muller, Volkmar',\n", - " 'Pantel, Klaus',\n", - " 'Minn, Andy J.',\n", - " 'Bissell, Mina J.',\n", - " 'Garcia, Benjamin A.',\n", - " 'Kang, Yibin',\n", - " 'Rajasekhar, Vinagolu K.',\n", - " 'Ghajar, Cyrus M.',\n", - " 'Matei, Irina',\n", - " 'Peinado, Hector',\n", - " 'Bromberg, Jacqueline',\n", - " 'Lyden, David'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"data\", \"url\": \"http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse68919\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"data\", \"url\": \"https://doi.org/10.6084/m9.figshare.1569781\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature15756\"}'],\n", - " 'title': ['Tumour exosome integrins determine organotropic metastasis']},\n", - " {'bibcode': '2016PLoSO..1165787H',\n", - " 'author': ['Huang, Jia-Hui',\n", - " 'Zhang, Cheng',\n", - " 'Zhang, Da-Gang',\n", - " 'Li, Lu',\n", - " 'Chen, Xi',\n", - " 'Xu, De-Xiang'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0165787\"}'],\n", - " 'title': ['Rifampicin-Induced Hepatic Lipid Accumulation: Association with Up-Regulation of Peroxisome Proliferator-Activated Receptor γ in Mouse Liver']},\n", - " {'bibcode': '2010ANSNN...1a5015T',\n", - " 'abstract': 'In this work, we present results of membrane proteome profiling from mouse liver tissues using a gel-based approach in combination with 2DnanoLC-Q-TOF-MS/MS. Following purification of the membrane fraction, SDS-PAGE was carried out as a useful separation step. After staining, gels with protein bands were cut, reduced, alkylated and trypsin-digested. The peptide mixtures extracted from each gel slice were fractionated by two-dimensional nano liquid chromatography (2DnanoLC) coupled online with tandem mass spectrometry analysis (NanoESI-Q-TOF-MS/MS). The proteins were identified by MASCOT search against a mouse protein database using a peptide and fragment mass tolerance of ±0.5\\u2009Da. Protein identification was carried out using a Mowse scoring algorithm with a confidence level of 95% and processed by MSQuant v1.5 software for further validation. In total, 318 verified membrane proteins from mouse liver tissues were identified; 66.67% of them (212 proteins) contained at least one or more transmembrane domains predicted by the SOSUI program and 43 were found to be unique microsome membranes. Furthermore, GRAVY values of membrane proteins varied in the range -1.1276 to 0.9016 and only 31 (9.76%) membrane proteins had positive values. The functions and subcellular locations of the identified proteins were categorized as well, according to universal GO annotations.',\n", - " 'author': ['Thanh Tran, The', 'Phan, Van Chi'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1088%2F2043-6254%2F1%2F1%2F015015\"}'],\n", - " 'title': ['Separation and identification of mouse liver membrane proteins using a gel-based approach in combination with 2DnanoLC-Q-TOF-MS/MS']},\n", - " {'bibcode': '2016NatSR...624023L',\n", - " 'abstract': 'Sexually dimorphic gene expression is commonly found in the liver, and many of these genes are linked to different incidences of liver diseases between sexes. However, the mechanism of sexually dimorphic expression is still not fully understood. In this study, a pCAG-eGFP transgenic mouse strain with a specific transgene integration site in the Akr1A1 locus presented male-biased EGFP expression in the liver, and the expression was activated by testosterone during puberty. The integration of the pCAG-eGFP transgene altered the epigenetic regulation of the adjacent chromatin, including increased binding of STAT5b, a sexually dimorphic expression regulator, and the transformation of DNA methylation from hypermethylation into male-biased hypomethylation. Through this de novo sexually dimorphic expression of the transgene, the Akr1A1eGFP mouse provides a useful model to study the mechanisms and the dynamic changes of sexually dimorphic gene expression during either development or pathogenesis of the liver.',\n", - " 'author': ['Lai, Cheng-Wei',\n", - " 'Chen, Hsiao-Ling',\n", - " 'Tsai, Tung-Chou',\n", - " 'Chu, Te-Wei',\n", - " 'Yang, Shang-Hsun',\n", - " 'Chong, Kowit-Yu',\n", - " 'Chen, Chuan-Mu'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep24023\"}'],\n", - " 'title': ['Sexually Dimorphic Expression of eGFP Transgene in the Akr1A1 Locus of Mouse Liver Regulated by Sex Hormone-Related Epigenetic Remodeling']},\n", - " {'bibcode': '2014PLoSO...986795S',\n", - " 'author': ['Szalowska, Ewa',\n", - " 'van der Burg, Bart',\n", - " 'Man, Hai-Yen',\n", - " 'Hendriksen, Peter J. M.',\n", - " 'Peijnenburg, Ad A. C. M.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0086795\"}'],\n", - " 'title': ['Model Steatogenic Compounds (Amiodarone, Valproic Acid, and Tetracycline) Alter Lipid Metabolism by Different Mechanisms in Mouse Liver Slices']},\n", - " {'bibcode': '2021NatSR..1113766A',\n", - " 'abstract': 'Sexual dimorphism in gene regulation, including DNA methylation, is the main driver of sexual dimorphism in phenotypes. However, the questions of how and when sex shapes DNA methylation remain unresolved. Recently, using mice with different combinations of genetic and phenotypic sex, we identified sex-associated differentially methylated regions (sDMRs) that depended on the sex phenotype. Focusing on a panel of validated sex-phenotype dependent male- and female-biased sDMRs, we tested the developmental dynamics of sex bias in liver methylation and the impacts of mutations in the androgen receptor, estrogen receptor alpha, or the transcriptional repressor Bcl6 gene. True hermaphrodites that carry both unilateral ovaries and contralateral testes were also tested. Our data show that sex bias in methylation either coincides with or follows sex bias in the expression of sDMR-proximal genes, suggesting that sex bias in gene expression may be required for demethylation at certain sDMRs. Global ablation of AR, ESR1, or a liver-specific loss of BCL6, all alter sDMR methylation, whereas presence of both an ovary and a testis delays the establishment of male-type methylation levels in hermaphrodites. Moreover, the Bcl6-LKO shows dissociation between expression and methylation, suggesting a distinct role of BCL6 in demethylation of intragenic sDMRs.',\n", - " 'author': ['AlOgayil, Najla',\n", - " 'Bauermeister, Klara',\n", - " 'Galvez, Jose Hector',\n", - " 'Venkatesh, Varun S.',\n", - " 'Zhuang, Qinwei Kim-wee',\n", - " 'Chang, Matthew L.',\n", - " 'Davey, Rachel A.',\n", - " 'Zajac, Jeffrey D.',\n", - " 'Ida, Kinuyo',\n", - " 'Kamiya, Akihide',\n", - " 'Taketo, Teruko',\n", - " 'Bourque, Guillaume',\n", - " 'Naumova, Anna K.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-021-93216-6\"}'],\n", - " 'title': ['Distinct roles of androgen receptor, estrogen receptor alpha, and BCL6 in the establishment of sex-biased DNA methylation in mouse liver']},\n", - " {'bibcode': '2008JNR....10..263W',\n", - " 'abstract': 'In this work, the acute oral toxicity of 20- and 120-nm ZnO powder at doses of 1-, 2-, 3-, 4-, 5-g/kg body weight was evaluated referred to the OECD guidelines for testing of chemicals. As the results, both 20- and 120-nm ZnO belong to non-toxic chemicals according to the Globally Harmonized Classification System (GHS) for the classification of chemicals. The distribution determination showed that Zn was mainly retained in the bone, kidney and pancreas after 20- and 120-nm ZnO administration. However, the results of blood measurement suggest that the increase in blood viscosity could be induced by low and median dose of 20-nm ZnO but high dose of 120-nm ZnO. The pathological examination showed that the 120-nm ZnO treated mice had dose-effect pathological damages in stomach, liver, heart and spleen, whereas, 20-nm ZnO displayed negative dose-effect damages in liver, spleen and pancreas. Therefore, we conclude that the liver, spleen, heart, pancreas and bone are the target organs for 20- and 120-nm ZnO oral exposure. More attention should be paid on the potential toxicity induced by low dose of 20-nm ZnO oral exposure.',\n", - " 'author': ['Wang, Bing',\n", - " 'Feng, Weiyue',\n", - " 'Wang, Meng',\n", - " 'Wang, Tiancheng',\n", - " 'Gu, Yiqun',\n", - " 'Zhu, Motao',\n", - " 'Ouyang, Hong',\n", - " 'Shi, Junwen',\n", - " 'Zhang, Fang',\n", - " 'Zhao, Yuliang',\n", - " 'Chai, Zhifang',\n", - " 'Wang, Haifang',\n", - " 'Wang, Jing'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1007%2Fs11051-007-9245-3\"}'],\n", - " 'title': ['Acute toxicological impact of nano- and submicro-scaled zinc oxide powder on healthy adult mice']},\n", - " {'bibcode': '2022SciA....8.6901H',\n", - " 'abstract': 'Hemophilia is a hereditary disease that remains incurable. Although innovative treatments such as gene therapy or bispecific antibody therapy have been introduced, substantial unmet needs still exist with respect to achieving long-lasting therapeutic effects and treatment options for inhibitor patients. Antithrombin (AT), an endogenous negative regulator of thrombin generation, is a potent genome editing target for sustainable treatment of patients with hemophilia A and B. In this study, we developed and optimized lipid nanoparticles (LNPs) to deliver Cas9 mRNA along with single guide RNA that targeted AT in the mouse liver. The LNP-mediated CRISPR-Cas9 delivery resulted in the inhibition of AT that led to improvement in thrombin generation. Bleeding-associated phenotypes were recovered in both hemophilia A and B mice. No active off-targets, liver-induced toxicity, and substantial anti-Cas9 immune responses were detected, indicating that the LNP-mediated CRISPR-Cas9 delivery was a safe and efficient approach for hemophilia therapy.We showed that lipid nanoparticle–packed CRISPR- mediated antithrombin gene editing offers a sustainable and safe hemophilia therapy.',\n", - " 'author': ['Han, Jeong Pil',\n", - " 'Kim, MinJeong',\n", - " 'Choi, Beom Seok',\n", - " 'Lee, Jeong Hyeon',\n", - " 'Lee, Geon Seong',\n", - " 'Jeong, Michaela',\n", - " 'Lee, Yeji',\n", - " 'Kim, Eun-Ah',\n", - " 'Oh, Hye-Kyung',\n", - " 'Go, Nanyeong',\n", - " 'Lee, Hyerim',\n", - " 'Lee, Kyu Jun',\n", - " 'Kim, Un Gi',\n", - " 'Lee, Jae Young',\n", - " 'Kim, Seokjoong',\n", - " 'Chang, Jun',\n", - " 'Lee, Hyukjin',\n", - " 'Song, Dong Woo',\n", - " 'Yeom, Su Cheong'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fsciadv.abj6901\"}'],\n", - " 'title': ['In vivo delivery of CRISPR-Cas9 using lipid nanoparticles enables antithrombin gene editing for sustainable hemophilia A and B therapy']},\n", - " {'bibcode': '2003MedPh..30.1241G',\n", - " 'abstract': 'Inductively coupled solenoid coils fitting to objects in the size of mice or rats were developed to adapt modern whole‑body MR scanners featuring sufficient gradient strength for animal examinations with high spatial resolution. Homogenous receiver characteristics is achievable over almost the whole inner region of the solenoid coils. The SNR can be increased by a factor 2 to 6 with the adapting coils for examinations using the head coil as connected receiver. Standard sequences on clinical 1.5 T scanners can be applied with adapted transmitter voltages. For example, a SNR value of about 30 is achievable in a mouse liver after 10 minutes measuring time using a 2‑D spin echo imaging sequence and a size of for the picture elements.',\n", - " 'author': ['Graf, Hansjörg',\n", - " 'Martirosian, Petros',\n", - " 'Schick, Fritz',\n", - " 'Grieser, Marco',\n", - " 'Bellemann, Matthias E.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1118%2F1.1576227\"}'],\n", - " 'title': ['Inductively coupled rf coils for examinations of small animals and objects in standard whole‑body MR scanners']},\n", - " {'bibcode': '2010PNAS..10716958D',\n", - " 'abstract': 'S-nitrosylation, the selective posttranslational modification of protein cysteine residues to form S-nitrosocysteine, is one of the molecular mechanisms by which nitric oxide influences diverse biological functions. In this study, unique MS-based proteomic approaches precisely pinpointed the site of S-nitrosylation in 328 peptides in 192 proteins endogenously modified in WT mouse liver. Structural analyses revealed that S-nitrosylated cysteine residues were equally distributed in hydrophobic and hydrophilic areas of proteins with an average predicted pKa of 10.01 ± 2.1. S-nitrosylation sites were over-represented in α-helices and under-represented in coils as compared with unmodified cysteine residues in the same proteins (χ2 test, P < 0.02). A quantile-quantile probability plot indicated that the distribution of S-nitrosocysteine residues was skewed toward larger surface accessible areas compared with the unmodified cysteine residues in the same proteins. Seventy percent of the S-nitrosylated cysteine residues were surrounded by negatively or positively charged amino acids within a 6-Å distance. The location of cysteine residues in α-helices and coils in highly accessible surfaces bordered by charged amino acids implies site directed S-nitrosylation mediated by protein-protein or small molecule interactions. Moreover, 13 modified cysteine residues were coordinated with metals and 15 metalloproteins were endogenously modified supporting metal-catalyzed S-nitrosylation mechanisms. Collectively, the endogenous S-nitrosoproteome in the liver has structural features that accommodate multiple mechanisms for selective site-directed S-nitrosylation.',\n", - " 'author': ['Doulias, Paschalis-Thomas',\n", - " 'Greene, Jennifer L.',\n", - " 'Greco, Todd M.',\n", - " 'Tenopoulou, Margarita',\n", - " 'Seeholzer, Steve H.',\n", - " 'Dunbrack, Roland L.',\n", - " 'Ischiropoulos, Harry'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/107/39/16958\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1008036107\"}'],\n", - " 'title': ['Structural profiling of endogenous S-nitrosocysteine residues reveals unique features that accommodate diverse mechanisms for protein S-nitrosylation']},\n", - " {'bibcode': '2000PNAS...97.3826H',\n", - " 'abstract': 'α-Thujone is the toxic agent in absinthe, a liqueur popular in the 19th and early 20th centuries that has adverse health effects. It is also the active ingredient of wormwood oil and some other herbal medicines and is reported to have antinociceptive, insecticidal, and anthelmintic activity. This study elucidates the mechanism of α-thujone neurotoxicity and identifies its major metabolites and their role in the poisoning process. Four observations establish that α-thujone is a modulator of the γ-aminobutyric acid (GABA) type A receptor. First, the poisoning signs (and their alleviation by diazepam and phenobarbital) in mice are similar to those of the classical antagonist picrotoxinin. Second, a strain of Drosophila specifically resistant to chloride channel blockers is also tolerant to α-thujone. Third, α-thujone is a competitive inhibitor of [3H]ethynylbicycloorthobenzoate binding to mouse brain membranes. Most definitively, GABA-induced peak currents in rat dorsal root ganglion neurons are suppressed by α-thujone with complete reversal after washout. α-Thujone is quickly metabolized in vitro by mouse liver microsomes with NADPH (cytochrome P450) forming 7-hydroxy-α-thujone as the major product plus five minor ones (4-hydroxy-α-thujone, 4-hydroxy-β-thujone, two other hydroxythujones, and 7,8-dehydro-α-thujone), several of which also are detected in the brain of mice treated i.p. with α-thujone. The major 7-hydroxy metabolite attains much higher brain levels than α-thujone but is less toxic to mice and Drosophila and less potent in the binding assay. The other metabolites assayed are also detoxification products. Thus, α-thujone in absinthe and herbal medicines is a rapid-acting and readily detoxified modulator of the GABA-gated chloride channel.',\n", - " 'author': ['Höld, Karin M.',\n", - " 'Sirisoma, Nilantha S.',\n", - " 'Ikeda, Tomoko',\n", - " 'Narahashi, Toshio',\n", - " 'Casida, John E.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/97/8/3826\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/97/8/3826\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/97/8/3826\"}'],\n", - " 'title': ['α-Thujone (the active component of absinthe): γ-Aminobutyric acid type A receptor modulation and metabolic detoxification']},\n", - " {'bibcode': '2021AngCh.133.4957M',\n", - " 'abstract': 'A bio‑coreactant‑enhanced electrochemiluminescence (ECL) microscopy realizes the ECL imaging of intracellular structure and dynamic transport. This microscopy uses Ru(bpy)32+ as the electrochemical molecular antenna connecting extracellular and intracellular environments, and uses intracellular biomolecules as the coreactants of ECL reactions via a \"catalytic route\". Accordingly, intracellular structures are identified without using multiple labels, and autophagy involving DNA oxidative damage is detected using nuclear ECL signals. A time‑resolved image sequence discloses the universal edge effect of cellular electroporation due to the influence of the geometric properties of cell membranes on the induced transmembrane voltage. The dynamic transport of Ru(bpy)33+ in the different cellular compartments unveils the heterogeneous intracellular diffusivity correlating with the actin cytoskeleton. In addition to single‑cell studies, the bio‑coreactant‑enhanced ECL microscopy is used to image a slice of a mouse liver and a colony of Shewanella oneidensis MR‑1.',\n", - " 'author': ['Ma, Cheng',\n", - " 'Wu, Shaojun',\n", - " 'Zhou, Yang',\n", - " 'Wei, Hui-Fang',\n", - " 'Zhang, Jianrong',\n", - " 'Chen, Zixuan',\n", - " 'Zhu, Jun-Jie',\n", - " 'Lin, Yuehe',\n", - " 'Zhu, Wenlei'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Fange.202012171\"}'],\n", - " 'title': ['Bio‑Coreactant‑Enhanced Electrochemiluminescence Microscopy of Intracellular Structure and Transport']},\n", - " {'bibcode': '2020Natur.583..265A',\n", - " 'abstract': 'Cancers arise through the acquisition of oncogenic mutations and grow by clonal expansion1,2. Here we reveal that most mutagenic DNA lesions are not resolved into a mutated DNA base pair within a single cell cycle. Instead, DNA lesions segregate, unrepaired, into daughter cells for multiple cell generations, resulting in the chromosome-scale phasing of subsequent mutations. We characterize this process in mutagen-induced mouse liver tumours and show that DNA replication across persisting lesions can produce multiple alternative alleles in successive cell divisions, thereby generating both multiallelic and combinatorial genetic diversity. The phasing of lesions enables accurate measurement of strand-biased repair processes, quantification of oncogenic selection and fine mapping of sister-chromatid-exchange events. Finally, we demonstrate that lesion segregation is a unifying property of exogenous mutagens, including UV light and chemotherapy agents in human cells and tumours, which has profound implications for the evolution and adaptation of cancer genomes.',\n", - " 'author': ['Aitken, Sarah J.',\n", - " 'Anderson, Craig J.',\n", - " 'Connor, Frances',\n", - " 'Pich, Oriol',\n", - " 'Sundaram, Vasavi',\n", - " 'Feig, Christine',\n", - " 'Rayner, Tim F.',\n", - " 'Lukk, Margus',\n", - " 'Aitken, Stuart',\n", - " 'Luft, Juliet',\n", - " 'Kentepozidou, Elissavet',\n", - " 'Arnedo-Pac, Claudia',\n", - " 'Beentjes, Sjoerd V.',\n", - " 'Davies, Susan E.',\n", - " 'Drews, Ruben M.',\n", - " 'Ewing, Ailith',\n", - " 'Kaiser, Vera B.',\n", - " 'Khamseh, Ava',\n", - " 'López-Arribillaga, Erika',\n", - " 'Redmond, Aisling M.',\n", - " 'Santoyo-Lopez, Javier',\n", - " 'Sentís, Inés',\n", - " 'Talmane, Lana',\n", - " 'Yates, Andrew D.',\n", - " 'Liver Cancer Evolution Consortium',\n", - " 'Semple, Colin A.',\n", - " 'López-Bigas, Núria',\n", - " 'Flicek, Paul',\n", - " 'Odom, Duncan T.',\n", - " 'Taylor, Martin S.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41586-020-2435-1\"}'],\n", - " 'title': ['Pervasive lesion segregation shapes cancer genome evolution']},\n", - " {'bibcode': '2009JThBi.260..151S',\n", - " 'abstract': 'The different behaviors of colonies of two cell lines, ARO (thyroid carcinoma-derived cells) and MLP-29 (mouse liver progenitor cells), in response to hepatocyte growth factor (HGF) are described deducing suitable cellular Potts models (CPM). It is shown how increased motility and decreased adhesiveness are responsible for cell-cell dissociation and tissue invasion in the ARO cells. On the other hand, it is shown that, in addition to the biological mechanisms above, it is necessary to include directional persistence in cell motility and HGF diffusion to describe the scattering and the branching processes characteristic of MLP-29 cells.',\n", - " 'author': ['Scianna, Marco',\n", - " 'Merks, Roeland M. H.',\n", - " 'Preziosi, Luigi',\n", - " 'Medico, Enzo'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.jtbi.2009.05.017\"}'],\n", - " 'title': ['Individual cell-based models of cell scatter of ARO and MLP-29 cells in response to hepatocyte growth factor']},\n", - " {'bibcode': '2017EnST...51.1775J',\n", - " 'author': ['Jia, Jianbo',\n", - " 'Li, Feifei',\n", - " 'Zhai, Shumei',\n", - " 'Zhou, Hongyu',\n", - " 'Liu, Sijin',\n", - " 'Jiang, Guibin',\n", - " 'Yan, Bing'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1021%2Facs.est.6b05200\"}'],\n", - " 'title': ['Susceptibility of Overweight Mice to Liver Injury as a Result of the ZnO Nanoparticle-Enhanced Liver Deposition of Pb2+']},\n", - " {'bibcode': '2016PLoSO..1152022H',\n", - " 'author': ['He, Jun-Jun',\n", - " 'Ma, Jun',\n", - " 'Elsheikha, Hany M.',\n", - " 'Song, Hui-Qun',\n", - " 'Zhou, Dong-Hui',\n", - " 'Zhu, Xing-Quan'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0152022\"}'],\n", - " 'title': ['Proteomic Profiling of Mouse Liver following Acute Toxoplasma gondii Infection']},\n", - " {'bibcode': '1966Sci...153..643V',\n", - " 'abstract': 'After hepatic injury induced by carbon tetrachloride, mitotically active hematopoietic cells of nonhepatic origin localize in the liver as judged by an increase in colony-forming nodules in the spleens of lethally irradiated recipient mice on intravenous injection of cells from these livers. The administration of warfarin suppresses the localization of colony-forming units in the regenerating liver by inhibiting the coagulation mechanism of the donor animals.',\n", - " 'author': ['Varon, Myron L.', 'Cole, Leonard J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.jstor.org/stable/1719413?origin=ads\"}'],\n", - " 'title': ['Hemopoietic Colony-Forming Units in Regenerating Mouse Liver: Suppression by Anticoagulants']},\n", - " {'bibcode': '1976JTEH....1..985F',\n", - " 'author': ['Farb, Roderick M.', 'Mego, John L.', 'Hayes, A. Wallace'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1080%2F15287397609529401\"}'],\n", - " 'title': ['Effect of mycotoxins on uptake and degradation of [125I]albumin in mouse liver and kidney lysosomes']},\n", - " {'bibcode': '1981PNAS...78.3697C',\n", - " 'abstract': 'We have compared poly(A)-mRNA isolated from mouse liver endoplasmic reticulum (ER) membranes (ER mRNA) with that from free polyribosomes (free mRNA) by translation in a cell-free system and by mRNA--cDNA reassociation analysis. The partitioning of certain translation products between the two fractions suggests that the physical contamination of the free mRNA by the ER is 10%, and contamination of the ER by the free is 1%. Reassociation crossreactions suggest that no sequences are totally absent from either fraction. In particular, the rare sequences are shared between the two fractions. Among the more abundant sequences, we detect three groups: (i) a group of about 10 sequences that are relatively abundant in both fractions; (ii) a group that occurs mostly in the free fraction; (iii) a group of about 12 sequences, 6 or 7 of them encoding secretory polypeptides. The members of this group are largely or entirely confined to the ER fraction. Secretory proteins are almost entirely absent from the products of th free mRNA fraction. Quantitation of individual mRNA sequences by hybridization with cDNA clones shows that a range of sequence concentrations exists within the abundant class of ER mRNA.',\n", - " 'author': ['Clissold, P. M.', 'Mason, P. J.', 'Bishop, J. O.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/78/6/3697\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/78/6/3697\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/78/6/3697\"}'],\n", - " 'title': ['Comparison of poly(A)-mRNA prepared from membranes and free polyribosomes of mouse liver.']},\n", - " {'bibcode': '1981RadR...88...79R',\n", - " 'author': ['Reddy, M. R.', 'Fuhr, J. E.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.2307%2F3575753\"}'],\n", - " 'title': ['The Effect of Ionizing Radiation In Vitro upon Fetal Mouse Liver Erythroid Cells']},\n", - " {'bibcode': '1991JTEH...34..367V',\n", - " 'author': ['Vorce, Roseann L.', 'Goodman, Jay I.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1080%2F15287399109531574\"}'],\n", - " 'title': ['Hypomethylation ofrasoncogenes in chemically induced and spontaneous b6c3f1 mouse liver tumors']},\n", - " {'bibcode': '2017HETox..36...33C',\n", - " 'abstract': 'Pentavalent antimonial (Sb5+) drugs such as meglumine antimoniate (MA) are the mainstay treatment of leishmaniases in developing countries. The effects of these compounds on drug-metabolizing enzymes have not been characterized and their potential pharmacokinetic interactions with other drugs are therefore unknown. The present study investigated whether treatment with MA (300 mg Sb5+/kg body weight/day, subcutaneously) for 24 days affected the activities of cytochrome P450 (CYP)1A (ethoxyresorufin- O-deethylase), CYP2A5 (coumarin 7-hydroxylase), CYP2E1 ( p-nitrophenol-hydroxylase), CYP2B9/10 (benzyloxy-resorufin- O-debenzylase), or CYP3A11 (erythromycin- N-demethylase) in the livers of Swiss Webster (SW) and DBA-2 male and female mice. The results showed that CYP2A5-, CYP2E1-, and CYP3A11-catalyzed reactions were unaffected by MA treatment. A decrease in CYP2B9/10 activity was noted in DBA-2 females (but not males) and was not observed in SW males or females. However, repeated MA administration reduced mouse liver CYP1A activity. CYP1A2 messenger RNA (mRNA) levels were not affected by MA and in vitro exposure of mouse liver microsomes to Sb3+ and Sb5+ did not reduce CYP1A activity. These findings suggested that in vivo treatment with Sb5+ drugs depressed CYP1A activity, without downregulating CYP1A2 mRNA expression. Since in vitro treatment of liver microsomes failed to inhibit CYP1A activity, this effect may require intact cells.',\n", - " 'author': ['Coelho, DR',\n", - " 'De-Oliveira, ACAX',\n", - " 'Parente, TEM',\n", - " 'Leal, BS',\n", - " 'das Chagas, LF',\n", - " 'Oliveira, TN',\n", - " \"Saint'Pierre, TD\",\n", - " 'Paumgartten, FJR'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1177%2F0960327116637110\"}'],\n", - " 'title': ['In vivo and in vitro effects of pentavalent antimony on mouse liver cytochrome P450s']},\n", - " {'bibcode': '2001JTEHA..63..541C',\n", - " 'author': ['Carlson, Gary P.',\n", - " 'Rivera, Alex A. Perez',\n", - " 'Mantick, Nancy A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1080%2F15287390152410165\"}'],\n", - " 'title': ['Metabolism of the Styrene Metabolite 4-VINYLPHENOL by Rat and Mouse Liver and Lung']},\n", - " {'bibcode': '1982JESHB..17..571E',\n", - " 'author': ['El-Sewedy, S. M.',\n", - " 'Mostafa, M. H.',\n", - " 'El-Bassiouni, E. A.',\n", - " 'Abdel-Rafee, A.',\n", - " 'El-Sebae, A. H.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1080%2F03601238209372342\"}'],\n", - " 'title': ['Effect of fenvalerate on kynurenine metabolizing enzymes and acid ribonuclease of mouse liver']},\n", - " {'bibcode': '1955Sci...121..143M',\n", - " 'author': ['Makino, Katashi', 'Arai, Kiyohisa'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.jstor.org/stable/1683079?origin=ads\"}'],\n", - " 'title': ['Conversion of 3-Hydroxykynurenine to 4,8-Dihydroxyquinoline by Mouse Liver Homogenate']},\n", - " {'bibcode': '2019BpJ...116..228A',\n", - " 'author': ['Amin, Anowarul', 'Mindell, Joseph A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.bpj.2018.11.1257\"}'],\n", - " 'title': ['The Role of the Chloride Transporter CLC-7 in Acidification in Mouse Liver Lysosomes']},\n", - " {'bibcode': '2012NaPho...6..845O',\n", - " 'abstract': 'To date, medical imaging of tissues has largely relied on time-consuming staining processes, and there is a need for rapid, label-free imaging techniques. Stimulated Raman scattering microscopy offers a three-dimensional, real-time imaging capability with chemical specificity. However, it can be difficult to differentiate between several constituents in tissues because their spectral characteristics can overlap. Furthermore, imaging speeds in previous multispectral stimulated Raman scattering imaging techniques were limited. Here, we demonstrate label-free imaging of tissues by 30 frames/s stimulated Raman scattering microscopy with frame-by-frame wavelength tunability. To produce multicolour images showing different constituents, spectral images were processed by modified independent component analysis, which can extract small differences in spectral features. We present various imaging modalities such as two-dimensional spectral imaging of rat liver, two-colour three-dimensional imaging of a vessel in rat liver, spectral imaging of several sections of intestinal villi in mouse, and in vivo spectral imaging of mouse ear skin.',\n", - " 'author': ['Ozeki, Yasuyuki',\n", - " 'Umemura, Wataru',\n", - " 'Otsuka, Yoichi',\n", - " 'Satoh, Shuya',\n", - " 'Hashimoto, Hiroyuki',\n", - " 'Sumimura, Kazuhiko',\n", - " 'Nishizawa, Norihiko',\n", - " 'Fukui, Kiichi',\n", - " 'Itoh, Kazuyoshi'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnphoton.2012.263\"}'],\n", - " 'title': ['High-speed molecular spectral imaging of tissue with stimulated Raman scattering']},\n", - " {'bibcode': '2023NatCo..14.2779C',\n", - " 'abstract': 'Reversible and sub-lethal stresses to the mitochondria elicit a program of compensatory responses that ultimately improve mitochondrial function, a conserved anti-aging mechanism termed mitohormesis. Here, we show that harmol, a member of the beta-carbolines family with anti-depressant properties, improves mitochondrial function and metabolic parameters, and extends healthspan. Treatment with harmol induces a transient mitochondrial depolarization, a strong mitophagy response, and the AMPK compensatory pathway both in cultured C2C12 myotubes and in male mouse liver, brown adipose tissue and muscle, even though harmol crosses poorly the blood-brain barrier. Mechanistically, simultaneous modulation of the targets of harmol monoamine-oxidase B and GABA-A receptor reproduces harmol-induced mitochondrial improvements. Diet-induced pre-diabetic male mice improve their glucose tolerance, liver steatosis and insulin sensitivity after treatment with harmol. Harmol or a combination of monoamine oxidase B and GABA-A receptor modulators extend the lifespan of hermaphrodite Caenorhabditis elegans or female Drosophila melanogaster. Finally, two-year-old male and female mice treated with harmol exhibit delayed frailty onset with improved glycemia, exercise performance and strength. Our results reveal that peripheral targeting of monoamine oxidase B and GABA-A receptor, common antidepressant targets, extends healthspan through mitohormesis.',\n", - " 'author': ['Costa-Machado, Luis Filipe',\n", - " 'Garcia-Dominguez, Esther',\n", - " 'McIntyre, Rebecca L.',\n", - " 'Lopez-Aceituno, Jose Luis',\n", - " 'Ballesteros-Gonzalez, Álvaro',\n", - " 'Tapia-Gonzalez, Andrea',\n", - " 'Fabregat-Safont, David',\n", - " 'Eisenberg, Tobias',\n", - " 'Gomez, Jesús',\n", - " 'Plaza, Adrian',\n", - " 'Sierra-Ramirez, Aranzazu',\n", - " 'Perez, Manuel',\n", - " 'Villanueva-Bermejo, David',\n", - " 'Fornari, Tiziana',\n", - " 'Loza, María Isabel',\n", - " 'Herradon, Gonzalo',\n", - " 'Hofer, Sebastian J.',\n", - " 'Magnes, Christoph',\n", - " 'Madeo, Frank',\n", - " 'Duerr, Janet S.',\n", - " 'Pozo, Oscar J.',\n", - " 'Galindo, Maximo-Ibo',\n", - " 'del Pino, Isabel',\n", - " 'Houtkooper, Riekelt H.',\n", - " 'Megias, Diego',\n", - " 'Viña, Jose',\n", - " 'Gomez-Cabrera, Mari Carmen',\n", - " 'Fernandez-Marcos, Pablo J.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41467-023-38410-y\"}'],\n", - " 'title': ['Peripheral modulation of antidepressant targets MAO-B and GABAAR by harmol induces mitohormesis and delays aging in preclinical models']},\n", - " {'bibcode': '1974Natur.249...32S',\n", - " 'abstract': 'PLANT virus RNA from the TYMV family1-3, TMV4,5 and BMV6 can be enzymatically esterfied with valine, histidine and tyrosine, respectively. The aminoacylation of intact or fragmented plant virus RNA7, may be an important biological function and, therefore, the question as to whether some mammalian viral RNA can be charged with amino acids becomes significant. In this work, we show that mengovirus RNA can, in fact, be specifically acylated with histidine by a mouse liver aminoacyl-tRNA synthetase preparation.',\n", - " 'author': ['Salomon, R.', 'Littauer, U. Z.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F249032a0\"}'],\n", - " 'title': ['Enzymatic acylation of histidine to mengovirus RNA']},\n", - " {'bibcode': '2018NatSR...8.2735B',\n", - " 'abstract': 'While the Wnt/β-catenin pathway plays a critical role in the maintenance of the zonation of ammonia metabolizing enzymes in the adult liver, the mechanisms responsible for inducing zonation in the embryo are not well understood. Herein we address the spatiotemporal role of the Wnt/β-catenin pathway in the development of zonation in embryonic mouse liver by conditional deletion of Apc and β-catenin at different stages of mouse liver development. In normal development, the ammonia metabolising enzymes carbamoylphosphate synthetase I (CPSI) and Glutamine synthetase (GS) begin to be expressed in separate hepatoblasts from E13.5 and E15.5 respectively and gradually increase in number thereafter. Restriction of GS expression occurs at E18 and becomes increasingly limited to the terminal perivenous hepatocytes postnatally. Expression of nuclear β-catenin coincides with the restriction of GS expression to the terminal perivenous hepatocytes. Conditional loss of Apc resulted in the expression of nuclear β-catenin throughout the developing liver and increased number of cells expressing GS. Conversely, conditional loss of β-catenin resulted in loss of GS expression. These data suggest that the Wnt pathway is critical to the development of zonation as well as maintaining the zonation in the adult liver.',\n", - " 'author': ['Burke, Zoë D.',\n", - " 'Reed, Karen R.',\n", - " 'Yeh, Sheng-Wen',\n", - " 'Meniel, Valerie',\n", - " 'Sansom, Owen J.',\n", - " 'Clarke, Alan R.',\n", - " 'Tosh, David'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-018-20888-y\"}'],\n", - " 'title': ['Spatiotemporal regulation of liver development by the Wnt/β-catenin pathway']},\n", - " {'bibcode': '1993Natur.364..806O',\n", - " 'abstract': 'DURING mammalian development, many cells are programmed to die1,2 most mediated by apoptosis3. The Fas antigen4 coded by the structural gene for mouse lymphoproliferation mutation (lpr)5,6, is a cell surface protein belonging to the tumour necrosis factor/nerve growth factor receptor family7,8, and mediates apoptosis7. The Fas antigen messenger RNA is expressed in the thymus, liver, heart, lung and ovary8. We prepared a monoclonal antibody against mouse Fas antigen, which immunoprecipitated the antigen (Mr 45K) and had cytolytic activity against cell lines expressing mouse Fas antigen. We report here that staining of mouse thymocytes with the antibody indicated that thymocytes from the wild-type and lpr cg mice expressed the Fas antigen, whereas little expression of the Fas antigen was found in lpr mice. Intraperitoneal administration of the anti-Fas antibody into mice rapidly killed the wild-type mice but neither lpr nor lpr cg mice. Biochemical, histological and electron microscope analyses indicated severe damage of the liver by apoptosis. These findings suggest that the Fas antigen is important in programmed cell death in the liver, and may be involved in fulminant hepatitis in some cases.',\n", - " 'author': ['Ogasawara, Jun',\n", - " 'Watanabe-Fukunaga, Rie',\n", - " 'Adachi, Masashi',\n", - " 'Matsuzawa, Akio',\n", - " 'Kasugai, Tsutomu',\n", - " 'Kitamura, Yukihiko',\n", - " 'Itoh, Naoto',\n", - " 'Suda, Takashi',\n", - " 'Nagata, Shigekazu'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F364806a0\"}'],\n", - " 'title': ['Lethal effect of the anti-Fas antibody in mice']},\n", - " {'bibcode': '2015PLoSO..1024224.',\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0124224\"}'],\n", - " 'title': ['Correction: Identification of Modulators of the Nuclear Receptor Peroxisome Proliferator-Activated Receptor α (PPARα) in a Mouse Liver Gene Expression Compendium']},\n", - " {'bibcode': '2016NatSR...627665X',\n", - " 'abstract': 'Macrophage migration inhibitor factor (MIF), a multipotent innate immune mediator, is an upstream component of the inflammatory cascade in diseases such as liver disease. Monocyte chemoattractant protein-1 (MCP-1), a highly representative chemokine, is critical in liver disease pathogenesis. We investigated the role of MIF in regulating hepatocytic MCP-1 expression. MIF and MCP-1 expression were characterized by immunochemistry, RT-PCR, ELISA, and immunoblotting in CCl4-treated mouse liver and isolated hepatocytes. MIF was primarily distributed in hepatocytes, and its expression increased upon acute liver injury. Its expression was also increased in injured hepatocytes, induced by LPS or CCl4, which mimic liver injury in vitro. MIF was expressed earlier than MCP-1, strongly inducing hepatocytic MCP-1 expression. Moreover, the increase in MCP-1 expression induced by MIF was inhibited by CD74- or CD44-specific siRNAs and SB203580, a p38 MAPK inhibitor. Further, CD74 or CD44 deficiency effectively inhibited MIF-induced p38 activation. MIF inhibitor ISO-1 reduced MCP-1 expression and p38 phosphorylation in CCl4-treated mouse liver. Our results showed that MIF regulates MCP-1 expression in hepatocytes of injured liver via CD74, CD44, and p38 MAPK in an autocrine manner, providing compelling information on the role of MIF in liver injury, and implying a new regulatory mechanism for liver inflammation.',\n", - " 'author': ['Xie, Jieshi',\n", - " 'Yang, Le',\n", - " 'Tian, Lei',\n", - " 'Li, Weiyang',\n", - " 'Yang, Lin',\n", - " 'Li, Liying'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep27665\"}'],\n", - " 'title': ['Macrophage Migration Inhibitor Factor Upregulates MCP-1 Expression in an Autocrine Manner in Hepatocytes during Acute Mouse Liver Injury']},\n", - " {'bibcode': '2006Sci...312..104L',\n", - " 'abstract': 'The liver can regenerate its volume after major tissue loss. In a mouse model of liver regeneration, thrombocytopenia, or impaired platelet activity resulted in the failure to initiate cellular proliferation in the liver. Platelets are major carriers of serotonin in the blood. In thrombocytopenic mice, a serotonin agonist reconstituted liver proliferation. The expression of 5-HT2A and 2B subtype serotonin receptors in the liver increased after hepatectomy. Antagonists of 5-HT2A and 2B receptors inhibited liver regeneration. Liver regeneration was also blunted in mice lacking tryptophan hydroxylase 1, which is the rate-limiting enzyme for the synthesis of peripheral serotonin. This failure of regeneration was rescued by reloading serotonin-free platelets with a serotonin precursor molecule. These results suggest that platelet-derived serotonin is involved in the initiation of liver regeneration.',\n", - " 'author': ['Lesurtel, Mickael',\n", - " 'Graf, Rolf',\n", - " 'Aleil, Boris',\n", - " 'Walther, Diego J.',\n", - " 'Tian, Yinghua',\n", - " 'Jochum, Wolfram',\n", - " 'Gachet, Christian',\n", - " 'Bader, Michael',\n", - " 'Clavien, Pierre-Alain'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.1123842\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.1123842\"}'],\n", - " 'title': ['Platelet-Derived Serotonin Mediates Liver Regeneration']},\n", - " {'bibcode': '2015JBO....20g6012K',\n", - " 'abstract': 'We propose an offset-sparsity decomposition method for the enhancement of a color microscopic image of a stained specimen. The method decomposes vectorized spectral images into offset terms and sparse terms. A sparse term represents an enhanced image, and an offset term represents a \"shadow.\" The related optimization problem is solved by computational improvement of the accelerated proximal gradient method used initially to solve the related rank-sparsity decomposition problem. Removal of an image-adapted color offset yields an enhanced image with improved colorimetric differences among the histological structures. This is verified by a no-reference colorfulness measure estimated from 35 specimens of the human liver, 1 specimen of the mouse liver stained with hematoxylin and eosin, 6 specimens of the mouse liver stained with Sudan III, and 3 specimens of the human liver stained with the anti-CD34 monoclonal antibody. The colorimetric difference improves on average by 43.86% with a 99% confidence interval (CI) of [35.35%, 51.62%]. Furthermore, according to the mean opinion score, estimated on the basis of the evaluations of five pathologists, images enhanced by the proposed method exhibit an average quality improvement of 16.60% with a 99% CI of [10.46%, 22.73%].',\n", - " 'author': ['Kopriva, Ivica',\n", - " 'Hadžija, Marijana Popović',\n", - " 'Hadžija, Mirko',\n", - " 'Aralica, Gorana'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1117%2F1.JBO.20.7.076012\"}'],\n", - " 'title': ['Offset-sparsity decomposition for automated enhancement of color microscopic image of stained specimen in histopathology']},\n", - " {'bibcode': '1981PNAS...78.2038H',\n", - " 'abstract': \"A recombinant lambda phage containing mouse mammary tumor virus (MMTV) proviral DNA was isolated from a gene library constructed from GR mouse liver DNA. Restriction enzyme analyses reveal that the cloned molecule contains a copy of one of the GR endogenous MMTV proviruses flanked on both sides by 2--3 kb of mouse genomic DNA. In this report we have examined the expression of the cloned MMTV provirus after cotransfection with the herpes thymidine kinase (TK; ATP:thymidine 5'-phosphotransferase,, EC 2.7.1.21) gene and integration into mouse LTK- cells. Nine individual TK+ transformants were selected, and all were found to contain MMTV-transfected DNA. One of the TK+ transformants was chosen for further study. Total poly(A)-containing RNA was isolated from the cells, and liquid hybridization analyses with MMTV cDNA showed that it contained 0.02% MMTV-specific RNA. The sizes of the MMTV-specific species were determined and found to correspond to the 35S and 24S mRNAs synthesized in MMTV-infected cells. Glucocorticoid hormones have been shown to increase the concentration of MMTV RNA in virus-infected cultured cells. Therefore, we tested the effect of dexamethasone on the concentration of MMTV-specific RNA in cells transfected with the MMTV proviral DNA. The amount of MMTV-specific poly(A)-containing RNA found in the cells grown in the presence of hormone was 0.17%. Therefore, dexamethasone causes an 8-fold increase in the amount of MMTV-specific RNA in mouse cells containing several copies of a cloned and transfected MMTV proviral gene.\",\n", - " 'author': ['Hynes, Nancy E.',\n", - " 'Kennedy, Nicholas',\n", - " 'Rahmsdorf, Ursula',\n", - " 'Groner, Bernd'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/78/4/2038\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/78/4/2038\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/78/4/2038\"}'],\n", - " 'title': ['Hormone-responsive expression of an endogenous proviral gene of mouse mammary tumor virus after molecular cloning and gene transfer into cultured cells.']},\n", - " {'bibcode': '1995Sci...269.1427K',\n", - " 'abstract': 'A method of gene targeting that allows the inducible inactivation of a target gene in mice is presented. The method uses an interferon-responsive promoter to control the expression of Cre recombinase. Here, Cre was used to delete a segment of the DNA polymerase β gene flanked by loxP recombinase recognition sites. Deletion was complete in liver and nearly complete in lymphocytes within a few days, whereas partial deletion was obtained in other tissues. This method can be used for the inducible inactivation of any other gene in vivo.',\n", - " 'author': ['Kuhn, Ralf',\n", - " 'Schwenk, Frieder',\n", - " 'Aguet, Michel',\n", - " 'Rajewsky, Klaus'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.7660125\"}'],\n", - " 'title': ['Inducible Gene Targeting in Mice']},\n", - " {'bibcode': '2007EnTox..22..630Y',\n", - " 'abstract': 'Methyl tert‑butyl ether (MTBE) is a currently worldwide used octane enhancer substituting for lead alkyls and gasoline oxygenate. Our previous study using doubly 14C‑labeled MTBE [(CH3)314CO14CH3] has shown that MTBE binds DNA to form DNA adducts at low dose levels in mice. To elucidate the mechanism of the binding reaction, in this study, the DNA adducts with singly 14C‑labeled MTBE, which was synthesized from 14C‑methanol and tert‑butyl alcohol (TBA), or 14C‑labeled TBA in mice have been measured by ultra sensitive accelerator mass spectrometry. The results show that the methyl group of MTBE and tert‑butyl alcohol definitely form adducts with DNA in mouse liver, lung, and kidney. The methyl group of MTBE is the predominant binding part in liver, while the methyl group and the tert‑butyl group give comparable contributions to the adduct formation in lung and kidney.',\n", - " 'author': ['Yuan, Y.',\n", - " 'Wang, H. F.',\n", - " 'Sun, H. F.',\n", - " 'Du, H. F.',\n", - " 'Xu, L. H.',\n", - " 'Liu, Y. F.',\n", - " 'Ding, X. F.',\n", - " 'Fu, D. P.',\n", - " 'Liu, K. X.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Ftox.20295\"}'],\n", - " 'title': ['Adduction of DNA with MTBE and TBA in mice studied by accelerator mass spectrometry']},\n", - " {'bibcode': '2022NaRes..15.2558L',\n", - " 'abstract': 'MXene, as an emerging two-dimensional (2D) material with ultrathin structure and fascinating physiochemical properties, has been widely explored in broad applications. Versatile functions of MXenes are continuously explored. This work presents distinctive feature of MXene-Ti3C2Tx nanosheets for free-radical (FRs) scavenging that never reported before. We demonstrated the mechanism and equation in regard to the reaction between Ti3C2Tx and H2O2, which was applied to design colorimetric H2O2 strip assay with good performance. The good FRs scavenging capability of Ti3C2Tx, including a series of reactive oxygen species (ROS) and reactive nitrogen species (RNS), was systemically confirmed. The antioxidation capability of Ti3C2Tx for protecting cells from oxidative damage was demonstrated using the oxidative damage model of alpha mouse liver 12 (AML-12) cells. This original work provides huge opportunities for MXenes in FR-related biomedical applications.',\n", - " 'author': ['Liu, Jiang',\n", - " 'Lu, Wei',\n", - " 'Lu, Xifeng',\n", - " 'Zhang, Lu',\n", - " 'Dong, Haifeng',\n", - " 'Li, Yingchun'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1007%2Fs12274-021-3751-y\"}'],\n", - " 'title': ['Versatile Ti3C2Tx MXene for free-radical scavenging']},\n", - " {'bibcode': '1962Natur.193...81B',\n", - " 'abstract': 'IN work on reactions between mouse tissues and heterologous antisera in gel-diffusion plates a faint line of precipitate sometimes appeared between wells containing normal mouse serum and normal mouse liver or kidney. In view of the possible significance of this finding for work on auto-immune reactions, it was investigated further.',\n", - " 'author': ['Berenbaum, M. C.', 'Kitch, Gillian M.', 'Cope, W. A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F193081a0\"}'],\n", - " 'title': [\"Spurious `Auto-Immune' Reactions in Gel-Diffusion Plates\"]},\n", - " {'bibcode': '2017Natur.545..234J',\n", - " 'abstract': 'Wnt proteins modulate cell proliferation and differentiation and the self-renewal of stem cells by inducing β-catenin-dependent signalling through the Wnt receptor frizzled (FZD) and the co-receptors LRP5 and LRP6 to regulate cell fate decisions and the growth and repair of several tissues. The 19 mammalian Wnt proteins are cross-reactive with the 10 FZD receptors, and this has complicated the attribution of distinct biological functions to specific FZD and Wnt subtype interactions. Furthermore, Wnt proteins are modified post-translationally by palmitoylation, which is essential for their secretion, function and interaction with FZD receptors. As a result of their acylation, Wnt proteins are very hydrophobic and require detergents for purification, which presents major obstacles to the preparation and application of recombinant Wnt proteins. This hydrophobicity has hindered the determination of the molecular mechanisms of Wnt signalling activation and the functional importance of FZD subtypes, and the use of Wnt proteins as therapeutic agents. Here we develop surrogate Wnt agonists, water-soluble FZD-LRP5/LRP6 heterodimerizers, with FZD5/FZD8-specific and broadly FZD-reactive binding domains. Similar to WNT3A, these Wnt agonists elicit a characteristic β-catenin signalling response in a FZD-selective fashion, enhance the osteogenic lineage commitment of primary mouse and human mesenchymal stem cells, and support the growth of a broad range of primary human organoid cultures. In addition, the surrogates can be systemically expressed and exhibit Wnt activity in vivo in the mouse liver, regulating metabolic liver zonation and promoting hepatocyte proliferation, resulting in hepatomegaly. These surrogates demonstrate that canonical Wnt signalling can be activated by bi-specific ligands that induce receptor heterodimerization. Furthermore, these easily produced, non-lipidated Wnt surrogate agonists facilitate functional studies of Wnt signalling and the exploration of Wnt agonists for translational applications in regenerative medicine.',\n", - " 'author': ['Janda, Claudia Y.',\n", - " 'Dang, Luke T.',\n", - " 'You, Changjiang',\n", - " 'Chang, Junlei',\n", - " 'de Lau, Wim',\n", - " 'Zhong, Zhendong A.',\n", - " 'Yan, Kelley S.',\n", - " 'Marecic, Owen',\n", - " 'Siepe, Dirk',\n", - " 'Li, Xingnan',\n", - " 'Moody, James D.',\n", - " 'Williams, Bart O.',\n", - " 'Clevers, Hans',\n", - " 'Piehler, Jacob',\n", - " 'Baker, David',\n", - " 'Kuo, Calvin J.',\n", - " 'Garcia, K. Christopher'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature22306\"}'],\n", - " 'title': ['Surrogate Wnt agonists that phenocopy canonical Wnt and β-catenin signalling']},\n", - " {'bibcode': '2021ScTEn.767n4485W',\n", - " 'author': ['Wang, Rongrong',\n", - " 'Han, Xi',\n", - " 'Pang, Huanhuan',\n", - " 'Hu, Zeping',\n", - " 'Shi, Chunzhen'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.scitotenv.2020.144485\"}'],\n", - " 'title': ['Illuminating a time-response mechanism in mice liver after PM2.5 exposure using metabolomics analysis']},\n", - " {'bibcode': '2018Natur.562..128L',\n", - " 'abstract': 'Angiocrine signals derived from endothelial cells are an important component of intercellular communication and have a key role in organ growth, regeneration and disease1-4. These signals have been identified and studied in multiple organs, including the liver, pancreas, lung, heart, bone, bone marrow, central nervous system, retina and some cancers1-4. Here we use the developing liver as a model organ to study angiocrine signals5,6, and show that the growth rate of the liver correlates both spatially and temporally with blood perfusion to this organ. By manipulating blood flow through the liver vasculature, we demonstrate that vessel perfusion activates β1 integrin and vascular endothelial growth factor receptor 3 (VEGFR3). Notably, both β1 integrin and VEGFR3 are strictly required for normal production of hepatocyte growth factor, survival of hepatocytes and liver growth. Ex vivo perfusion of adult mouse liver and in vitro mechanical stretching of human hepatic endothelial cells illustrate that mechanotransduction alone is sufficient to turn on angiocrine signals. When the endothelial cells are mechanically stretched, angiocrine signals trigger in vitro proliferation and survival of primary human hepatocytes. Our findings uncover a signalling pathway in vascular endothelial cells that translates blood perfusion and mechanotransduction into organ growth and maintenance.',\n", - " 'author': ['Lorenz, Linda',\n", - " 'Axnick, Jennifer',\n", - " 'Buschmann, Tobias',\n", - " 'Henning, Carina',\n", - " 'Urner, Sofia',\n", - " 'Fang, Shentong',\n", - " 'Nurmi, Harri',\n", - " 'Eichhorst, Nicole',\n", - " 'Holtmeier, Richard',\n", - " 'Bódis, Kálmán',\n", - " 'Hwang, Jong-Hee',\n", - " 'Müssig, Karsten',\n", - " 'Eberhard, Daniel',\n", - " 'Stypmann, Jörg',\n", - " 'Kuss, Oliver',\n", - " 'Roden, Michael',\n", - " 'Alitalo, Kari',\n", - " 'Häussinger, Dieter',\n", - " 'Lammert, Eckhard'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41586-018-0522-3\"}'],\n", - " 'title': ['Mechanosensing by β1 integrin induces angiocrine signals for liver growth and survival']},\n", - " {'bibcode': '2007PNAS..104.1661M',\n", - " 'abstract': 'Hepatitis C virus (HCV) is a major cause of chronic liver disease that frequently leads to steatosis, cirrhosis, and eventually hepatocellular carcinoma (HCC). HCV core protein is not only a component of viral particles but also a multifunctional protein because liver steatosis and HCC are developed in HCV core gene-transgenic (CoreTg) mice. Proteasome activator PA28γ/REGγ regulates host and viral proteins such as nuclear hormone receptors and HCV core protein. Here we show that a knockout of the PA28γ gene induces the accumulation of HCV core protein in the nucleus of hepatocytes of CoreTg mice and disrupts development of both hepatic steatosis and HCC. Furthermore, the genes related to fatty acid biosynthesis and srebp-1c promoter activity were up-regulated by HCV core protein in the cell line and the mouse liver in a PA28γ-dependent manner. Heterodimer composed of liver X receptor α (LXRα) and retinoid X receptor α (RXRα) is known to up-regulate srebp-1c promoter activity. Our data also show that HCV core protein enhances the binding of LXRα/RXRα to LXR-response element in the presence but not the absence of PA28γ. These findings suggest that PA28γ plays a crucial role in the development of liver pathology induced by HCV infection.',\n", - " 'author': ['Moriishi, Kohji',\n", - " 'Mochizuki, Rika',\n", - " 'Moriya, Kyoji',\n", - " 'Miyamoto, Hironobu',\n", - " 'Mori, Yoshio',\n", - " 'Abe, Takayuki',\n", - " 'Murata, Shigeo',\n", - " 'Tanaka, Keiji',\n", - " 'Miyamura, Tatsuo',\n", - " 'Suzuki, Tetsuro',\n", - " 'Koike, Kazuhiko',\n", - " 'Matsuura, Yoshiharu'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/104/5/1661\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0607312104\"}'],\n", - " 'title': ['Critical role of PA28γ in hepatitis C virus-associated steatogenesis and hepatocarcinogenesis']},\n", - " {'bibcode': '2018NatSR...8.9072T',\n", - " 'abstract': 'A number of diverse cell-surface proteins are anchored to the cytoskeleton via scaffold proteins. Na+/H+ exchanger regulatory factor-1 (NHERF1), encoded by the Slc9a3r1 gene, functions as a scaffold protein, which is implicated in the regulation of membrane expression of various cell-surface proteins. Here, we demonstrate that the circadian clock component PERIOD2 (PER2) modulates transcription of the mouse Slc9a3r1 gene, generating diurnal accumulation of NHERF1 in the mouse liver. Basal expression of Slc9a3r1 was dependent on transcriptional activation by p65/p50. PER2 bound to p65 protein and prevented p65/p50-mediated transactivation of Slc9a3r1. The time-dependent interaction between PER2 and p65 underlay diurnal oscillation in the hepatic expression of Slc9a3r1/NHERF1. The results of immunoprecipitation experiments and liquid chromatography-mass spectrometry analysis of mouse liver revealed that NHERF1 time-dependently interacted with fatty acid transport protein-5 (FATP5). Temporary accumulation of NHERF1 protein stabilized plasmalemmal localization of FATP5, thereby enhancing hepatic uptake of fatty acids at certain times of the day. Our results suggest an unacknowledged role for PER2 in regulating the diurnal expression of NHERF1 in mouse liver. This machinery also contributed to diurnal changes in the ability of hepatic cells to uptake fatty acids.',\n", - " 'author': ['Tsurudome, Yuya',\n", - " 'Koyanagi, Satoru',\n", - " 'Kanemitsu, Takumi',\n", - " 'Katamune, Chiharu',\n", - " 'Oda, Masayuki',\n", - " 'Kanado, Yuki',\n", - " 'Kato, Mizuki',\n", - " 'Morita, Akari',\n", - " 'Tahara, Yu',\n", - " 'Matsunaga, Naoya',\n", - " 'Shibata, Shigenobu',\n", - " 'Ohdo, Shigehiro'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-018-27280-w\"}'],\n", - " 'title': ['Circadian clock component PERIOD2 regulates diurnal expression of Na+/H+ exchanger regulatory factor-1 and its scaffolding function']},\n", - " {'bibcode': '1979JRadR..20..329G',\n", - " 'author': ['Gupta, M. L.', 'Singh, R. P.', 'Devi, P. Uma'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1269%2Fjrr.20.329\"}'],\n", - " 'title': ['Protection of mouse liver by 2-mercaptopropionylglycine against beta radiations from injected tritiated water.']},\n", - " {'bibcode': '1977JTEH....2..639W',\n", - " 'author': ['Watson, Sharon A.', 'Hayes, A. Wallace'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1080%2F15287397709529465\"}'],\n", - " 'title': ['Evaluation of possible sites of action of rubratoxin B‑induced polyribosomal disaggregation in mouse liver']},\n", - " {'bibcode': '2023NatSR..13.4632P',\n", - " 'abstract': 'The liver plays a vital role in maintaining whole-body metabolic homeostasis, compound detoxification and has the unique ability to regenerate itself post-injury. Ageing leads to functional impairment of the liver and predisposes the liver to non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). Mapping the molecular changes of the liver with ageing may help to understand the crosstalk of ageing with different liver diseases. A systems-level analysis of the ageing-induced liver changes and its crosstalk with liver-associated conditions is lacking. In the present study, we performed network-level analyses of the ageing liver using mouse transcriptomic data and a protein-protein interaction (PPI) network. A sample-wise analysis using network entropy measure was performed, which showed an increasing trend with ageing and helped to identify ageing genes based on local entropy changes. To gain further insights, we also integrated the differentially expressed genes (DEGs) between young and different age groups with the PPI network and identified core modules and nodes associated with ageing. Finally, we computed the network proximity of the ageing network with different networks of liver diseases and regeneration to quantify the effect of ageing. Our analysis revealed the complex interplay of immune, cancer signalling, and metabolic genes in the ageing liver. We found significant network proximities between ageing and NAFLD, HCC, liver damage conditions, and the early phase of liver regeneration with common nodes including NLRP12, TRP53, GSK3B, CTNNB1, MAT1 and FASN. Overall, our study maps the network-level changes of ageing and their interconnections with the physiology and pathology of the liver.',\n", - " 'author': ['Porukala, Manisri', 'Vinod, P. K.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-023-31315-2\"}'],\n", - " 'title': ['Network-level analysis of ageing and its relationship with diseases and tissue regeneration in the mouse liver']},\n", - " {'bibcode': '2017PLoSO..1287557P',\n", - " 'author': ['Pope, Chad',\n", - " 'Piekos, Stephanie C.',\n", - " 'Chen, Liming',\n", - " 'Mishra, Shashank',\n", - " 'Zhong, Xiao-bo'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0187557\"}'],\n", - " 'title': ['The role of H19, a long non-coding RNA, in mouse liver postnatal maturation']},\n", - " {'bibcode': '2019PLoSO..1427102C',\n", - " 'author': ['Chen, Liming',\n", - " 'Wang, Pei',\n", - " 'Bahal, Raman',\n", - " 'Manautou, José E.',\n", - " 'Zhong, Xiao-bo'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0227102\"}'],\n", - " 'title': ['Ontogenic mRNA expression of RNA modification writers, erasers, and readers in mouse liver']},\n", - " {'bibcode': '2012TRACE..24..183T',\n", - " 'abstract': 'Cryosurgery and hyperthermia treatment are used as a treatment method for malignant tumors. Since liquid nitrogen is used as the cryogens, it is difficult to control the freezing rate and thawing rate. In hyperthermia, there are problems of thermotolerance acquisition by heat shock protein (HSP) and only a few studies regarding hyperthermia with cryosurgery have been investigated. The aims of this study are to produce cryosurgery-hyperthermia system utilizing Stirling Cooler and Peltier device and evaluate hyperthermia after cryosurgery by comparing cryosurgery and hyperthermia on the mouse liver. Normal living liver tissues of mice are divided into 3 groups (cryosurgery and cryosurgery-hyperthermia, hyperthermia), then performed cryosurgery, hyperthermia and hyperthermia followed cryosurgery, applying a 1 cycle rapid freezing and slow thawing method for cryosurgery. The temperatures of the tissue surface and probe were measured during operation, the liver was stained by Hematoxylin-Eosin (HE) after operation and observed under an optical microscope. The results showed measured temperature of rapid freezing and slow thawing. HE stained tissue showed stasis, pyknosis, nucleus disappearance and decreasing stainability in cryosurgery and cryosurgery-hyperthermia group, stasis, pyknosis and degreasing stainability in hyperthermia group. The results suggested cryosurgery-hyperthermia was the most effective to destroy the tissue.',\n", - " 'author': ['Takahashi, Daishi', 'Sone, Kazuya', 'Fukumoto, Ichiro'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://joi.jlc.jst.go.jp/JST.JSTAGE/tjsrae/24.183?from=ADS\"}'],\n", - " 'title': ['Evaluation of Cryosurgery-Hyperthermia Treatment Utilizing Peltier Thermoelectric Effect for Living Tissue']},\n", - " {'bibcode': '2000PNAS...9711198K',\n", - " 'abstract': 'Overexpression of c-Myc in immortalized cells increases cell proliferation, inhibits cell differentiation, and promotes cell transformation. Recent evidence suggests that these effects, however, do not necessarily occur when c-Myc is overexpressed in primary mammalian cells. We sought to determine the immediate effects of transient overexpression of c-Myc in primary cells in vivo by using recombinant adenovirus to overexpress human MYC in mouse liver. Mice were intravenously injected with adenoviruses encoding MYC (Ad/Myc), E2F-1 (Ad/E2F-1), or β-galactosidase (Ad/LacZ). Transgene expression was detectable 4 days after injection. Expression of ectopic c-Myc was immediately accompanied by enlarged and dysmorphic hepatocytes in the absence of significant cell proliferation or apoptosis. These findings were not present in the livers of mice injected with Ad/E2F-1 or Ad/LacZ. Prominent hepatocyte nuclei and nucleoli were associated with the up-regulation of large- and small-subunit ribosomal and nucleolar genes, suggesting that c-Myc may induce their expression to increase cell mass. Our studies support a role for c-Myc in the in vivo control of vertebrate cell size and metabolism independent of cell proliferation.',\n", - " 'author': ['Kim, Sunkyu', 'Li, Qing', 'Dang, Chi V.', 'Lee, Linda A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/97/21/11198\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/97/21/11198\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/97/21/11198\"}'],\n", - " 'title': ['Induction of ribosomal genes and hepatocyte hypertrophy by adenovirus-mediated expression of c-Myc in vivo']},\n", - " {'bibcode': '1998PNAS...95..310P',\n", - " 'abstract': 'To investigate host and viral mechanisms determining hepadnaviral persistence and hepatocarcinogenesis, we developed a mouse model by transplanting woodchuck hepatocytes into the liver of mice that contain the urokinase-type plasminogen activator transgene (uPA) and lack mature B and T lymphocytes due to a recombination activation gene 2 (RAG-2) gene knockout. The woodchuck hepatocytes were transplanted via intrasplenic injection and were found to integrate into the recipient mouse liver cord structure. Normal adult woodchuck hepatocytes proliferated and reconstituted up to 90% of the uPA/RAG-2 mouse liver. uPA/RAG-2 mice containing woodchuck hepatocytes were infectable with woodchuck hepatitis virus (WHV) and showed WHV replication for at least 10 months with titers up to 1 × 1011 virions per ml in the peripheral blood. WHV-infected hepatocytes from chronic carrier woodchucks also established a persistent infection in uPA/RAG-2 mice after an 8- to 12-week lag period of viremia. Although WHV envelope, core, and X proteins were produced in the uPA/RAG-2 mice, no inflammatory host immune response was observed in the liver of WHV-replicating mice. A first antiviral test demonstrated a greater than four orders of magnitude drop in WHV titer in response to interferon α treatment. WHV replication was up-regulated by dexamethasone treatment. Comparison of precancerous lesions in donor woodchucks versus recipient uPA/RAG-2 mice revealed an enrichment of dysplastic precancerous hepatocytes in transplanted mice. Clonal amplification of hepatocytes from a woodchuck with hepatocellular carcinomas was demonstrated by the detection of unique WHV DNA integration patterns in hepatocellular carcinomas that arose in uPA/RAG-2 mice. In the absence of B or T cell-mediated immune responses, WHV establishes a persistent noncytotoxic infection of woodchuck hepatocytes in uPA/RAG-2 chimeric mouse livers. Further studies of the kinetics of hepadnavirus infection and replication in quiescent and proliferating hepatocytes should increase our understanding of hepadnavirus spread and aid in the design of therapies to block or cure persistent infection.',\n", - " 'author': ['Petersen, Joerg',\n", - " 'Dandri, Maura',\n", - " 'Gupta, Sanjeev',\n", - " 'Rogler, Charles E.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/95/1/310\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/95/1/310\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/95/1/310\"}'],\n", - " 'title': ['Liver repopulation with xenogenic hepatocytes in B and T cell-<break/>deficient mice leads to chronic hepadnavirus infection and clonal growth of hepatocellular carcinoma']},\n", - " {'bibcode': '1998EnvMM..32..314T',\n", - " 'author': ['Taras-Valéro, Danièle',\n", - " 'Périn-Roussel, Odette',\n", - " 'Plessis, Marie-José',\n", - " 'Périn, François'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2F%28SICI%291098-2280%281998%2932%3A4%3C314%3A%3AAID-EM4%3E3.0.CO%3B2-9\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2F%28SICI%291098-2280%281998%2932%3A4%3C314%3A%3AAID-EM4%3E3.0.CO2-9\"}'],\n", - " 'title': ['Inhibition of 5,9-dimethyldibenzo[c,g]carbazole-DNA adduct formation in mouse liver by pretreatment with cytochrome P4501A inducers in vivo']},\n", - " {'bibcode': '1981PNAS...78...91H',\n", - " 'abstract': 'We have tested rat liver fructose-bisphosphatase (D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11) and three other gluconeogenic fructose-bisphosphatases as substrates for the catalytic subunit of cyclic AMP-dependent protein kinase. In contrast to the rat liver enzyme, homogeneous preparations of mouse liver, rabbit liver, and pig kidney fructose-bisphosphatase could not be phosphorylated by the kinase. Comparative sodium dodecyl sulfate/polyacrylamide gel electrophoresis of the four above fructose-bisphosphatases revealed that the subunit molecular weight of the isolated rat liver enzyme (ca. 40,000-42,000) was greater than that of mouse liver, rabbit liver, and pig kidney fructose-bisphosphatases (ca. 36,000-37,000). Treatment of 32P-labeled rat liver fructose-bisphosphatase with trypsin resulted in the conversion of the rat liver enzyme to an active species with a subunit molecular weight identical to that of the three other enzymes, with complete loss of the 32P-labeled site. Identical trypsin treatment of pig kidney fructose-bisphosphatase caused no change in the molecular weight of the enzyme. The results suggest that the purified mouse liver, rabbit liver, and pig kidney fructose-bisphosphatases are not substrates for the cyclic AMP-dependent protein kinase in vitro because they lack the phosphorylation-site peptide.',\n", - " 'author': ['Hosey, M. Marlene', 'Marcus, Frank'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/78/1/91\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.78.1.91\"}'],\n", - " 'title': ['Fructose-bisphosphatase as a substrate of cyclic AMP-dependent protein kinase.']},\n", - " {'bibcode': '2023EnTox..38.1153X',\n", - " 'abstract': 'Clinical application of doxorubicin is limited because of its potential side effects. The present study examined whether naringin had protective actions on doxorubicin-induced liver injury. Male BALB/c mice and alpha mouse liver 12 (AML-12) cells were used in this paper. The results showed that AML-12 cells treated with naringin significantly reduced cell injury, reactive oxygen species release and apoptosis level; Moreover, naringin notably alleviated liver injury by decreasing aspartate transaminase, alanine transaminase and malondialdehyde, and increasing superoxide dismutase, glutathione and catalase levels. Mechanism researches indicated that naringin increased the expression levels of sirtuin 1 (SIRT1), and inhibited the downstream inflammatory, apoptotic and oxidative stress signaling pathways. Further validation was obtained by knocking down SIRT1 in vitro, which proved the effects of naringin on doxorubicin-induced liver injury. Therefore, naringin is a valuable lead compound for preventing doxorubicin-induced liver damage by reducing oxidative stress, inflammation, and apoptosis via up-regulation of SIRT1.',\n", - " 'author': ['Xi, Yan',\n", - " 'Chi, Zhongchao',\n", - " 'Tao, Xufeng',\n", - " 'Zhai, Xiaohan',\n", - " 'Zhao, Zirui',\n", - " 'Ren, Jiaqi',\n", - " 'Yang, Shilei',\n", - " 'Dong, Deshi'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Ftox.23755\"}'],\n", - " 'title': ['Naringin against doxorubicin-induced hepatotoxicity in mice through reducing oxidative stress, inflammation, and apoptosis via the up-regulation of SIRT1']},\n", - " {'bibcode': '2023NatCo..14.6827C',\n", - " 'abstract': 'Technologies capable of programmable translation activation offer strategies to develop therapeutics for diseases caused by insufficient gene expression. Here, we present \"translation-activating RNAs\" (taRNAs), a bifunctional RNA-based molecular technology that binds to a specific mRNA of interest and directly upregulates its translation. taRNAs are constructed from a variety of viral or mammalian RNA internal ribosome entry sites (IRESs) and upregulate translation for a suite of target mRNAs. We minimize the taRNA scaffold to 94 nucleotides, identify two translation initiation factor proteins responsible for taRNA activity, and validate the technology by amplifying SYNGAP1 expression, a haploinsufficiency disease target, in patient-derived cells. Finally, taRNAs are suitable for delivery as RNA molecules by lipid nanoparticles (LNPs) to cell lines, primary neurons, and mouse liver in vivo. taRNAs provide a general and compact nucleic acid-based technology to upregulate protein production from endogenous mRNAs, and may open up possibilities for therapeutic RNA research.',\n", - " 'author': ['Cao, Yang',\n", - " 'Liu, Huachun',\n", - " 'Lu, Shannon S.',\n", - " 'Jones, Krysten A.',\n", - " 'Govind, Anitha P.',\n", - " 'Jeyifous, Okunola',\n", - " 'Simmons, Christine Q.',\n", - " 'Tabatabaei, Negar',\n", - " 'Green, William N.',\n", - " 'Holder, Jimmy. L.',\n", - " 'Tahmasebi, Soroush',\n", - " 'George, Alfred L.',\n", - " 'Dickinson, Bryan C.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41467-023-42252-z\"}'],\n", - " 'title': ['RNA-based translation activators for targeted gene upregulation']},\n", - " {'bibcode': '2016Chmsp.163...14L',\n", - " 'author': ['Liu, Jinghui',\n", - " 'Wang, Beilei',\n", - " 'Huang, Pu',\n", - " 'Wang, Hanying',\n", - " 'Xu, Kailun',\n", - " 'Wang, Xiaofeng',\n", - " 'Xu, Lihong',\n", - " 'Guo, Zonglou'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.chemosphere.2016.08.002\"}'],\n", - " 'title': ['Microcystin-LR promotes cell proliferation in the mice liver by activating Akt and p38/ERK/JNK cascades']},\n", - " {'bibcode': '1993WatRe..27..495K',\n", - " 'abstract': 'The occurrence of neuro- and hepatotoxins produced by cyanobacteria (blue-green algae) was assessed in eight lakes and six farm dugouts, located in Alberta. Anatoxin-a, an alkaloid neurotoxin produced by Anabaena flos-aquae, was not detected in the lake blooms with gas chromatography-mass spectrometry (GC-MS). Algal blooms which contained Microcystis aeruginosa almost always had detectable concentrations of microcystin-LR, a peptide hepatotoxin, based on high performance liquid chromatography (HPLC) analyses. Bloom samples from the six farm dugouts contained no detectable quantity of either anatoxin-a or microcystin-LR. However, anatoxin-a and microcystin-LR were detected in algae isolated and subsequently cultured from two separate dugouts. Microcystin-RR was not detected in any bloom sample collected.

Among three lakes studied in greater detail, the concentration of microcystin-LR present in the blooms was highly variable between lakes and temporally within each lake over the limited sampling period. Fast atom bombardment-mass spectrometry (FAB-MS) performed on a composite of several bloom samples from one lake confirmed the identity of microcystin-LR. Bioassays were performed with a subset of the bloom samples to determine acute toxicity to mice. Intraperitoneal injection of bloom extracts containing microcystin-LR resulted in a massive dose-dependent pooling of blood in the liver, shock and very rapid (as quickly as 50 min post-injection) death of injected mice.',\n", - " 'author': ['Kotak, Brian G.',\n", - " 'Kenefick, Sandra L.',\n", - " 'Fritz, David L.',\n", - " 'Rousseaux, Colin G.',\n", - " 'Prepas, Ellie E.',\n", - " 'Hrudey, Steve E.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2F0043-1354%2893%2990050-R\"}'],\n", - " 'title': ['Occurrence and toxicological evaluation of cyanobacterial toxins in Alberta lakes and farm dugouts']},\n", - " {'bibcode': '2008PNAS..10518919R',\n", - " 'abstract': 'Dysregulated Wnt signaling is seen in approximately 30% of hepatocellular carcinomas; thus, finding pathways downstream of the activation of Wnt signaling is key. Here, using cre-lox technology, we deleted the Apc gene in the adult mouse liver and observed a rapid increase in nuclear β-catenin and c-Myc, which is associated with an induction of proliferation that led to hepatomegaly within 4 days of gene deletion. To investigate the downstream pathways responsible for these phenotypes, we analyzed the impact of inactivating APC in the context of deficiency of the potentially key effectors β-catenin and c-Myc. β-catenin loss rescues both the proliferation and hepatomegaly phenotypes after APC loss. However, c-Myc deletion, which rescues the phenotypes of APC loss in the intestine, had no effect on the phenotypes of APC loss in the liver. The consequences of the deregulation of the Wnt pathway within the liver are therefore strikingly different from those observed within the intestine, with the vast majority of Wnt targets being β-catenin-dependent but c-Myc-independent in the liver.',\n", - " 'author': ['Reed, Karen R.',\n", - " 'Athineos, Dimitris',\n", - " 'Meniel, Valerie S.',\n", - " 'Wilkins, Julie A.',\n", - " 'Ridgway, Rachel A.',\n", - " 'Burke, Zoé D.',\n", - " 'Muncan, Vanesa',\n", - " 'Clarke, Alan R.',\n", - " 'Sansom, Owen J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/105/48/18919\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/105/48/18919.full.pdf\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0805778105\"}'],\n", - " 'title': ['B-catenin deficiency, but not Myc deletion, suppresses the immediate phenotypes of APC loss in the liver']},\n", - " {'bibcode': '1974Natur.251..419C',\n", - " 'abstract': 'CELLS growing in a chemically defined, sterol-free medium must synthesise cholesterol or, in the case of L cells, desmosterol1 for membrane formation. Studies by others showed that when cholesterol or desmosterol was added to L-cell cultures the exogenous sterol was utilised and the rate of sterol synthesis was diminished, presumably by a negative feedback mechanism2,3. Our observations4, however, provide new information regarding the structures of sterols that affect sterol synthesis. Exogenous cholesterol and various metabolically related steroids do not inhibit sterol synthesis in mouse liver cell or fibroblast cultures under conditions where derivatives of cholesterol oxygenated in the 7, 20, 22 or 25 positions are highly inhibitory. These inhibitory sterols, at concentrations of 0.02-0.2 µg ml-1 specifically depress the activity of the regulatory enzyme in the sterol synthetic pathway, 3-hydroxy-3-methylgrutaryl-coenzyme A (HMG-CoA) reductase (EC 1.1.1.34), within 6 h.',\n", - " 'author': ['Chen, Harry W.', 'Kandutsch, Andrew A.', 'Waymouth, Charity'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F251419a0\"}'],\n", - " 'title': ['Inhibition of cell growth by oxygenated derivatives of cholesterol']},\n", - " {'bibcode': '1989PNAS...86.7971G',\n", - " 'abstract': 'To study gene mutations in different organs and tissues of an experimental animal, we produced transgenic mice harboring bacteriophage lambda shuttle vectors integrated in the genome in a head-to-tail arrangement. As a target for mutagenesis, the selectable bacterial lacZ gene was cloned in the vector. The integrated vectors were rescued from total genomic DNA with high efficiency by in vitro packaging and propagation of the phages in a LacZ- strain of Escherichia coli C. The background mutation frequencies in brain and liver DNA appeared to be low, as was indicated by the absence of colorless plaques among 138,816 and 168,160 phage isolated from brain and liver DNA, respectively. Treatment of adult female transgenic mice with N-ethyl-N-nitrosourea resulted in a dose-dependent increase of the frequency of mutated vectors isolated from brain DNA, up to 7.4 x 10(-5) at 250 mg of the alkylating agent per kilogram of body weight. At this dose, in liver DNA of the same mice, mutation frequencies were approximately 3 x 10(-5). DNA sequence analysis of four mutant vectors isolated from brain DNA indicated predominantly G.C----A.T transitions. These results demonstrate the value of this transgenic mouse model in studying gene mutations in vivo. In addition to its use in fundamental research, the system could be used as a sensitive, organ-specific, short-term mutagenicity assay.',\n", - " 'author': ['Gossen, Jan A.',\n", - " 'de Leeuw, Wiljo J. F.',\n", - " 'Tan, Cecilia H. T.',\n", - " 'Zwarthoff, Ellen C.',\n", - " 'Berends, Frits',\n", - " 'Lohman, Paul H. M.',\n", - " 'Knook, Dick L.',\n", - " 'Vijg, Jan'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/86/20/7971\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/86/20/7971\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/86/20/7971\"}'],\n", - " 'title': ['Efficient rescue of integrated shuttle vectors from transgenic mice: a model for studying mutations in vivo.']},\n", - " {'bibcode': '2013PNAS..11017975H',\n", - " 'abstract': 'This study shows that absence of the orphan nuclear receptor estrogen-related receptor α (ERR&alpha), a master regulator of cellular energy metabolism, predisposes mice to hepatocellular cancer development when exposed to a known carcinogen. Biochemical and metabolomics studies revealed that loss of ERRα promotes hepatocyte necrosis over apoptosis in response to a carcinogen due to a deficiency in energy production. In addition, we demonstrate that loss of ERRα-dependent regulation of the nuclear factor κB (NF-κB) inhibitor IκBα leads to enhanced NF-κB activity and cytokine gene activation. These findings have particular biological significance in view that rapamycin, a drug currently in use in various clinical settings, has been shown recently to decrease ERRα protein levels and activity in mouse liver.',\n", - " 'author': ['Hong, Eui-Ju',\n", - " 'Levasseur, Marie-Pier',\n", - " 'Dufour, Catherine R.',\n", - " 'Perry, Marie-Claude',\n", - " 'Giguère, Vincent'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/110/44/17975\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1315319110\"}'],\n", - " 'title': ['Loss of estrogen-related receptor α promotes hepatocarcinogenesis development via metabolic and inflammatory disturbances']},\n", - " {'bibcode': '2023RSMS...6403036S',\n", - " 'abstract': \"The toxicity assessment of Lagocephalus inermis, commonly known as smooth blassop, which is commercially exploited in the south-eastern Arabian Sea, was conducted in this study, marking the first of its kind for the region. The experiment involved testing control and standard samples during pre-monsoon and post-monsoon seasons. Gross anatomical features were observed, followed by histopathological examination of hearts, livers, and kidneys of deceased mice to determine toxicity. High-performance liquid chromatography (HPLC) was used to analyze standard tetrodotoxin (TTX) concentrations, which showed characteristic peaks at retention times of 4.83 min (mins), 4.792 min, 4.748 min, and 4.729 min for concentrations of 0.1 mg/ml, 0.08 mg/ml, 0.06 mg/ml, and 0.04 mg/ml, respectively. However, the test samples consisting of liver, ovary, and muscle extracts did not exhibit any characteristic peak indicating the presence of TTX in both seasons. Furthermore, bioassays conducted on the test samples did not show any toxicity symptoms, while standard test mice exhibited characteristic symptoms of TTX poisoning. Histopathological examinations revealed congestion, necrosis, degeneration, and hemorrhages in the liver, heart, and kidney tissues of the standard sample, but no changes were observed in the test sample. Based on the findings, it was concluded that Lagocephalus inermis, as exploited along the Karnataka coast, is not toxic at present. However, considering that the bacteria responsible for the species' toxicity may not be sufficiently present to cause toxicity at the current time, it is imperative for Indian food sanitation authorities to continuously monitor and assess the toxicity of pufferfish consumed in terms of food safety.\",\n", - " 'author': ['Saha, Purbali',\n", - " 'Thomas, Sujitha',\n", - " 'Badanthadka, Murali',\n", - " 'Sharma, Krupesha',\n", - " 'Mathias, Michelle'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.rsma.2023.103036\"}'],\n", - " 'title': ['Toxicity assessment of Tetrodotoxin of commercially exploited smooth blassop Lagocephalus inermis in south-eastern Arabian Sea']},\n", - " {'bibcode': '2022SciA....8N5683T',\n", - " 'abstract': 'Mechanistic study and precision treatment of primary liver cancer (PLC) are hindered by marked heterogeneity, which is challenging to recapitulate in any given liver cancer mouse model. Here, we report the generation of 25 mouse models of PLC by in situ genome editing of hepatocytes recapitulating 25 single or combinations of human cancer driver genes. These mouse tumors represent major histopathological types of human PLCs and could be divided into three human-matched molecular subtypes based on transcriptomic and proteomic profiles. Phenotypical characterization identified subtype- or genotype-specific alterations in immune microenvironment, metabolic reprogramming, cell proliferation, and expression of drug targets. Furthermore, single-cell analysis and expression tracing revealed spatial and temporal dynamics in expression of pyruvate kinase M2 ( Pkm2 ). Tumor-specific knockdown of Pkm2 by multiplexed genome editing reversed the Warburg effect and suppressed tumorigenesis in a genotype-specific manner. Our study provides mouse PLC models with defined genetic drivers and characterized phenotypical heterogeneity suitable for mechanistic investigation and preclinical testing. Mouse liver tumor model panel reveals diverse human-matched and therapy-related phenotypical and molecular characters.',\n", - " 'author': ['Tang, Mei',\n", - " 'Zhao, Yang',\n", - " 'Zhao, Jianhui',\n", - " 'Wei, Shumei',\n", - " 'Liu, Mingwei',\n", - " 'Zheng, Nairen',\n", - " 'Geng, Didi',\n", - " 'Han, Shixun',\n", - " 'Zhang, Yuchao',\n", - " 'Zhong, Guoxuan',\n", - " 'Li, Shuaifeng',\n", - " 'Zhang, Xiuming',\n", - " 'Wang, Chenliang',\n", - " 'Yan, Huan',\n", - " 'Cao, Xiaolei',\n", - " 'Li, Li',\n", - " 'Bai, Xueli',\n", - " 'Ji, Junfang',\n", - " 'Feng, Xin-Hua',\n", - " 'Qin, Jun',\n", - " 'Liang, Tingbo',\n", - " 'Zhao, Bin'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fsciadv.abn5683\"}'],\n", - " 'title': ['Liver cancer heterogeneity modeled by in situ genome editing of hepatocytes']},\n", - " {'bibcode': '2022Chmsp.300m4566Z',\n", - " 'author': ['Zhong, Gaolong',\n", - " 'Rao, Gan',\n", - " 'Tang, Lixuan',\n", - " 'Wu, Shaofeng',\n", - " 'Tang, Zhaoxin',\n", - " 'Huang, Riming',\n", - " 'Ruan, Zhiyan',\n", - " 'Hu, Lianmei'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.chemosphere.2022.134566\"}'],\n", - " 'title': ['Combined effect of arsenic and polystyrene-nanoplastics at environmentally relevant concentrations in mice liver: Activation of apoptosis, pyroptosis and excessive autophagy']},\n", - " {'bibcode': '1996Sci...274.1379C',\n", - " 'abstract': 'Liver regeneration stimulated by a loss of liver mass leads to hepatocyte and nonparenchymal cell proliferation and rapid restoration of liver parenchyma. Mice with targeted disruption of the interleukin-6 (IL-6) gene had impaired liver regeneration characterized by liver necrosis and failure. There was a blunted DNA synthetic response in hepatocytes of these mice but not in nonparenchymal liver cells. Furthermore, there were discrete G_1 phase (prereplicative stage in the cell cycle) abnormalities including absence of STAT3 (signal transducer and activator of transcription protein 3) activation and depressed AP-1, Myc, and cyclin D1 expression. Treatment of IL-6-deficient mice with a single preoperative dose of IL-6 returned STAT3 binding, gene expression, and hepatocyte proliferation to near normal and prevented liver damage, establishing that IL-6 is a critical component of the regenerative response.',\n", - " 'author': ['Cressman, Drew E.',\n", - " 'Greenbaum, Linda E.',\n", - " 'Deangelis, Robert A.',\n", - " 'Ciliberto, Gennaro',\n", - " 'Furth, Emma E.',\n", - " 'Poli, Valeria',\n", - " 'Taub, Rebecca'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.274.5291.1379\"}'],\n", - " 'title': ['Liver Failure and Defective Hepatocyte Regeneration in Interleukin-6-Deficient Mice']},\n", - " {'bibcode': '1976Natur.263..146E',\n", - " 'abstract': 'α-FOETOPROTEIN (AFP) is a serum protein present in large amounts during embryonic life and preserved in only nanogram quantities in adult mammals1. Increased levels of AFP are seen in adults in association with two forms of tumours-teratocarcinomas and hepatocarcinomas-and also during liver regeneration2. In early development AFP is synthesised in the yolk sac and in the liver2,3 where it has been demonstrated by immunofluorescence in the majority of the hepatocytes4. Detailed aspects of AFP synthesis by hepatocytes, however, remain to be established. It has been suggested that it is synthesised by a definite population of hepatocytes5, by one of the stages in their differentiation6,7, or by liver cell precursors8. Sufficient data to decide between these alternatives are not presently available. We describe here the immunohistochemical localisation of AFP in regenerating mouse livers, in which DNA-synthesising cells have been identified by thymidine incorporation. AFP was found in a minority of adult differentiated hepatocytes, many of which had not progressed through S phase. Thus DNA synthesis is not a prerequisite for the induction of AFP synthesis in the adult liver.',\n", - " 'author': ['Engelhardt, N. V.',\n", - " 'Lazareva, M. N.',\n", - " 'Abelev, G. I.',\n", - " 'Uryvaeva, I. V.',\n", - " 'Factor, V. M.',\n", - " 'Brodsky, V. Ya.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F263146a0\"}'],\n", - " 'title': ['Detection of α-foetoprotein in mouse liver differentiated hepatocytes before their progression through S phase']},\n", - " {'bibcode': '1959Natur.183.1674N',\n", - " 'abstract': 'THE amount of diphosphopyridine nucleotide in mouse liver has been shown to increase upon the intraperitoneal injection of a number of pyridine derivatives1,2; nicotinamide is the most effective, raising the level 8-10 times. Although nicotinic acid is as effective as many of the analogues, it appears to inhibit the synthesis when administered with nicotinamide, as compared with nicotinamide alone. Inhibition of synthesis from nicotinamide injection has also been reported with the administration of the purine antagonists 6-mercaptopurine and thioguanine1,3. These inhibitions appear to affect only the level of diphosphopyridine nucleotide attained from nicotinamide injection and the rate of its subsequent return to the normal level, but do not appear to affect the basal level normally found in the liver.',\n", - " 'author': ['Narrod, Stuart A.',\n", - " 'Langan, Thomas A.',\n", - " 'Kaplan, Nathan O.',\n", - " 'Goldin, Abraham'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F1831674b0\"}'],\n", - " 'title': ['Effect of Azaserine (o-Diazoacetyl-L- serine) on the Pyridine Nucleotide Levels of Mouse Liver']},\n", - " {'bibcode': '2016NatSR...635898S',\n", - " 'author': ['Szunyogova, Eva',\n", - " 'Zhou, Haiyan',\n", - " 'Maxwell, Gillian K.',\n", - " 'Powis, Rachael A.',\n", - " 'Muntoni, Francesco',\n", - " 'Gillingwater, Thomas H.',\n", - " 'Parson, Simon H.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep35898\"}'],\n", - " 'title': ['Corrigendum: Survival Motor Neuron (SMN) protein is required for normal mouse liver development']},\n", - " {'bibcode': '2016PLoSO..1146730N',\n", - " 'author': ['Nakajima, Tetsuo',\n", - " 'Vares, Guillaume',\n", - " 'Wang, Bing',\n", - " 'Nenoi, Mitsuru'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0146730\"}'],\n", - " 'title': ['Chronic Intake of Japanese Sake Mediates Radiation-Induced Metabolic Alterations in Mouse Liver']},\n", - " {'bibcode': '2022PLoSO..1773049S',\n", - " 'abstract': 'Nonalcoholic fatty liver disease (NALFD), characterized by an abnormal accumulation of triglycerides in hepatocytes, is closely linked to insulin resistance, metabolic syndrome, and changes in lipogenesis in the liver. The accumulation of hepatic lipids can lead to a range of pathologies from mild steatosis to severe cirrhosis. Endurance exercise is known to ameliorate the adverse health effects of NAFLD. Therefore, we aimed to investigate the effect of voluntary wheel running (VWR) on the metabolic changes in the livers of high-fat diet (HFD)-induced NAFLD mice and used LC-MS/MS (Liquid chromatography–mass spectrometry) to determine whether the tested intervention affected the protein expression profiles of the mouse livers. Male C57BL/6 mice were randomly divided into three groups: control (CON), high-fat diet sedentary group (HFD), high-fat diet VWR group (HFX). HFX group performed voluntary wheel running into individually cages, given a high-fat diet for 12 weeks. Food consumption, body weight, and running distance were measured every week. Using 2D (2-dimensional)-gel electrophoresis, we detected and quantitatively analyzed the protein expression with >2.0-fold change in the livers of HFD-fed mice, HFD-fed exercise (HFX) mice, and chow-fed mice. Body weight was significantly increased in HFD compared to CON (P < 0.05). The 2D-gel electrophoresis analysis indicated that there was a difference between CON and HFD groups, showing 31 increased and 27 decreased spots in the total 302 paired spots in the HFD group compared to CON. The analysis showed 43 increased and 17 decreased spots in the total 258 spots in the HFX group compared to CON. Moreover, 12 weeks of VWR showed an increase of 35 and a decrease of 8 spots in a total of 264 paired spots between HFD and HFX. LC-MS/MS of HFD group revealed that proteins involved in ketogenesis, lipid metabolism, and the metabolism of drugs and xenobiotics were upregulated, whereas detoxifying proteins, mitochondrial precursors, transport proteins, proteasomes, and proteins involved in amino acid metabolism were downregulated. On the other hand, VWR counteracted the protein expression profile of HFD-fed mice by upregulating molecular chaperones, gluconeogenesis-, detoxification-, proteasome-, and energy metabolism-related proteins. This study provided a molecular understanding of the HFD- and exercise-induced protein marker expression and presented the beneficial effects of exercise during pathophysiological conditions.',\n", - " 'author': ['So, Byunghun', 'Ji, Li Li', 'Imdad, Saba', 'Kang, Chounghun'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0273049\"}'],\n", - " 'title': ['Proteomic analysis of the effect of high-fat-diet and voluntary physical activity on mouse liver']},\n", - " {'bibcode': '2014PLoSO...9j0170.',\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0100170\"}'],\n", - " 'title': ['Correction: Dual Mode Action of Mangiferin in Mouse Liver under High Fat Diet']},\n", - " {'bibcode': '1982JESHB..17..527E',\n", - " 'author': ['El-Scwedy, S. M.',\n", - " 'Zahran, M. A.',\n", - " 'Zeidan, M. A.',\n", - " 'Mostafa, M. H.',\n", - " 'El-Bassiouni, E. A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1080%2F03601238209372339\"}'],\n", - " 'title': ['Effect and mechanism of action of methomyl and cypermethrin insecticides on kynurenine metabolizing enzymes of mouse liver']},\n", - " {'bibcode': '2016SQER...27..559Z',\n", - " 'author': ['Zhu, X. -W.', 'Xin, Y. -J.', 'Chen, Q. -H.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1080%2F1062936X.2016.1201142\"}'],\n", - " 'title': ['Chemical and in vitro biological information to predict mouse liver toxicity using recursive random forests']},\n", - " {'bibcode': '2023ScTEn.905p7316Z',\n", - " 'author': ['Zhang, Yaru',\n", - " 'Yan, Zhipeng',\n", - " 'Nan, Nan',\n", - " 'Qin, Guohua',\n", - " 'Sang, Nan'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.scitotenv.2023.167316\"}'],\n", - " 'title': ['Circadian rhythm disturbances involved in ozone-induced glucose metabolism disorder in mouse liver']},\n", - " {'bibcode': '2014PLoSO...9j6371H',\n", - " 'author': ['Haddock, Christopher J.',\n", - " 'Blomenkamp, Keith',\n", - " 'Gautam, Madhav',\n", - " 'James, Jared',\n", - " 'Mielcarska, Joanna',\n", - " 'Gogol, Edward',\n", - " 'Teckman, Jeffrey',\n", - " 'Skowyra, Dorota'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0106371\"}'],\n", - " 'title': ['PiZ Mouse Liver Accumulates Polyubiquitin Conjugates That Associate with Catalytically Active 26S Proteasomes']},\n", - " {'bibcode': '1991JTEH...34..385V',\n", - " 'author': ['Vorce, Roseann L.', 'Goodman, Jay I.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1080%2F15287399109531575\"}'],\n", - " 'title': ['Differential DNase I hypersensitivity ofrasoncogenes in B6C3F1, C3H/He, and C57BL/6 mouse liver']},\n", - " {'bibcode': '1993RadR..133..334M',\n", - " 'author': ['Maisin, J. R.',\n", - " 'Vankerkom, J.',\n", - " 'de Saint-Georges, L.',\n", - " 'Janowski, M.',\n", - " 'Lambiet-Collier, M.',\n", - " 'Mattelin, G.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.2307%2F3578218\"}'],\n", - " 'title': ['Effect of X Rays Alone or Combined with Diethylnitrosamine on Tumor Induction in Infant Mouse Liver']},\n", - " {'bibcode': '1969RadR...40..213K',\n", - " 'author': ['Kleinbergs, S.', 'Bernstein, I. A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.2307%2F3572995\"}'],\n", - " 'title': ['The Effects of Whole-Body X-Irradiation on Mouse Liver Alpha-Hydroxy Acid Oxidase']},\n", - " {'bibcode': '1982NIMPR.197..185L',\n", - " 'abstract': 'It is well known that certain diseases and environmental pollution effects are manifested in changes of microelement levels in the blood. A study was initiated to elucidate whether such variations of microelement levels are reflected even at the tissue level. Two pools of samples were studied, viz. healthy tissue and tissue where perturbation of the microelement level had occurred through exposure to lead. The organ selected was the mouse liver. Small samples were excised from the same location of each of the four lobes and tissue sections prepared for elemental characterisation in the nuclear microprobe. The specimens were scanned in a raster pattern. The X-ray spectrum was continuously recorded together with the actual Cartesian coordinates. The tissue sections were thus characterised through elemental maps. The maps from the control group displayed small variations between the elemental contents of the different sampling areas; the elements considered were sulphur, chlorine, potassium, calcium, manganese, iron, copper, zinc and bromine. The inter-cellular variations were generally small. The maps from the group which had been exposed to lead showed a marked variation in lead content both between different individual parts of the sections and between different sampling areas.',\n", - " 'author': ['Lindh, Ulf'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2F0167-5087%2882%2990135-1\"}'],\n", - " 'title': ['Elemental mapping of tissue sections at cellular resolution: A nuclear microprobe investigation']},\n", - " {'bibcode': '2015JMSp...50..951D',\n", - " 'author': ['dos Santos, Gustavo Aparecido',\n", - " 'Ferreira, Mônica Siqueira',\n", - " 'de Oliveira, Diogo Noin',\n", - " 'de Oliveira, Vanessa',\n", - " 'Siqueira-Santos, Edilene S.',\n", - " 'Cintra, Dennys Esper Corrêa',\n", - " 'Castilho, Roger Frigério',\n", - " 'Velloso, Lício Augusto',\n", - " 'Catharino, Rodrigo Ramos'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Fjms.3609\"}'],\n", - " 'title': ['Identification of compounds from high-fat and extra virgin olive oil-supplemented diets in whole mouse liver extracts and isolated mitochondria using mass spectrometry']},\n", - " {'bibcode': '2020JMoSt121528251C',\n", - " 'abstract': \"The hearts, kidneys, livers, spleens and brains of 57Fe enriched wild-type and heterozygous β-thalassaemic mice at 1, 3, 6 and 9 months of age were studied by means of Mössbauer Spectroscopy at 80 K. Ferritin-like iron depositions in the heart and the brain of the thalassaemic mice were found to be slightly increased while significant amounts of Ferritin-like iron were found in the kidneys, liver and spleen. The Ferritin-like iron doublet, found in the organs, could be further separated into two sub-doublets representing the inner and surface structures of ferritin's mineral core. Surface iron sites were found to be predominant in the hearts and brains of all mice and in the kidneys of the wild-type animals. Ferritin rich in inner iron sites was predominant in the kidneys of the thalassaemic mice, as well as in the livers and in the spleens. The inner-to-surface iron sites ratio was elevated in all thalassaemic samples indicating that besides ferritin amount, the disease can also affect ferritin's mineral core structure.\",\n", - " 'author': ['Charitou, George',\n", - " 'Tsertos, Charalambos',\n", - " 'Parpottas, Yiannis',\n", - " 'Kleanthous, Marina',\n", - " 'Lederer, Carsten W.',\n", - " 'Phylactides, Marios'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.molstruc.2020.128251\"}'],\n", - " 'title': ['Study of iron complexes in visceral organs and brain from a 57Fe enriched β-thalassaemia mouse model via Mössbauer spectroscopy']},\n", - " {'bibcode': '2007PNAS..104.3342M',\n", - " 'abstract': 'Circadian rhythms of cell and organismal physiology are controlled by an autoregulatory transcription-translation feedback loop that regulates the expression of rhythmic genes in a tissue-specific manner. Recent studies have suggested that components of the circadian pacemaker, such as the Clock and Per2 gene products, regulate a wide variety of processes, including obesity, sensitization to cocaine, cancer susceptibility, and morbidity to chemotherapeutic agents. To identify a more complete cohort of genes that are transcriptionally regulated by CLOCK and/or circadian rhythms, we used a DNA array interrogating the mouse protein-encoding transcriptome to measure gene expression in liver and skeletal muscle from WT and Clock mutant mice. In WT tissue, we found that a large percentage of expressed genes were transcription factors that were rhythmic in either muscle or liver, but not in both, suggesting that tissue-specific output of the pacemaker is regulated in part by a transcriptional cascade. In comparing tissues from WT and Clock mutant mice, we found that the Clock mutation affects the expression of many genes that are rhythmic in WT tissue, but also profoundly affects many nonrhythmic genes. In both liver and skeletal muscle, a significant number of CLOCK-regulated genes were associated with the cell cycle and cell proliferation. To determine whether the observed patterns in cell-cycle gene expression in Clock mutants resulted in functional dysregulation, we compared proliferation rates of fibroblasts derived from WT or Clock mutant embryos and found that the Clock mutation significantly inhibits cell growth and proliferation.',\n", - " 'author': ['Miller, Brooke H.',\n", - " 'McDearmon, Erin L.',\n", - " 'Panda, Satchidananda',\n", - " 'Hayes, Kevin R.',\n", - " 'Zhang, Jie',\n", - " 'Andrews, Jessica L.',\n", - " 'Antoch, Marina P.',\n", - " 'Walker, John R.',\n", - " 'Esser, Karyn A.',\n", - " 'Hogenesch, John B.',\n", - " 'Takahashi, Joseph S.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/104/9/3342\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0611724104\"}'],\n", - " 'title': ['Circadian and CLOCK-controlled regulation of the mouse transcriptome and cell proliferation']},\n", - " {'bibcode': '2015NatSR...512801J',\n", - " 'abstract': 'Circadian clocks orchestrate essential physiology in response to various cues, yet their mechanistic and functional plasticity remains unclear. Here, we investigated ClockΔ19/+ heterozygous (Clk/+) mice, known to display lengthened periodicity and dampened amplitude, as a model of partially perturbed clocks. Interestingly, Clk/+ mice exhibited improved glycemic control and resistance to circadian period lengthening under high-fat diet (HFD). Furthermore, BMAL1 protein levels in Clk/+ mouse liver were upregulated compared with wild-type (WT) mice under HFD. Pharmacological and molecular studies showed that BMAL1 turnover entailed proteasomal and autophagic activities, and CLOCKΔ19 attenuated both processes. Consistent with an important role of BMAL1 in glycemic control, enhanced activation of insulin signaling was observed in Clk/+ mice relative to WT in HFD. Finally, transcriptome analysis revealed reprogramming of clock-controlled metabolic genes in Clk/+ mice. Our results demonstrate a novel role of autophagy in circadian regulation and reveal an unforeseen plasticity of circadian and metabolic networks.',\n", - " 'author': ['Jeong, Kwon',\n", - " 'He, Baokun',\n", - " 'Nohara, Kazunari',\n", - " 'Park, Noheon',\n", - " 'Shin, Youngmin',\n", - " 'Kim, Seonghwa',\n", - " 'Shimomura, Kazuhiro',\n", - " 'Koike, Nobuya',\n", - " 'Yoo, Seung-Hee',\n", - " 'Chen, Zheng'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep12801\"}'],\n", - " 'title': ['Dual attenuation of proteasomal and autophagic BMAL1 degradation in ClockΔ19/+ mice contributes to improved glucose homeostasis']},\n", - " {'bibcode': '2014Natur.505...97D',\n", - " 'abstract': 'Chemical or traumatic damage to the liver is frequently associated with aberrant healing (fibrosis) that overrides liver regeneration. The mechanism by which hepatic niche cells differentially modulate regeneration and fibrosis during liver repair remains to be defined. Hepatic vascular niche predominantly represented by liver sinusoidal endothelial cells deploys paracrine trophogens, known as angiocrine factors, to stimulate regeneration. Nevertheless, it is not known how pro-regenerative angiocrine signals from liver sinusoidal endothelial cells is subverted to promote fibrosis. Here, by combining an inducible endothelial-cell-specific mouse gene deletion strategy and complementary models of acute and chronic liver injury, we show that divergent angiocrine signals from liver sinusoidal endothelial cells stimulate regeneration after immediate injury and provoke fibrosis after chronic insult. The pro-fibrotic transition of vascular niche results from differential expression of stromal-derived factor-1 receptors, CXCR7 and CXCR4 (refs 18, 19, 20, 21), in liver sinusoidal endothelial cells. After acute injury, CXCR7 upregulation in liver sinusoidal endothelial cells acts with CXCR4 to induce transcription factor Id1, deploying pro-regenerative angiocrine factors and triggering regeneration. Inducible deletion of Cxcr7 in sinusoidal endothelial cells (Cxcr7iΔEC/iΔEC) from the adult mouse liver impaired liver regeneration by diminishing Id1-mediated production of angiocrine factors. By contrast, after chronic injury inflicted by iterative hepatotoxin (carbon tetrachloride) injection and bile duct ligation, constitutive FGFR1 signalling in liver sinusoidal endothelial cells counterbalanced CXCR7-dependent pro-regenerative response and augmented CXCR4 expression. This predominance of CXCR4 over CXCR7 expression shifted angiocrine response of liver sinusoidal endothelial cells, stimulating proliferation of desmin+ hepatic stellate-like cells and enforcing a pro-fibrotic vascular niche. Endothelial-cell-specific ablation of either Fgfr1 (Fgfr1iΔEC/iΔEC) or Cxcr4 (Cxcr4iΔEC/iΔEC) in mice restored the pro-regenerative pathway and prevented FGFR1-mediated maladaptive subversion of angiocrine factors. Similarly, selective CXCR7 activation in liver sinusoidal endothelial cells abrogated fibrogenesis. Thus, we demonstrate that in response to liver injury, differential recruitment of pro-regenerative CXCR7-Id1 versus pro-fibrotic FGFR1-CXCR4 angiocrine pathways in vascular niche balances regeneration and fibrosis. These results provide a therapeutic roadmap to achieve hepatic regeneration without provoking fibrosis.',\n", - " 'author': ['Ding, Bi-Sen',\n", - " 'Cao, Zhongwei',\n", - " 'Lis, Raphael',\n", - " 'Nolan, Daniel J.',\n", - " 'Guo, Peipei',\n", - " 'Simons, Michael',\n", - " 'Penfold, Mark E.',\n", - " 'Shido, Koji',\n", - " 'Rabbany, Sina Y.',\n", - " 'Rafii, Shahin'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature12681\"}'],\n", - " 'title': ['Divergent angiocrine signals from vascular niche balance liver regeneration and fibrosis']},\n", - " {'bibcode': '1994PNAS...91.3107V',\n", - " 'abstract': 'Peroxisomal acyl-CoA oxidase (ACOX; EC 1.3.3.6) is the first enzyme of the fatty acid beta-oxidation pathway, which catalyzes the desaturation of acyl-CoAs to 2-trans-enoyl-CoAs, and it donates electrons directly to molecular oxygen, thereby producing H2O2. The discovery of carcinogenic peroxisome proliferators, which markedly increase the levels of this H2O2-producing ACOX in rat and mouse liver, generated interest in peroxisomal beta-oxidation system genes. The present study deals with the structural organization of human ACOX gene. This gene spans approximately 33 kb and consists of 14 exons and 13 introns. Primer-extension analysis revealed three principal cap sites, which were mapped at 50, 52, and 53 nt upstream of the initiator methionine codon. The 5\\' flanking region of the ACOX gene was sequenced up to 500 bp upstream of the cap sites. This promoter region is G + C-rich and contains three copies of the \"GC box\" hexanucleotides. Multiple GC boxes are a characteristic feature of the rat ACOX and bifunctional protein genes of the beta-oxidation system. A + T-rich TATA-boxlike sequences, TTTATTT and TTATT, have also been identified in this human ACOX gene, but typical CCAAT motifs are absent. This ACOX gene has been mapped to chromosome 17q25 by in situ hybridization, using a biotinlabeled probe.',\n", - " 'author': ['Varanasi, Usha',\n", - " 'Chu, Ruiyin',\n", - " 'Chu, Su',\n", - " 'Espinosa, Rafael',\n", - " 'Lebeau, Michelle M.',\n", - " 'Reddy, Janardan K.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/91/8/3107\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/91/8/3107\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/91/8/3107\"}'],\n", - " 'title': ['Isolation of the human peroxisomal acyl-CoA oxidase gene: organization, promoter analysis, and chromosomal localization.']},\n", - " {'bibcode': '1997PNAS...94.6831L',\n", - " 'abstract': 'We present a novel subtractive enrichment protocol for the identification of differentially expressed mRNA species. This procedure, called SABRE (selective amplification via biotin- and restriction-mediated enrichment), uses selective streptavidin-biotin affinity and restriction enzyme site reconstitution to enrich for cDNA species more abundant in one population than in another. Analysis of liver cDNA from a mouse strain expressing the neomycin resistance gene demonstrated that this procedure is capable of identifying species present in one population but absent from another. Furthermore, experiments to identify genes with circadian expression patterns in mouse liver demonstrated that SABRE is capable of detecting even modest 2- to 10-fold differences in accumulation of moderately rare mRNA species, representing as little as 0.03% of total mRNA. These experiments identified the gene encoding coumarin 7-hydroxylase as displaying circadian expression in mouse liver.',\n", - " 'author': ['Lavery, Daniel J.',\n", - " 'Lopez-Molina, Luis',\n", - " 'Fleury-Olela, Fabienne',\n", - " 'Schibler, Ueli'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/94/13/6831\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/94/13/6831\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/94/13/6831\"}'],\n", - " 'title': ['Selective Amplification via Biotin- and Restriction-Mediated Enrichment (SABRE), a Novel Selective Amplification Procedure for Detection of Differentially Expressed mRNAs']},\n", - " {'bibcode': '1963Sci...142..392R',\n", - " 'abstract': 'Delayed utilization of tritiated thymidine by regenerating mouse liver can be almost completely suppressed by a continuous infusion of nonradioactive thymidine. In addition, as shown earlier for lymphocytes, labeled granulocytes are a potential source of the tritium marker. These observations suggest that the delayed incorporation of label into DNA must be due to the transfer of labeled nucleoside, which may be derived either from the degradation of DNA or from a long-lived intracellular pool. In either case, the transferred material probably originates from all tissues that have a high rate of cell turnover.',\n", - " 'author': ['Robinson, Stephen H.', 'Brecher, George'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.jstor.org/stable/1712263?origin=ads\"}'],\n", - " 'title': ['Delayed Incorporation of Tritiated Thymidine into DNA']},\n", - " {'bibcode': '2001Sci...292.1546K',\n", - " 'abstract': 'Mature erythrocytes in mammals have no nuclei, although they differentiate from nucleated precursor cells. The mechanism by which enucleation occurs is not well understood. Here we show that deoxyribonuclease II (DNase II) is indispensable for definitive erythropoiesis in mouse fetal liver. No live DNase II-null mice were born, owing to severe anemia. When mutant fetal liver cells were transferred into lethally irradiated wild-type mice, mature red blood cells were generated from the mutant cells, suggesting that DNase II functions in a non-cell-autonomous manner. Histochemical analyses indicated that the critical cellular sources of DNase II are macrophages present at the site of definitive erythropoiesis in the fetal liver. Thus, DNase II in macrophages appears to be responsible for destroying the nuclear DNA expelled from erythroid precursor cells.',\n", - " 'author': ['Kawane, Kohki',\n", - " 'Fukuyama, Hidehiro',\n", - " 'Kondoh, Gen',\n", - " 'Takeda, Junji',\n", - " 'Ohsawa, Yoshiyuki',\n", - " 'Uchiyama, Yasuo',\n", - " 'Nagata, Shigekazu'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.292.5521.1546\"}'],\n", - " 'title': ['Requirement of DNase II for Definitive Erythropoiesis in the Mouse Fetal Liver']},\n", - " {'bibcode': '2017PNAS..114..722X',\n", - " 'abstract': 'Because genome-wide CRISPR/Cas9 libraries are mostly constructed in lentiviral vectors, direct in vivo screening has not been possible as a result of low efficiency in delivery. Here, we examined the piggyBac (PB) transposon as an alternative vehicle to deliver a guide RNA (gRNA) library for in vivo screening. Through hydrodynamic tail vein injections, we delivered a PB-CRISPR library into mouse liver. Rapid tumor formation could be observed in less than 2 mo. By sequencing analysis of PB-mediated gRNA insertions, we identified corresponding genes mediating tumorigenesis. Our results demonstrate that PB is a simple and nonviral choice for efficient in vivo delivery of CRISPR libraries for phenotype-driven screens.',\n", - " 'author': ['Xu, Chunlong',\n", - " 'Qi, Xiaolan',\n", - " 'Du, Xuguang',\n", - " 'Zou, Huiying',\n", - " 'Gao, Fei',\n", - " 'Feng, Tao',\n", - " 'Lu, Hengxing',\n", - " 'Li, Shenglan',\n", - " 'An, Xiaomeng',\n", - " 'Zhang, Lijun',\n", - " 'Wu, Yuanyuan',\n", - " 'Liu, Ying',\n", - " 'Li, Ning',\n", - " 'Capecchi, Mario R.',\n", - " 'Wu, Sen'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1615735114\"}'],\n", - " 'title': ['piggyBac mediates efficient in vivo CRISPR library screening for tumorigenesis in mice']},\n", - " {'bibcode': '2014PNAS..111.6269K',\n", - " 'abstract': 'In response to a variety of extracellular stimuli, signal transducer and activator of transcription 3 (STAT3) is phosphorylated on Tyr705 (pYSTAT3) or Ser727 (pSSTAT3), and signal transmission by those stimuli depend on pYSTAT3 as well as pSSTAT3 and unphosphorylated protein (USTAT3). Here we prepared an intrabody (an antibody that is expressed within the cell) that binds specifically to the tyrosine-phosphorylated site of pYSTAT3 and demonstrated that the engineered intrabody is able to block selectively the downstream effects of pYSTAT3 without influencing those of pSSTAT3 and USTAT3 in cultured cells as well as mouse liver. Our results demonstrate the potential of intrabodies as tools to dissect the cellular functions of specific modified forms of proteins that exist as multiple species.',\n", - " 'author': ['Koo, Mi Young',\n", - " 'Park, Jiyoung',\n", - " 'Lim, Jung Mi',\n", - " 'Joo, Sei Yoon',\n", - " 'Shin, Seung-Pil',\n", - " 'Shim, Hyun Bo',\n", - " 'Chung, Junho',\n", - " 'Kang, Dongmin',\n", - " 'Woo, Hyun Ae',\n", - " 'Rhee, Sue Goo'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/111/17/6269\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1316815111\"}'],\n", - " 'title': ['Selective inhibition of the function of tyrosine-phosphorylated STAT3 with a phosphorylation site-specific intrabody']},\n", - " {'bibcode': '2018cosp...42E3745Y',\n", - " 'abstract': 'Diosmin (Diosmetin 7-O-rutinoside) is a natural flavonoid compound extracted from Galium verum L. (Rubiaceae) and has significant effects on the treatment of chronic venous insufficiency, postoperative edema and hemorrhoids. Our research group found that Diosmin also has anti-radiation effect, and the anti-radiation mechanism of Diosmin was studied through in vitro cell experiments, animal experiments and differential protein spots of mouse liver radiation-damaged proteins to obtain the following results: (1) Cell experiment: The splenic lymphocytes of Rattus norvegicus (SD rats) and PC12 cells were cultured in vitro and irradiated by 60Co-γ ray. It has been experimentally demonstrated that the addition of Diosmin to the cells before irradiation to the final concentration of 80μg/ml, can promote cell proliferation and improve cell survival. Meanwhile, at this dose, the activities of superoxide dismutase (SOD) Glutathione peroxidase (GSH-px) increased and the content of intracellular malondialdehyde (MDA) decreased. By measuring the cell cycle and apoptosis in PC12 cells, it was found that Diosmin can promote cell differentiation and reduce the damage brought about by irradiation of cells. (2) Animal experiments: By establishing 60Co-γray irradiation model, the indices of Kunming mice given Diosmin continually for 14 days were measured. It was noted that Diosmin can play a protective role in white blood cells and immune organs such as liver and spleen. The activities of SOD and GSH-px in mouse tissues were improved and the content of MDA, the rate of chromosome aberration and micronuclei in bone marrow decreased. The experimental results above suggested that Diosmin can enhance the antioxidant activity by increasing endogenous antioxidant enzyme activity, decrease DNA damage and protect mice from radiation damage. (3) Through the 2D-PAGE analysis of the liver protein of mice in radiation protection experiment, 10 protein spots with significant difference were selected for MALDI-TOF-MS analysis and proved to be acetylcholinesterase A-acylase 2, peptidyl-proline cis-transisomerase A, 3-hydroxybenzoate 3, 4 double oxidase, three-dimensional structure - myosin-V, heterogeneous nuclear ribonucleoprotein A2 / B1, (TPI), fructose-bisphosphate aldolase B, protein disulfide isomerase, hemoglobin β subunit, and mitochondrial ATP synthase β subunit.',\n", - " 'author': ['Yang, Yuming',\n", - " 'Lu, Weihong*',\n", - " 'Liu, Mengyao',\n", - " 'Cheng, Cuilin'],\n", - " 'title': ['Study on anti-radiation mechanism of Diosmin']},\n", - " {'bibcode': '2013AcSpA.110..241S',\n", - " 'abstract': 'In this study, we made a new approach to evaluate aluminium induced metabolic changes in liver tissue of mice using Fourier transform infrared spectroscopy analysis taking one step further in correlation with strong biochemical evidence. This finding reveals the alterations on the major biochemical constituents, such as lipids, proteins, nucleic acids and glycogen of the liver tissues of mice. The peak area value of amide A significantly decrease from 288.278 ± 3.121 to 189.872 ± 2.012 between control and aluminium treated liver tissue respectively. Amide I and amide II peak area value also decrease from 40.749 ± 2.052 to 21.170 ± 1.311 and 13.167 ± 1.441 to 8.953 ± 0.548 in aluminium treated liver tissue respectively. This result suggests an alteration in the protein profile. The absence of olefinicdbnd CH stretching band and Cdbnd O stretching of triglycerides in aluminium treated liver suggests an altered lipid levels due to aluminium exposure. Significant shift in the peak position of glycogen may be the interruption of aluminium in the calcium metabolism and the reduced level of calcium. The overall findings exhibit that the liver metabolic program is altered through increasing the structural modification in proteins, triglycerides and quantitative alteration in proteins, lipids, and glycogen. All the above mentioned modifications were protected in desferrioxamine treated mice. Histopathological results also revealed impairment of aluminium induced alterations in liver tissue. The results of the FTIR study were found to be in agreement with biochemical studies and which demonstrate FTIR can be used successfully to indicate the molecular level changes.',\n", - " 'author': ['Sivakumar, S.',\n", - " 'Sivasubramanian, J.',\n", - " 'Khatiwada, Chandra Prasad',\n", - " 'Manivannan, J.',\n", - " 'Raja, B.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.saa.2013.03.056\"}'],\n", - " 'title': ['Determination of aluminium induced metabolic changes in mice liver: A Fourier transform infrared spectroscopy study']},\n", - " {'bibcode': '2016NatSR...619694G',\n", - " 'abstract': 'Oxysterols are bioactive lipids derived from cholesterol that are linked to inflammatory processes. Because obesity and metabolic syndrome are characterized by inflammation and altered cholesterol metabolism, we sought to investigate the variations of oxysterol levels and their metabolic pathways induced by obesity in the liver, hypothalamus, adipose tissue and plasma. To this end, we used diet-induced and genetic (ob/ob and db/db) models of obesity. Among the oxysterols measured, we found that 4β-oxysterol levels were consistently decreased in the high-fat diet study, at different time-points, and in the ob/ob model. Overall, we did not find any correlation between cytochromes mRNA expression and variations of oxysterol levels. We also measured the levels of hepatic primary bile acids, in these three models and found similar profiles between HFD and ob/ob mice. However, although they are downstream metabolites of oxysterols, the variations in bile acid levels did not reflect the variations of their precursors. Our data show that, when considering oxysterol metabolism, the high-fat diet and ob/ob models are more closely related when compared to the db/db model. However, we were able to discriminate between lean and obese phenotypes based on liver oxysterol (4β-hydroxycholesterol, 27- hydroxycholesterol, 7-hydroxycholestenone) levels and enzyme (CYP3A11, CYP27A1, CYP7A1) expression.',\n", - " 'author': ['Guillemot-Legris, Owein',\n", - " 'Mutemberezi, Valentin',\n", - " 'Cani, Patrice D.',\n", - " 'Muccioli, Giulio G.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep19694\"}'],\n", - " 'title': ['Obesity is associated with changes in oxysterol metabolism and levels in mice liver, hypothalamus, adipose tissue and plasma']},\n", - " {'bibcode': '2016NatSR...627351S',\n", - " 'abstract': 'The mitochondria-associated membrane (MAM) is a specialized subdomain of the endoplasmic reticulum (ER) which acts as an intracellular signaling hub. MAM dysfunction has been related to liver disease. We report a high-throughput mass spectrometry-based proteomics characterization of MAMs from mouse liver, which portrays them as an extremely complex compartment involved in different metabolic processes, including steroid metabolism. Interestingly, we identified caveolin-1 (CAV1) as an integral component of hepatic MAMs, which determine the relative cholesterol content of these ER subdomains. Finally, a detailed comparative proteomics analysis between MAMs from wild type and CAV1-deficient mice suggests that functional CAV1 contributes to the recruitment and regulation of intracellular steroid and lipoprotein metabolism-related processes accrued at MAMs. The potential impact of these novel aspects of CAV1 biology on global cell homeostasis and disease is discussed.',\n", - " 'author': ['Sala-Vila, Aleix',\n", - " 'Navarro-Lérida, Inmaculada',\n", - " 'Sánchez-Alvarez, Miguel',\n", - " 'Bosch, Marta',\n", - " 'Calvo, Carlos',\n", - " 'López, Juan Antonio',\n", - " 'Calvo, Enrique',\n", - " 'Ferguson, Charles',\n", - " 'Giacomello, Marta',\n", - " 'Serafini, Annalisa',\n", - " 'Scorrano, Luca',\n", - " 'Enriquez, José Antonio',\n", - " 'Balsinde, Jesús',\n", - " 'Parton, Robert G.',\n", - " 'Vázquez, Jesús',\n", - " 'Pol, Albert',\n", - " 'Del Pozo, Miguel A.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep27351\"}'],\n", - " 'title': ['Interplay between hepatic mitochondria-associated membranes, lipid metabolism and caveolin-1 in mice']},\n", - " {'bibcode': '2017NatCo...816017M',\n", - " 'abstract': 'The presence of senescent, transformed or damaged cells can impair tissue function or lead to tumorigenesis; therefore, organisms have evolved quality control mechanisms to eliminate them. Here, we show that YAP activation induced by inactivation of the Hippo pathway specifically in damaged hepatocytes promotes their selective elimination by using in vivo mosaic analysis in mouse liver. These damaged hepatocytes migrate into the hepatic sinusoids, undergo apoptosis and are engulfed by Kupffer cells. In contrast, YAP activation in undamaged hepatocytes leads to proliferation. Cellular stresses such as ethanol that damage both liver sinusoidal endothelial cells and hepatocytes switch cell fate from proliferation to migration/apoptosis in the presence of activated YAP. This involves the activation of CDC42 and Rac that regulate cell migration. Thus, we suggest that YAP acts as a stress sensor that induces elimination of injured cells to maintain tissue and organ homeostasis.',\n", - " 'author': ['Miyamura, Norio',\n", - " 'Hata, Shoji',\n", - " 'Itoh, Tohru',\n", - " 'Tanaka, Minoru',\n", - " 'Nishio, Miki',\n", - " 'Itoh, Michiko',\n", - " 'Ogawa, Yoshihiro',\n", - " 'Terai, Shuji',\n", - " 'Sakaida, Isao',\n", - " 'Suzuki, Akira',\n", - " 'Miyajima, Atsushi',\n", - " 'Nishina, Hiroshi'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fncomms16017\"}'],\n", - " 'title': ['YAP determines the cell fate of injured mouse hepatocytes in vivo']},\n", - " {'bibcode': '2003Natur.423..302P',\n", - " 'abstract': 'A central issue in stem cell biology is to understand the mechanisms that regulate the self-renewal of haematopoietic stem cells (HSCs), which are required for haematopoiesis to persist for the lifetime of the animal. We found that adult and fetal mouse and adult human HSCs express the proto-oncogene Bmi-1. The number of HSCs in the fetal liver of Bmi-1-/- mice was normal. In postnatal Bmi-1-/- mice, the number of HSCs was markedly reduced. Transplanted fetal liver and bone marrow cells obtained from Bmi-1-/- mice were able to contribute only transiently to haematopoiesis. There was no detectable self-renewal of adult HSCs, indicating a cell autonomous defect in Bmi-1-/- mice. A gene expression analysis revealed that the expression of stem cell associated genes, cell survival genes, transcription factors, and genes modulating proliferation including p16Ink4a and p19Arf was altered in bone marrow cells of the Bmi-1-/- mice. Expression of p16Ink4a and p19Arf in normal HSCs resulted in proliferative arrest and p53-dependent cell death, respectively. Our results indicate that Bmi-1 is essential for the generation of self-renewing adult HSCs.',\n", - " 'author': ['Park, In-kyung',\n", - " 'Qian, Dalong',\n", - " 'Kiel, Mark',\n", - " 'Becker, Michael W.',\n", - " 'Pihalja, Michael',\n", - " 'Weissman, Irving L.',\n", - " 'Morrison, Sean J.',\n", - " 'Clarke, Michael F.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature01587\"}'],\n", - " 'title': ['Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells']},\n", - " {'bibcode': '2007Natur.447..477L',\n", - " 'abstract': 'The mammalian clock regulates major aspects of energy metabolism, including glucose and lipid homeostasis and mitochondrial oxidative metabolism. The biochemical basis for coordinated control of the circadian clock and diverse metabolic pathways is not well understood. Here we show that PGC-1α (Ppargc1a), a transcriptional coactivator that regulates energy metabolism, is rhythmically expressed in the liver and skeletal muscle of mice. PGC-1α stimulates the expression of clock genes, notably Bmal1 (Arntl) and Rev-erbα (Nr1d1), through coactivation of the ROR family of orphan nuclear receptors. Mice lacking PGC-1α show abnormal diurnal rhythms of activity, body temperature and metabolic rate. The disruption of physiological rhythms in these animals is correlated with aberrant expression of clock genes and those involved in energy metabolism. Analyses of PGC-1α-deficient fibroblasts and mice with liver-specific knockdown of PGC-1α indicate that it is required for cell-autonomous clock function. We have thus identified PGC-1α as a key component of the circadian oscillator that integrates the mammalian clock and energy metabolism.',\n", - " 'author': ['Liu, Chang',\n", - " 'Li, Siming',\n", - " 'Liu, Tiecheng',\n", - " 'Borjigin, Jimo',\n", - " 'Lin, Jiandie D.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature05767\"}'],\n", - " 'title': ['Transcriptional coactivator PGC-1α integrates the mammalian clock and energy metabolism']},\n", - " {'bibcode': '2009Nanot..20R5101J',\n", - " 'abstract': 'The hepatotoxicity of two types of multi-walled carbon nanotubes (MWCNTs), acid-oxidized MWCNTs (O-MWCNTs) and Tween-80-dispersed MWCNTs (T-MWCNTs), were investigated with Kunming mice exposed to 10 and 60 mg kg-1 by intravenous injection for 15 and 60 d. Compared with the PBS group, the body-weight gain of the mice decreased and the level of total bilirubin and aspartate aminotransferase increased in the MWCNT-exposed group with a significant dose-effect relationship, while tumor necrosis factor alpha level did not show significant statistical change within 60 d. Spotty necrosis, inflammatory cell infiltration in portal region, hepatocyte mitochondria swelling and lysis were observed with a significant dose-effect relationship in the MWCNT groups. Liver damage of the T-MWCNT group was more severe than that of the O-MWCNT group according to the Roenigk classification system. Furthermore, T-MWCNTs induce slight liver oxidative damage in mice at 15 d, which was recovered at 60 d. Part of the gene expressions of mouse liver in the MWCNT groups changed compared to the PBS group, including GPCRs (G protein-coupled receptors), cholesterol biosynthesis, metabolism by cytochrome P450, natural-killer-cell-mediated cytotoxicity, TNF- α, NF-κB signaling pathway, etc. In the P450 pathway, the gene expressions of Gsta2 (down-regulated), Cyp2B19 (up-regulated) and Cyp2C50 (down-regulated) had significant changes in the MWCNT groups. These results show that a high dose of T-MWCNTs can induce hepatic toxicity in mice while O-MWCNTs seem to have less toxicity.',\n", - " 'author': ['Ji, Zongfei',\n", - " 'Zhang, Danying',\n", - " 'Li, Ling',\n", - " 'Shen, Xizhong',\n", - " 'Deng, Xiaoyong',\n", - " 'Dong, Ling',\n", - " 'Wu, Minhong',\n", - " 'Liu, Yuanfang'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1088%2F0957-4484%2F20%2F44%2F445101\"}'],\n", - " 'title': ['The hepatotoxicity of multi-walled carbon nanotubes in mice']},\n", - " {'bibcode': '1976PNAS...73.3984R',\n", - " 'abstract': 'An accurate assay of diadenosine 5\\',5\\'\\'\\'- P1,P4-tetraphosphate [A(5\\') pppp(5\\')A], which was shown to be formed in vitro in the backreaction of the amino acid activation step, has been developed in various cell lines in culture and in normal mouse liver or hepatoma in vivo. Use of radioactive labeling of acid-soluble nucleotides to high specific activity followed by chromatographic separation techniques yielded levels of Ap4A varying from 5 to 0.05 muM (from 30 pmol/mg of protein to 0.15 pmol), depending on the doubling time of the cell line or the proliferative state of the cells. The levels of Ap4A incells is inversely related to their doubling time, varying from 0.1 X 10(-4) of the cellular ATP levels in slowly growing cells to 20 X 10(-4) of the ATP levels of cells with rapid doubling times. The steady-state levels of ATP of different cell lines, although showing some fluctuations, are not related to the doubling time of the cells. Arrest of cellular proliferation by serum deprivation or amino acid starvation, which does not alter the cellular ATP levels more than 2-fold, does nevertheless cause a decrease of 30 to 50-fold in the Ap4A levels. Inhibition of protein synthesis by pactamycin or puromycin, or inhibition of DNA synthesis by hydroxyurea, leads to a more dramatic decrease of 50 to 100-fold in intracellular Ap4A levels. The metabolic lability of Ap4A is also demonstrated by its rapid depletion after decreases in the ATP/ADP ratio. The possibility of Ap4A being a metabolic \"signal nucleotide\" that is formed at the onset of protein synthesis and is active in positive growth regulation (positive pleiotypic activation) is discussed.',\n", - " 'author': ['Rapaport, Eliezer', 'Zamecnik, Paul C.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/73/11/3984\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/73/11/3984\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/73/11/3984\"}'],\n", - " 'title': [\"Presence of Diadenosine 5',5' ' '-P1,P4-tetraphosphate (Ap4A) in Mammalian Cells in Levels Varying Widely with Proliferative Activity of the Tissue: A Possible Positive ``Pleiotypic Activator''\"]},\n", - " {'bibcode': '1964Natur.202.1009W',\n", - " 'abstract': 'Toxic materials are obtained by oxidation of highly unsaturated fatty acids, and significant effects are produced by these products on biological systems. Methyl linoleate and methyl linolenate are readily oxidized on exposure to ultra-violet radiation to yield products which inhibit enzymatic reactions1 and cellular respiration2 and interrupt division of yeast cells3. Other consequences of the autoxidation of lipids are detailed in a recent symposium4. This communication deals with an in vivo response of the mouse liver to an aqueous extract of ultraviolet-irradiated linolenic acid.',\n", - " 'author': ['Waravdekar, V. S.',\n", - " 'Anderson, H. J.',\n", - " 'Saslaw, L. D.',\n", - " 'Smetana, H. F.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F2021009a0\"}'],\n", - " 'title': ['Hepatotropic Effect in Mice by an Aqueous Extract of Ultra-violet-irradiated Linolenic Acid']},\n", - " {'bibcode': '2007Sci...317..121N',\n", - " 'abstract': 'Hepatocellular carcinoma (HCC), the most common liver cancer, occurs mainly in men. Similar gender disparity is seen in mice given a chemical carcinogen, diethylnitrosamine (DEN). DEN administration caused greater increases in serum interleukin-6 (IL-6) concentration in males than it did in females. Furthermore, ablation of IL-6 abolished the gender differences in hepatocarcinogenesis in mice. DEN exposure promoted production of IL-6 in Kupffer cells (KCs) in a manner dependent on the Toll-like receptor adaptor protein MyD88, ablation of which also protected male mice from DEN-induced hepatocarcinogenesis. Estrogen inhibited secretion of IL-6 from KCs exposed to necrotic hepatocytes and reduced circulating concentrations of IL-6 in DEN-treated male mice. We propose that estrogen-mediated inhibition of IL-6 production by KCs reduces liver cancer risk in females, and these findings may be used to prevent HCC in males.',\n", - " 'author': ['Naugler, Willscott E.',\n", - " 'Sakurai, Toshiharu',\n", - " 'Kim, Sunhwa',\n", - " 'Maeda, Shin',\n", - " 'Kim, KyoungHyun',\n", - " 'Elsharkawy, Ahmed M.',\n", - " 'Karin, Michael'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.1140485\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.1140485\"}'],\n", - " 'title': ['Gender Disparity in Liver Cancer Due to Sex Differences in MyD88-Dependent IL-6 Production']},\n", - " {'bibcode': '2013Nanos...512464Y',\n", - " 'abstract': 'Magnetic resonance (MR) imaging using magnetic nanoparticles as the contrast agent has been extensively explored in biomedical imaging and disease diagnosis. Herein, we develop biocompatible polymer coated ultra-small Pt3Co magnetic nanoparticles as a new T2-weighted MR imaging contrast agent. A unique class of alloy Pt3Co nanoparticles is synthesized through a thermal decomposition method. After being modified with polyethylene glycol (PEG), the obtained Pt3Co-PEG nanoparticles exhibit an extremely high T2-weighted relaxivity rate (r2) up to 451.2 mM s-1, which is much higher than that of Resovist®, a commercial T2-MR contrast agent used in the clinic. In vitro experiments indicate no obvious cytotoxicity of Pt3Co-PEG nanoparticles to various cell lines. After intravenous injection of Pt3Co-PEG nanoparticles, in vivo T2-weighted MR imaging of tumor-bearing mice reveals strong tumor contrast, which is much higher than that offered by injecting Resovist®. We further study the long-term biodistribution and toxicology of this new type of MR contrast nanoparticles after intravenous injection into healthy mice. Despite the significant retention of Pt3Co-PEG nanoparticles in the mouse liver and spleen, no appreciable toxicity of these nanoparticles to the treated animals has been noted in our detailed histological and hematological analysis over a course of 60 days. Our work demonstrates that functionalized Pt3Co nanoparticles may be a promising new type of T2-weighted MR contrast agent potentially useful in biomedical imaging and diagnosis.Magnetic resonance (MR) imaging using magnetic nanoparticles as the contrast agent has been extensively explored in biomedical imaging and disease diagnosis. Herein, we develop biocompatible polymer coated ultra-small Pt3Co magnetic nanoparticles as a new T2-weighted MR imaging contrast agent. A unique class of alloy Pt3Co nanoparticles is synthesized through a thermal decomposition method. After being modified with polyethylene glycol (PEG), the obtained Pt3Co-PEG nanoparticles exhibit an extremely high T2-weighted relaxivity rate (r2) up to 451.2 mM s-1, which is much higher than that of Resovist®, a commercial T2-MR contrast agent used in the clinic. In vitro experiments indicate no obvious cytotoxicity of Pt3Co-PEG nanoparticles to various cell lines. After intravenous injection of Pt3Co-PEG nanoparticles, in vivo T2-weighted MR imaging of tumor-bearing mice reveals strong tumor contrast, which is much higher than that offered by injecting Resovist®. We further study the long-term biodistribution and toxicology of this new type of MR contrast nanoparticles after intravenous injection into healthy mice. Despite the significant retention of Pt3Co-PEG nanoparticles in the mouse liver and spleen, no appreciable toxicity of these nanoparticles to the treated animals has been noted in our detailed histological and hematological analysis over a course of 60 days. Our work demonstrates that functionalized Pt3Co nanoparticles may be a promising new type of T2-weighted MR contrast agent potentially useful in biomedical imaging and diagnosis.

Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr04212j',\n", - " 'author': ['Yin, Shengnan',\n", - " 'Li, Zhiwei',\n", - " 'Cheng, Liang',\n", - " 'Wang, Chao',\n", - " 'Liu, Yumeng',\n", - " 'Chen, Qian',\n", - " 'Gong, Hua',\n", - " 'Guo, Liang',\n", - " 'Li, Yonggang',\n", - " 'Liu, Zhuang'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1039%2Fc3nr04212j\"}'],\n", - " 'title': ['Magnetic PEGylated Pt3Co nanoparticles as a novel MR contrast agent: in vivo MR imaging and long-term toxicity study']},\n", - " {'bibcode': '2020PLSCB..16E8412S',\n", - " 'abstract': 'How epithelial cells coordinate their polarity to form functional tissues is an open question in cell biology. Here, we characterize a unique type of polarity found in liver tissue, nematic cell polarity, which is different from vectorial cell polarity in simple, sheet-like epithelia. We propose a conceptual and algorithmic framework to characterize complex patterns of polarity proteins on the surface of a cell in terms of a multipole expansion. To rigorously quantify previously observed tissue-level patterns of nematic cell polarity (Morales-Navarette et al., eLife 8:e44860, 2019), we introduce the concept of co-orientational order parameters, which generalize the known biaxial order parameters of the theory of liquid crystals. Applying these concepts to three-dimensional reconstructions of single cells from high-resolution imaging data of mouse liver tissue, we show that the axes of nematic cell polarity of hepatocytes exhibit local coordination and are aligned with the biaxially anisotropic sinusoidal network for blood transport. Our study characterizes liver tissue as a biological example of a biaxial liquid crystal. The general methodology developed here could be applied to other tissues or in-vitro organoids.',\n", - " 'author': ['Scholich, André',\n", - " 'Syga, Simon',\n", - " 'Morales-Navarrete, Hernán',\n", - " 'Segovia-Miranda, Fabián',\n", - " 'Nonaka, Hidenori',\n", - " 'Meyer, Kirstin',\n", - " 'de Back, Walter',\n", - " 'Brusch, Lutz',\n", - " 'Kalaidzidis, Yannis',\n", - " 'Zerial, Marino',\n", - " 'Jülicher, Frank',\n", - " 'Friedrich, Benjamin M.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"preprint\", \"url\": \"http://arxiv.org/abs/1904.08886\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pcbi.1008412\"}'],\n", - " 'title': ['Quantification of nematic cell polarity in three-dimensional tissues']},\n", - " {'bibcode': '2014PLoSO...992884K',\n", - " 'author': ['Kuroda, Noriyuki',\n", - " 'Inoue, Kouji',\n", - " 'Ikeda, Tadayuki',\n", - " 'Hara, Yaiko',\n", - " 'Wake, Kenjiro',\n", - " 'Sato, Tetsuji'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0092884\"}'],\n", - " 'title': ['Apoptotic Response through a High Mobility Box 1 Protein-Dependent Mechanism in LPS/GalN-Induced Mouse Liver Failure and Glycyrrhizin-Mediated Inhibition']},\n", - " {'bibcode': '1971PNAS...68..411A',\n", - " 'abstract': 'The glycerol portion of lipids may be derived biosynthetically by reduction of dihydroxyacetone phosphate to glycerolphosphate, and then be acylated with fatty acids or, alternatively, dihydroxyacetone phosphate may first be acylated and then reduced to 1-acyl sn glcerol-3-phosphate. Since the former pathway utilizes NADH for reduction of the C-2 carbonyl, while the latter requires NADPH, we were able to compare the relative participation of the two pathways for phospholipid synthesis by measuring the incorporation of radioactivity from tritiumlabeled NADH and NADPH into C-2 of lipid glycerol. The acyl-dihydroxyacetone phosphate pathway plays a significant role in glycerolipid synthesis in mouse liver homogenates and a clearly dominant one in Ehrlich ascites tumor cell homogenates. This finding is related to a reported lack of glycerol-3-phosphate dehydrogenase in tumor cells and to their high glycerol ether lipid content.',\n", - " 'author': ['Agranoff, Bernard W.', 'Hajra, Amiya K.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/68/2/411\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/68/2/411\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/68/2/411\"}'],\n", - " 'title': ['The Acyl Dihydroxyacetone Phosphate Pathway for Glycerolipid Biosynthesis in Mouse Liver and Ehrlich Ascites Tumor Cells']},\n", - " {'bibcode': '1999EnvMM..34..121H',\n", - " 'author': ['Hara, Takumi',\n", - " 'Sui, Hajime',\n", - " 'Kawakami, Kumiko',\n", - " 'Shimada, Yasushi',\n", - " 'Shibuya, Tohru'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2F%28SICI%291098-2280%281999%2934%3A2%2F3%3C121%3A%3AAID-EM10%3E3.0.CO%3B2-R\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2F%28SICI%291098-2280%281999%2934%3A2%2F3%3C121%3A%3AAID-EM10%3E3.0.CO2-R\"}'],\n", - " 'title': ['Partial hepatectomy strongly increased the mutagenicity ofN-ethyl-N-nitrosourea in Muta?Mouse liver']},\n", - " {'bibcode': '2019PLoSO..1419747V',\n", - " 'author': ['Villaseñor-Altamirano, Ana B.',\n", - " 'Watson, John D.',\n", - " 'Prokopec, Stephenie D.',\n", - " 'Yao, Cindy Q.',\n", - " 'Boutros, Paul C.',\n", - " 'Pohjanvirta, Raimo',\n", - " 'Valdés-Flores, Jesús',\n", - " 'Elizondo, Guillermo'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0219747\"}'],\n", - " 'title': ['2,3,7,8-Tetrachlorodibenzo-p-dioxin modifies alternative splicing in mouse liver']},\n", - " {'bibcode': '2019RSCAd...9.6510M',\n", - " 'author': ['Ma, Ying',\n", - " 'Tian, Haigang',\n", - " 'Jin, Zhengyu',\n", - " 'Li, Xiaoyong',\n", - " 'Li, Yiping'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1039%2FC8RA10053E\"}'],\n", - " 'title': ['Observation of the generation of peroxynitrite in mouse liver after acetaminophen overdose with a boronate-based ratiometric fluorescence probe']},\n", - " {'bibcode': '2023ESPR...30.7510L',\n", - " 'author': ['Li, Ying',\n", - " 'Cai, Wenjie',\n", - " 'Ai, Zichun',\n", - " 'Xue, Chenyu',\n", - " 'Cao, Rujing',\n", - " 'Dong, Na'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1007%2Fs11356-022-22386-1\"}'],\n", - " 'title': ['Protective effects of sinomenine hydrochloride on lead-induced oxidative stress, inflammation, and apoptosis in mouse liver']},\n", - " {'bibcode': '1974JRadR..15..204B',\n", - " 'author': ['Brown, P. C.', 'Kleinbergs-Krisans, S.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1269%2Fjrr.15.204\"}'],\n", - " 'title': ['Effect of X-irradiation on the Permeability of L-Alpha Hydroxy Acid Oxidase From Mouse Liver Peroxisomes']},\n", - " {'bibcode': '1998PNAS...95.8750V',\n", - " 'abstract': \"The mouse genes encoding the constitutively expressed complement component C4 and its closely related isoform C4-Slp (sex-limited protein), which is expressed only in male animals of several strains, provide a unique model to study sequence elements and trans-acting factors responsible for androgen responsiveness. Our previous studies have shown that hormonal induction of C4-Slp is mediated by a sex-specific pattern of growth hormone secretion. Promoter analyses in vitro have led to contradictory conclusions concerning the significance of C4-Slp-specific sequences in the 5' flanking region. Mutant mice carrying the H-2aw18 haplotype, which is characterized by a large deletion in the S region covering the C4 and 21-OHase A genes, permit the direct in vivo analysis of C4-Slp transcription, unhindered by the presence of C4. Run-on analysis of transcription in liver nuclei of males and females of this strain demonstrated a 100-fold higher transcriptional activity in males, essentially determined at the transcription initiation level. The androgen dependence of transcription initiation was confirmed by run-on analysis of testosterone-treated females, where transcriptional activity started after 6 days of androgen treatment and reached male levels after 20 days. Conversely, the growth hormone-regulated activity of transcription factor STAT5 was already detected in liver nuclei after 48 hr of androgen treatment. Furthermore, we demonstrate that activated STAT5 recognizes in vitro two upstream γ interferon-activated sequence (GAS) elements of the C4-Slp gene, centered at positions -1969 and -1831. We postulate that binding of STAT5 to these C4-Slp-specific GAS elements plays a crucial role in the chromatin remodelings that lead to transcriptional competence of the C4-Slp gene in the liver.\",\n", - " 'author': ['Varin-Blank, N.',\n", - " 'Dondi, E.',\n", - " 'Tosi, M.',\n", - " 'Hernandez, C.',\n", - " 'Boucontet, L.',\n", - " 'Gotoh, H.',\n", - " 'Shiroishi, T.',\n", - " 'Moriwaki, K.',\n", - " 'Meo, T.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/95/15/8750\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/95/15/8750\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/95/15/8750\"}'],\n", - " 'title': ['Male-Specific Transcription Initiation of the C4-Slp Gene in Mouse Liver Follows Activation of STAT5']},\n", - " {'bibcode': '2001PNAS...9811468W',\n", - " 'abstract': 'The forkhead box (Fox) family of transcription factors share homology in the winged helix/forkhead DNA-binding domain and play important roles in regulating cellular proliferation, differentiation, longevity, and cellular transformation. Forkhead box M1B (FoxM1B) is a ubiquitously expressed member of the Fox transcription factor family whose expression is restricted to proliferating cells and that mediates hepatocyte entry into DNA synthesis and mitosis during liver regeneration. Recent cDNA microarray studies indicated that age-related defects in cellular proliferation are associated with diminished expression of the FoxM1B transcription factor. Here, we show that increased levels of FoxM1B in regenerating liver of old transgenic mice restore the sharp peaks in hepatocyte DNA replication and mitosis that are the hallmarks of young regenerating mouse liver. Restoration of the young regenerating liver phenotype is associated with increased expression of numerous cell cycle regulatory genes that include cyclin D1, cyclin A2, cyclin F, cyclin B1, cyclin B2, Cdc25B, and p55cdc. Cotransfection assays in the human hepatoma HepG2 cell line demonstrated that FoxM1B protein stimulated expression of both the cyclin B1 and cyclin D1 promoters, suggesting that these cyclin genes are a direct FoxM1B transcriptional target. These results suggest that FoxM1B controls the transcriptional network of genes that are essential for cell division and exit from mitosis. Our results indicate that reduced expression of the FoxM1B transcription factor contributes to the decline in cellular proliferation observed in the aging process.',\n", - " 'author': ['Wang, Xinhe',\n", - " 'Quail, Elizabeth',\n", - " 'Hung, Nai-Jung',\n", - " 'Tan, Yongjun',\n", - " 'Ye, Honggang',\n", - " 'Costa, Robert H.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/98/20/11468\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/98/20/11468\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/98/20/11468\"}'],\n", - " 'title': ['Increased levels of forkhead box M1B transcription factor in transgenic mouse hepatocytes prevent age-related proliferation defects in regenerating liver']},\n", - " {'bibcode': '2018Natur.557..247S',\n", - " 'abstract': 'Transdifferentiation is a complete and stable change in cell identity that serves as an alternative to stem-cell-mediated organ regeneration. In adult mammals, findings of transdifferentiation have been limited to the replenishment of cells lost from preexisting structures, in the presence of a fully developed scaffold and niche1. Here we show that transdifferentiation of hepatocytes in the mouse liver can build a structure that failed to form in development—the biliary system in a mouse model that mimics the hepatic phenotype of human Alagille syndrome (ALGS)2. In these mice, hepatocytes convert into mature cholangiocytes and form bile ducts that are effective in draining bile and persist after the cholestatic liver injury is reversed, consistent with transdifferentiation. These findings redefine hepatocyte plasticity, which appeared to be limited to metaplasia, that is, incomplete and transient biliary differentiation as an adaptation to cell injury, based on previous studies in mice with a fully developed biliary system3-6. In contrast to bile duct development7-9, we show that de novo bile duct formation by hepatocyte transdifferentiation is independent of NOTCH signalling. We identify TGFβ signalling as the driver of this compensatory mechanism and show that it is active in some patients with ALGS. Furthermore, we show that TGFβ signalling can be targeted to enhance the formation of the biliary system from hepatocytes, and that the transdifferentiation-inducing signals and remodelling capacity of the bile-duct-deficient liver can be harnessed with transplanted hepatocytes. Our results define the regenerative potential of mammalian transdifferentiation and reveal opportunities for the treatment of ALGS and other cholestatic liver diseases.',\n", - " 'author': ['Schaub, Johanna R.',\n", - " 'Huppert, Kari A.',\n", - " 'Kurial, Simone N. T.',\n", - " 'Hsu, Bernadette Y.',\n", - " 'Cast, Ashley E.',\n", - " 'Donnelly, Bryan',\n", - " 'Karns, Rebekah A.',\n", - " 'Chen, Feng',\n", - " 'Rezvani, Milad',\n", - " 'Luu, Hubert Y.',\n", - " 'Mattis, Aras N.',\n", - " 'Rougemont, Anne-Laure',\n", - " 'Rosenthal, Philip',\n", - " 'Huppert, Stacey S.',\n", - " 'Willenbring, Holger'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41586-018-0075-5\"}'],\n", - " 'title': ['De novo formation of the biliary system by TGFβ-mediated hepatocyte transdifferentiation']},\n", - " {'bibcode': '2009PNAS..106.4402W',\n", - " 'abstract': 'Drug-induced liver injury is a frequent side effect of many drugs, constitutes a significant threat to patient health and has an enormous economic impact on health care expenditures. Numerous efforts have been made to identify reliable and predictive markers to detect the early signs of drug-induced injury to the liver, one of the most vulnerable organs in the body. These studies have, however, not delivered any more informative candidates than the serum aminotransferase markers that have been available for ≈30 years. Using acetaminophen overdose-induced liver injury in the mouse as a model system, we have observed highly significant differences in the spectrum and levels of microRNAs in both liver tissues and in plasma between control and overdosed animals. Based on our survey of microRNA expression among normal tissues, some of the microRNAs, like messenger RNAs, display restricted tissue distributions. A number of elevated circulating microRNAs in plasma collected from acetaminophen-overdosed animals are highly expressed in the liver. We have demonstrated that specific microRNA species, such as mir-122 and mir-192, both are enriched in the liver tissue and exhibit dose- and exposure duration-dependent changes in the plasma that parallel serum aminotransferase levels and the histopathology of liver degeneration, but their changes can be detected significantly earlier. These findings suggest the potential of using specific circulating microRNAs as sensitive and informative biomarkers for drug-induced liver injury.',\n", - " 'author': ['Wang, Kai',\n", - " 'Zhang, Shile',\n", - " 'Marzolf, Bruz',\n", - " 'Troisch, Pamela',\n", - " 'Brightman, Amy',\n", - " 'Hu, Zhiyuan',\n", - " 'Hood, Leroy E.',\n", - " 'Galas, David J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/106/11/4402\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/106/11/4402.full.pdf+html\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0813371106\"}'],\n", - " 'title': ['Circulating microRNAs, potential biomarkers for drug-induced liver injury']},\n", - " {'bibcode': '2011PNAS..108.3906D',\n", - " 'abstract': 'Recent studies of several key developmental transitions have brought into question the long held view of the basal transcriptional apparatus as ubiquitous and invariant. In an effort to better understand the role of core promoter recognition and coactivator complex switching in cellular differentiation, we have examined changes in transcription factor IID (TFIID) and cofactor required for Sp1 activation/Mediator during mouse liver development. Here we show that the differentiation of fetal liver progenitors to adult hepatocytes involves a wholesale depletion of canonical cofactor required for Sp1 activation/Mediator and TFIID complexes at both the RNA and protein level, and that this alteration likely involves silencing of transcription factor promoters as well as protein degradation. It will be intriguing for future studies to determine if a novel and as yet unknown core promoter recognition complex takes the place of TFIID in adult hepatocytes and to uncover the mechanisms that down-regulate TFIID during this critical developmental transition.',\n", - " 'author': [\"D'Alessio, Joseph A.\",\n", - " 'Ng, Raymond',\n", - " 'Willenbring, Holger',\n", - " 'Tjian, Robert'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/108/10/3906\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1100640108\"}'],\n", - " 'title': ['Core promoter recognition complex changes accompany liver development']},\n", - " {'bibcode': '1968Sci...159..886R',\n", - " 'abstract': 'Dialyzed homogenates prepared from Escherichia coli, Tetrahymena pyriformis, sea anemone (Anthopleura elegantissima), and mouse liver were tested for ability to transaminate 17 aminoalkylphosphonic acids with α -ketoglutarate. 2-Aminoethylphosphonic acid (2-AEP), which occurs naturally in Tetrahymena and anemone, was transaminated by these latter organisms more than any of the substances tested, but not by preparation from liver or E. coli. 3-Aminopropylphosphonic acid was transaminated by all preparations, but much less by Tetrahymena or anemone than was 2-AEP. 2-Amino-3-phosphonopropionic acid was transaminated by all preparations. 2-Amino-4-phosphonobutyric acid was transaminated by three of the preparations, but not by liver. Of the other 13 substances tested, the following gave positive results: DL-1,2-diaminoethylphosphonic acid with E. coli, DL-1,2-diaminoethylphosphonic and aminomethylphosphonic acids with Tetrahymena, DL-1-aminopropylphosphonic acid with anemone, and DL-1-aminoethylphosphonic and DL-1-aminobutylphosphonic acids with liver. The significance of these transaminations is discussed.',\n", - " 'author': ['Roberts, Eugene',\n", - " 'Simonsen, Daisy G.',\n", - " 'Horiguchi, Masaaki',\n", - " 'Kittredge, James S.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.jstor.org/stable/1724286?origin=ads\"}'],\n", - " 'title': ['Transamination of Aminoalkylphosphonic Acids with Alpha Ketoglutarate']},\n", - " {'bibcode': '2010TxEC...92..175L',\n", - " 'author': ['Liu, Huiting',\n", - " 'Ma, Linglan',\n", - " 'Liu, Jie',\n", - " 'Zhao, Jingfang',\n", - " 'Yan, Jingying',\n", - " 'Hong, Fashui'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1080%2F02772240902732530\"}'],\n", - " 'title': ['Toxicity of nano-anatase TiO2to mice: Liver injury, oxidative stress']},\n", - " {'bibcode': '1998PNAS...95.7385C',\n", - " 'abstract': \"The recent discovery of leptin receptors in peripheral tissue raises questions about which of leptin's biological actions arise from direct effects of the hormone on extraneural tissues and what intracellular mechanisms are responsible for leptin's effects on carbohydrate and lipid metabolism. The present study is focused on the action of leptin on hepatic metabolism. Nondestructive 13C NMR methodology was used to follow the kinetics of intermediary metabolism by monitoring flux of 13C-labeled substrate through several multistep pathways. In perfused liver from either ob/ob or lean mice, we found that acute treatment with leptin in vitro modulates pathways controlling carbohydrate flux into 13C-labeled glycogen, thereby rapidly enhancing synthesis by an insulin-independent mechanism. Acute treatment of ob/ob liver also caused a rapid stimulation of long-chain fatty acid synthesis from 13C-labeled acetyl-CoA by the de novo synthesis route. Chronic leptin treatment in vivo induced homeostatic changes that resulted in a tripling of the rate of glycogen synthesis via the gluconeogenic pathway from [2-13C]pyruvate in ob/ob mouse liver perfused in the absence of the hormone. Consistent with the 13C NMR results, leptin treatment of the ob/ob mouse in vivo resulted in significantly increased hepatic glycogen synthase activity. Chronic treatment with leptin in vivo exerted the opposite effect of acute treatment in vitro and markedly decreased hepatic de novo synthesis of fatty acids in ob/ob mouse liver. In agreement with the 13C NMR findings, activities of hepatic acetyl-CoA carboxylase and fatty acid synthase were significantly reduced by chronic treatment of the ob/ob mouse with leptin. Our data represent a demonstration of direct effects of leptin in the regulation of metabolism in the intact functioning liver.\",\n", - " 'author': ['Cohen, Sheila M.', 'Werrmann, Jeffrey G.', 'Tota, Michael R.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/95/13/7385\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/95/13/7385\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/95/13/7385\"}'],\n", - " 'title': ['13C NMR Study of the Effects of Leptin Treatment on Kinetics of Hepatic Intermediary Metabolism']},\n", - " {'bibcode': '1972Natur.235..439G',\n", - " 'abstract': 'THE role of adenyl cyclase in cholera enteropathy has been extensively documented1. We describe here experiments with mouse liver adenyl cyclase which suggest a possible mechanism for the stimulatory effects of cholera toxin.',\n", - " 'author': ['Gorman, Ronnie E.', 'Bitensky, Mark W.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F235439a0\"}'],\n", - " 'title': ['Selective Effects of Cholera Toxin on the Adrenaline Responsive Component of Hepatic Adenyl Cyclase']},\n", - " {'bibcode': '2018Natur.556..181Z',\n", - " 'abstract': 'Cell-tracing analysis reveals that a disperse group of cells in the mouse liver express the enzyme telomerase, which preserves chromosome ends. These cells contribute to liver maintenance and regeneration.',\n", - " 'author': ['Zaret, Kenneth S.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fd41586-018-02684-w\"}'],\n", - " 'title': ['The telomerase enzyme and liver renewal']},\n", - " {'bibcode': '2015NatSR...515212T',\n", - " 'abstract': 'The mammalian clock system is composed of a master clock and peripheral clocks. At the molecular level, the rhythm-generating mechanism is controlled by a molecular clock composed of positive and negative feedback loops. However, the underlying mechanisms for molecular clock regulation that affect circadian clock function remain unclear. Here, we show that Egr1 (early growth response 1), an early growth response gene, is expressed in mouse liver in a circadian manner. Consistently, Egr1 is transactivated by the CLOCK/BMAL1 heterodimer through a conserved E-box response element. In hepatocytes, EGR1 regulates the transcription of several core clock genes, including Bmal1, Per1, Per2, Rev-erbα and Rev-erbβ, and the rhythm amplitude of their expression is dependent on EGR1’s transcriptional function. Further mechanistic studies indicated that EGR1 binds to the proximal region of the Per1 promoter to activate its transcription directly. When the peripheral clock is altered by light or feeding behavior transposition in Egr1-deficient mice, the expression phase of hepatic clock genes shifts normally, but the amplitude is also altered. Our data reveal a critical role for EGR1 in the regulation of hepatic clock circuitry, which may contribute to the rhythm stability of peripheral clock oscillators.',\n", - " 'author': ['Tao, Weiwei',\n", - " 'Wu, Jing',\n", - " 'Zhang, Qian',\n", - " 'Lai, Shan-Shan',\n", - " 'Jiang, Shan',\n", - " 'Jiang, Chen',\n", - " 'Xu, Ying',\n", - " 'Xue, Bin',\n", - " 'Du, Jie',\n", - " 'Li, Chao-Jun'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep15212\"}'],\n", - " 'title': ['EGR1 regulates hepatic clock gene amplitude by activating Per1 transcription']},\n", - " {'bibcode': '1998PNAS...95.8847D',\n", - " 'abstract': 'Hepatocellular carcinoma (HCC) is the major primary malignant tumor in the human liver, but the molecular changes leading to liver cell transformation remain largely unknown. The Wnt-β-catenin pathway is activated in colon cancers and some melanoma cell lines, but has not yet been investigated in HCC. We have examined the status of the β-catenin gene in different transgenic mouse lines of HCC obtained with the oncogenes c-myc or H-ras. Fifty percent of the hepatic tumors in these transgenic mice had activating somatic mutations within the β-catenin gene similar to those found in colon cancers and melanomas. These alterations in the β-catenin gene (point mutations or deletions) lead to a disregulation of the signaling function of β-catenin and thus to carcinogenesis. We then analyzed human HCCs and found similar mutations in eight of 31 (26%) human liver tumors tested and in HepG2 and HuH6 hepatoma cells. The mutations led to the accumulation of β-catenin in the nucleus. Thus alterations in the β-catenin gene frequently are selected for during liver tumorigenesis and suggest that disregulation of the Wnt-β-catenin pathway is a major event in the development of HCC in humans and mice.',\n", - " 'author': ['de La Coste, Alix',\n", - " 'Romagnolo, Béatrice',\n", - " 'Billuart, Pierre',\n", - " 'Renard, Claire-Angélique',\n", - " 'Buendia, Marie-Annick',\n", - " 'Soubrane, Olivier',\n", - " 'Fabre, Monique',\n", - " 'Chelly, Jamel',\n", - " 'Beldjord, Cherif',\n", - " 'Kahn, Axel',\n", - " 'Perret, Christine'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/95/15/8847\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/95/15/8847\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/95/15/8847\"}'],\n", - " 'title': ['Somatic mutations of the β-catenin gene are frequent in mouse and human hepatocellular carcinomas']},\n", - " {'bibcode': '2021NatNa..16..365F',\n", - " 'abstract': 'Targeting of the peptide hormone relaxin to injured mouse liver, via a nanoparticle/gene therapy approach, switches pro-fibrotic hepatic macrophages to a restorative phenotype that orchestrates tissue repair.',\n", - " 'author': ['Fallowfield, Jonathan A.', 'Ramachandran, Prakash'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41565-020-00832-w\"}'],\n", - " 'title': ['A relaxin-based nanotherapy for liver fibrosis']},\n", - " {'bibcode': '2004PNAS..101.2112S',\n", - " 'abstract': 'Recent studies have shown that recombinant adeno-associated virus (rAAV) can persist in episomal form; however, factors affecting rAAV persistence are poorly understood. DNA-dependent PK (DNA-PK) is a DNA repair enzyme, which we previously found played an important role in determining the molecular fate of the rAAV genome in mouse skeletal muscle. In the present study, we tested the effect of DNA-PK on AAV serotype 2 integration in vitro and in vivo in mouse liver. In an in vitro integration system, addition of DNA-PK decreased AAV integration, whereas antibody against DNA-PKcs increased integration. In vivo, matched doses of a recombinant AAV serotype 2 vector were injected into the portal vein of either C57BL/6 (DNA-PKcs+/+) or severe combined immunodeficient (DNA-PKcs-/-) mice. After partial hepatectomy to stimulate hepatocyte proliferation, retention of vector genomes and of transgene expression was substantially higher in severe combined immunodeficient mice, indicating that in the absence of DNA-PKcs, a greater proportion of genomes integrated into the cellular genome. In summary, we have provided evidence that DNA-PK inhibits AAV integration both in vitro and in vivo.',\n", - " 'author': ['Song, Sihong',\n", - " 'Lu, Yuanqing',\n", - " 'Choi, Young-Kook',\n", - " 'Han, Yinong',\n", - " 'Tang, Qiushi',\n", - " 'Zhao, Ge',\n", - " 'Berns, Kenneth I.',\n", - " 'Flotte, Terence R.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/101/7/2112\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0307833100\"}'],\n", - " 'title': ['DNA-dependent PK inhibits adeno-associated virus DNA integration']},\n", - " {'bibcode': '1999PatRe..32..605B',\n", - " 'abstract': 'A new set of texture features based on the complexity curve is proposed for texture analysis. The complexity curve is obtained by computing the number of black-to-white transitions observed in a binary image for all possible threshold values in a gray-level texture image. The new features characterize the first-order statistics of the complexity curve, and therefore give a second-order description of texture. The set of features is applied to texture classification, and to capture the directionality and the periodicity of texture. For texture classification, two experiments are performed. First, some Brodatz textures are used to evaluate the classification performance of the features. Some of the traditional texture features, extracted from the co-occurrence matrix, have also been used for comparison. Secondly, the features are applied to the classification of Transmission Electron Micrographs of premalignant and malignant cell nuclei in a controlled mouse liver carcinogenesis experiment. Directionality and periodicity are two high-level texture features that guide the process of perceptual grouping of texture images. Therefore, two additional experiments have been performed to evaluate the performance of the complexity curve features in estimating the texture directionality and periodicity.

The experimental results demonstrate that the new texture features based on the complexity curve are very useful tools for texture analysis.',\n", - " 'author': ['Baheerathan, S.', 'Albregtsen, F.', 'Danielsen, H. E.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2FS0031-3203%2898%2900122-8\"}'],\n", - " 'title': ['New texture features based on the complexity curve']},\n", - " {'bibcode': '2013NatCo...4.2562J',\n", - " 'abstract': 'Transforming growth factor (TGF)-β, a pivotal cytokine involved in a variety of cellular functions, transmits signals through Smad-dependent canonical and Smad-independent noncanonical pathways. In contrast to the canonical TGF-β pathway, it is unknown how noncanonical TGF-β pathways are negatively regulated. Here we demonstrate that the inhibitory Smad Smad6, but not Smad7, negatively regulates TGF-β1-induced activation of the TRAF6-TAK1-p38 MAPK/JNK pathway, a noncanonical TGF-β pathway. TGF-β1-induced Smad6 abolishes K63-linked polyubiquitination of TRAF6 by recruiting the A20 deubiquitinating enzyme in AML-12 mouse liver cells and primary hepatocytes. In addition, the knockdown of Smad6 or A20 in an animal model or cell culture system maintains TAK1 and p38 MAPK/JNK phosphorylation and increases apoptosis, emphasizing the crucial role of the Smad6-A20 axis in negative regulation of the TGF-β1-TRAF6-TAK1-p38 MAPK/JNK pathway. Therefore, our findings provide insight into the molecular mechanisms underlying negative regulation of noncanonical TGF-β pathways.',\n", - " 'author': ['Jung, Su Myung',\n", - " 'Lee, Ji-Hyung',\n", - " 'Park, Jinyoung',\n", - " 'Oh, Young Sun',\n", - " 'Lee, Sung Kyun',\n", - " 'Park, Jin Seok',\n", - " 'Lee, Youn Sook',\n", - " 'Kim, Jun Hwan',\n", - " 'Lee, Jae Young',\n", - " 'Bae, Yoe-Sik',\n", - " 'Koo, Seung-Hoi',\n", - " 'Kim, Seong-Jin',\n", - " 'Park, Seok Hee'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fncomms3562\"}'],\n", - " 'title': ['Smad6 inhibits non-canonical TGF-β1 signalling by recruiting the deubiquitinase A20 to TRAF6']},\n", - " {'bibcode': '2000PNAS...97..779S',\n", - " 'abstract': 'The contribution of the aryl hydrocarbon receptor (AhR) in induction of a battery of xenobiotic-metabolizing enzymes has been studied extensively. However, no direct proof has been obtained that it plays a role in modulating carcinogenesis. To address the question of whether AhR is required for tumor induction, we have investigated the response of AhR-deficient mice to benzo[a]pyrene (B[a]P), a widely distributed environmental carcinogen. B[a]P treatment induced expression of the cytochrome P450 gene Cyp1a1 in the skin and liver of AhR-positive mice bearing +/+ and +/- genotypes and did not induce expression of the cytochrome P450 gene Cyp1a1 in AhR-null mice in either skin or liver. In contrast, Cyp1a2 gene expression was positive in liver irrespective of the presence or absence of the AhR gene, or B[a]P treatment, although its inducibility was lost in the AhR(-/-) mouse. All AhR-positive male mice of both +/+ and +/- genotypes that received subcutaneous injection of B[a]P (2 mg) on the first and the eighth days had developed subcutaneous tumors at the site of injection at the end of the 18-week experiment. In contrast, no tumors were apparent in any of the AhR-deficient mice. Likewise, topical application of B[a]P (200 μg) at weekly intervals to the skin of female mice for 25 weeks produced skin tumors only in the AhR-positive mice. Thus the carcinogenic action of B[a]P may be determined primarily by AhR, a transcriptional regulator of the gene for CYP1A1. The results of the present study provide direct evidence that AhR is involved in carcinogenesis.',\n", - " 'author': ['Shimizu, Yasuhito',\n", - " 'Nakatsuru, Yoko',\n", - " 'Ichinose, Masao',\n", - " 'Takahashi, Yoshihisa',\n", - " 'Kume, Haruki',\n", - " 'Mimura, Junsei',\n", - " 'Fujii-Kuriyama, Yoshiaki',\n", - " 'Ishikawa, Takatoshi'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/97/2/779\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/97/2/779\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/97/2/779\"}'],\n", - " 'title': ['Benzo[a]pyrene carcinogenicity is lost in mice lacking the aryl hydrocarbon receptor']},\n", - " {'bibcode': '1968Natur.217..370P',\n", - " 'abstract': \"THE mouse mutant ``nude'' has been described by Flanagan1. It is an autosomal recessive. The homozygotes, nu nu, are hairless and their growth is retarded. More than half die before weaning and none survives for as long as 25 weeks. Other parts of the syndrome were: sulphydryl group deficiency and abnormal keratinization of hair follicles, and necrosis of the liver, associated with Toxoplasma gondii infection. No single primary defect of development responsible for these pleiotropic effects could be suggested.\",\n", - " 'author': ['Pantelouris, E. M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F217370a0\"}'],\n", - " 'title': ['Absence of Thymus in a Mouse Mutant']},\n", - " {'bibcode': '1991PNAS...88.9417B',\n", - " 'abstract': 'The murine alpha 1-protease inhibitors (alpha 1-PI) are encoded by a small gene family on chromosome 12. Studies of alpha 1-PI and other serine protease inhibitor genes have revealed an unusually high rate of mutation of the reactive centers of the inhibitors. Using a modification of the PCR technique, we have previously identified five distinct alpha 1 PI reactive site sequences present in the genome of C57BL/6 mice. In this report, we use cDNA cloning techniques to demonstrate that all five genes are expressed in the adult mouse liver. DNA sequence analysis shows that three of the five mRNAs expressed have a substitution for methionine-353, which is essential for normal activity of the homologous human protein, alpha 1-antitrypsin (alpha 1-AT). Comparison of the DNA sequences of the five cDNAs indicates a higher degree of polymorphism in the carboxyl-terminal half of the protein and an extraordinarily replacement/silent ratio of nucleotide changes in a narrow region surrounding the reactive site. The clustering of polymorphisms near the reactive site combined with the high replacement/silent ratio suggest an evolutionary mechanism that apparently selects for functional diversity of the alpha 1-PI genes. Finally, modeling of the three-dimensional positions of the alpha 1-PI polymorphic residues into the homologous positions of the crystallographic structure of ovalbumin, a member of the alpha 1-PI supergene family, predicts that many of these amino acids are on the surfaces, which are likely to interact with the protease targets.',\n", - " 'author': ['Borriello, Frank', 'Krauter, Kenneth S.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/88/21/9417\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/88/21/9417\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/88/21/9417\"}'],\n", - " 'title': ['Multiple Murine α_1-Protease Inhibitor Genes Show Unusual Evolutionary Divergence']},\n", - " {'bibcode': '2003EnTox..18..142G',\n", - " 'abstract': 'The presence of cyanobacterial toxins in drinking and recreational waters represents a potential public health risk. Microcystin‑LR (MC‑LR) is a potent cyclic heptapeptide hepatotoxin produced by the blue‑green alga Microcystis aeruginosa. Chemoprotectant studies have indicated that membrane‑active antioxidants such as vitamin E may offer protection against microcystin toxicity. This study investigated the effect of vitamin E supplementation on microcystin toxicity in mouse liver. Groups of mice were fed vitamin E supplements (8.33 or 33.3 U/mouse/day) for 4 weeks, with intraperitoneal doses of MC‑LR extract (70% LD50) every 3 days from day 8. The potential benefits of vitamin E were evaluated based on lipid peroxidation, alanine transaminase (ALT), and glutathione S‑transferase (GST) levels. Vitamin E supplementation at 33.3 U/mouse/day offered some protection against lipid peroxidation induced by repeated exposure to MC‑LR extract and limited both the toxin‑induced increase in ALT leakage and decrease in GST activity. Vitamin E supplementation at 66.6 U/mouse/day significantly increased the time to death and reduced the increase in liver percentage body weight induced in mice given a lethal dose challenge of MC‑LR extract. Therefore, vitamin E, taken as a dietary supplement, may have a protective effect against chronic exposure to MC‑LR.',\n", - " 'author': ['Gehringer, Michelle M.',\n", - " 'Govender, Sharlene',\n", - " 'Shah, Mrinal',\n", - " 'Downing, Timothy G.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Ftox.10110\"}'],\n", - " 'title': ['An investigation of the role of vitamin E in the protection of mice against microcystin toxicity']},\n", - " {'bibcode': '1978JRadR..19..153B',\n", - " 'author': ['Bhatia, A. L.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1269%2Fjrr.19.153\"}'],\n", - " 'title': ['Effects of Tritiated Water on Mice Liver, in Relation to Age']},\n", - " {'bibcode': '1969PNAS...64..913L',\n", - " 'abstract': 'A protein extracted and partially purified (about 100-fold) from mouse liver is able to inhibit the acid DNases from different tissues and species, whereas pancreatic DNase and E. coli endonuclease I are not inhibited. The acid DNase displays typical Michaelis-Menten kinetics in the absence of this inhibitor, but the kinetics become sigmoidal in its presence. The existence of a DNase-inhibitor complex is demonstrated by physicochemical experiments. Moreover, the inhibitor is able to reactivate the DNase treated by urea, probably through a reassociation of the inactive monomers to a dimeric state. An allosteric model in which the DNase-inhibitor complex is composed of catalytic (DNase) and regulatory (inhibitor) subunits could explain these data.',\n", - " 'author': ['Lesca, Pierre', 'Paoletti, Claude'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/64/3/913\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/64/3/913\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/64/3/913\"}'],\n", - " 'title': ['A Protein Inhibitor of Acid Deoxyribonucleases']},\n", - " {'bibcode': '2020PNAS..117.3144Z',\n", - " 'abstract': 'Glycogen is the primary form of glucose storage in mammals and plays a vital role in cellular energy homeostasis. Mapping glycogen in vivo is useful in diagnosis and assessment of diseases where glucose metabolism is altered, such as diabetes, tumors, and liver diseases. Currently, imaging glycogen in the clinic is not done due to the lack of a practical approach. We report a noninvasive MRI method for imaging glycogen with enhanced detection sensitivity and high specificity. We performed mouse liver glycogen mapping, showing a heterogenous distribution of glycogen and regions of metabolism. This work opens up opportunities for studying glycogen metabolism in vivo at high temporal and spatial resolution.',\n", - " 'author': ['Zhou, Yang',\n", - " 'van Zijl, Peter C. M.',\n", - " 'Xu, Xiang',\n", - " 'Xu, Jiadi',\n", - " 'Li, Yuguo',\n", - " 'Chen, Lin',\n", - " 'Yadav, Nirbhay N.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1909921117\"}'],\n", - " 'title': ['Magnetic resonance imaging of glycogen using its magnetic coupling with water']},\n", - " {'bibcode': '1962Natur.193..778E',\n", - " 'abstract': 'ZONE electrophoresis in a starch column has been found valuable for fractionation of proteins1 and enzymes2. Hunter and Burstone3 recently studied the substrate specificity of esterases of the mouse liver by starch electrophoresis, using thirty different substrates. They came to the conclusion that although substrate-dependent differences were found in the intensity of the reaction in the different bands obtained, the band patterns were essentially similar, and the differences were apparently due to differing reaction-rates on the part of the enzymes in the column rather than to all-or-none substrate specificity. In the kidney, one apparently substrate-specific band was found. The present communication aims at demonstrating that esterases of the brain, which have not previously been examined with this technique, can be resolved into separate bands which possess different substrate characteristics.',\n", - " 'author': ['Eränkö, Olavi', 'Kokko, Aulikki', 'Söderholm, Ulla'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F193778a0\"}'],\n", - " 'title': ['Separation of Substrate-specific Brain Esterases by Starch-gel Electrophoresis']},\n", - " {'bibcode': '2023PLoSO..1883996W',\n", - " 'abstract': 'Targeting the Kv1.3 potassium channel has proven effective in reducing obesity and the severity of animal models of autoimmune disease. Stichodactyla toxin (ShK), isolated from the sea anemone Stichodactyla helianthus, is a potent blocker of Kv1.3. Several of its analogs are some of the most potent and selective blockers of this channel. However, like most biologics, ShK and its analogs require injections for their delivery, and repeated injections reduce patient compliance during the treatment of chronic diseases. We hypothesized that inducing the expression of an ShK analog by hepatocytes would remove the requirement for frequent injections and lead to a sustained level of Kv1.3 blocker in the circulation. To this goal, we tested the ability of Adeno-Associated Virus (AAV)8 vectors to target hepatocytes for expressing the ShK analog, ShK-235 (AAV-ShK-235) in rodents. We designed AAV8 vectors expressing the target transgene, ShK-235, or Enhanced Green fluorescent protein (EGFP). Transduction of mouse livers led to the production of sufficient levels of functional ShK-235 in the serum from AAV-ShK-235 single-injected mice to block Kv1.3 channels. However, AAV-ShK-235 therapy was not effective in reducing high-fat diet-induced obesity in mice. In addition, injection of even high doses of AAV8-ShK-235 to rats resulted in a very low liver transduction efficiency and failed to reduce inflammation in a well-established rat model of delayed-type hypersensitivity. In conclusion, the AAV8-based delivery of ShK-235 was highly effective in inducing the secretion of functional Kv1.3-blocking peptide in mouse, but not rat, hepatocytes yet did not reduce obesity in mice fed a high-fat diet.',\n", - " 'author': ['Wang, Yuqing',\n", - " 'Hurley, Ayrea',\n", - " 'De Giorgi, Marco',\n", - " 'Tanner, Mark R.',\n", - " 'Hu, Rong-Chi',\n", - " 'Pennington, Michael W.',\n", - " 'Lagor, William R.',\n", - " 'Beeton, Christine'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0283996\"}'],\n", - " 'title': ['Adeno-Associated virus 8 delivers an immunomodulatory peptide to mouse liver more efficiently than to rat liver']},\n", - " {'bibcode': '2014PLoSO...9j5096W',\n", - " 'author': ['Wang, Yan',\n", - " 'Tian, Yang',\n", - " 'Ding, Yuan',\n", - " 'Wang, Jingcheng',\n", - " 'Yan, Sheng',\n", - " 'Zhou, Lin',\n", - " 'Xie, Haiyang',\n", - " 'Chen, Hui',\n", - " 'Li, Hui',\n", - " 'Zhang, Jinhua',\n", - " 'Zhao, Jiacong',\n", - " 'Zheng, Shusen'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0105096\"}'],\n", - " 'title': ['MiR-152 May Silence Translation of CaMK II and Induce Spontaneous Immune Tolerance in Mouse Liver Transplantation']},\n", - " {'bibcode': '2018NatSR...811537S',\n", - " 'abstract': 'Long non-coding RNAs (lncRNAs) regulate expression of protein-coding genes in cis through chromatin modifications including DNA methylation. Here we interrogated whether lncRNA genes may regulate transcription and methylation of their flanking or overlapping protein-coding genes in livers of mice exposed to a 12-week cholesterol-rich Western-style high fat diet (HFD) relative to a standard diet (STD). Deconvolution analysis of cell type-specific marker gene expression suggested similar hepatic cell type composition in HFD and STD livers. RNA-seq and validation by nCounter technology revealed differential expression of 14 lncRNA genes and 395 protein-coding genes enriched for functions in steroid/cholesterol synthesis, fatty acid metabolism, lipid localization, and circadian rhythm. While lncRNA and protein-coding genes were co-expressed in 53 lncRNA/protein-coding gene pairs, both were differentially expressed only in 4 lncRNA/protein-coding gene pairs, none of which included protein-coding genes in overrepresented pathways. Furthermore, 5-methylcytosine DNA immunoprecipitation sequencing and targeted bisulfite sequencing revealed no differential DNA methylation of genes in overrepresented pathways. These results suggest lncRNA/protein-coding gene interactions in cis play a minor role mediating hepatic expression of lipid metabolism/localization and circadian clock genes in response to chronic HFD feeding.',\n", - " 'author': ['Silva, Jose P.', 'van Booven, Derek'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-018-29993-4\"}'],\n", - " 'title': ['Analysis of diet-induced differential methylation, expression, and interactions of lncRNA and protein-coding genes in mouse liver']},\n", - " {'bibcode': '2022HETox..4111350Z',\n", - " 'abstract': 'Carbon tetrachloride (CCl4) is a widely used hepatotoxin for the studies of liver fibrosis and cirrhosis, and taurine has function to abate liver fibrosis induced by CCl4. But the interacting mechanisms between taurine and CCl4 in liver are still largely unknown. These made us to hypothesize that CCl4 may induce liver fibrosis by affecting the expressions of taurine biosynthetic enzymes and taurine synthesis. We thus assayed the expressions of hepatic cysteine dioxygenase (CDO), cysteine sulfonate acid decarboxylase (CSAD) and taurine transporter (TauT) in the progression of mouse liver fibrosis induced by CCl4. The results demonstrated that CCl4 treatment markedly decreased hepatic CSAD, CDO expressions, and taurine levels in hepatic tissue, although TauT expression did not exhibit significant decline. It was contrasting that hepatic α-SMA, serum AST, ALT, ALP kept increasing, which were accompanied by the pathological characters of liver, whereas taurine supplement attenuated the progression of liver fibrosis induced by CCl4. These results demonstrate that CCl4 may induce liver fibrosis by inhibiting hepatic CSAD and CDO expressions and taurine synthesis, which are crucial for our understanding the mechanisms of liver fibrosis induced by CCl4, and also potential for establishing therapeutic strategies of liver fibrosis and related diseases.',\n", - " 'author': ['Zhang, Di',\n", - " 'Zheng, Jiaming',\n", - " 'Qiu, Guobin',\n", - " 'Niu, Tongjuan',\n", - " 'Gong, Yuneng',\n", - " 'Cui, Sheng'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1177%2F09603271221135033\"}'],\n", - " 'title': ['CCl4 inhibits the expressions of hepatic taurine biosynthetic enzymes and taurine synthesis in the progression of mouse liver fibrosis']},\n", - " {'bibcode': '1997PNAS...94.2295C',\n", - " 'abstract': 'Using the cytoplasmic domain of the insulin receptor (IR) in a yeast two-hybrid screen, we identified a cDNA clone encoding the C-terminal 308 amino acids of human Stat5b (Stat5b-Ct). Stat5b-Ct is tyrosine phosphorylated by purified IR kinase domain in vitro. Insulin stimulates tyrosine phosphorylation of overexpressed Stat5b-Ct and endogenous Stat5 in cells overexpressing IR. Stat5 may be a direct target of the IR and, as a member of the Stat family of transcription factors, may play a role in the regulation of gene transcription by insulin. In support of this hypothesis, perfusion of mouse liver with insulin promotes rapid tyrosine phosphorylation of Stat5 and activation of Stat5 DNA binding. Moreover, refeeding of fasted mice leads to rapid tyrosine phosphorylation and stimulation of enhanced DNA-binding activity of Stat5 extracted from liver, skeletal muscle, and adipose tissues. Taken together, our data strongly suggest that IR interacts with and phosphorylates Stat5 in vitro and in tissues physiologically sensitive to insulin.',\n", - " 'author': ['Chen, Jing',\n", - " 'Sadowski, Henry B.',\n", - " 'Kohanski, Ronald A.',\n", - " 'Wang, Lu-Hai'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/94/6/2295\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/94/6/2295\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/94/6/2295\"}'],\n", - " 'title': ['Stat5 is a Physiological Substrate of the Insulin Receptor']},\n", - " {'bibcode': '2020SPIE11553E..2BS',\n", - " 'abstract': 'Fluorescence pharmacokinetics can analyze the absorption, distribution, metabolism and other pharmacokinetic processes of fluorescence agents in biological tissues over time, which can provide more specific and quantitative physiological and pathological information for the evaluation of organ function. This paper is devoted to studying pharmacokinetics of indocyanine green (ICG) in healthy mice and mice with acute alcoholic liver injury based on a home-made dynamic diffuse fluorescence tomography system that possesses high sensitivity and large dynamic measurement range on account of digital lock-in-photon-counting technique. In this study, four-week-old Kunming mice were randomly divided into experimental and control groups. The time-varying distribution of ICG in mice was obtained by diffuse fluorescence tomography reconstruction, and the pharmacokinetic parameters were further extracted from the ICG concentration-time curve. The results showed that the dynamic diffuse fluorescence tomography system successfully captured the ICG metabolism process in mouse liver, and the ICG excretion rate demonstrated an obvious difference between healthy mice and the mice with acute alcoholic liver injury.',\n", - " 'author': ['Shi, Ke',\n", - " 'Zhang, Limin',\n", - " 'Zhao, Zhichao',\n", - " 'Cao, Bin',\n", - " 'Chen, Nan',\n", - " 'Li, Jiao',\n", - " 'Zhou, Zhongxing',\n", - " 'Gao, Feng'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1117%2F12.2574153\"}'],\n", - " 'title': ['Assessing pharmacokinetics of indocyanine green in liver injury mice using dynamic diffuse fluorescence tomography system']},\n", - " {'bibcode': '2010PNAS..10714508P',\n", - " 'abstract': 'Advances in systems biology have allowed for global analyses of mRNA and protein expression, but large-scale studies of protein dynamics and turnover have not been conducted in vivo. Protein turnover is an important metabolic and regulatory mechanism in establishing proteome homeostasis, impacting many physiological and pathological processes. Here, we have used organism-wide isotopic labeling to measure the turnover rates of ~2,500 proteins in multiple mouse tissues, spanning four orders of magnitude. Through comparison of the brain with the liver and blood, we show that within the respective tissues, proteins performing similar functions often have similar turnover rates. Proteins in the brain have significantly slower turnover (average lifetime of 9.0 d) compared with those of the liver (3.0 d) and blood (3.5 d). Within some organelles (such as mitochondria), proteins have a narrow range of lifetimes, suggesting a synchronized turnover mechanism. Protein subunits within complexes of variable composition have a wide range of lifetimes, whereas those within well-defined complexes turn over in a coordinated manner. Together, the data represent the most comprehensive in vivo analysis of mammalian proteome turnover to date. The developed methodology can be adapted to assess in vivo proteome homeostasis in any model organism that will tolerate a labeled diet and may be particularly useful in the analysis of neurodegenerative diseases in vivo.',\n", - " 'author': ['Price, John C.',\n", - " 'Guan, Shenheng',\n", - " 'Burlingame, Alma',\n", - " 'Prusiner, Stanley B.',\n", - " 'Ghaemmaghami, Sina'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/107/32/14508\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1006551107\"}'],\n", - " 'title': ['Analysis of proteome dynamics in the mouse brain']},\n", - " {'bibcode': '2016ChJOL..34..399X',\n", - " 'abstract': 'Excessive alcohol consumption leads to liver disease. Extensive evidence suggests that C-phycocyanin (C-PC), a chromophore phycocyanobilin derived from Spirulina platensis, exerts protective effects against chemical-induced organ damage. In this study, we investigated whether C-PC could protect against ethanol-induced acute liver injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (CHOL), low-density lipoprotein (LDL), liver homogenate malondialdehyde (MDA), superoxide dismutase (SOD) content were measured, and pathological examination of liver sections were examined. C-PC showed obvious inhibitory effects on serum ALT, AST, TG, CHOL, LDL and MDA, and SOD content significantly increased in the liver. The structure of hepatic lobules was clear, liver sinus returned to normal, and liver cell cords were arranged in neat rows. Cloudiness, swelling, inflammatory cell infiltration and spotty necrosis of liver cells were significantly reduced. Therefore, C-PC can significantly protect against ethanol-induced acute liver injury.',\n", - " 'author': ['Xia, Dong',\n", - " 'Liu, Bing',\n", - " 'Luan, Xiying',\n", - " 'Sun, Junyan',\n", - " 'Liu, Nana',\n", - " 'Qin, Song',\n", - " 'Du, Zhenning'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://dx.doi.org/10.1007/s00343-015-4312-6\"}'],\n", - " 'title': ['Protective effects of C-phycocyanin on alcohol-induced acute liver injury in mice']},\n", - " {'bibcode': '1972Sci...177..894M',\n", - " 'abstract': 'Changing concentrations of β -glucuronidase and β -galactosidase are coordinated during the development of mouse liver, heart, and brain. Although coordinate, the developmental patterns for the two enzymes are under independent control by genetic elements apparently linked to the respective structural genes.',\n", - " 'author': ['Meisler, Miriam', 'Paigen, Kenneth'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.177.4052.894\"}'],\n", - " 'title': ['Coordinated Development of β -Glucuronidase and β -Galactosidase in Mouse Organs']},\n", - " {'bibcode': '1964Natur.201..709T',\n", - " 'abstract': 'Maynard and Schenker1 have reported that monoamine oxidase from mouse liver is inhibited by ethanol in vitro; however, these authors could not obtain similar inhibition of monoamine oxidase of mouse brain. The fact that the liver of mammals contains alcohol dehydrogenase suggests that the inhibition of liver monoamine oxidase may occur via the transformation of ethanol to the reactive acetaldehyde, which is responsible for the observed effects. Further, the level of inhibition observed by Maynard and Schenker is low and requires what amounts to be substrate concentrations of ethanol (0.022 M-0.087 M). The absence, or a low level, of alcohol dehydrogenase in brain would account for the failure to observe inhibition of monoamine oxidase from this source by ethanol.',\n", - " 'author': ['Towne, Jack C.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F201709b0\"}'],\n", - " 'title': ['Effect of Ethanol and Acetaldehyde on Liver and Brain Monoamine Oxidase']},\n", - " {'bibcode': '2011PNAS..108.9715C',\n", - " 'abstract': \"Methyl-sensitive cut counting (MSCC) with the HpaII methylation-sensitive restriction enzyme is a cost-effective method to pinpoint unmethylated CpGs at single base-pair resolution. However, it has the drawback of addressing only CpGs in the context of the CCGG site, leaving out the remainder of the possible 16 XCGX tetranucleotides in which CpGs are found. We expanded MSCC to include three additional enzymes to address a total of 5 of the 16 XCGX combinations. This allowed us to survey methylation at about one-third of all a mammalian genome's CpGs. Applied to mouse liver DNA, we correctly confirmed data reported with other methods showing hypomethylation to be concentrated at promoters and in CpG islands (CGIs), with gene bodies and intergenic regions being mostly methylated. Grouping unmethylated CpGs, characterized by high MSCC scores (7% false discovery rate), we found a large number of unmethylated regions not qualifying as CGIs located in intergenic and intronic regions, which are highly enriched in functional DNA sequences (open regulatory annotation database) as well as in noncoding yet highly conserved mammalian sequences thought to be important but with as yet unknown function. About 50% of MSCC-defined unmethylated regions do not overlap algorithm-defined CGIs and offer a novel search space in which new functionalities of DNA may be found in health and disease.\",\n", - " 'author': ['Colaneri, Alejandro',\n", - " 'Staffa, Nickolas',\n", - " 'Fargo, David C.',\n", - " 'Gao, Yuan',\n", - " 'Wang, Tianyuan',\n", - " 'Peddada, Shyamal D.',\n", - " 'Birnbaumer, Lutz'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/108/23/9715\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1105713108\"}'],\n", - " 'title': ['Expanded methyl-sensitive cut counting reveals hypomethylation as an epigenetic state that highlights functional sequences of the genome']},\n", - " {'bibcode': '2022AdM....3410618X',\n", - " 'abstract': 'Clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9) may offer new therapeutics for genetic diseases through gene disruption via nonhomologous end joining (NHEJ) or gene correction via homology-directed repair (HDR). However, clinical translation of CRISPR technology is limited by the lack of safe and efficient delivery systems. Here, facilely fabricated pH-responsive polymer nanoparticles capable of safely and efficiently delivering Cas9 ribonucleoprotein alone (termed NHEJ-NP, diameter = 29.4 nm), or together with donor DNA (termed HDR-NP, diameter = 33.3 nm) are reported. Moreover, intravenously, intratracheally, and intramuscularly injected NHEJ-NP induces efficient gene editing in mouse liver, lung, and skeletal muscle, respectively. Intramuscularly injected HDR-NP also leads to muscle strength recovery in a Duchenne muscular dystrophy mouse model. NHEJ-NP and HDR-NP possess many desirable properties including high payload loading content, small and uniform sizes, high editing efficiency, good biocompatibility, low immunogenicity, and ease of production, storage, and transport, making them great interest for various genome editing applications with clinical potentials.',\n", - " 'author': ['Xie, Ruosen',\n", - " 'Wang, Xiuxiu',\n", - " 'Wang, Yuyuan',\n", - " 'Ye, Mingzhou',\n", - " 'Zhao, Yi',\n", - " 'Yandell, Brian S.',\n", - " 'Gong, Shaoqin'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Fadma.202110618\"}'],\n", - " 'title': ['pH-Responsive Polymer Nanoparticles for Efficient Delivery of Cas9 Ribonucleoprotein With or Without Donor DNA']},\n", - " {'bibcode': '2023PatRe.13809355B',\n", - " 'abstract': 'Detecting recurrent patterns in time series data is an important capability. The reason is that repeating patterns on the one hand indicate well defined processes that can be further analyzed once detected and on the other hand are a reliable feature to predict future occurrences and adapt accordingly. The challenge in real data to define a period is that a time series is usually also influenced by non-periodic dynamics and noise. In this work, a mathematical framework is proved to define regular patterns. Their properties are used within a suggested algorithm based on the concept of autocorrelation and function approximation to fit a model capturing the periodic part of the time series. Based on that model and a corresponding autocorrelation, a new score is defined to evaluate how well a hypothesized period fits to the time series. This score is particularly useful in a big data scenario where decisions for periodicity are needed to be taken automatically, which is one of the main achievement of the presented work. The period analysis algorithm is applied to data from two different use cases. The first one is a data center scenario where the information of the periodic pattern is used to create a feature that improves a machine learning framework predicting future resource demands. The feature represents the phase of the repeating pattern. In a second scenario, expression data from mice liver cells are investigated concerning periodic rhythms. A Python implementation of the presented algorithm is provided via a github repository under https://github.com/LauritzR/period-detection.',\n", - " 'author': ['Breitenbach, Tim',\n", - " 'Wilkusz, Bartosz',\n", - " 'Rasbach, Lauritz',\n", - " 'Jahnke, Patrick'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.patcog.2023.109355\"}'],\n", - " 'title': ['On a method for detecting periods and repeating patterns in time series data with autocorrelation and function approximation']},\n", - " {'bibcode': '2011PNAS..10819581G',\n", - " 'abstract': 'The process of lipid droplet (LD) formation is an evolutionarily conserved process among all eukaryotes and plays an important role in both cellular physiology and disease. Recently, fat storage-inducing transmembrane proteins 1 and 2 (FIT1/FITM1 and FIT2/FITM2) were discovered as an evolutionarily conserved family of proteins involved in fat storage. In mammals, FIT1 is expressed primarily in skeletal muscle and FIT2 is expressed primarily in adipose, raising the possibility that FIT1 and FIT2 have unique functions. These proteins are exclusively localized to the endoplasmic reticulum (ER) and mediate triglyceride-rich LD accumulation when overexpressed in cells, mouse liver, or muscle. Unlike the ER-resident diacylglycerol O-acyltransferase family of triglyceride-synthesizing enzymes, FITs do not synthesize triglyceride, but rather partition triglyceride into LDs. The mechanism by which FIT proteins mediate this process has not been determined. A simple hypothesis was tested that FIT proteins bind to triglyceride to mediate LD formation. Here, it is shown that FIT proteins purified in detergent micelles directly bind triolein with specificity and saturation-binding kinetics. A FIT2 gain-of-function mutant that formed larger LDs, FLL(157-9)AAA, showed increased binding to triolein relative to wild-type FIT2, whereas FIT1 and a FIT2 partial loss-of-function mutant, N80A, had significantly lower triolein binding and produced smaller LDs. In summary, FIT proteins are transmembrane domain-containing proteins shown to bind triglyceride. These findings indicate that FITs have a unique biochemical mechanism in mediating LD formation and implicates triglyceride binding as important for FIT-mediated LD formation.',\n", - " 'author': ['Gross, David A.', 'Zhan, Chenyang', 'Silver, David L.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/108/49/19581\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1110817108\"}'],\n", - " 'title': ['Direct binding of triglyceride to fat storage-inducing transmembrane proteins 1 and 2 is important for lipid droplet formation']},\n", - " {'bibcode': '2009PNAS..106.2377L',\n", - " 'abstract': 'Niemann-Pick type C disease is largely attributable to an inactivating mutation of NPC1 protein, which normally aids movement of unesterified cholesterol (C) from the endosomal/lysosomal (E/L) compartment to the cytosolic compartment of cells throughout the body. This defect results in activation of macrophages in many tissues, progressive liver disease, and neurodegeneration. In the npc1−/− mouse, a model of this disease, the whole-animal C pool expands from 2,082 to 4,925 mg/kg body weight (bw) and the hepatic C pool increases from 132 to 1,485 mg/kg bw between birth and 49 days of age. A single dose of 2-hydroxypropyl-β-cyclodextrin (CYCLO) administered at 7 days of age immediately caused this sequestered C to flow from the lysosomes to the cytosolic pool in many organs, resulting in a marked increase in cholesteryl esters, suppression of C but not fatty acid synthesis, down-regulation of genes controlled by sterol regulatory element 2, and up-regulation of many liver X receptor target genes. There was also decreased expression of proinflammatory proteins in the liver and brain. In the liver, where the rate of C sequestration equaled 79 mg.d−1.kg−1, treatment with CYCLO within 24 h increased C movement out of the E/L compartment from near 0 to 233 mg.d−1.kg−1. By 49 days of age, this single injection of CYCLO resulted in a reduction in whole-body C burden of >900 mg/kg, marked improvement in liver function tests, much less neurodegeneration, and, ultimately, significant prolongation of life. These findings suggest that CYCLO acutely reverses the lysosomal transport defect seen in NPC disease.',\n", - " 'author': ['Liu, Benny',\n", - " 'Turley, Stephen D.',\n", - " 'Burns, Dennis K.',\n", - " 'Miller, Anna M.',\n", - " 'Repa, Joyce J.',\n", - " 'Dietschy, John M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/106/7/2377\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/106/7/2377.full.pdf+html\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0810895106\"}'],\n", - " 'title': ['Reversal of defective lysosomal transport in NPC disease ameliorates liver dysfunction and neurodegeneration in the npc1−/− mouse']},\n", - " {'bibcode': '2003PNAS..10012027H',\n", - " 'abstract': 'The synthesis of fatty acids and cholesterol, the building blocks of membranes, is regulated by three membrane-bound transcription factors: sterol regulatory element-binding proteins (SREBP)-1a, -1c, and -2. Their function in liver has been characterized in transgenic mice that overexpress each SREBP isoform and in mice that lack all three nuclear SREBPs as a result of gene knockout of SREBP cleavage-activating protein (SCAP), a protein required for nuclear localization of SREBPs. Here, we use oligonucleotide arrays hybridized with RNA from livers of three lines of mice (transgenic for SREBP-1a, transgenic for SREBP-2, and knockout for SCAP) to identify genes that are likely to be direct targets of SREBPs in liver. A total of 1,003 genes showed statistically significant increased expression in livers of transgenic SREBP-1a mice, 505 increased in livers of transgenic SREBP-2 mice, and 343 showed decreased expression in Scap-/- livers. A subset of 33 genes met the stringent combinatorial criteria of induction in both SREBP transgenics and decreased expression in SCAP-deficient mice. Of these 33 genes, 13 were previously identified as direct targets of SREBP action. Of the remaining 20 genes, 13 encode enzymes or carrier proteins involved in cholesterol metabolism, 3 participate in fatty acid metabolism, and 4 have no known connection to lipid metabolism. Through application of stringent combinatorial criteria, the transgenic/knockout approach allows identification of genes whose activities are likely to be controlled directly by one family of transcription factors, in this case the SREBPs.',\n", - " 'author': ['Horton, Jay D.',\n", - " 'Shah, Nila A.',\n", - " 'Warrington, Janet A.',\n", - " 'Anderson, Norma N.',\n", - " 'Park, Sahng Wook',\n", - " 'Brown, Michael S.',\n", - " 'Goldstein, Joseph L.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/100/21/12027\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1534923100\"}'],\n", - " 'title': ['Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes']},\n", - " {'bibcode': '2019AIPC.2108b0016N',\n", - " 'abstract': 'The aim of our study was to investigate the efficacy of Bryophyllum pinnatum leaves ethanol extract in pristane-induce systemic lupus erythematosus (SLE) BALB/c mice model. Forty female BALB/c mice, aged 6-8 weeks old received a single i.p. injection of 0.5 cc pristane for lupus induction. 16 weeks after injection, pristane-induced lupus mice were divided into four groups based on the doses of Bryophyllum pinnatum received intragastrically: 0, 10.5 mg/kg/, 21 mg/kg/, and 42 mg/kg/day for 12 weeks. At 38 weeks after injection, all mice were assessed for inflammation marker. Side effects study results suggest that there were no signs of side effects generally. No significant changes of blood pressure, liver and mice renal function were observed. The efficacy study showed that percentages of matured B cells, TNF-α, CRP, IL-17, and IL-12 decreased (p<0.05) and percentages of TGF-β and complement C3 and C4 increased (p>0.05) in Bryophyllum pinnatum treated mice. Bryophyllum pinnatum crude extract has the potential to be further developed as a new, safe, and effective agent of delivery to modulate immune cells against pristane-induced SLE BALB/c mice.',\n", - " 'author': ['Nurdiana, Dantara, Tri Wahyudi Iman',\n", - " 'Syaban, Mokhamad Fahmi Rizki',\n", - " 'Mustafa, Siti Asyifa',\n", - " 'Ikhsani, Hanifah',\n", - " 'Syafitri, Febrinda Esti',\n", - " 'Hapsari, Novi Kurnia',\n", - " 'Khoirunnisa, Auliya'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1063%2F1.5109991\"}'],\n", - " 'title': ['Efficacy and side effects studies of Bryophyllum pinnatum leaves ethanol extract in pristane-induced SLE BALB/c mice model']},\n", - " {'bibcode': '2013Natur.499...97Y',\n", - " 'abstract': 'Obesity has become more prevalent in most developed countries over the past few decades, and is increasingly recognized as a major risk factor for several common types of cancer. As the worldwide obesity epidemic has shown no signs of abating, better understanding of the mechanisms underlying obesity-associated cancer is urgently needed. Although several events were proposed to be involved in obesity-associated cancer, the exact molecular mechanisms that integrate these events have remained largely unclear. Here we show that senescence-associated secretory phenotype (SASP) has crucial roles in promoting obesity-associated hepatocellular carcinoma (HCC) development in mice. Dietary or genetic obesity induces alterations of gut microbiota, thereby increasing the levels of deoxycholic acid (DCA), a gut bacterial metabolite known to cause DNA damage. The enterohepatic circulation of DCA provokes SASP phenotype in hepatic stellate cells (HSCs), which in turn secretes various inflammatory and tumour-promoting factors in the liver, thus facilitating HCC development in mice after exposure to chemical carcinogen. Notably, blocking DCA production or reducing gut bacteria efficiently prevents HCC development in obese mice. Similar results were also observed in mice lacking an SASP inducer or depleted of senescent HSCs, indicating that the DCA-SASP axis in HSCs has key roles in obesity-associated HCC development. Moreover, signs of SASP were also observed in the HSCs in the area of HCC arising in patients with non-alcoholic steatohepatitis, indicating that a similar pathway may contribute to at least certain aspects of obesity-associated HCC development in humans as well. These findings provide valuable new insights into the development of obesity-associated cancer and open up new possibilities for its control.',\n", - " 'author': ['Yoshimoto, Shin',\n", - " 'Loo, Tze Mun',\n", - " 'Atarashi, Koji',\n", - " 'Kanda, Hiroaki',\n", - " 'Sato, Seidai',\n", - " 'Oyadomari, Seiichi',\n", - " 'Iwakura, Yoichiro',\n", - " 'Oshima, Kenshiro',\n", - " 'Morita, Hidetoshi',\n", - " 'Hattori, Masahisa',\n", - " 'Honda, Kenya',\n", - " 'Ishikawa, Yuichi',\n", - " 'Hara, Eiji',\n", - " 'Ohtani, Naoko'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature12347\"}'],\n", - " 'title': ['Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome']},\n", - " {'bibcode': '1994Natur.371..606J',\n", - " 'abstract': 'THE mammalian pancreas is a mixed exocrine and endocrine gland that, in most species, arises from ventral and dorsal buds which subsequently merge to form the pancreas. In both mouse and rat the first histological sign of morphogenesis of the dorsal pancreas is a dorsal evagination of the duodenum at the level of the liver at around the 22-25-somite stage, and shortly thereafter a ventral evagination appears as a derivative of the liver diverticulum1-3. Low levels of insulin gene transcripts are already present and restricted to the dorsal foregut endoderm at 20 somites, suggesting that pancreas- or insulin gene-specific transcriptional factors are present in this region before the onset of morphogenesis4. Insulin-promoter-factor 1 (IPF1) is a homeodomain protein which, in the adult mouse pancreas, is selectively expressed in the β-cells and binds to and transactivates the insulin promoter5. In mouse embryos, IPF1 expression is restricted to the developing pancreatic anlagen and is initiated when the foregut endoderm is committed to a pancreatic fate5. We now show that mice homozygous for a targeted mutation in the Ipf1 gene selectively lack a pancreas. The mutant pups survive fetal development but die within a few days after birth. The gastrointestinal part and all other internal organs were normal in appearance. No pancreatic tissue and no ectopic expression of insulin or pancreatic amylase could be detected in mutant embryos and neonates. These findings show that IPF1 is needed for the formation of the pancreas and suggest that it acts to determine the fate of common pancreatic precursor cells and/ or to regulate their propagation.',\n", - " 'author': ['Jonsson, Jörgen',\n", - " 'Carlsson, Lena',\n", - " 'Edlund, Thomas',\n", - " 'Edlund, Helena'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F371606a0\"}'],\n", - " 'title': ['Insulin-promoter-factor 1 is required for pancreas development in mice']},\n", - " {'bibcode': '1974PNAS...71.2491F',\n", - " 'abstract': 'As previously shown, purified 14S RNA of mouse myeloma MOPC-41 forms a single peak on sucrose gradients and gel electrophoresis and codes for a single polypeptide chain, the immunoglobulin light chain produced by the same myeloma in vivo. This 14S mRNA was used for the enzymatic synthesis of DNA (cDNA) which is complementary to the RNA template. A DNA fraction was isolated which has an average size of 300 nucleotides. Kinetic studies of the hybridization of the 14S RNA with the cDNA indicate that about 40% of the RNA consists of a single RNA sequence. From the size of the cDNA fraction and from the direction of DNA synthesis, it can be concluded that the cDNA includes the sequence complementary to the constant region of light chain mRNA. This radioactive cDNA was used for DNA.DNA reannealing experiments with unlabeled DNA from mouse liver or myeloma tumor in 3 × 106-fold excess. This allowed the determination of the number of copies in the mouse genome of those sequences represented in the cDNA. The data show no significant reiteration in either liver or myeloma DNA and suggest that the gene coding for the constant part of immunoglobins is present in the haploid genome in one to five copies. Furthermore, this gene is not \"amplified\" in nuclear DNA of myeloma plasmocytes.',\n", - " 'author': ['Faust, C. H.', 'Diggelmann, H.', 'Mach, B.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/71/6/2491\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/71/6/2491\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/71/6/2491\"}'],\n", - " 'title': ['Estimation of the Number of Genes Coding for the Constant Part of the Mouse Immunoglobulin Kappa Light Chain']},\n", - " {'bibcode': '2013SPIE.8676E..0DS',\n", - " 'abstract': 'Image-based analysis of the vascular structures of murine liver samples is an important tool for scientists to understand liver physiology and morphology. Typical assessment methods are MicroCT, which allows for acquiring images of the whole organ while lacking resolution for fine details, and confocal laser scanning microscopy, which allows detailed insights into fine structures while lacking the broader context. Imaging of histological serial whole slide sections is a recent technology able to fill this gap, since it provides a fine resolution up to the cellular level, but on a whole organ scale. However, whole slide imaging is a modality providing only 2D images. Therefore the challenge is to use stacks of serial sections from which to reconstruct the 3D vessel structures. In this paper we present a semi-automatic procedure to achieve this goal. We employ an automatic method that detects vessel structures based on continuity and shape characteristics. Furthermore it supports the user to perform manual corrections where required. With our methods we were able to successfully extract and reconstruct vessel structures from a stack of 100 and a stack of 397 serial sections of a mouse liver lobe, thus proving the potential of our approach.',\n", - " 'author': ['Schwier, Michael',\n", - " 'Hahn, Horst K.',\n", - " 'Dahmen, Uta',\n", - " 'Dirsch, Olaf'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1117%2F12.2008112\"}'],\n", - " 'title': ['Reconstruction of vessel structures from serial whole slide sections of murine liver samples']},\n", - " {'bibcode': '2018NatCo...9.4399S',\n", - " 'abstract': 'Pantothenate kinase (PANK) is a metabolic enzyme that regulates cellular coenzyme A (CoA) levels. There are three human PANK genes, and inactivating mutations in PANK2 lead to pantothenate kinase associated neurodegeneration (PKAN). Here we performed a library screen followed by chemical optimization to produce PZ-2891, an allosteric PANK activator that crosses the blood brain barrier. PZ-2891 occupies the pantothenate pocket and engages the dimer interface to form a PANK•ATP•Mg2+•PZ-2891 complex. The binding of PZ-2891 to one protomer locks the opposite protomer in a catalytically active conformation that is refractory to acetyl-CoA inhibition. Oral administration of PZ-2891 increases CoA levels in mouse liver and brain. A knockout mouse model of brain CoA deficiency exhibited weight loss, severe locomotor impairment and early death. Knockout mice on PZ-2891 therapy gain weight, and have improved locomotor activity and life span establishing pantazines as novel therapeutics for the treatment of PKAN.',\n", - " 'author': ['Sharma, Lalit Kumar',\n", - " 'Subramanian, Chitra',\n", - " 'Yun, Mi-Kyung',\n", - " 'Frank, Matthew W.',\n", - " 'White, Stephen W.',\n", - " 'Rock, Charles O.',\n", - " 'Lee, Richard E.',\n", - " 'Jackowski, Suzanne'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41467-018-06703-2\"}'],\n", - " 'title': ['A therapeutic approach to pantothenate kinase associated neurodegeneration']},\n", - " {'bibcode': '2019PNAS..11611408M',\n", - " 'abstract': 'Oxidative DNA damage is considered carcinogenic, yet the increased oxidative stress in cancer cells could make these cells critically dependent on endogenous antioxidant systems for survival. Accordingly, activation of the major cellular antioxidant network correlates with increased malignancy in many cancers. This report shows that genetic co-disruption of the two major reductase systems within this network in mouse liver increases oxidative stress yet is apparently neither carcinogenic nor tumoricidal. Instead, chronic lifetime oxidative stress in the liver strongly augments the malignant progression of chemically induced cancers. Thus, the balance between oxidative stress and the endogenous antioxidant network is shown to have a much greater impact on determining malignant progression of cancers than on determining rates of cancer initiation.',\n", - " 'author': ['McLoughlin, Michael R.',\n", - " 'Orlicky, David J.',\n", - " 'Prigge, Justin R.',\n", - " 'Krishna, Pushya',\n", - " 'Talago, Emily A.',\n", - " 'Cavigli, Ian R.',\n", - " 'Eriksson, Sofi',\n", - " 'Miller, Colin G.',\n", - " 'Kundert, Jean A.',\n", - " 'Sayin, Volkan I.',\n", - " 'Sabol, Rachel A.',\n", - " 'Heinemann, Joshua',\n", - " 'Brandenberger, Luke O.',\n", - " 'Iverson, Sonya V.',\n", - " 'Bothner, Brian',\n", - " 'Papagiannakopoulos, Thales',\n", - " 'Shearn, Colin T.',\n", - " 'Arnér, Elias S. J.',\n", - " 'Schmidt, Edward E.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1903244116\"}'],\n", - " 'title': ['TrxR1, Gsr, and oxidative stress determine hepatocellular carcinoma malignancy']},\n", - " {'bibcode': '2005Sci...310.1642S',\n", - " 'abstract': 'The Peutz-Jegher syndrome tumor-suppressor gene encodes a protein-threonine kinase, LKB1, which phosphorylates and activates AMPK [adenosine monophosphate (AMP)-activated protein kinase]. The deletion of LKB1 in the liver of adult mice resulted in a nearly complete loss of AMPK activity. Loss of LKB1 function resulted in hyperglycemia with increased gluconeogenic and lipogenic gene expression. In LKB1-deficient livers, TORC2, a transcriptional coactivator of CREB (cAMP response element-binding protein), was dephosphorylated and entered the nucleus, driving the expression of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), which in turn drives gluconeogenesis. Adenoviral small hairpin RNA (shRNA) for TORC2 reduced PGC-1α expression and normalized blood glucose levels in mice with deleted liver LKB1, indicating that TORC2 is a critical target of LKB1/AMPK signals in the regulation of gluconeogenesis. Finally, we show that metformin, one of the most widely prescribed type 2 diabetes therapeutics, requires LKB1 in the liver to lower blood glucose levels.',\n", - " 'author': ['Shaw, Reuben J.',\n", - " 'Lamia, Katja A.',\n", - " 'Vasquez, Debbie',\n", - " 'Koo, Seung-Hoi',\n", - " 'Bardeesy, Nabeel',\n", - " 'DePinho, Ronald A.',\n", - " 'Montminy, Marc',\n", - " 'Cantley, Lewis C.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.1120781\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.1120781\"}'],\n", - " 'title': ['The Kinase LKB1 Mediates Glucose Homeostasis in Liver and Therapeutic Effects of Metformin']},\n", - " {'bibcode': '1993Natur.364...64M',\n", - " 'abstract': 'IT is widely accepted that during murine embryogenesis, totipotent haematopoietic stem cells first originate in the yolk sac, then migrate to the fetal liver and finally colonize the bone marrow shortly before birth1,2. This view is based on in vitro studies showing that yolk sac cells can differentiate into various haematopoietic lineages1,3-7 and in vivo studies showing that yolk sac contains spleen colony-forming units (CFU-S) beginning at day 8 of gestation1. However, some investigators have failed to find statistically significant numbers of CFU-S arising from day 9 yolk sac3,8-11 and, although one group reported that yolk sac could repopulate the haematopoietic system of W mutant mice2, others have failed to confirm yolk sac-derived repopulation of adults3,12. In the avian and amphibian systems, the yolk sac gives rise only to early, transitory haematopoiesis whereas the definitive adult haematopoietic stem cells in these vertebrates are derived from the mesodermal region containing the dorsal aorta13-17. Because this analogous area of the mouse embryo has not been previously examined for haematopoietic activity, we directly compared the CFU-S activity of the aorta, gonad, mesonephros (AGM) region with the yolk sac and fetal liver during embryogenesis. Here we report that this intra-embryonic AGM region contains CFU-S activity at a higher frequency than that in embryonic yolk sac and that such activity appears in the AGM region before the fetal liver.',\n", - " 'author': ['Medvinsky, Alexander L.',\n", - " 'Samoylina, Nina L.',\n", - " 'Müller, Albrecht M.',\n", - " 'Dzierzak, Elaine A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F364064a0\"}'],\n", - " 'title': ['An early pre-liver intraembryonic source of CFU-S in the developing mouse']},\n", - " {'bibcode': '2016PLoSO..1151511K',\n", - " 'author': ['Komiya, Chikara',\n", - " 'Tsuchiya, Kyoichiro',\n", - " 'Shiba, Kumiko',\n", - " 'Miyachi, Yasutaka',\n", - " 'Furuke, Shunsaku',\n", - " 'Shimazu, Noriko',\n", - " 'Yamaguchi, Shinobu',\n", - " 'Kanno, Kazuo',\n", - " 'Ogawa, Yoshihiro'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0151511\"}'],\n", - " 'title': ['Ipragliflozin Improves Hepatic Steatosis in Obese Mice and Liver Dysfunction in Type 2 Diabetic Patients Irrespective of Body Weight Reduction']},\n", - " {'bibcode': '1999PNAS...96.1563P',\n", - " 'abstract': 'Pten/Mmac1+/- heterozygous mice exhibited neoplasms in multiple organs including the endometrium, liver, prostate, gastrointestinal tract, thyroid, and thymus. Loss of the wild-type allele was detected in neoplasms of the thymus and liver. Surprisingly, tumors of the gastrointestinal epithelium developed in association with gut lymphoid tissue. Tumors of the endometrium, thyroid, prostate, and liver were not associated with lymphoid tissue and appeared to be highly mitotic. In addition, these mice have nonneoplastic hyperplasia of lymph nodes that was caused by an inherited defect in apoptosis detected in B cells and macrophages. Examination of peripheral lymphoid tissue including lymphoid aggregates associated with polyps revealed that the normal organization of B and T cells was disrupted in heterozygous animals. Taken together, these data suggest that PTEN is a regulator of apoptosis and proliferation that behaves as a \"landscaper\" tumor suppressor in the gut and a \"gatekeeper\" tumor suppressor in other organs.',\n", - " 'author': ['Podsypanina, Katrina',\n", - " 'Ellenson, Lora Hedrick',\n", - " 'Nemes, Adriana',\n", - " 'Gu, Jianguo',\n", - " 'Tamura, Masahito',\n", - " 'Yamada, Kenneth M.',\n", - " 'Cordon-Cardo, Carlos',\n", - " 'Catoretti, Giorgio',\n", - " 'Fisher, Peter E.',\n", - " 'Parsons, Ramon'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/96/4/1563\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/96/4/1563\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/96/4/1563\"}'],\n", - " 'title': ['Mutation of Pten/Mmac1 in Mice Causes Neoplasia in Multiple Organ Systems']},\n", - " {'bibcode': '2016NatSR...630986K',\n", - " 'abstract': 'The mechanism of Amifostine (WR-2721) mediated radioprotection is poorly understood. The effects of amifostine on human basal metabolism, mouse liver metabolism and on normal and tumor hepatic cells were studied. Indirect calorimetric canopy tests showed significant reductions in oxygen consumption and of carbon dioxide emission in cancer patients receiving amifostine. Glucose levels significantly decreased and lactate levels increased in patient venous blood. Although amifostine in vitro did not inhibit the activity of the prolyl-hydroxylase PHD2, experiments with mouse liver showed that on a short timescale WR-1065 induced expression of the Hypoxia Inducible Factor HIF1α, lactate dehydrogenase LDH5, glucose transporter GLUT2, phosphorylated pyruvate dehydrogenase pPDH and PDH-kinase. This effect was confirmed on normal mouse NCTC hepatocytes, but not on hepatoma cells. A sharp reduction of acetyl-CoA and ATP levels in NCTC cells indicated reduced mitochondrial usage of pyruvate. Transient changes of mitochondrial membrane potential and reactive oxygen species ROS production were evident. Amifostine selectively protects NCTC cells against radiation, whilst HepG2 neoplastic cells are sensitized. The radiation protection was correlates with HIF levels. These findings shed new light on the mechanism of amifostine cytoprotection and encourage clinical research with this agent for the treatment of primary and metastatic liver cancer.',\n", - " 'author': ['Koukourakis, Michael I.',\n", - " 'Giatromanolaki, Alexandra',\n", - " 'Zois, Christos E.',\n", - " 'Kalamida, Dimitra',\n", - " 'Pouliliou, Stamatia',\n", - " 'Karagounis, Ilias V.',\n", - " 'Yeh, Tzu-Lan',\n", - " 'Abboud, Martine I.',\n", - " 'Claridge, Timothy D. W.',\n", - " 'Schofield, Christopher J.',\n", - " 'Sivridis, Efthimios',\n", - " 'Simopoulos, Costantinos',\n", - " 'Tokmakidis, Savvas P.',\n", - " 'Harris, Adrian L.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep30986\"}'],\n", - " 'title': ['Normal tissue radioprotection by amifostine via Warburg-type effects']},\n", - " {'bibcode': '2008cosp...37.1805L',\n", - " 'abstract': 'Purpose: The aim of this study was to evaluate the different protective efficacy of N-acetylcysteine (NAC, 200 mg/kg dose) against 12C6+ ion (4 Gy) and X-rays (4 Gy) - induced damage in vivo model. Method: Kung-Ming female mice were divided into six groups, each composed of twelve animals: control group, two irradiation groups, and two NAC-treated groups, as well as NAC alone-treated group. An acute study was carried out to determine alterations in the oxidative stress (malondialdehyde level) using with colorimetric method and cell apoptosis measuring by flow cytometry as well as DNA-single strand break analyzing by comet assay at 2h after irradiation in mouse liver. Results: Compared with respective irradiation group, NAC can significantly ameliorate injury induced by two types of ionizing irradiation, which marked by the decrease of malondialdehyde level, and the reduction of apoptosis cells percentage and DNA damage. But the greater efficacy of NAC was prominently observed to inhibit the damage induced by X-rays, suggesting that NAC-mediated protective effect is more advisable to X-rays than 12C6+ ion irradiation. Moreover, NAC treatment alone did not result in any damage as compared to the control group. Conclusion: NAC may merit development as a potential radioprotective agent. Furthermore, NAC might exert its best effort to respond X rays-caused damage.',\n", - " 'author': ['Liu, Yang', 'Zhang, Hong', 'Zhang, Luwei'],\n", - " 'title': ['A comparative study on radioprotective effect of N-acetylcysteine against 12C6+ ion versus X-rays']},\n", - " {'bibcode': '2008JRadR..49..653J',\n", - " 'author': ['Jeong, Da-Hee',\n", - " 'Goo, Moon-Jung',\n", - " 'Hong, Il-Hwa',\n", - " 'Yang, Hai-Jie',\n", - " 'Ki, Mi-Ran',\n", - " 'Do, Sun-Hee',\n", - " 'Ha, Jeoung-Hee',\n", - " 'Lee, Seung-Sook',\n", - " 'Park, Jin-Kyu',\n", - " 'Jeong, Kyu-Shik'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1269%2Fjrr.08042\"}'],\n", - " 'title': ['Inhibition of Radiation-Induced Apoptosis via Overexpression of SMP30 in Smad3-Knockout Mice Liver']},\n", - " {'bibcode': '2017NatCo...814477C',\n", - " 'abstract': 'Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder in obese individuals. Adenine nucleotide translocase (ANT) exchanges ADP/ATP through the mitochondrial inner membrane, and Ant2 is the predominant isoform expressed in the liver. Here we demonstrate that targeted disruption of Ant2 in mouse liver enhances uncoupled respiration without damaging mitochondrial integrity and liver functions. Interestingly, liver specific Ant2 knockout mice are leaner and resistant to hepatic steatosis, obesity and insulin resistance under a lipogenic diet. Protection against fatty liver is partially recapitulated by the systemic administration of low-dose carboxyatractyloside, a specific inhibitor of ANT. Targeted manipulation of hepatic mitochondrial metabolism, particularly through inhibition of ANT, may represent an alternative approach in NAFLD and obesity treatment.',\n", - " 'author': ['Cho, Joonseok',\n", - " 'Zhang, Yujian',\n", - " 'Park, Shi-Young',\n", - " 'Joseph, Anna-Maria',\n", - " 'Han, Chul',\n", - " 'Park, Hyo-Jin',\n", - " 'Kalavalapalli, Srilaxmi',\n", - " 'Chun, Sung-Kook',\n", - " 'Morgan, Drake',\n", - " 'Kim, Jae-Sung',\n", - " 'Someya, Shinichi',\n", - " 'Mathews, Clayton E.',\n", - " 'Lee, Young Jae',\n", - " 'Wohlgemuth, Stephanie E.',\n", - " 'Sunny, Nishanth E.',\n", - " 'Lee, Hui-Young',\n", - " 'Choi, Cheol Soo',\n", - " 'Shiratsuchi, Takayuki',\n", - " 'Oh, S. Paul',\n", - " 'Terada, Naohiro'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fncomms14477\"}'],\n", - " 'title': ['Mitochondrial ATP transporter depletion protects mice against liver steatosis and insulin resistance']},\n", - " {'bibcode': '2006PNAS..10312511D',\n", - " 'abstract': 'Here, we study the intricate relationship between gut microbiota and host cometabolic phenotypes associated with dietary-induced impaired glucose homeostasis and nonalcoholic fatty liver disease (NAFLD) in a mouse strain (129S6) known to be susceptible to these disease traits, using plasma and urine metabotyping, achieved by 1H NMR spectroscopy. Multivariate statistical modeling of the spectra shows that the genetic predisposition of the 129S6 mouse to impaired glucose homeostasis and NAFLD is associated with disruptions of choline metabolism, i.e., low circulating levels of plasma phosphatidylcholine and high urinary excretion of methylamines (dimethylamine, trimethylamine, and trimethylamine-N-oxide), coprocessed by symbiotic gut microbiota and mammalian enzyme systems. Conversion of choline into methylamines by microbiota in strain 129S6 on a high-fat diet reduces the bioavailability of choline and mimics the effect of choline-deficient diets, causing NAFLD. These data also indicate that gut microbiota may play an active role in the development of insulin resistance.',\n", - " 'author': ['Dumas, Marc-Emmanuel',\n", - " 'Barton, Richard H.',\n", - " 'Toye, Ayo',\n", - " 'Cloarec, Olivier',\n", - " 'Blancher, Christine',\n", - " 'Rothwell, Alice',\n", - " 'Fearnside, Jane',\n", - " 'Tatoud, Roger',\n", - " 'Blanc, Véronique',\n", - " 'Lindon, John C.',\n", - " 'Mitchell, Steve C.',\n", - " 'Holmes, Elaine',\n", - " 'McCarthy, Mark I.',\n", - " 'Scott, James',\n", - " 'Gauguier, Dominique',\n", - " 'Nicholson, Jeremy K.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/103/33/12511\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/103/33/12511\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/full/103/33/12511\"}'],\n", - " 'title': ['Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice']},\n", - " {'bibcode': '2022NatCo..13.6062S',\n", - " 'abstract': 'Almost all effective treatments for non-alcoholic fatty liver disease (NAFLD) involve reduction of adiposity, which suggests the metabolic axis between liver and adipose tissue is essential to NAFLD development. Since excessive dietary sugar intake may be an initiating factor for NAFLD, we have characterized the metabolic effects of liquid sucrose intake at concentrations relevant to typical human consumption in mice. We report that sucrose intake induces sexually dimorphic effects in liver, adipose tissue, and the microbiome; differences concordant with steatosis severity. We show that when steatosis is decoupled from impairments in insulin responsiveness, sex is a moderating factor that influences sucrose-driven lipid storage and the contribution of de novo fatty acid synthesis to the overall hepatic triglyceride pool. Our findings provide physiologic insight into how sex influences the regulation of adipose-liver crosstalk and highlight the importance of extrahepatic metabolism in the pathogenesis of diet-induced steatosis and NAFLD.',\n", - " 'author': ['Stephenson, Erin J.',\n", - " 'Stayton, Amanda S.',\n", - " 'Sethuraman, Aarti',\n", - " 'Rao, Prahlad K.',\n", - " 'Meyer, Alice',\n", - " 'Gomes, Charles Klazer',\n", - " 'Mulcahy, Molly C.',\n", - " 'McAllan, Liam',\n", - " 'Puchowicz, Michelle A.',\n", - " 'Pierre, Joseph F.',\n", - " 'Bridges, Dave',\n", - " 'Han, Joan C.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41467-022-33840-6\"}'],\n", - " 'title': ['Chronic intake of high dietary sucrose induces sexually dimorphic metabolic adaptations in mouse liver and adipose tissue']},\n", - " {'bibcode': '2023NatSR..13.4138C',\n", - " 'abstract': '2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant that induces the progression of steatosis to steatohepatitis with fibrosis in mice. Furthermore, TCDD reprograms hepatic metabolism by redirecting glycolytic intermediates while inhibiting lipid metabolism. Here, we examined the effect of TCDD on hepatic acetyl-coenzyme A (acetyl-CoA) and β-hydroxybutyrate levels as well as protein acetylation and β-hydroxybutyrylation. Acetyl-CoA is not only a central metabolite in multiple anabolic and catabolic pathways, but also a substrate used for posttranslational modification of proteins and a surrogate indicator of cellular energy status. Targeted metabolomic analysis revealed a dose-dependent decrease in hepatic acetyl-CoA levels coincident with the phosphorylation of pyruvate dehydrogenase (E1), and the induction of pyruvate dehydrogenase kinase 4 and pyruvate dehydrogenase phosphatase, while repressing ATP citrate lyase and short-chain acyl-CoA synthetase gene expression. In addition, TCDD dose-dependently reduced the levels of hepatic β-hydroxybutyrate and repressed ketone body biosynthesis gene expression. Moreover, levels of total hepatic protein acetylation and β-hydroxybutyrylation were reduced. AMPK phosphorylation was induced consistent with acetyl-CoA serving as a cellular energy status surrogate, yet subsequent targets associated with re-establishing energy homeostasis were not activated. Collectively, TCDD reduced hepatic acetyl-CoA and β-hydroxybutyrate levels eliciting starvation-like conditions despite normal levels of food intake.',\n", - " 'author': ['Cholico, Giovan N.',\n", - " 'Orlowska, Karina',\n", - " 'Fling, Russell R.',\n", - " 'Sink, Warren J.',\n", - " 'Zacharewski, Nicholas A.',\n", - " 'Fader, Kelly A.',\n", - " 'Nault, Rance',\n", - " 'Zacharewski, Tim'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-023-31087-9\"}'],\n", - " 'title': ['Consequences of reprogramming acetyl-CoA metabolism by 2,3,7,8-tetrachlorodibenzo-p-dioxin in the mouse liver']},\n", - " {'bibcode': '2020NatSR..10.1517B',\n", - " 'abstract': 'An amendment to this paper has been published and can be accessed via a link at the top of the paper.',\n", - " 'author': ['Beheshti, Afshin',\n", - " 'Chakravarty, Kaushik',\n", - " 'Fogle, Homer',\n", - " 'Fazelinia, Hossein',\n", - " 'Silveira, Willian A. da',\n", - " 'Boyko, Valery',\n", - " 'Polo, San-Huei Lai',\n", - " 'Saravia-Butler, Amanda M.',\n", - " 'Hardiman, Gary',\n", - " 'Taylor, Deanne',\n", - " 'Galazka, Jonathan M.',\n", - " 'Costes, Sylvain V.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-020-58490-w\"}'],\n", - " 'title': ['Author Correction: Multi-omics analysis of multiple missions to space reveal a theme of lipid dysregulation in mouse liver']},\n", - " {'bibcode': '2010EHPM...15..105I',\n", - " 'author': ['Inadera, Hidekuni',\n", - " 'Tachibana, Shinjiro',\n", - " 'Suzuki, Aya',\n", - " 'Shimomura, Akiko'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1007%2Fs12199-009-0117-6\"}'],\n", - " 'title': ['Carbon tetrachloride affects inflammation-related biochemical networks in the mouse liver as identified by a customized cDNA microarray system']},\n", - " {'bibcode': '2014PLoSO...9k3022N',\n", - " 'author': ['Nagasaki, Haruka',\n", - " 'Katsumata, Tokio',\n", - " 'Oishi, Hisashi',\n", - " 'Tai, Pei-Han',\n", - " 'Sekiguchi, Yukari',\n", - " 'Koshida, Ryusuke',\n", - " 'Jung, Yunshin',\n", - " 'Kudo, Takashi',\n", - " 'Takahashi, Satoru'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0113022\"}'],\n", - " 'title': ['Generation of Insulin-Producing Cells from the Mouse Liver Using β Cell-Related Gene Transfer Including Mafa and Mafb']},\n", - " {'bibcode': '2001Sci...292.1728C',\n", - " 'abstract': 'Glucose homeostasis depends on insulin responsiveness in target tissues, most importantly, muscle and liver. The critical initial steps in insulin action include phosphorylation of scaffolding proteins and activation of phosphatidylinositol 3-kinase. These early events lead to activation of the serine-threonine protein kinase Akt, also known as protein kinase B. We show that mice deficient in Akt2 are impaired in the ability of insulin to lower blood glucose because of defects in the action of the hormone on liver and skeletal muscle. These data establish Akt2 as an essential gene in the maintenance of normal glucose homeostasis.',\n", - " 'author': ['Cho, Han',\n", - " 'Mu, James',\n", - " 'Kim, Jason K.',\n", - " 'Thorvaldsen, Joanne L.',\n", - " 'Chu, Qingwei',\n", - " 'Crenshaw, E. Bryan',\n", - " 'Kaestner, Klaus H.',\n", - " 'Bartolomei, Marisa S.',\n", - " 'Shulman, Gerald I.',\n", - " 'Birnbaum, Morris J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.292.5522.1728\"}'],\n", - " 'title': ['Insulin Resistance and a Diabetes Mellitus-Like Syndrome in Mice Lacking the Protein Kinase Akt2 (PKBβ)']},\n", - " {'bibcode': '1982Natur.300..611P',\n", - " 'abstract': 'A DNA fragment containing the promoter of the mouse metallothionein-I gene fused to the structural gene of rat growth hormone was microinjected into the pronuclei of fertilized mouse eggs. Of 21 mice that developed from these eggs, seven carried the fusion gene and six of these grew significantly larger than their littermates. Several of these transgenic mice had extraordinarily high levels of the fusion mRNA in their liver and growth hormone in their serum. This approach has implications for studying the biological effects of growth hormone, as a way to accelerate animal growth, as a model for gigantism, as a means of correcting genetic disease, and as a method of farming valuable gene products.',\n", - " 'author': ['Palmiter, Richard D.',\n", - " 'Brinster, Ralph L.',\n", - " 'Hammer, Robert E.',\n", - " 'Trumbauer, Myrna E.',\n", - " 'Rosenfeld, Michael G.',\n", - " 'Birnberg, Neal C.',\n", - " 'Evans, Ronald M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F300611a0\"}'],\n", - " 'title': ['Dramatic growth of mice that develop from eggs microinjected with metallothionein-growth hormone fusion genes']},\n", - " {'bibcode': '2008PNAS..105.3891R',\n", - " 'abstract': 'The apical sodium-dependent bile acid transporter (Asbt) is responsible for transport across the intestinal brush border membrane; however, the carrier(s) responsible for basolateral bile acid export into the portal circulation remains to be determined. Although the heteromeric organic solute transporter Ostα-Ostβ exhibits many properties predicted for a candidate intestinal basolateral bile acid transporter, the in vivo functions of Ostα-Ostβ have not been investigated. To determine the role of Ostα-Ostβ in intestinal bile acid absorption, the Ostα gene was disrupted by homologous recombination in mice. Ostα−/− mice were physically indistinguishable from wild-type mice. In everted gut sac experiments, transileal transport of taurocholate was reduced by >80% in Ostα−/− vs. wild-type mice; the residual taurocholate transport was further reduced to near-background levels in gut sacs prepared from Ostα−/−Mrp3−/− mice. The bile acid pool size was significantly reduced (>65%) in Ostα−/− mice, but fecal bile acid excretion was not elevated. The decreased pool size in Ostα−/− mice resulted from reduced hepatic Cyp7a1 expression that was inversely correlated with ileal expression of fibroblast growth factor 15 (FGF15). These data indicate that Ostα-Ostβ is essential for intestinal bile acid transport in mice. Unlike a block in intestinal apical bile acid uptake, genetic ablation of basolateral bile acid export disrupts the classical homeostatic control of hepatic bile acid biosynthesis.',\n", - " 'author': ['Rao, Anuradha',\n", - " 'Haywood, Jamie',\n", - " 'Craddock, Ann L.',\n", - " 'Belinsky, Martin G.',\n", - " 'Kruh, Gary D.',\n", - " 'Dawson, Paul A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/105/10/3891\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/105/10/3891.full.pdf\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0712328105\"}'],\n", - " 'title': ['The organic solute transporter α-β, Ostα-Ostβ, is essential for intestinal bile acid transport and homeostasis']},\n", - " {'bibcode': '2015NatCo...6.8704W',\n", - " 'abstract': 'Hyperactivation of the transcriptional factor E2F1 occurs frequently in human cancers and contributes to malignant progression. E2F1 activity is regulated by proteolysis mediated by the ubiquitin-proteasome system. However, the deubiquitylase that controls E2F1 ubiquitylation and stability remains undefined. Here we demonstrate that the deubiquitylase POH1 stabilizes E2F1 protein through binding to and deubiquitylating E2F1. Conditional knockout of Poh1 alleles results in reduced E2F1 expression in primary mouse liver cells. The POH1-mediated regulation of E2F1 expression strengthens E2F1-downstream prosurvival signals, including upregulation of Survivin and FOXM1 protein levels, and efficiently facilitates tumour growth of liver cancer cells in nude mice. Importantly, human hepatocellular carcinomas (HCCs) recapitulate POH1 regulation of E2F1 expression, as nuclear abundance of POH1 is increased in HCCs and correlates with E2F1 overexpression and tumour growth. Thus, our study suggests that the hyperactivated POH1-E2F1 regulation may contribute to the development of liver cancer.',\n", - " 'author': ['Wang, Boshi',\n", - " 'Ma, Aihui',\n", - " 'Zhang, Li',\n", - " 'Jin, Wei-Lin',\n", - " 'Qian, Yu',\n", - " 'Xu, Guiqin',\n", - " 'Qiu, Bijun',\n", - " 'Yang, Zhaojuan',\n", - " 'Liu, Yun',\n", - " 'Xia, Qiang',\n", - " 'Liu, Yongzhong'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fncomms9704\"}'],\n", - " 'title': ['POH1 deubiquitylates and stabilizes E2F1 to promote tumour formation']},\n", - " {'bibcode': '2003Sci...299..890L',\n", - " 'abstract': 'The vascular endothelium was once thought to function primarily in nutrient and oxygen delivery, but recent evidence suggests that it may play a broader role in tissue homeostasis. To explore the role of sinusoidal endothelial cells (LSECs) in the adult liver, we studied the effects of vascular endothelial growth factor (VEGF) receptor activation on mouse hepatocyte growth. Delivery of VEGF-A increased liver mass in mice but did not stimulate growth of hepatocytes in vitro, unless LSECs were also present in the culture. Hepatocyte growth factor (HGF) was identified as one of the LSEC-derived paracrine mediators promoting hepatocyte growth. Selective activation of VEGF receptor-1 (VEGFR-1) stimulated hepatocyte but not endothelial proliferation in vivo and reduced liver damage in mice exposed to a hepatotoxin. Thus, VEGFR-1 agonists may have therapeutic potential for preservation of organ function in certain liver disorders.',\n", - " 'author': ['LeCouter, Jennifer',\n", - " 'Moritz, Dirk R.',\n", - " 'Li, Bing',\n", - " 'Phillips, Gail Lewis',\n", - " 'Liang, Xiao Huan',\n", - " 'Gerber, Hans-Peter',\n", - " 'Hillan, Kenneth J.',\n", - " 'Ferrara, Napoleone'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.1079562\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.1079562\"}'],\n", - " 'title': ['Angiogenesis-Independent Endothelial Protection of Liver: Role of VEGFR-1']},\n", - " {'bibcode': '2006JaJAP..45.5254M',\n", - " 'abstract': 'The X-ray phase tomography of biological samples is reported, which is based on X-ray Talbot interferometry. Its imaging principle is described in detail, and imaging results obtained for a cancerous rabbit liver and a mouse tail with synchrotron radiation are presented. Because an amplitude grating is needed to construct an X-ray Talbot interferometer, a high-aspect-ratio grating pattern was fabricated by X-ray lithography and gold electroplating. X-ray Talbot interferometry has an advantage that it functions with polychromatic cone-beam X-rays. Finally, the compatibility with a compact X-ray source is discussed.',\n", - " 'author': ['Momose, Atsushi',\n", - " 'Yashiro, Wataru',\n", - " 'Takeda, Yoshihiro',\n", - " 'Suzuki, Yoshio',\n", - " 'Hattori, Tadashi'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1143%2FJJAP.45.5254\"}'],\n", - " 'title': ['Phase Tomography by X-ray Talbot Interferometry for Biological Imaging']},\n", - " {'bibcode': '2016EnTox..31.1147B',\n", - " 'author': ['Badgujar, Prarabdh C.',\n", - " 'Chandratre, Gauri A.',\n", - " 'Pawar, Nitin N.',\n", - " 'Telang, A. G.',\n", - " 'Kurade, N. P.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Ftox.22125\"}'],\n", - " 'title': ['Fipronil induced oxidative stress involves alterations in SOD1 and catalase gene expression in male mice liver: Protection by vitamins E and C']},\n", - " {'bibcode': '2012Natur.482..179H',\n", - " 'abstract': 'Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and the leading cause of chronic liver disease in the Western world. Twenty per cent of NAFLD individuals develop chronic hepatic inflammation (non-alcoholic steatohepatitis, NASH) associated with cirrhosis, portal hypertension and hepatocellular carcinoma, yet the causes of progression from NAFLD to NASH remain obscure. Here, we show that the NLRP6 and NLRP3 inflammasomes and the effector protein IL-18 negatively regulate NAFLD/NASH progression, as well as multiple aspects of metabolic syndrome via modulation of the gut microbiota. Different mouse models reveal that inflammasome-deficiency-associated changes in the configuration of the gut microbiota are associated with exacerbated hepatic steatosis and inflammation through influx of TLR4 and TLR9 agonists into the portal circulation, leading to enhanced hepatic tumour-necrosis factor (TNF)-α expression that drives NASH progression. Furthermore, co-housing of inflammasome-deficient mice with wild-type mice results in exacerbation of hepatic steatosis and obesity. Thus, altered interactions between the gut microbiota and the host, produced by defective NLRP3 and NLRP6 inflammasome sensing, may govern the rate of progression of multiple metabolic syndrome-associated abnormalities, highlighting the central role of the microbiota in the pathogenesis of heretofore seemingly unrelated systemic auto-inflammatory and metabolic disorders.',\n", - " 'author': ['Henao-Mejia, Jorge',\n", - " 'Elinav, Eran',\n", - " 'Jin, Chengcheng',\n", - " 'Hao, Liming',\n", - " 'Mehal, Wajahat Z.',\n", - " 'Strowig, Till',\n", - " 'Thaiss, Christoph A.',\n", - " 'Kau, Andrew L.',\n", - " 'Eisenbarth, Stephanie C.',\n", - " 'Jurczak, Michael J.',\n", - " 'Camporez, Joao-Paulo',\n", - " 'Shulman, Gerald I.',\n", - " 'Gordon, Jeffrey I.',\n", - " 'Hoffman, Hal M.',\n", - " 'Flavell, Richard A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature10809\"}'],\n", - " 'title': ['Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity']},\n", - " {'bibcode': '2014PNAS..111E3297I',\n", - " 'abstract': 'Liver resident activated hepatic stellate cells (aHSCs), and activated portal fibroblasts (aPFs) are the major source of the fibrous scar in the liver. aPFs have been implicated in liver fibrosis caused by cholestatic liver injury, whereas fibrosis in hepatotoxic liver injury is attributed to aHSCs. However, the contribution of aPFs to cholestatic fibrosis is not well characterized because of difficulties in cell purification and the lack of identified aPF-specific markers. We have developed a novel flow cytometry-based method of aPFs purification from the nonparenchymal cell fraction of collagen-α1(I)-GFP mice and have identified potential aPF-specific markers. The goal of this study is to determine whether aPFs contribute to cholestatic liver fibrosis and identify the mechanism(s) of their activation.',\n", - " 'author': ['Iwaisako, Keiko',\n", - " 'Jiang, Chunyan',\n", - " 'Zhang, Mingjun',\n", - " 'Cong, Min',\n", - " 'Moore-Morris, Thomas Joseph',\n", - " 'Park, Tae Jun',\n", - " 'Liu, Xiao',\n", - " 'Xu, Jun',\n", - " 'Wang, Ping',\n", - " 'Paik, Yong-Han',\n", - " 'Meng, Fanli',\n", - " 'Asagiri, Masataka',\n", - " 'Murray, Lynne A.',\n", - " 'Hofmann, Alan F.',\n", - " 'Iida, Takashi',\n", - " 'Glass, Christopher K.',\n", - " 'Brenner, David A.',\n", - " 'Kisseleva, Tatiana'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/111/32/E3297\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1400062111\"}'],\n", - " 'title': ['Origin of myofibroblasts in the fibrotic liver in mice']},\n", - " {'bibcode': '1991PNAS...88.9402S',\n", - " 'abstract': 'Mouse vitronectin (Vn) was isolated from serum by heparin affinity chromatography. The purified protein (Mr 71,000) supported adhesion of mouse and human cells in an Arg-Gly-Asp-dependent manner and bound to type 1 plasminogen activator inhibitor with kinetics similar to those observed using human and bovine Vn. To further characterize murine Vn and its biosynthesis in vivo, a mouse Vn cDNA was isolated from a liver cDNA library. The amino acid sequence of mouse Vn was deduced from the cDNA and was aligned with that of human Vn. Based on this alignment, mouse Vn was inferred to be 457 amino acids long and to have extensive (82%) homology with human Vn. Northern blot hybridization analysis of RNA from mouse tissues, using the mouse Vn cDNA as a hybridization probe, revealed the presence of a single transcript of 1.7 kilobases in mouse liver. Vn mRNA was not detectable in heart, lung, kidney, spleen, muscle, brain, thymus, testes, uterus, skin, adipose tissue, and aorta. The cellular localization of liver Vn mRNA was studied by in situ hybridization. Strong staining was observed only in hepatocytes, suggesting that these cells are the primary source of Vn in vivo.',\n", - " 'author': ['Seiffert, Dietmar',\n", - " 'Keeton, Mark',\n", - " 'Eguchi, Yutaka',\n", - " 'Sawdey, Mike',\n", - " 'Loskutoff, David J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/88/21/9402\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/88/21/9402\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/88/21/9402\"}'],\n", - " 'title': ['Detection of vitronectin mRNA in tissues and cells of the mouse.']},\n", - " {'bibcode': '2016RSCAd...663788R',\n", - " 'abstract': 'We report on the synthesis, characterization, stability and pharmacokinetics of novel iron based contrast agents for magnetic resonance imaging (MRI). Statistical copolymers combining multiple phosphonic acid groups and poly(ethylene glycol) (PEG) were synthesized and used as coating agents for 10 nm iron oxide nanocrystals. In vitro, protein corona and stability assays show that phosphonic acid PEG copolymers outperform all other coating types examined, including low molecular weight anionic ligands and polymers. In vivo, the particle pharmacokinetics is investigated by monitoring the MRI signal intensity from mouse liver, spleen and arteries as a function of the time, between one minute and seven days after injection. Iron oxide particles coated with multi-phosphonic acid PEG polymers are shown to have a blood circulation lifetime of 250 minutes, i.e. 10 to 50 times greater than that of recently published PEGylated probes and benchmarks. The clearance from the liver takes in average 2 to 3 days and is independent of the core size, coating and particle stability. By comparing identical core particles with different coatings, we are able to determine the optimum conditions for stealth MRI probes.',\n", - " 'author': ['Ramniceanu, G.',\n", - " 'Doan, B. -T.',\n", - " 'Vezignol, C.',\n", - " 'Graillot, A.',\n", - " 'Loubat, C.',\n", - " 'Mignet, N.',\n", - " 'Berret, J. -F.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"preprint\", \"url\": \"http://arxiv.org/abs/1607.01656\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1039%2FC6RA09896G\"}'],\n", - " 'title': ['Delayed hepatic uptake of multi-phosphonic acid poly(ethylene glycol) coated iron oxide measured by real-time magnetic resonance imaging']},\n", - " {'bibcode': '2000PNAS...97.2196F',\n", - " 'abstract': 'We have previously shown that chronic activation of mitogenic signaling induced by over-expression of c-myc and transforming growth factor-α (TGFα) transgenes in mouse liver induces a state of oxidative stress. We therefore proposed that increased reactive oxygen species (ROS) generation might be responsible for the extensive chromosomal damage and acceleration of hepatocarcinogenesis characteristic for TGFα/c-myc mice. In this study, we show that vitamin E (VE), a potent free radical scavenging antioxidant, is able to protect liver tissue against oxidative stress and suppress tumorigenic potential of c-myc oncogene. Dietary supplementation with VE, starting from weaning, decreased ROS generation coincident with a marked inhibition of hepatocyte proliferation while increasing the chromosomal as well as mtDNA stability in the liver. Similarly, dietary VE reduced liver dysplasia and increased viability of hepatocytes. At 6 mo of age, VE treatment decreased the incidence of adenomas by 65% and prevented malignant conversion. These results indicate that ROS generated by over-expression of c-myc and TGFα in the liver are the primary carcinogenic agents in this animal model. Furthermore, the data demonstrate that dietary supplementation of VE can effectively inhibit liver cancer development.',\n", - " 'author': ['Factor, Valentina M.',\n", - " 'Laskowska, Danuta',\n", - " 'Jensen, Michael Rugaard',\n", - " 'Woitach, Joseph T.',\n", - " 'Popescu, Nicholas C.',\n", - " 'Thorgeirsson, Snorri S.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/97/5/2196\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/97/5/2196\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/97/5/2196\"}'],\n", - " 'title': ['Vitamin E reduces chromosomal damage and inhibits hepatic tumor formation in a transgenic mouse model']},\n", - " {'bibcode': '2007PMB....52..577D',\n", - " 'abstract': 'We have constructed a three-dimensional (3D) whole body mouse atlas from coregistered x-ray CT and cryosection data of a normal nude male mouse. High quality PET, x-ray CT and cryosection images were acquired post mortem from a single mouse placed in a stereotactic frame with fiducial markers visible in all three modalities. The image data were coregistered to a common coordinate system using the fiducials and resampled to an isotropic 0.1 mm voxel size. Using interactive editing tools we segmented and labelled whole brain, cerebrum, cerebellum, olfactory bulbs, striatum, medulla, masseter muscles, eyes, lachrymal glands, heart, lungs, liver, stomach, spleen, pancreas, adrenal glands, kidneys, testes, bladder, skeleton and skin surface. The final atlas consists of the 3D volume, in which the voxels are labelled to define the anatomical structures listed above, with coregistered PET, x-ray CT and cryosection images. To illustrate use of the atlas we include simulations of 3D bioluminescence and PET image reconstruction. Optical scatter and absorption values are assigned to each organ to simulate realistic photon transport within the animal for bioluminescence imaging. Similarly, 511 keV photon attenuation values are assigned to each structure in the atlas to simulate realistic photon attenuation in PET. The Digimouse atlas and data are available at http://neuroimage.usc.edu/Digimouse.html.',\n", - " 'author': ['Dogdas, Belma',\n", - " 'Stout, David',\n", - " 'Chatziioannou, Arion F.',\n", - " 'Leahy, Richard M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1088%2F0031-9155%2F52%2F3%2F003\"}'],\n", - " 'title': ['Digimouse: a 3D whole body mouse atlas from CT and cryosection data']},\n", - " {'bibcode': '1988Sci...241.1632M',\n", - " 'abstract': 'The study of human hematopoietic cells and the human immune system is hampered by the lack of a suitable experimental model. Experimental data are presented showing that human fetal liver hematopoietic cells, human fetal thymus, and human fetal lymph node support the differentiation of mature human T cells and B cells after engraftment into mice with genetically determined severe combined immunodeficiency. The resultant SCID-hu mice are found to have a transient wave of human CD4+ and CD8+ T cells and human IgG (immunoglobulin G) in the peripheral circulation. The functional status of the human immune system within this mouse model is not yet known.',\n", - " 'author': ['McCune, J. M.',\n", - " 'Namikawa, R.',\n", - " 'Kaneshima, H.',\n", - " 'Shultz, L. D.',\n", - " 'Lieberman, M.',\n", - " 'Weissman, I. L.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.2971269\"}'],\n", - " 'title': ['The SCID-hu Mouse: Murine Model for the Analysis of Human Hematolymphoid Differentiation and Function']},\n", - " {'bibcode': '2010Sci...328.1570R',\n", - " 'abstract': 'Cholesterol metabolism is tightly regulated at the cellular level. Here we show that miR-33, an intronic microRNA (miRNA) located within the gene encoding sterol-regulatory element-binding factor-2 (SREBF-2), a transcriptional regulator of cholesterol synthesis, modulates the expression of genes involved in cellular cholesterol transport. In mouse and human cells, miR-33 inhibits the expression of the adenosine triphosphate-binding cassette (ABC) transporter, ABCA1, thereby attenuating cholesterol efflux to apolipoprotein A1. In mouse macrophages, miR-33 also targets ABCG1, reducing cholesterol efflux to nascent high-density lipoprotein (HDL). Lentiviral delivery of miR-33 to mice represses ABCA1 expression in the liver, reducing circulating HDL levels. Conversely, silencing of miR-33 in vivo increases hepatic expression of ABCA1 and plasma HDL levels. Thus, miR-33 appears to regulate both HDL biogenesis in the liver and cellular cholesterol efflux.',\n", - " 'author': ['Rayner, Katey J.',\n", - " 'Suárez, Yajaira',\n", - " 'Dávalos, Alberto',\n", - " 'Parathath, Saj',\n", - " 'Fitzgerald, Michael L.',\n", - " 'Tamehiro, Norimasa',\n", - " 'Fisher, Edward A.',\n", - " 'Moore, Kathryn J.',\n", - " 'Fernández-Hernando, Carlos'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.1189862\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.1189862\"}'],\n", - " 'title': ['MiR-33 Contributes to the Regulation of Cholesterol Homeostasis']},\n", - " {'bibcode': '2023Optic..10.1605A',\n", - " 'abstract': 'Histological staining of tissue biopsies, especially hematoxylin and eosin (H&E) staining, serves as the benchmark for disease diagnosis and comprehensive clinical assessment of tissue. However, the typical formalin-fixation, paraffin-embedding (FFPE) process is laborious and time consuming, often limiting its usage in time-sensitive applications such as surgical margin assessment. To address these challenges, we combine an emerging 3D quantitative phase imaging technology, termed quantitative oblique back illumination microscopy (qOBM), with an unsupervised generative adversarial network pipeline to map qOBM phase images of unaltered thick tissues (i.e., label- and slide-free) to virtually stained H&E-like (vH&E) images. We demonstrate that the approach achieves high-fidelity conversions to H&E with subcellular detail using fresh tissue specimens from mouse liver, rat gliosarcoma, and human gliomas. We also show that the framework directly enables additional capabilities such as H&E-like contrast for volumetric imaging. The quality and fidelity of the vH&E images are validated using both a neural network classifier trained on real H&E images and tested on virtual H&E images, and a user study with neuropathologists. Given its simple and low-cost embodiment and ability to provide real-time feedback in vivo, this deep-learning-enabled qOBM approach could enable new workflows for histopathology with the potential to significantly save time, labor, and costs in cancer screening, detection, treatment guidance, and more.',\n", - " 'author': ['Abraham, Tanishq Mathew',\n", - " 'Costa, Paloma Casteleiro',\n", - " 'Filan, Caroline',\n", - " 'Guang, Zhe',\n", - " 'Zhang, Zhaobin',\n", - " 'Neill, Stewart',\n", - " 'Olson, Jeffrey J.',\n", - " 'Levenson, Richard',\n", - " 'Robles, Francisco E.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"preprint\", \"url\": \"http://arxiv.org/abs/2306.00548\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1364%2FOPTICA.502859\"}'],\n", - " 'title': ['Label- and slide-free tissue histology using 3D epi-mode quantitative phase imaging and virtual hematoxylin and eosin staining']},\n", - " {'bibcode': '1975Natur.253..744H',\n", - " 'abstract': 'IN addition to the well-known, individually unique tumour-specific antigens in chemically induced neoplasms and the common ones in neoplasms induced by the same virus, there is evidence that neoplastic cells have antigens which are present in certain normal, syngeneic cells, but which may still be reacted against immunologically1. Most notable has been the demonstration that many tumours share antigens with normal embryonic cells2. Immunity to these antigens can be detected in various ways. It has been shown, for example, that lymphocytes from multiparous mice are cytotoxic to cultivated neoplastic but not to normal adult cells3-5 and that serum from pregnant mice can inhibit (block) this cytotoxic effect4-7.',\n", - " 'author': ['Hellstrom, Ingegerd',\n", - " 'Hellstrom, Karl Erik',\n", - " 'Nishioka, Mikio'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F253744a0\"}'],\n", - " 'title': ['Reactivity to tumour-associated antigens detected in mice undergoing liver regeneration']},\n", - " {'bibcode': '1991PNAS...88.1217P',\n", - " 'abstract': 'One approach to gene therapy for hepatic diseases is to remove hepatocytes from an affected individual, genetically alter them in vitro, and reimplant them into a receptive locus. Although returning hepatocytes to the liver itself would be advantageous, the feasibility of this approach has never been evaluated due to the inability to distinguish donor from host hepatocytes. To unambiguously identify transplanted hepatocytes after transplantation, and to better quantitate their number and degree of liver function, two transgenic mouse lines were generated in a C57BL/6 background. The first expresses the Escherichia coli beta-galactosidase gene from the relatively liver-specific human alpha 1-antitrypsin (hAAT) promoter and allows transgenic hepatocytes to be readily identified after 5-bromo-4-chloro-3-indolyl beta-D-galactoside staining; the second produces the hAAT protein under control of the same promoter, which enables hepatocyte survival and maintenance of liver function to be quantitated by measuring the serum levels of hAAT. Hepatocytes isolated from transgenic donors were transplanted into nontransgenic C57BL/6 recipients by intrasplenic injection. Surprisingly, a large fraction of these cells were identified within the liver parenchyma but not the spleen at 2 months after transplantation. The high levels of serum hAAT detected in transplant recipients were stable for greater than 6 months, suggesting that established cells will survive indefinitely. These results have important implications for liver organogenesis and hepatic gene therapy.',\n", - " 'author': ['Parker Ponder, Katherine',\n", - " 'Gupta, Sanjeev',\n", - " 'Leland, Frances',\n", - " 'Darlington, Gretchen',\n", - " 'Finegold, Milton',\n", - " 'Demayo, Janet',\n", - " 'Ledley, Fred D.',\n", - " 'Chowdhury, Jayanta Roy',\n", - " 'Woo, Savio L. C.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/88/4/1217\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/88/4/1217\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/88/4/1217\"}'],\n", - " 'title': ['Mouse hepatocytes migrate to liver parenchyma and function indefinitely after intrasplenic transplantation.']},\n", - " {'bibcode': '2010cosp...38.3511F',\n", - " 'abstract': \"Liver is a important and largest parenchymatous organ in vivo, and have complex and diverse structures and functions. In the world, there are many peoples suffers from liver injury and dis-ease, especially in Asia, but serious shortage of donor organ, especially for organic pathological changes, is a big problem in the world. Stem cells have the capabilities to self-renew and differ-entiate into multiple lineages, and are very significant in both theoretical research and clinical applications. Compared with traditional cell culture, cells of 3D growth are more close to their situation in vivo. The specific physics environment in space provides a great opportunity for 3D growth of cells and tissues. Due to the chance for entering into the space is so scarce, to mimic microgravity effects using a rotating cell culture system (RCCS) designed by NASA, and some other methods were studied for cellular 3D growth in vitro. Neonatal mouse liver Cells, hepatic progenitor/stem cells from fetal liver and WB-F344 cells were cultured in a 1:1 mixture of DMEM and F-12 supplemented with 10 % FCS and several factors, and seeded into the RCCS, 6-well and 24-well plates. Their growth characteristic, metabolism, differentiation and gene expression were studied by SEM, Histochemistry, Flow Cytometry, RT-PCR and so on. The results showed: 1. Neonatal mouse liver Cells (1day after birth) seem easy to grow for a three-dimentional-like structure, when the cells were cultured in the RCCS, a cell aggregate formed after 1 day of culture and were kept during 10 days culture. The size of aggregate was about 1 2 mm in diameter. 2. Hepatic progenitor/stem cells from fetal liver seem a good cell resource for liver disease'cell therapy. They expressed AFP and CKs, and no mature hepato-cytes marker and bile duct epithelial cells marker were detected. When were transplanted into Nod-Scid mice, they had multi-potential differentiation. 3. WB-F344 cells, a liver epithelial cell line, could grew well on Cytodex 3 microcarrier beads, and expressed OV6 at a higher level and Cykt-18 and Cykt-19 at a lower level, but no Cykt-7 and Cykt-8. They are easy to get a large amount of cells, and could be thought as a convenient cell resource. The experiments are going on, and their differentiation and 3D growth are being studied.\",\n", - " 'author': ['Feng, Mei Fu'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.cospar-assembly.org/abstractcd/OLD/COSPAR-10/abstracts/data/pdf/abstracts/F51-0007-10.pdf\"}'],\n", - " 'title': ['Three-dimentional growth of liver / stem cells in vitro under simulated microgravity']},\n", - " {'bibcode': '2015Sci...350.1089K',\n", - " 'abstract': 'The invasion of a suitable host hepatocyte by mosquito-transmitted Plasmodium sporozoites is an essential early step in successful malaria parasite infection. Yet precisely how sporozoites target their host cell and facilitate productive infection remains largely unknown. We found that the hepatocyte EphA2 receptor was critical for establishing a permissive intracellular replication compartment, the parasitophorous vacuole. Sporozoites productively infected hepatocytes with high EphA2 expression, and the deletion of EphA2 protected mice from liver infection. Lack of host EphA2 phenocopied the lack of the sporozoite proteins P52 and P36. Our data suggest that P36 engages EphA2, which is likely to be a key step in establishing the permissive replication compartment.',\n", - " 'author': ['Kaushansky, Alexis',\n", - " 'Douglass, Alyse N.',\n", - " 'Arang, Nadia',\n", - " 'Vigdorovich, Vladimir',\n", - " 'Dambrauskas, Nicholas',\n", - " 'Kain, Heather S.',\n", - " 'Austin, Laura S.',\n", - " 'Sather, D. Noah',\n", - " 'Kappe, Stefan H. I.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.aad3318\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.aad3318\"}'],\n", - " 'title': ['Malaria parasites target the hepatocyte receptor EphA2 for successful host infection']},\n", - " {'bibcode': '1977PNAS...74.1558P',\n", - " 'abstract': 'The electron spin resonance spectra at g = 2 of the structural and soluble proteins of mouse liver have been investigated separately. The structural materials have signals an order of magnitude stronger. Radicals with important similarities to those occurring in natural tissue can be induced by treating casein with methylglyoxal or crotonaldehyde. The structural proteins of cancer give little or no signal. The color of the proteins and their electron spin resonance signal seem closely related.',\n", - " 'author': ['Pohl, Herbert A.',\n", - " 'Gascoyne, Peter R. C.',\n", - " 'Szent-Gyorgyi, Albert'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/74/4/1558\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/74/4/1558\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/74/4/1558\"}'],\n", - " 'title': ['Electron spin resonance absorption of tissue constituents.']},\n", - " {'bibcode': '2013NatCo...4.2823M',\n", - " 'abstract': 'Although organ fibrosis causes significant morbidity and mortality in chronic diseases, the lack of detailed knowledge about specific cellular contributors mediating fibrogenesis hampers the design of effective antifibrotic therapies. Different cellular sources, including tissue-resident and bone marrow-derived fibroblasts, pericytes and epithelial cells, have been suggested to give rise to myofibroblasts, but their relative contributions remain controversial, with profound differences between organs and different diseases. Here we employ a novel Cre-transgenic mouse that marks 99% of hepatic stellate cells (HSCs), a liver-specific pericyte population, to demonstrate that HSCs give rise to 82-96% of myofibroblasts in models of toxic, cholestatic and fatty liver disease. Moreover, we exclude that HSCs function as facultative epithelial progenitor cells in the injured liver. On the basis these findings, HSCs should be considered the primary cellular target for antifibrotic therapies across all types of liver disease.',\n", - " 'author': ['Mederacke, Ingmar',\n", - " 'Hsu, Christine C.',\n", - " 'Troeger, Juliane S.',\n", - " 'Huebener, Peter',\n", - " 'Mu, Xueru',\n", - " 'Dapito, Dianne H.',\n", - " 'Pradere, Jean-Philippe',\n", - " 'Schwabe, Robert F.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fncomms3823\"}'],\n", - " 'title': ['Fate tracing reveals hepatic stellate cells as dominant contributors to liver fibrosis independent of its aetiology']},\n", - " {'bibcode': '2007PNAS..104.9266L',\n", - " 'abstract': \"Fluorescence is increasingly used for in vivo imaging and has provided remarkable results. Yet this technique presents several limitations, especially due to tissue autofluorescence under external illumination and weak tissue penetration of low wavelength excitation light. We have developed an alternative optical imaging technique by using persistent luminescent nanoparticles suitable for small animal imaging. These nanoparticles can be excited before injection, and their in vivo distribution can be followed in real-time for more than 1 h without the need for any external illumination source. Chemical modification of the nanoparticles' surface led to lung or liver targeting or to long-lasting blood circulation. Tumor mass could also be identified on a mouse model.\",\n", - " 'author': ['le Masne de Chermont, Quentin',\n", - " 'Chanéac, Corinne',\n", - " 'Seguin, Johanne',\n", - " 'Pellé, Fabienne',\n", - " 'Maîtrejean, Serge',\n", - " 'Jolivet, Jean-Pierre',\n", - " 'Gourier, Didier',\n", - " 'Bessodes, Michel',\n", - " 'Scherman, Daniel'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/104/22/9266\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0702427104\"}'],\n", - " 'title': ['Nanoprobes with near-infrared persistent luminescence for in vivo imaging']},\n", - " {'bibcode': '2001Sci...294..559M',\n", - " 'abstract': 'The embryonic role of endothelial cells and nascent vessels in promoting organogenesis, prior to vascular function, is unclear. We find that early endothelial cells in mouse embryos surround newly specified hepatic endoderm and delimit the mesenchymal domain into which the liver bud grows. In flk-1 mutant embryos, which lack endothelial cells, hepatic specification occurs, but liver morphogenesis fails prior to mesenchyme invasion. We developed an embryo tissue explant system that permits liver bud vasculogenesis and show that in the absence of endothelial cells, or when the latter are inhibited, there is a selective defect in hepatic outgrowth. We conclude that vasculogenic endothelial cells and nascent vessels are critical for the earliest stages of organogenesis, prior to blood vessel function.',\n", - " 'author': ['Matsumoto, Kunio',\n", - " 'Yoshitomi, Hideyuki',\n", - " 'Rossant, Janet',\n", - " 'Zaret, Kenneth S.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.1063889\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.1063889\"}'],\n", - " 'title': ['Liver Organogenesis Promoted by Endothelial Cells Prior to Vascular Function']},\n", - " {'bibcode': '2004PNAS..10110608B',\n", - " 'abstract': 'Genetic analysis in mice has demonstrated a crucial role of the Met tyrosine kinase receptor and its ligand, hepatocyte growth factor/scatter factor (HGF/SF), in development of the liver, muscle, and placenta. Here, we use conditional mutagenesis in mice to analyze the function of Met during liver regeneration, using the Mx-cre transgene to introduce the mutation in the adult. After partial hepatectomy in mice carrying the Mx-cre-induced Met mutation, regeneration of the liver is impaired. Comparison of signal transduction pathways in control and mutant livers indicates that Met and other signaling receptors cooperate to fully activate particular signaling molecules, for instance, the protein kinase Akt. However, activation of the Erk1/2 kinase during liver regeneration depends exclusively on Met. Signaling crosstalk is thus an important aspect of the regulation of liver regeneration. Analysis of cell cycle progression of hepatocytes in conditional Met mutant mice indicates a defective exit from quiescence and diminished entry into S phase. Impaired liver regeneration is accompanied by compensatory physiological responses that include prolonged up-regulation of HGF/SF and IL-6 in peripheral blood. Our data demonstrate that the HGF/SF/Met signaling system is essential not only during liver development but also for the regeneration of the organ in the adult.',\n", - " 'author': ['Borowiak, Malgorzata',\n", - " 'Garratt, Alistair N.',\n", - " 'Wüstefeld, Torsten',\n", - " 'Strehle, Michael',\n", - " 'Trautwein, Christian',\n", - " 'Birchmeier, Carmen'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/101/29/10608\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0403412101\"}'],\n", - " 'title': ['Met provides essential signals for liver regeneration']},\n", - " {'bibcode': '2023Heliy...916978S',\n", - " 'abstract': 'Biopsy is a commonly used method for determining pathological diagnoses by directly using human tissues and cells. Biopsies are widely used to determine disease progression and treatment efficacy. Although organs and tissues are usually obtained by sacrifice during animal experiments, it is theoretically possible to use the same biopsy techniques in humans. In the present study, we examined the feasibility of performing four repeated liver biopsies in a spontaneous metabolic syndrome mouse model. Even though a small number of mice died accidently, most mice were able to undergo four liver biopsies without significant adverse events. We also performed three liver biopsies in mouse liver tumor carcinogen models at 4, 8, and 12 weeks of age. In addition to the sample collected at 16 weeks of age during sacrifice, we successfully collected four liver samples from the same mice at different stages of disease progression. The application of this liver biopsy technique might make it possible for direct evaluation of pathological conditions in the same individual over time, thereby reducing the number of experimental animals.',\n", - " 'author': ['Shao, Wenhua',\n", - " 'Ichimura-Shimizu, Mayuko',\n", - " 'Ogawa, Hirohisa',\n", - " 'Jin, Shengjian',\n", - " 'Sutoh, Mitsuko',\n", - " 'Nakamura, Satoko',\n", - " 'Onodera, Miki',\n", - " 'Tawara, Hirosuke',\n", - " 'Toyohara, Shunji',\n", - " 'Hokao, Ryoji',\n", - " 'Kudo, Yasusei',\n", - " 'Oya, Takeshi',\n", - " 'Tsuneyama, Koichi'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.heliyon.2023.e16978\"}'],\n", - " 'title': ['Establishment of repeated liver biopsy technique in experimental mice']},\n", - " {'bibcode': '1992EnvMM..19...98D',\n", - " 'abstract': 'Twenty‑eight chlorinated organic compounds were evaluated for their ability to induce DNA damage using the Microscreen prophage‑induction assay in Escherichia coli. Comparison of the performance characteristics of the prophage‑induction and Salmonella assays to rodent carcinogenicity assays showed that the prophage‑induction assay had a somewhat higher specificity than did the Salmonella assay (70% vs. 50%); sensitivity, concordance, and positive and negative predictivity were similar for the two microbial assays. The Microscreen prophage‑induction assay failed to detect eight carcinogens, perhaps due to toxicity or other unknown factors; five of these eight carcinogens were detected by the Salmonella assay. However, the prophage‑induction assay did detect six carcinogens that were not detected by the Salmonella assay, and five of these were single‑species, single‑site carcinogens, mostly mouse liver carcinogens. Some of these carcinogens, such as the chloroethanes, produce free radicals, which may be the basis for their carcinogenicity and ability to induce prophage. The prophage‑induction (or other SOS) assay may be useful in identifying some genotoxic chlorinated carcinogens that induce DNA damage that does not revert the standard Salmonella tester strains.',\n", - " 'author': ['Demarini, David M.', 'Brooks, Harold G.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Fem.2850190204\"}'],\n", - " 'title': ['Induction of prophage lambda by chlorinated organics: Detection of some single‑species/single‑site carcinogens']},\n", - " {'bibcode': '2021NatCo..12.6350Q',\n", - " 'abstract': 'Transcription modulated by the circadian clock is diverse across cell types, underlying circadian control of peripheral metabolism and its observed perturbation in human diseases. We report that knockout of the lineage-specifying Hnf4a gene in mouse liver causes associated reductions in the genome-wide distribution of core clock component BMAL1 and accessible chromatin marks (H3K4me1 and H3K27ac). Ectopically expressing HNF4A remodels chromatin landscape and nucleates distinct tissue-specific BMAL1 chromatin binding events, predominantly in enhancer regions. Circadian rhythms are disturbed in Hnf4a knockout liver and HNF4A-MODY diabetic model cells. Additionally, the epigenetic state and accessibility of the liver genome dynamically change throughout the day, synchronized with chromatin occupancy of HNF4A and clustered expression of circadian outputs. Lastly, Bmal1 knockout attenuates HNF4A genome-wide binding in the liver, likely due to downregulated Hnf4a transcription. Our results may provide a general mechanism for establishing circadian rhythm heterogeneity during development and disease progression, governed by chromatin structure.',\n", - " 'author': ['Qu, Meng', 'Qu, Han', 'Jia, Zhenyu', 'Kay, Steve A.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41467-021-26567-3\"}'],\n", - " 'title': ['HNF4A defines tissue-specific circadian rhythms by beaconing BMAL1::CLOCK chromatin binding and shaping the rhythmic chromatin landscape']},\n", - " {'bibcode': '2021NatCo..12.7123H',\n", - " 'abstract': 'Queuosine (Q) is a structurally complex, non-canonical RNA nucleoside. It is present in many eukaryotic and bacterial species, where it is part of the anticodon loop of certain tRNAs. In higher vertebrates, including humans, two further modified queuosine-derivatives exist - galactosyl- (galQ) and mannosyl-queuosine (manQ). The function of these low abundant hypermodified RNA nucleosides remains unknown. While the structure of galQ was elucidated and confirmed by total synthesis, the reported structure of manQ still awaits confirmation. By combining total synthesis and LC-MS-co-injection experiments, together with a metabolic feeding study of labelled hexoses, we show here that the natural compound manQ isolated from mouse liver deviates from the literature-reported structure. Our data show that manQ features an α-allyl connectivity of its sugar moiety. The yet unidentified glycosylases that attach galactose and mannose to the Q-base therefore have a maximally different constitutional connectivity preference. Knowing the correct structure of manQ will now pave the way towards further elucidation of its biological function.',\n", - " 'author': ['Hillmeier, Markus',\n", - " 'Wagner, Mirko',\n", - " 'Ensfelder, Timm',\n", - " 'Korytiakova, Eva',\n", - " 'Thumbs, Peter',\n", - " 'Müller, Markus',\n", - " 'Carell, Thomas'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41467-021-27371-9\"}'],\n", - " 'title': ['Synthesis and structure elucidation of the human tRNA nucleoside mannosyl-queuosine']},\n", - " {'bibcode': '2003Sci...300.1574D',\n", - " 'abstract': 'Insulin resistance is a major hallmark in the development of type II diabetes, which is characterized by the failure of insulin to promote glucose uptake in muscle and to suppress glucose production in liver. The serine-threonine kinase Akt (PKB) is a principal target of insulin signaling that inhibits hepatic glucose output when glucose is available from food. Here we show that TRB3, a mammalian homolog of Drosophila tribbles, functions as a negative modulator of Akt. TRB3 expression is induced in liver under fasting conditions, and TRB3 disrupts insulin signaling by binding directly to Akt and blocking activation of the kinase. Amounts of TRB3 RNA and protein were increased in livers of db/db diabetic mice compared with those in wild-type mice. Hepatic overexpression of TRB3 in amounts comparable to those in db/db mice promoted hyperglycemia and glucose intolerance. Our results suggest that, by interfering with Akt activation, TRB3 contributes to insulin resistance in individuals with susceptibility to type II diabetes.',\n", - " 'author': ['Du, Keyong',\n", - " 'Herzig, Stephan',\n", - " 'Kulkarni, Rohit N.',\n", - " 'Montminy, Marc'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.1079817\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.1079817\"}'],\n", - " 'title': ['TRB3: A tribbles Homolog That Inhibits Akt/PKB Activation by Insulin in Liver']},\n", - " {'bibcode': '1976PNAS...73.3122R',\n", - " 'abstract': 'The incorporation of [3H]adenosine, [3H]adenine, and [3H]hypoxanthine into adenine nucleotides of nude (athymic) mouse liver and human hepatoma grown subcutaneously in nude mice was studied. 3H and 32P radioactive labeling in vivo of acid-soluble nucleotides followed by chromatographic procedures indicated that, in contrast to [3H]adenine and [3H]hypoxanthine, [3H]adenosine is preferentially incorporated into ATP in comparison with its incorporation into AMP and ADP. This phenomenon, as well as complementing the recently reported 3-fold increase in total cellular ATP upon treatmen- with 0.5-1.0 mM concentrations of adenosine, indicates the formation from adenosine of compartmentalized ATP that is not produced from either adenine or hypoxanthine. The observed effect is of larger magnitude in the growth-arrested normal liver than in the actively growing tumor.',\n", - " 'author': ['Rapaport, Eliezer', 'Zamecnik, Paul C.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/73/9/3122\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/73/9/3122\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/73/9/3122\"}'],\n", - " 'title': ['Incorporation of adenosine into ATP: formation of compartmentalized ATP.']},\n", - " {'bibcode': '2017PNAS..114.4691K',\n", - " 'abstract': 'The Hippo pathway restricts cell proliferation and plays key roles in organ size control and tissue homeostasis. The crucial step of this pathway is the regulation of the transcriptional coactivators YAP/TAZ by LATS1/2 kinases. We report in the present study that deubiquitinase YOD1 acts as a positive regulator of YAP/TAZ in controlling organ size. The significance of our study is the discovery of a regulatory mechanism for the Hippo pathway: high cell density miR-21-YOD1-ITCH-LATS signaling cascade, which is parallel to a previously known high cell density MST1/2-LATS signaling cascade. Data from harnessing a mouse model that allowed inducible human YOD1 expression in mouse liver and liver cancer patients suggest mechanistic insights to expand our understanding about regulation of the Hippo pathway.',\n", - " 'author': ['Kim, Youngeun',\n", - " 'Kim, Wantae',\n", - " 'Song, Yonghee',\n", - " 'Kim, Jeong-Rae',\n", - " 'Cho, Kyungjoo',\n", - " 'Moon, Hyuk',\n", - " 'Ro, Simon Weonsang',\n", - " 'Seo, Eunjeong',\n", - " 'Ryu, Yeon-Mi',\n", - " 'Myung, Seung-Jae',\n", - " 'Jho, Eek-Hoon'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1620306114\"}'],\n", - " 'title': ['Deubiquitinase YOD1 potentiates YAP/TAZ activities through enhancing ITCH stability']},\n", - " {'bibcode': '2022EnTox..37..362L',\n", - " 'abstract': 'Polystyrene nanoparticles (PS-NPs) as an issue of global environmental concern, have been shown to induce hepatic toxicity via triggering oxidative injury and inflammation. Non-alcoholic fatty liver disease (NAFLD) is initiated when excessive lipid is accumulated in the liver and will proceed to liver fibrosis with repeatedly chronic liver injury. In this study, we examined whether intravenous injection of PS-NPs could enhance the hepatic toxicity and potentiate the development of liver fibrosis in experimental high fat diet (HFD)-induced mice. The results demonstrated that PS-NPs could aggravate chronic hepatitis by interfere with liver lipid metabolism in HFD induced mice. Further, hepatic tissue in PS-NPs treated HFD mice displayed substantially lowered superoxide dismutase (SOD) activity, which confirming the oxidative stress induced by PS-NPs. PS-NPs exposure also resulted in the up-regulation of inflammation response in liver, as evidenced by the enhanced infiltration of Kupffer cells (KCs) and elevated expression of pro-inflammatory related indicators. Meanwhile, Masson trichrome staining revealed that PS-NPs could aggravate steatohepatitis with higher collagen fiber in HFD fed mice. Our data suggests that PS-NPs can induce oxidative stress and inflammation in HDF-induced experimental mice and further aggravate liver fibrosis, which highlight the potential health risks of PS-NPs.',\n", - " 'author': ['Li, Ling',\n", - " 'Xu, Minjie',\n", - " 'He, Chao',\n", - " 'Wang, Hui',\n", - " 'Hu, Qinglian'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Ftox.23404\"}'],\n", - " 'title': ['Polystyrene nanoplastics potentiate the development of hepatic fibrosis in high fat diet fed mice']},\n", - " {'bibcode': '2015PLoSO..1031436L',\n", - " 'author': ['Liu, Xiqiang',\n", - " 'Hu, Zhiqiu',\n", - " 'Zhou, Bin',\n", - " 'Li, Xiang',\n", - " 'Tao, Ran'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0131436\"}'],\n", - " 'title': ['Chinese Herbal Preparation Xuebijing Potently Inhibits Inflammasome Activation in Hepatocytes and Ameliorates Mouse Liver Ischemia-Reperfusion Injury']},\n", - " {'bibcode': '2005ToxIH..21..231Y',\n", - " 'abstract': '2,4-Dichlorophenoxyacetic acid (2,4-D), which is a plant auxin analogue, is lethal to broad leaved weeds within days at high dosages and is considered as having low toxicity to mammals. Some studies have reported that exposure to this compound may cause damage to organs such as liver. The aim of this study was to investigate the effects of 2,4-D in mouse liver on chromosomes as well as hexokinase (HK), glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) which are required for the generation of the pyridine nucleotide pool. The experiments were carried out with a 2,4-D group, an ethanol control for 2,4-D, and saline group for ethanol control group on three generations of mice. Only female parents were given 2,4-D during the gestation period, lactation period and for 33 days following the lactation period. In females of the first cross, 2,4-D caused a significant increase in the activity of LDH, and ethanol alone caused a significant increase in the activities of HK and LDH. In the male offspring of the first cross maternal, 2,4-D caused a significant increase in the activity of LDH, and ethanol alone caused a significant decrease in the activity of 6PGD. In the female offspring of the first cross maternal, ethanol caused a significant increase in the activities of G6PD and MDH. In the female offsprings of the third cross maternal, 2,4-D caused a significant increase in the activity of MDH. No gross morphological changes were observed in internal organs, such as liver, kidney and spleen of the affected animals. Also, a chromosomal study from bone marrow cells indicated no anomalies in chromosomal sets and structures. As a result, 2,4-D had an effect on the first cross maternal and their offsprings. The compound did not affect the parameters studied except MDH enzyme activity in the second and third generation of mice.',\n", - " 'author': ['Yilmaz, H. Ramazan', 'Yuksel, Esref'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1191%2F0748233705th231oa\"}'],\n", - " 'title': ['Effect of 2,4-dichlorophenoxyacetic acid on the activities of some metabolic enzymes for generating pyridine nucleotide pool of cells from mouse liver']},\n", - " {'bibcode': '2022IJEHR..32.2123W',\n", - " 'author': ['Wang, Rui',\n", - " 'Liu, Haohao',\n", - " 'Du, Xingde',\n", - " 'Ma, Ya',\n", - " 'Tian, Zhihui',\n", - " 'Zhang, Shiyu',\n", - " 'Shi, Linjia',\n", - " 'Guo, Hongxiang',\n", - " 'Zhang, Huizhen'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1080%2F09603123.2021.1946489\"}'],\n", - " 'title': ['MicroRNA-122 overexpression promotes apoptosis and tumor suppressor gene expression induced by microcystin-leucine arginine in mouse liver']},\n", - " {'bibcode': '2017PLoSO..1270461T',\n", - " 'author': ['Tsutsumi, Takeya',\n", - " 'Okushin, Kazuya',\n", - " 'Enooku, Kenichiro',\n", - " 'Fujinaga, Hidetaka',\n", - " 'Moriya, Kyoji',\n", - " 'Yotsuyanagi, Hiroshi',\n", - " 'Aizaki, Hideki',\n", - " 'Suzuki, Tetsuro',\n", - " 'Matsuura, Yoshiharu',\n", - " 'Koike, Kazuhiko'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0170461\"}'],\n", - " 'title': ['Nonstructural 5A Protein of Hepatitis C Virus Interferes with Toll-Like Receptor Signaling and Suppresses the Interferon Response in Mouse Liver']},\n", - " {'bibcode': '2013PLoSO...874948M',\n", - " 'author': ['Moreno, Daniel',\n", - " 'Balasiddaiah, Anangi',\n", - " 'Lamas, Oscar',\n", - " 'Duret, Cedric',\n", - " 'Neri, Leire',\n", - " 'Guembe, Laura',\n", - " 'Galarraga, Miguel',\n", - " 'Larrea, Esther',\n", - " 'Daujat-Chavanieu, Martine',\n", - " 'Muntane, Jordi',\n", - " 'Maurel, Patrick',\n", - " 'Riezu, Jose Ignacio',\n", - " 'Prieto, Jesus',\n", - " 'Aldabe, Rafael'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0074948\"}'],\n", - " 'title': ['Usage of Adenovirus Expressing Thymidine Kinase Mediated Hepatocellular Damage for Enabling Mouse Liver Repopulation with Allogenic or Xenogenic Hepatocytes']},\n", - " {'bibcode': '2012EnvMM..53..350W',\n", - " 'abstract': 'One model for cancer initiation by 4‑aminobiphenyl (ABP) involves N‑oxidation by cytochrome P450 CYP1A2 followed by O‑conjugation by N‑acetyltransferase(s) NAT1 and/or NAT2 and decomposition to a DNA‑binding nitrenium ion. We recently observed that neonatal ABP exposure produced liver tumors in male but not in female mice, and that NAT deficiency reduced liver tumor incidence. However, ABP‑induced liver tumor incidence did not correlate with liver levels of N‑(deoxyguanosin‑8‑yl)‑ABP adducts 24 hr after exposure. In this study, we compared in vivo ABP‑induced DNA mutant frequencies and spectra between male and female wild‑type and NAT‑deficient Muta™Mouse using both the tumor‑inducing neonatal exposure protocol and a 28‑day repetitive dosing adult exposure protocol. ABP produced an increase in liver DNA mutant frequencies in both neonates and adults. However, we observed no sex or strain differences in mutant frequencies in neonatally exposed mice, and higher frequencies in adult females than males. Neonatal ABP exposure of wild‑type mice increased the proportion of G‑T transversions in both males and females, while exposure of Nat1/2(‑/‑) mice produced increased G‑T transversions in males and a decrease in females, even though females had higher levels of N‑(deoxyguanosin‑8‑yl)‑4‑ABP adducts. There was no correlation of mutant frequencies or spectra between mice dosed as neonates or as adults. These results suggest that observed sex‑ and NAT‑dependent differences in ABP‑induced liver tumor incidence in mice are not due to differences in either mutation rates or mutational spectra, and that mechanisms independent of carcinogen bioactivation, covalent DNA binding and mutation may be responsible for these differences. Environ. Mol. Mutagen., 2012.',\n", - " 'author': ['Wang, Shuang',\n", - " 'Sugamori, Kim S.',\n", - " 'Brenneman, Debbie',\n", - " 'Hsu, Ivy',\n", - " 'Calce, Adriana',\n", - " 'Grant, Denis M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Fem.21695\"}'],\n", - " 'title': ['Influence of arylamine n‑acetyltransferase, sex, and age on 4‑aminobiphenyl‑induced in vivo mutant frequencies and spectra in mouse liver']},\n", - " {'bibcode': '2013PLoSO...858797R',\n", - " 'author': ['Roncero, Isabel',\n", - " 'Alvarez, Elvira',\n", - " 'Acosta, Carlos',\n", - " 'Sanz, Carmen',\n", - " 'Barrio, Pedro',\n", - " 'Hurtado-Carneiro, Veronica',\n", - " 'Burks, Deborah',\n", - " 'Blázquez, Enrique'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0058797\"}'],\n", - " 'title': ['Insulin-Receptor Substrate-2 (IRS-2) Is Required for Maintaining Glucokinase and Glucokinase Regulatory Protein Expression in Mouse Liver']},\n", - " {'bibcode': '2023E&ES.1174a2011W',\n", - " 'abstract': \"The protozoan parasite Plasmodium infection can cause malaria in both humans and animals. There are reports about the resistance to certain antimalarial medications. Therefore, searching for alternative medicine, such as herbal remedies, is important. This study focused on the pathophysiology of the livers of mice infected intraperitoneally with Plasmodium berghei and the efficacy of ethanol extract from breadfruit peel. Fifty male DDY mice weighing 25 and 35 grams were placed into five treatment groups. The treatment group was infected with P. berghei and administered with breadfruit peel extract at 100 mg/kg: 200 mg/kg, and 300 mg/kg, respectively, for P1, P2, and P3, P4 treated with 100 mg/kg of Doxycycline and the P5 group received no therapy. After one and two weeks, five mice from each group terminated, and then Histopathological of the liver organs were observed and scored microscopically. The results indicated that Plasmodium infection produced varied degrees of liver damage in mice. The liver's gross pathology revealed hepatomegaly, a deeper hue than normal animal liver, and flattened edges. After two weeks of infection, histopathological examination revealed that breadfruit extract could lower the amount of Plasmodium in the liver, as indicated by decreased hemozoin, and the l iver in the healing process.\",\n", - " 'author': ['Wahyuwardani, S.',\n", - " 'Wardhana, A. H.',\n", - " 'Putra, G. I. S.',\n", - " 'Putri, R.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1088%2F1755-1315%2F1174%2F1%2F012011\"}'],\n", - " 'title': ['Pathology of Plasmodium berghei-Infected Mice Liver Treated with Extract of Breadfruit Peel (Artocarpus communis)']},\n", - " {'bibcode': '1995Sci...269..230T',\n", - " 'abstract': 'Gene targeting was used to create a null allele at the epidermal growth factor receptor locus (Egfr). The phenotype was dependent on genetic background. EGFR deficiency on a CF-1 background resulted in peri-implantation death due to degeneration of the inner cell mass. On a 129/Sv background, homozygous mutants died at mid-gestation due to placental defects; on a CD-1 background, the mutants lived for up to 3 weeks and showed abnormalities in skin, kidney, brain, liver, and gastrointestinal tract. The multiple abnormalities associated with EGFR deficiency indicate that the receptor is involved in a wide range of cellular activities.',\n", - " 'author': ['Threadgill, David W.',\n", - " 'Dlugosz, Andrzej A.',\n", - " 'Hansen, Laura A.',\n", - " 'Tennenbaum, Tamar',\n", - " 'Lichti, Ulrike',\n", - " 'Yee, Della',\n", - " 'Lamantia, Christian',\n", - " 'Mourton, Tracy',\n", - " 'Herrup, Karl',\n", - " 'Harris, Raymond C.',\n", - " 'Barnard, John A.',\n", - " 'Yuspa, Stuart H.',\n", - " 'Coffey, Robert J.',\n", - " 'Magnuson, Terry'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.7618084\"}'],\n", - " 'title': ['Targeted Disruption of Mouse EGF Receptor: Effect of Genetic Background on Mutant Phenotype']},\n", - " {'bibcode': '2023NatSR..1314186D',\n", - " 'abstract': 'Senescent cells are predicted to occur and increase in animal tissues with aging. However, senescent cells in the tissues of aged animals remain to be identified. We refer to the marker genes to identify senescent cells in tissues as \"age-associated genes\". In this study, we searched for age-associated genes to identify senescent cells in the livers of aged animals. We performed single-cell RNA sequencing (scRNA-seq) to screen candidates for age-associated genes using young and aged rat primary hepatocytes. To remove animal species specificity, gene expression analyses in mouse livers were performed, confirming age-associated increases in the mRNA expression levels of Glipr1, Clec12a, and Phlda3. Moreover, the mRNA expression levels of Glipr1 and Phlda3 were increased by stress-induced premature senescence using doxorubicin in primary hepatocytes and livers of young mice. Transcriptome data of aged rat hepatocytes suggested that Glipr1, Clec12a, and Phlda3 were expressed in almost identical cells. Fluorescence in situ hybridization (FISH) confirmed the presence of cells with abundant Glipr1, Clec12a, and Phlda3 mRNA in 27-month-old mouse primary hepatocytes, which are considered to be senescent cells. This study is the first to identify Glipr1, Clec12a, and Phlda3 as age-associated genes in the mouse liver.',\n", - " 'author': ['Doshida, Yuta',\n", - " 'Hashimoto, Shinichi',\n", - " 'Iwabuchi, Sadahiro',\n", - " 'Takino, Yuka',\n", - " 'Ishiwata, Toshiyuki',\n", - " 'Aigaki, Toshiro',\n", - " 'Ishigami, Akihito'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-023-41352-6\"}'],\n", - " 'title': ['Single-cell RNA sequencing to detect age-associated genes that identify senescent cells in the liver of aged mice']},\n", - " {'bibcode': '2007EnTox..22..620T',\n", - " 'abstract': 'Microcystin‑LR (MCLR) produced by freshwater cyanobacteria is a potent hepatotoxin and inhibits protein serine/threonine phosphatases 1 and 2A (PP1 and PP2A). Okadaic acid (OA) is a similar phosphatase inhibitor, which has less affinity to PP1 than PP2A. MCLR and OA behave similarly with primary culture hepatocytes with the induction of phosphorylation of the cytokeratins, morphological changes, and apoptosis. The purpose of this study was to investigate the in vivo relationship between the protein phosphatase inhibitory activities and the acute hepatotoxicity of MCLR compared to OA. MCLR and OA were intraperitoneally administrated to mice at ∼220 μg/kg. After 30 min, the liver of only the MCLR‑treated mouse was dark‑colored and heavier than that of the control mouse. Subsequently, the phosphoproteins of the mouse liver were chemically modified with reversible biotinylation reagent and selectively analyzed by LC/MS/MS. Consequently, the phosphorylated Ser 354 of formyltetrahydrofolate dehydrogenase, which is an abundant enzyme in the liver cytoplasm, was observed in the MCLR‑ and the OA‑treated mice 9.5 and 5.3 times more intensely than in the control mouse respectively, suggesting that MCLR and OA inhibited PP2A and induced the resulting phosphorylation. These results supported the hypothesis that the acute hepatotoxicity is possibly caused by the PP1 inhibition, and not by the PP2A inhibition.',\n", - " 'author': ['Tachi, Masahiko', 'Imanishi, Susumu Y.', 'Harada, Ken-ichi'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Ftox.20294\"}'],\n", - " 'title': ['Phosphoprotein analysis for investigation of in vivo relationship between protein phosphatase inhibitory activities and acute hepatotoxicity of microcystin‑LR']},\n", - " {'bibcode': '2010PNAS..107.8248L',\n", - " 'abstract': 'Loss of Hippo signaling in Drosophila leads to tissue overgrowth as a result of increased cell proliferation and decreased cell death. YAP (a homolog of Drosophila Yorkie and target of the Hippo pathway) was recently implicated in control of organ size, epithelial tissue development, and tumorigenesis in mammals. However, the role of the mammalian Hippo pathway in such regulation has remained unclear. We now show that mice with liver-specific ablation of WW45 (a homolog of Drosophila Salvador and adaptor for the Hippo kinase) manifest increased liver size and expansion of hepatic progenitor cells (oval cells) and eventually develop hepatomas. Moreover, ablation of WW45 increased the abundance of YAP and induced its localization to the nucleus in oval cells, likely accounting for their increased proliferative capacity, but not in hepatocytes. Liver tumors that developed in mice heterozygous for WW45 deletion or with liver-specific WW45 ablation showed a mixed pathology combining characteristics of hepatocellular carcinoma and cholangiocarcinoma and seemed to originate from oval cells. Together, our results suggest that the mammalian Hippo-Salvador pathway restricts the proliferation of hepatic oval cells and thereby controls liver size and prevents the development of oval cell-derived tumors.',\n", - " 'author': ['Lee, Kwang-Pyo',\n", - " 'Lee, Joo-Hyeon',\n", - " 'Kim, Tae-Shin',\n", - " 'Kim, Tack-Hoon',\n", - " 'Park, Hee-Dong',\n", - " 'Byun, Jin-Seok',\n", - " 'Kim, Min-Chul',\n", - " 'Jeong, Won-Il',\n", - " 'Calvisi, Diego F.',\n", - " 'Kim, Jin-Man',\n", - " 'Lim, Dae-Sik'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/107/18/8248\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0912203107\"}'],\n", - " 'title': ['The Hippo-Salvador pathway restrains hepatic oval cell proliferation, liver size, and liver tumorigenesis']},\n", - " {'bibcode': '2013NatSR...3E3470S',\n", - " 'abstract': 'Hepatic stellate cells (HSCs) are the primary source of matrix components in liver disease such as fibrosis. Phosphatidylinositol 3-kinase (PI3K) signaling in HSCs has been shown to induce fibrogenesis. In this study, we evaluated the anti-fibrotic activity of a novel imidazopyridine analogue (HS-173) in human HSCs as well as mouse liver fibrosis. HS-173 strongly suppressed the growth and proliferation of HSCs and induced the arrest at the G2/M phase and apoptosis in HSCs. Furthermore, it reduced the expression of extracellular matrix components such as collagen type I, which was confirmed by an in vivo study. We also observed that HS-173 blocked the PI3K/Akt signaling pathway in vitro and in vivo. Taken together, HS-173 suppressed fibrotic responses such as cell proliferation and collagen synthesis by blocking PI3K/Akt signaling. Therefore, we suggest that this compound may be an effective therapeutic agent for ameliorating liver fibrosis through the inhibition of PI3K signaling.',\n", - " 'author': ['Son, Mi Kwon',\n", - " 'Ryu, Ye-Lim',\n", - " 'Jung, Kyung Hee',\n", - " 'Lee, Hyunseung',\n", - " 'Lee, Hee Seung',\n", - " 'Yan, Hong Hua',\n", - " 'Park, Heon Joo',\n", - " 'Ryu, Ji-Kan',\n", - " 'Suh, Jun-Kyu',\n", - " 'Hong, Sungwoo',\n", - " 'Hong, Soon-Sun'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep03470\"}'],\n", - " 'title': ['HS-173, a Novel PI3K Inhibitor, Attenuates the Activation of Hepatic Stellate Cells in Liver Fibrosis']},\n", - " {'bibcode': '2017NatSR...7.4200L',\n", - " 'abstract': 'The mouse has been widely used as a model organism for studying human diseases and for evaluating drug safety and efficacy. Many diseases and drug effects exhibit tissue specificity that may be reflected by tissue-specific gene-expression profiles. Here we construct a comprehensive mouse transcriptomic BodyMap across 17 tissues of six-weeks old C57BL/6JJcl mice using RNA-seq. We find different expression patterns between protein-coding and non-coding genes. Liver expressed the least complex transcriptomes, that is, the smallest number of genes detected in liver across all 17 tissues, whereas testis and ovary harbor more complex transcriptomes than other tissues. We report a comprehensive list of tissue-specific genes across 17 tissues, along with a list of 4,781 housekeeping genes in mouse. In addition, we propose a list of 27 consistently and highly expressed genes that can be used as reference controls in expression-profiling analysis. Our study provides a unique resource of mouse gene-expression profiles, which is helpful for further biomedical research.',\n", - " 'author': ['Li, Bin',\n", - " 'Qing, Tao',\n", - " 'Zhu, Jinhang',\n", - " 'Wen, Zhuo',\n", - " 'Yu, Ying',\n", - " 'Fukumura, Ryutaro',\n", - " 'Zheng, Yuanting',\n", - " 'Gondo, Yoichi',\n", - " 'Shi, Leming'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-017-04520-z\"}'],\n", - " 'title': ['A Comprehensive Mouse Transcriptomic BodyMap across 17 Tissues by RNA-seq']},\n", - " {'bibcode': '2003EnTox..18..243F',\n", - " 'abstract': 'The toxicology of the cyanobacterial alkaloid cylindrospermopsin (CYN), a potent inhibitor of protein synthesis, appears complex and is not well understood. In exposed mice the liver is the main target for the toxic effects of CYN. In this study primary mouse hepatocyte cultures were used to investigate the mechanisms involved in CYN toxicity. The results show that 1–5 μM CYN caused significant concentration‑dependent cytotoxicity (52%–82% cell death) at 18 h. Protein synthesis inhibition was a sensitive, early indicator of cellular responses to CYN. Following removal of the toxin, the inhibition of protein synthesis could not be reversed, showing behavior similar to that of the irreversible inhibitor emetine. In contrast to the LDH leakage, protein synthesis was maximally inhibited by 0.5 μM CYN. No protein synthesis occurred over 4–18 h at or above this concentration. Inhibition of cytochrome P450 (CYP450) activity with 50 μM proadifen or 50 μM ketoconazole diminished the toxicity of CYN but not the effects on protein synthesis. These findings imply a dissociation of the two events and implicate the involvement of CYP450‑derived metabolites in the toxicity process, but not in the impairment of protein synthesis. Thus, the total abolition of protein synthesis may exaggerate the metabolite effects but cannot be considered a primary cause of cell death in hepatocytes over an acute time frame. In cell types deficient in CYP450 enzymes, protein synthesis inhibition may play a more crucial role in the development of cytotoxicity.',\n", - " 'author': ['Froscio, Suzanne M.',\n", - " 'Humpage, Andrew R.',\n", - " 'Burcham, Philip C.',\n", - " 'Falconer, Ian R.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Ftox.10121\"}'],\n", - " 'title': ['Cylindrospermopsin‑induced protein synthesis inhibition and its dissociation from acute toxicity in mouse hepatocytes']},\n", - " {'bibcode': '2004PNAS..101.4477H',\n", - " 'abstract': 'Hepatocyte growth factor/scatter factor c-met signaling pathway is of central importance during development as well as in tumorigenesis. Because homozygous null mice for either hgf/sf or c-met die in utero, we used Cre/loxP-mediated gene targeting to investigate the function of c-met specifically in the adult liver. Loss of c-met appeared not to be detrimental to hepatocyte function under physiological conditions. Nonetheless, the adaptive responses of the liver to injury were dramatically affected. Mice lacking c-met gene in hepatocytes were hypersensitive to Fas-induced apoptosis. When injected with a low dose of anti-Fas antibody, the majority of these mice died from massive apoptosis and hemorrhagic necrosis, whereas all wild-type mice survived with signs of minor injury. After a challenge with a single necrogenic dose of CCl4, c-met conditional knockout mice exhibited impaired recovery from centrolobular lesions rather than a deficit in hepatocyte proliferation. The delayed healing was associated with a persistent inflammatory reaction, over-production of osteopontin, early and prominent dystrophic calcification, and impaired hepatocyte scattering/migration into diseased areas. These studies provide direct genetic evidence in support of the critical role of c-met in efficient liver regeneration and suggest that disruption of c-met affects primarily hepatocyte survival and tissue remodeling.',\n", - " 'author': ['Huh, Chang-Goo',\n", - " 'Factor, Valentina M.',\n", - " 'Sánchez, Aránzazu',\n", - " 'Uchida, Koichi',\n", - " 'Conner, Elizabeth A.',\n", - " 'Thorgeirsson, Snorri S.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/101/13/4477\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0306068101\"}'],\n", - " 'title': ['Hepatocyte growth factor/c-met signaling pathway is required for efficient liver regeneration and repair']},\n", - " {'bibcode': '2008PNAS..105.6662I',\n", - " 'abstract': 'Primitive erythroid cells (EryP) are the earliest differentiated cell type of the mammalian embryo. They appear in the yolk sac by embryonic day 7.5, begin to enter the embryonic circulation 2 days later and continue to mature in a stepwise and synchronous fashion. Like their adult counterparts, EryP enucleate. However, EryP circulate throughout the embryo for several days before the first enucleated forms can be identified in the blood. We have used transgenic mouse lines in which GFP marks EryP to investigate this seemingly long lag and have identified a previously unrecognized developmental niche for EryP maturation. After exiting the yolk sac, EryP begin to express cell adhesion proteins, including α4, α5, and β1 integrins, on their surface and migrate into the fetal liver (FL), where they interact with macrophages within erythroblastic islands. Binding of EryP to FL macrophages in vitro is stage-specific and partly depends on VCAM-1. The ability to tag and track EryP nuclei using a transgenic mouse line expressing an H2B-EGFP fusion allowed us to identify and characterize extruded EryP nuclei and to demonstrate that molecules such as α4, α5, and β1 integrins are redistributed onto the plasma membrane surrounding the extruding nucleus. FL macrophages engulf extruded EryP nuclei in cocultures and in the native FL in vivo. We conclude that EryP home to, complete their maturation, and enucleate within the FL, a tissue that is just developing as EryP begin to circulate. Our observations suggest a simple solution for a puzzling aspect of the development of the primitive erythroid lineage.',\n", - " 'author': ['Isern, Joan',\n", - " 'Fraser, Stuart T.',\n", - " 'He, Zhiyong',\n", - " 'Baron, Margaret H.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/105/18/6662\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/105/18/6662.full.pdf\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0802032105\"}'],\n", - " 'title': ['The fetal liver is a niche for maturation of primitive erythroid cells']},\n", - " {'bibcode': '1992EnvMM..20...39L',\n", - " 'abstract': 'Previous studies have shown that the rat liver carcinogen quinoline is essentially nongenotoxic to the rat liver in vivo. Those studies also established it as a potent mitogen to rat liver. The present experiments have established quinoline as a mitogen to the mouse liver, a tissue in which it is also reported to be carcinogenic. In contrast, quinoline is reported to be noncarcinogenic to the guinea pig liver, and the present data establish it to be essentially nonmitogenic to the guinea pig liver. It is concluded that the mitogenicity of quinoline correlates better with its hepatocarcinogenic properties than does its genotoxicity in vivo.',\n", - " 'author': ['Lefevre, P.', 'Ashby, J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Fem.2850200107\"}'],\n", - " 'title': ['Mitogenic activity of quinoline to the rat, mouse, and guinea pig liver: Empirical correlations with hepatic carcinogenicity']},\n", - " {'bibcode': '1985PNAS...82.8085R',\n", - " 'abstract': \"Apolipoprotein E (apo E) is responsible for the binding of very low density lipoprotein and chylomicron remnants to cellular receptors thereby removing them from circulation. We have isolated and determined the sequence of a cDNA encoding 285 amino acids and the entire 3' untranslated region of 112 nucleotides of mouse apo E. The remaining coding sequence was determined by sequencing mouse liver mRNA. Comparisons with rat and human apo E sequences showed a high degree of conservation although there were regions in each species that were characterized by unique insertions and deletions. Analysis of the sequence homologies within apo E revealed that the entire sequence is made up of repetitive units. The most primitive unit appeared to be an 11-nucleotide repeat within higher order repeats of 22 or 33 nucleotides. The 11-nucleotide unit -TCGGACGAGGC- is read in all three reading frames, and when tandemly repeated, it encodes the highly conserved amino acid sequence Xaa-(Glu/Asp)-(Glu/Asp)-Xaa-Arg-Xaa-Arg-Leu-Gly-Xaa-Xaa. We postulate that apo E and those other apolipoproteins related to it have arisen by duplications and subsequent modifications of this or a closely related 11-nucleotide ancestral sequence.\",\n", - " 'author': ['Rajavashisth, Tripathi B.',\n", - " 'Kaptein, John S.',\n", - " 'Reue, Karen L.',\n", - " 'Lusis, Aldons J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/82/23/8085\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/82/23/8085\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/82/23/8085\"}'],\n", - " 'title': ['Evolution of apolipoprotein E: mouse sequence and evidence for an 11-nucleotide ancestral unit.']},\n", - " {'bibcode': '1985PNAS...82..445B',\n", - " 'abstract': 'The uncoupling protein (UCP) of mammalian brown fat is a specialized and unique component responsible for energy dissipation as heat. Translation and immunoprecipitation from sucrose-fractionated mRNA indicated that the mRNA of UCP sedimented at 14-16 S. A recombinant cDNA library prepared from mRNA of thermoactive brown fat enriched for UCP mRNA has been constructed and cloned in Escherichia coli. Recombinant plasmids were screened by differential colony hybridization to a cDNA probe complementary to poly(A)+ RNA isolated from thermogenic or from weakly thermogenic brown fat. Several differentially hybridizing plasmids were shown to contain UCP cDNA sequences by their ability to select a mRNA coding for an in vitro translation product that was immunoprecipitable with antibodies against UCP. Blot hybridization of brown fat mRNA to a 32P-labeled UCP cDNA probe revealed two major species of mRNA (15S and 18S). As compared to non-thermogenic tissue, a strikingly increased hybridization to the probe was observed with brown fat mRNA from thermoactive tissue. Moreover, hybridization was observed with RNA of brown adipose tissue from rat, hamster, or mouse but not with RNA from rat or mouse liver.',\n", - " 'author': ['Bouillaud, Frederic',\n", - " 'Ricquier, Daniel',\n", - " 'Thibault, Jean',\n", - " 'Weissenbach, Jean'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/82/2/445\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/82/2/445\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/82/2/445\"}'],\n", - " 'title': ['Molecular approach to thermogenesis in brown adipose tissue: cDNA cloning of the mitochondrial uncoupling protein.']},\n", - " {'bibcode': '2022arXiv220812811W',\n", - " 'abstract': \"The disruption of circadian rhythm is a cardinal symptom for Alzheimer's disease (AD) patients. The full circadian rhythm orchestration of gene expression in the human brain and its inherent associations with AD remain largely unknown. We present a novel comprehensive approach, PRIME, to detect and analyze rhythmic oscillation patterns in untimed high-dimensional gene expression data across multiple datasets. To demonstrate the utility of PRIME, firstly, we validate it by a time course expression dataset from mouse liver as a cross-species and cross-organ validation. Then, we apply it to study oscillation patterns in untimed genome-wide gene expression from 19 human brain regions of controls and AD patients. Our findings reveal clear, synchronized oscillation patterns in 15 pairs of brain regions of control, while these oscillation patterns either disappear or dim for AD. It is worth noting that PRIME discovers the circadian rhythmic patterns without requiring the sample's timestamps. The codes for PRIME, along with codes to reproduce the figures in this paper, are available at https://github.com/xinxingwu-uk/PRIME.\",\n", - " 'author': ['Wu, Xinxing',\n", - " 'Peng, Chong',\n", - " 'Jicha, Gregory',\n", - " 'Wilcock, Donna',\n", - " 'Cheng, Qiang'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"preprint\", \"url\": \"http://arxiv.org/abs/2208.12811\"}'],\n", - " 'title': ['PRIME: Uncovering Circadian Oscillation Patterns and Associations with AD in Untimed Genome-wide Gene Expression across Multiple Brain Regions']},\n", - " {'bibcode': '1991PNAS...88.9468K',\n", - " 'abstract': 'In situ hybridization showed that the mRNA for ornithine aminotransferase (OAT; ornithine-oxo-acid aminotransferase; L-ornithine: 2-oxo-acid aminotransferase, EC 2.6.1.13) colocalized with glutamine synthetase [GS; glutamate-ammonia ligase; L-glutamate: ammonia ligase (ADP-forming), EC 6.3.1.2] in pericentral hepatocytes of the adult mouse liver. In addition to an identical distribution in adult hepatocytes, OAT and GS have very similar expression patterns in fetal and neonatal liver. As was earlier described for GS, there is a low level of OAT mRNA in fetal cells and increasing pericentral levels in neonates that reach adult patterns within 2 weeks. These results suggest that the transcriptional regulation of the two genes is similar in the liver. However, there was a lack of colocalization of the mRNAs for the two enzymes in cells of the kidney, intestine, and brain, suggesting different regulatory decisions for the OAT and GS genes in the cells of these different tissues. The metabolic consequences of these localized expression patterns favor ammonia clearance from the blood by the liver and urea synthesis by the kidney.',\n", - " 'author': ['Kuo, Frank C.',\n", - " 'Hwu, W. L.',\n", - " 'Valle, D.',\n", - " 'Darnell, James E., Jr.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/88/21/9468\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/88/21/9468\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/88/21/9468\"}'],\n", - " 'title': ['Colocalization in pericentral hepatocytes in adult mice and similarity in developmental expression pattern of ornithine aminotransferase and glutamine synthetase mRNA.']},\n", - " {'bibcode': '2015NatSR...515807L',\n", - " 'abstract': 'The deregulation of autophagy is involved in liver regeneration. Here, we investigated the role of autophagy in the regulation of liver regeneration after partial hepatectomy (PHx) and the development of pharmacological interventions for improved liver regeneration after PHx. We show that autophagy was activated in the early stages of liver regeneration following 70% PHx in vivo. Moreover, amiodarone was associated with a significant enhancement of autophagy, liver growth, and hepatocyte proliferation, along with reduced liver injury and the termination of liver regeneration due to decreased transforming growth factor-β1 expression after 70% PHx. The promotion of autophagy appeared to selectively increase the removal of damaged mitochondria. We also found that Atg7 knockdown or pretreatment with chloroquine aggravated the liver injury associated with 70% PHx and reduced liver growth and hepatocyte proliferation. Finally, amiodarone improved liver regeneration, survival, and liver injury after 90% PHx. In conclusion, our results indicate that autophagy plays an important role in mouse liver regeneration and that modulating autophagy with amiodarone may be an effective method of improving liver regeneration, increasing survival, and ameliorating liver injury following PHx.',\n", - " 'author': ['Lin, Chih-Wen',\n", - " 'Chen, Yaw-Sen',\n", - " 'Lin, Chih-Che',\n", - " 'Chen, Yun-Ju',\n", - " 'Lo, Gin-Ho',\n", - " 'Lee, Po-Huang',\n", - " 'Kuo, Po-Lin',\n", - " 'Dai, Chia-Yen',\n", - " 'Huang, Jee-Fu',\n", - " 'Chung, Wang-Long',\n", - " 'Yu, Ming-Lung'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep15807\"}'],\n", - " 'title': ['Amiodarone as an autophagy promoter reduces liver injury and enhances liver regeneration and survival in mice after partial hepatectomy']},\n", - " {'bibcode': '2016NatSR...628183H',\n", - " 'abstract': 'Soy protein β-conglycinin has serum lipid-lowering and anti-obesity effects. We showed that single ingestion of β-conglycinin after fasting alters gene expression in mouse liver. A sharp increase in fibroblast growth factor 21 (FGF21) gene expression, which is depressed by normal feeding, resulted in increased postprandial circulating FGF21 levels along with a significant decrease in adipose tissue weights. Most increases in gene expressions, including FGF21, were targets for the activating transcription factor 4 (ATF4), but not for peroxisome proliferator-activated receptor α. Overexpression of a dominant-negative form of ATF4 significantly reduced β-conglycinin-induced increases in hepatic FGF21 gene expression. In FGF21-deficient mice, β-conglycinin effects were partially abolished. Methionine supplementation to the diet or primary hepatocyte culture medium demonstrated its importance for activating liver or hepatocyte ATF4-FGF21 signaling. Thus, dietary β-conglycinin intake can impact hepatic and systemic metabolism by increasing the postprandial circulating FGF21 levels.',\n", - " 'author': ['Hashidume, Tsutomu',\n", - " 'Kato, Asuka',\n", - " 'Tanaka, Tomohiro',\n", - " 'Miyoshi, Shoko',\n", - " 'Itoh, Nobuyuki',\n", - " 'Nakata, Rieko',\n", - " 'Inoue, Hiroyasu',\n", - " 'Oikawa, Akira',\n", - " 'Nakai, Yuji',\n", - " 'Shimizu, Makoto',\n", - " 'Inoue, Jun',\n", - " 'Sato, Ryuichiro'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep28183\"}'],\n", - " 'title': ['Single ingestion of soy β-conglycinin induces increased postprandial circulating FGF21 levels exerting beneficial health effects']},\n", - " {'bibcode': '2015Natur.518..547G',\n", - " 'abstract': 'Most haematopoietic cells renew from adult haematopoietic stem cells (HSCs), however, macrophages in adult tissues can self-maintain independently of HSCs. Progenitors with macrophage potential in vitro have been described in the yolk sac before emergence of HSCs, and fetal macrophages can develop independently of Myb, a transcription factor required for HSC, and can persist in adult tissues. Nevertheless, the origin of adult macrophages and the qualitative and quantitative contributions of HSC and putative non-HSC-derived progenitors are still unclear. Here we show in mice that the vast majority of adult tissue-resident macrophages in liver (Kupffer cells), brain (microglia), epidermis (Langerhans cells) and lung (alveolar macrophages) originate from a Tie2+ (also known as Tek) cellular pathway generating Csf1r+ erythro-myeloid progenitors (EMPs) distinct from HSCs. EMPs develop in the yolk sac at embryonic day (E) 8.5, migrate and colonize the nascent fetal liver before E10.5, and give rise to fetal erythrocytes, macrophages, granulocytes and monocytes until at least E16.5. Subsequently, HSC-derived cells replace erythrocytes, granulocytes and monocytes. Kupffer cells, microglia and Langerhans cells are only marginally replaced in one-year-old mice, whereas alveolar macrophages may be progressively replaced in ageing mice. Our fate-mapping experiments identify, in the fetal liver, a sequence of yolk sac EMP-derived and HSC-derived haematopoiesis, and identify yolk sac EMPs as a common origin for tissue macrophages.',\n", - " 'author': ['Gomez Perdiguero, Elisa',\n", - " 'Klapproth, Kay',\n", - " 'Schulz, Christian',\n", - " 'Busch, Katrin',\n", - " 'Azzoni, Emanuele',\n", - " 'Crozet, Lucile',\n", - " 'Garner, Hannah',\n", - " 'Trouillet, Celine',\n", - " 'de Bruijn, Marella F.',\n", - " 'Geissmann, Frederic',\n", - " 'Rodewald, Hans-Reimer'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature13989\"}'],\n", - " 'title': ['Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors']},\n", - " {'bibcode': '1979Sci...203..544H',\n", - " 'abstract': 'A sensitive and specific radioimmunoassay for the insulin receptor has been developed employing receptor autoantibodies from the serum of a patient with insulin-resistant diabetes. The assay detects insulin binding sites at concentrations as low as 0.1 nanomolar; distinguishes between receptors originating from human placental membranes, human lymphoblastoid cells, and mouse liver membranes; and measures the receptor independently of its binding function. Down-regulation, or loss of binding after exposure to insulin, is associated with loss of immunoreactive receptor.',\n", - " 'author': ['Harrison, Len C.',\n", - " 'Flier, Jeffrey',\n", - " 'Itin, Ahuva',\n", - " 'Kahn, C. Ronald',\n", - " 'Roth, Jesse'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.83675\"}'],\n", - " 'title': ['Radioimmunoassay of the Insulin Receptor: A New Probe of Receptor Structure and Function']},\n", - " {'bibcode': '2008PNAS..10519378S',\n", - " 'abstract': 'The mammalian insulin-like growth factor 1 (IGF1), which is a member of a major growth-promoting signaling system, is produced by many tissues and functions throughout embryonic and postnatal development in an autocrine/paracrine fashion. In addition to this local action, IGF1 secreted by the liver and circulating in the plasma presumably acts systemically as a classical hormone. However, an endocrine role of IGF1 in growth control was disputed on the basis of the results of a conditional, liver-specific Igf1 gene knockout in mice, which reduced significantly the level of serum IGF1, but did not affect average body weight. Because alternate interpretations of these negative data were tenable, we addressed genetically the question of hormonal IGF1 action by using a positive experimental strategy based on the features of the cre/loxP recombination system. Thus, we generated bitransgenic mice carrying in an Igf1 null background a dormant Igf1 cDNA placed downstream of a transcriptional \"stop\" DNA sequence flanked by loxP sites (floxed) and also a cre transgene driven by a liver-specific promoter. The Igf1 cDNA, which was inserted by knock-in into the mutated and inactive Igf1 locus itself to ensure proper transcriptional regulation, was conditionally expressed from cognate promoters exclusively in the liver after Cre-mediated excision of the floxed block. Our genetic study demonstrated that the endocrine IGF1 plays a very significant role in mouse growth, as its action contributes approximately30% of the adult body size and sustains postnatal development, including the reproductive functions of both mouse sexes.',\n", - " 'author': ['Stratikopoulos, Elias',\n", - " 'Szabolcs, Matthias',\n", - " 'Dragatsis, Ioannis',\n", - " 'Klinakis, Apostolos',\n", - " 'Efstratiadis, Argiris'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/105/49/19378\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/105/49/19378.full.pdf\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0809223105\"}'],\n", - " 'title': ['The hormonal action of IGF1 in postnatal mouse growth']},\n", - " {'bibcode': '2006PNAS..103.8552M',\n", - " 'abstract': 'In animals, liver and white adipose are the main sites for the de novo fatty acid synthesis. Deletion of fatty acid synthase or acetyl-CoA carboxylase (ACC) 1 in mice resulted in embryonic lethality, indicating that the de novo fatty acid synthesis is essential for embryonic development. To understand the importance of de novo fatty acid synthesis and the role of ACC1-produced malonyl-CoA in adult mouse tissues, we generated liver-specific ACC1 knockout (LACC1KO) mice. LACC1KO mice have no obvious health problem under normal feeding conditions. Total ACC activity and malonyl-CoA levels were ≈70-75% lower in liver of LACC1KO mice compared with that of the WT mice. In addition, the livers of LACC1KO mice accumulated 40-70% less triglycerides. Unexpectedly, when fed fat-free diet for 10 days, there was significant up-regulation of PPARγ and several enzymes in the lipogenic pathway in the liver of LACC1KO mice compared with the WT mice. Despite the significant up-regulation of the lipogenic enzymes, including a >2-fold increase in fatty acid synthase mRNA, protein, and activity, there was significant decrease in the de novo fatty acid synthesis and triglyceride accumulation in the liver. However, there were no significant changes in blood glucose and fasting ketone body levels. Hence, reducing cytosolic malonyl-CoA and, therefore, the de novo fatty acid synthesis in the liver, does not affect fatty acid oxidation and glucose homeostasis under lipogenic conditions.',\n", - " 'author': ['Mao, Jianqiang',\n", - " 'DeMayo, Francesco J.',\n", - " 'Li, Huiguang',\n", - " 'Abu-Elheiga, Lutfi',\n", - " 'Gu, Ziwei',\n", - " 'Shaikenov, Tattym E.',\n", - " 'Kordari, Parichher',\n", - " 'Chirala, Subrahmanyam S.',\n", - " 'Heird, William C.',\n", - " 'Wakil, Salih J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/103/22/8552\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/103/22/8552\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/full/103/22/8552\"}'],\n", - " 'title': ['Liver-specific deletion of acetyl-CoA carboxylase 1 reduces hepatic triglyceride accumulation without affecting glucose homeostasis']},\n", - " {'bibcode': '2010RadR..174..786.',\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1667%2F0033-7587-174.6.786\"}'],\n", - " 'title': [\"Corrections: in the article ``Gene Expression Profiles in Mouse Liver after Long-Term Low-Dose-Rate Irradiation with Gamma Rays'' by Ueharaet al.\"]},\n", - " {'bibcode': '2005PNAS..102.4120X',\n", - " 'abstract': 'Knockout studies have shown that the transcription factor Nrf1 is essential for embryonic development. Nrf1 has been implicated to play a role in mediating activation of oxidative stress response genes through the antioxidant response element (ARE). Because of embryonic lethality in knockout mice, analysis of this function in the adult knockout mouse was not possible. We report here that mice with somatic inactivation of nrf1 in the liver developed hepatic cancer. Before cancer development, mutant livers exhibited steatosis, apoptosis, necrosis, inflammation, and fibrosis. In addition, hepatocytes lacking Nrf1 showed oxidative stress, and gene expression analysis showed decreased expression of various ARE-containing genes, and up-regulation of CYP4A genes. These results suggest that reactive oxygen species generated from CYP4A-mediated fatty acid oxidation work synergistically with diminished expression of ARE-responsive genes to cause oxidative stress in mutant hepatocytes. Thus, Nrf1 has a protective function against oxidative stress and, potentially, a function in lipid homeostasis in the liver. Because the phenotype is similar to nonalcoholic steatohepatitis, these animals may prove useful as a model for investigating molecular mechanisms of nonalcoholic steatohepatitis and liver cancer.',\n", - " 'author': ['Xu, Zhenrong',\n", - " 'Chen, Linyun',\n", - " 'Leung, Laura',\n", - " 'Yen, T. S. Benedict',\n", - " 'Lee, Candy',\n", - " 'Chan, Jefferson Y.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/102/11/4120\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0500660102\"}'],\n", - " 'title': ['Liver-specific inactivation of the Nrf1 gene in adult mouse leads to nonalcoholic steatohepatitis and hepatic neoplasia']},\n", - " {'bibcode': '2020NatSR..10.3386T',\n", - " 'abstract': 'Ibuprofen, an inhibitor of prostanoid biosynthesis, is a common pharmacological agent used for the management of pain, inflammation and fever. However, the chronic use of ibuprofen at high doses is associated with increased risk for cardiovascular, renal, gastrointestinal and liver injuries. The underlying mechanisms of ibuprofen-mediated effects on liver remain unclear. To determine the mechanisms and signaling pathways affected by ibuprofen (100 mg/kg/day for seven days), we performed proteomic profiling of male mice liver with quantitative liquid chromatography tandem mass spectrometry (LC-MS/MS) using ten-plex tandem mass tag (TMT) labeling. More than 300 proteins were significantly altered between the control and ibuprofen-treated groups. The data suggests that several major pathways including (1) energy metabolism, (2) protein degradation, (3) fatty acid metabolism and (4) antioxidant system are altered in livers from ibuprofen treated mice. Independent validation of protein changes in energy metabolism and the antioxidant system was carried out by Western blotting and showed sex-related differences. Proteasome and immunoproteasome activity/expression assays showed ibuprofen induced gender-specific proteasome and immunoproteasome dysfunction in liver. The study observed multifactorial gender-specific ibuprofen-mediated effects on mice liver and suggests that males and females are affected differently by ibuprofen.',\n", - " 'author': ['Tiwari, Shuchita',\n", - " 'Mishra, Manish',\n", - " 'Salemi, Michelle R.',\n", - " 'Phinney, Brett S.',\n", - " 'Newens, Joanne L.',\n", - " 'Gomes, Aldrin V.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-020-60053-y\"}'],\n", - " 'title': ['Gender-specific changes in energy metabolism and protein degradation as major pathways affected in livers of mice treated with ibuprofen']},\n", - " {'bibcode': '2002PNAS...9913825Y',\n", - " 'abstract': 'Hepatitis B virus (HBV) is a prototype for liver-specific pathogens in which the failure of the immune system to mount an effective response leads to chronic infection. Our understanding of the immune response to HBV is incomplete, largely due to the narrow host restriction of this pathogen and the limitations of existing experimental models. We have developed a murine model for studying human HBV replication, immunogenicity, and control. After transfection of hepatocytes in vivo with a replication-competent, over-length, linear HBV genome, viral antigens and replicative intermediates were synthesized and virus was secreted into the blood. Viral antigens disappeared from the blood as early as 7 days after transfection, coincident with the appearance of antiviral antibodies. HBV transcripts and replicative intermediates disappeared from the liver by day 15, after the appearance of antiviral CD8 + T cells. In contrast, the virus persisted for at least 81 days after transfection of NOD/Scid mice, which lack functional T cells, B cells, and natural killer (NK) cells. Thus, the outcome of hydrodynamic transfection of HBV depends on the host immune response, as it is during a natural infection. The methods we describe will allow the examination of viral dynamics in a tightly controlled in vivo system, the application of mutagenesis methods to the study of the HBV life cycle in vivo, and the dissection of the immune response to HBV using genetically modified mice whose immunoregulatory and immune effector functions have been deleted or overexpressed. In addition, this methodology represents a prototype for the study of other known and to-be-discovered liver-specific pathogens.',\n", - " 'author': ['Yang, Priscilla L.',\n", - " 'Althage, Alana',\n", - " 'Chung, Josan',\n", - " 'Chisari, Francis V.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/99/21/13825\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/99/21/13825\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/99/21/13825\"}'],\n", - " 'title': ['Hydrodynamic injection of viral DNA: A mouse model of acute hepatitis B virus infection']},\n", - " {'bibcode': '2009NRL.....4.1275M',\n", - " 'abstract': 'Although it is known that nano-TiO2 or other nanoparticles can induce liver toxicities, the mechanisms and the molecular pathogenesis are still unclear. In this study, nano-anatase TiO2 (5 nm) was injected into the abdominal cavity of ICR mice for consecutive 14 days, and the inflammatory responses of liver of mice was investigated. The results showed the obvious titanium accumulation in liver DNA, histopathological changes and hepatocytes apoptosis of mice liver, and the liver function damaged by higher doses nano-anatase TiO2. The real-time quantitative RT-PCR and ELISA analyses showed that nano-anatase TiO2 can significantly alter the mRNA and protein expressions of several inflammatory cytokines, including nucleic factor-κB, macrophage migration inhibitory factor, tumor necrosis factor-α, interleukin-6, interleukin-1β, cross-reaction protein, interleukin-4, and interleukin-10. Our results also implied that the inflammatory responses and liver injury may be involved in nano-anatase TiO2-induced liver toxicity.',\n", - " 'author': ['Ma, Linglan',\n", - " 'Zhao, Jinfang',\n", - " 'Wang, Jue',\n", - " 'Liu, Jie',\n", - " 'Duan, Yanmei',\n", - " 'Liu, Huiting',\n", - " 'Li, Na',\n", - " 'Yan, Jingying',\n", - " 'Ruan, Jie',\n", - " 'Wang, Han',\n", - " 'Hong, Fashui'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1007%2Fs11671-009-9393-8\"}'],\n", - " 'title': ['The Acute Liver Injury in Mice Caused by Nano-Anatase TiO2']},\n", - " {'bibcode': '2019BpJ...116..423S',\n", - " 'author': ['Sule, Rasheed'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.bpj.2018.11.2278\"}'],\n", - " 'title': ['Effects of Ibuprofen on Mice Liver Proteasome']},\n", - " {'bibcode': '2004PNAS..101..737N',\n", - " 'abstract': 'Beauveriolides I and III, isolated from the culture broth of fungal Beauveria sp. FO-6979, showed potent inhibitory activity of lipid droplet accumulation in primary mouse peritoneal macrophages. The cellular molecular target of this inhibitory activity was studied in macrophages. Beauveriolides I and III strongly inhibited the cholesteryl ester (CE) synthesis with IC50 values of 0.78 and 0.41 μM, respectively, without showing significant effects on the triacylglycerol and phospholipid synthesis. Furthermore, lysosomal cholesterol metabolism to CE in macrophages was inhibited by the compounds, indicating that the inhibition site lies within steps between cholesterol departure from the lysosome and CE synthesis in the endoplasmic reticulum. Therefore, acyl-CoA:cholesterol acyltransferase (ACAT) activity in the membrane fractions prepared from mouse macrophages was studied, resulting in a dose-dependent inhibition by beauveriolides I and III with IC50 values of 6.0 and 5.5 μM, respectively. Thus, we showed that the beauveriolides inhibit macrophage ACAT activity specifically, resulting in blockage of the CE synthesis, leading to a reduction of lipid droplets in macrophages. ACAT activity in the membrane fractions prepared from mouse liver and Caco-2 cells was also inhibited, indicating that the beauveriolides block both ACAT-1 and -2. Moreover, beauveriolides I and III exert antiatherogenic activity in both low-density lipoprotein receptor- and apolipoprotein E-knockout mice without any side effects such as diarrhea or cytotoxicity to adrenal tissues as observed for many synthetic ACAT inhibitors. Beauveriolides I and III are the first microbial cyclodepsipeptides having an in vivo antiatherosclerotic effect and show promise as potential lead compounds for antiatherosclerotic agents.',\n", - " 'author': ['Namatame, Ichiji',\n", - " 'Tomoda, Hiroshi',\n", - " 'Ishibashi, Shun',\n", - " 'Ōmura, Satoshi'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/101/3/737\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0307757100\"}'],\n", - " 'title': ['Antiatherogenic activity of fungal beauveriolides, inhibitors of lipid droplet accumulation in macrophages']},\n", - " {'bibcode': '1984PNAS...81.1609O',\n", - " 'abstract': 'Splenic cells from one BALB/c mouse and one C57/BL mouse, immunized with purified rat liver glucocorticoid receptor (GR), were fused with the mouse myeloma cell line Sp 2/0-Ag 14. Screening for production of anti-GR-antibodies by the hybridomas was carried out with an enzyme-linked immunosorbent assay, using partially purified rat liver GR as antigen. Further screening was by a second-antibody immunoprecipitation assay using [3H]triamcinolone acetonide-GR complex from rat liver cytosol as tracer. Hybridomas from 10 different microplate wells, positive in both assays, were successfully cloned by the limiting dilution method to monoclonality. The different origins of the monoclonal antibodies were confirmed by their various isoelectric points when analyzed by isoelectric focusing. Four of the monoclonal hybridoma cell lines secreted IgM antibodies; two, IgG1; three, IgG2a; and one, IgG2b. The GR-antibody complex was identified in glycerol density gradients by a shift of the 4S GR to an 8.5S or 19S GR-antibody complex when incubated with monoclonal IgG or IgM antibody, respectively. The 10 monoclonal antibodies recognized different determinants on the GR, all situated on that domain of the receptor that is separate from the ligand and DNA-binding domains. Also, the cross-reactivity to the mouse liver GR varied among the monoclonal antibodies. No cross-reactivity was observed to the human lymphocytic GR. NaDodSO4 electrophoresis of a 0.5% pure GR preparation followed by immunoblotting using one of the monoclonal antibodies identified a single peptide with a molecular weight of 94,000, identical to the purified rat liver GR.',\n", - " 'author': ['Okret, Sam',\n", - " 'Wikstrom, Ann-Charlotte',\n", - " 'Wrange, Orjan',\n", - " 'Andersson, Birger',\n", - " 'Gustafsson, Jan-Ake'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/81/6/1609\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/81/6/1609\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/81/6/1609\"}'],\n", - " 'title': ['Monoclonal antibodies against the rat liver glucocorticoid receptor.']},\n", - " {'bibcode': '2012PNAS..10913561T',\n", - " 'abstract': 'The Kelch-like ECH-associated protein 1 (Keap1)-NF-E2-related factor 2 (Nrf2) system is essential for cytoprotection against oxidative and electrophilic insults. Under unstressed conditions, Keap1 serves as an adaptor for ubiquitin E3 ligase and promotes proteasomal degradation of Nrf2, but Nrf2 is stabilized when Keap1 is inactivated under oxidative/electrophilic stress conditions. Autophagy-deficient mice show aberrant accumulation of p62, a multifunctional scaffold protein, and develop severe liver damage. The p62 accumulation disrupts the Keap1-Nrf2 association and provokes Nrf2 stabilization and accumulation. However, individual contributions of p62 and Nrf2 to the autophagy-deficiency-driven liver pathogenesis have not been clarified. To examine whether Nrf2 caused the liver injury independent of p62, we crossed liver-specific Atg7::Keap1-Alb double-mutant mice into p62- and Nrf2-null backgrounds. Although Atg7::Keap1-Alb::p62-/- triple-mutant mice displayed defective autophagy accompanied by the robust accumulation of Nrf2 and severe liver injury, Atg7::Keap1-Alb::Nrf2-/- triple-mutant mice did not show any signs of such hepatocellular damage. Importantly, in this study we noticed that Keap1 accumulated in the Atg7- or p62-deficient mouse livers and the Keap1 level did not change by a proteasome inhibitor, indicating that the Keap1 protein is constitutively degraded through the autophagy pathway. This finding is in clear contrast to the Nrf2 degradation through the proteasome pathway. We also found that treatment of cells with tert-butylhydroquinone accelerated the Keap1 degradation. These results thus indicate that Nrf2 accumulation is the dominant cause to provoke the liver damage in the autophagy-deficient mice. The autophagy pathway maintains the integrity of the Keap1-Nrf2 system for the normal liver function by governing the Keap1 turnover.',\n", - " 'author': ['Taguchi, Keiko',\n", - " 'Fujikawa, Nanako',\n", - " 'Komatsu, Masaaki',\n", - " 'Ishii, Tetsuro',\n", - " 'Unno, Michiaki',\n", - " 'Akaike, Takaaki',\n", - " 'Motohashi, Hozumi',\n", - " 'Yamamoto, Masayuki'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/109/34/13561\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1121572109\"}'],\n", - " 'title': ['Keap1 degradation by autophagy for the maintenance of redox homeostasis']},\n", - " {'bibcode': '1976PNAS...73.1950K',\n", - " 'abstract': 'Serine transhydroxymethylase (5,10-methylenetetrahydrofolate: glycine hydroxymethyl transferase, EC 2.1.2.1) purified 200-fold from pig kidneys showed cooperative interactions with tetrahydrofolate with a Hill coefficient (n value) of 3.9 and a substrate concentration at 50% of maximum velocity, the S(0.5) value, of 0.5 mM. The enzyme in mouse liver and kidney homogenates also showed cooperative interactions with tetrahydrofolate. However, the enzyme obtained from L1210 solid tumors of mice, and from livers and kidneys of mice inoculated with L1210 cells exhibited hyperbolic saturation kinetics and gave a Michaelis constant, Km, value of 0.5 mM for tetrahydrofolate. The interaction of serine with the enzyme from pig kidney, from tissues of normal or tumor-bearing mice, or from L1210 tumors was hyperbolic with a Km of 0.9 mM. The specific activities of the enzyme in the L1210 tumor and in mouse liver were 10-fold higher than in pig or mouse kidney. There was no significant change in the levels of the enzyme in mouse liver and kidney on inoculation with L1210 cells. These results suggest that a tumor can bring about biochemical changes in tissues that are distal to the tumor.',\n", - " 'author': ['Kumar, P. M. Harish',\n", - " 'North, James A.',\n", - " 'Mangum, John H.',\n", - " 'Appaji Rao, N.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/73/6/1950\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/73/6/1950\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/73/6/1950\"}'],\n", - " 'title': ['Cooperative interactions of tetrahydrofolate with purified pig kidney serine transhydroxymethylase and loss of this cooperativity in L1210 tumors and in tissues of mice bearing these tumors.']},\n", - " {'bibcode': '1959Natur.184.1709C',\n", - " 'abstract': 'IT has been shown by Walker1 that in a mouse-liver homogenate in isotonic sucrose solution by far the greater part of the β-glucuronidase activity sediments in the cytoplasmic granules (mitochondria and microsomes). It was concluded that little, if any, of the enzyme is present in the nuclei or free in the cytoplasm. This was also true of rapidly growing or regenerating liver. Within the granules the enzyme displayed only fractional activity due to its inaccessibility to substrate. In these respects β-glucuronidase, in rat liver at least, resembles a number of hydrolytic enzymes, which, it has been suggested, are enclosed together within a special type of subcellular particle, the lysosome2.',\n", - " 'author': ['Conchie, J.', 'Levvy, G. A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F1841709a0\"}'],\n", - " 'title': ['Localization of β-Glucuronidase in Normal and Cancer Cells']},\n", - " {'bibcode': '2019NatSR...9..832T',\n", - " 'abstract': 'Mammalian hibernation is a seasonal phenomenon. The hibernation season consists of torpor periods with a reduced body temperature (Tb), interrupted by euthermic arousal periods (interbout arousal, IBA). The physiological changes associated with hibernation are assumed to be under genetic control. However, the molecular mechanisms that govern hibernation-associated gene regulation are still unclear. We found that HSP70 transcription is upregulated in the liver of nonhibernating (summer-active) chipmunks compared with hibernating (winter-torpid) ones. In parallel, HSF1, the major transcription factor for HSP70 expression, is abundant in the liver-cell nuclei of nonhibernating chipmunks, and disappears from the nuclei of hibernating ones. Moreover, during IBA, HSF1 reappears in the nuclei and drives HSP70 transcription. In mouse liver, HSF1 is regulated by the daily Tb rhythm, and acts as a circadian transcription factor. Taken together, chipmunks similarly use the Tb rhythm to regulate gene expression via HSF1 during the torpor-arousal cycle in the hibernation season.',\n", - " 'author': ['Tsukamoto, Daisuke',\n", - " 'Hasegawa, Tomoko',\n", - " 'Hirose, Shin-ichi',\n", - " 'Sakurai, Yukina',\n", - " 'Ito, Michihiko',\n", - " 'Takamatsu, Nobuhiko'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-018-37022-7\"}'],\n", - " 'title': ['Circadian transcription factor HSF1 regulates differential HSP70 gene transcription during the arousal-torpor cycle in mammalian hibernation']},\n", - " {'bibcode': '2022NatCo..13.3486L',\n", - " 'abstract': 'Mitochondria generate ATP and play regulatory roles in various cellular activities. Cancer cells often exhibit fragmented mitochondria. However, the underlying mechanism remains elusive. Here we report that a mitochondrial protein FUN14 domain containing 2 (FUNDC2) is transcriptionally upregulated in primary mouse liver tumors, and in approximately 40% of human hepatocellular carcinoma (HCC). Importantly, elevated FUNDC2 expression inversely correlates with patient survival, and its knockdown inhibits liver tumorigenesis in mice. Mechanistically, the amino-terminal region of FUNDC2 interacts with the GTPase domain of mitofusin 1 (MFN1), thus inhibits its activity in promoting fusion of outer mitochondrial membrane. As a result, loss of FUNDC2 leads to mitochondrial elongation, decreased mitochondrial respiration, and reprogrammed cellular metabolism. These results identified a mechanism of mitochondrial fragmentation in cancer through MFN1 inhibition by FUNDC2, and suggested FUNDC2 as a potential therapeutic target of HCC.',\n", - " 'author': ['Li, Shuaifeng',\n", - " 'Han, Shixun',\n", - " 'Zhang, Qi',\n", - " 'Zhu, Yibing',\n", - " 'Zhang, Haitao',\n", - " 'Wang, Junli',\n", - " 'Zhao, Yang',\n", - " 'Zhao, Jianhui',\n", - " 'Su, Lin',\n", - " 'Li, Li',\n", - " 'Zhou, Dawang',\n", - " 'Ye, Cunqi',\n", - " 'Feng, Xin-Hua',\n", - " 'Liang, Tingbo',\n", - " 'Zhao, Bin'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41467-022-31187-6\"}'],\n", - " 'title': ['FUNDC2 promotes liver tumorigenesis by inhibiting MFN1-mediated mitochondrial fusion']},\n", - " {'bibcode': '2016NatSR...629539Z',\n", - " 'abstract': 'Lipid droplet (LD), a multi-functional organelle, is often found to associate with other cellular membranous structures and vary in size in a given cell, which may be related to their functional diversity. Here we established a method to separate LD subpopulations from isolated CHO K2 LDs into three different size categories. The subpopulation with smallest LDs was nearly free of ER and other membranous structures while those with larger LDs contained intact ER. These distinct subpopulations of LDs differed in their protein composition and ability to recruit proteins. This method was also applicable to LDs obtained from other sources, such as Huh7 cells, mouse liver and brown adipose tissue, et al. We developed an in vitro assay requiring only isolated LDs, Coenzyme A, and ATP to drive lipid synthesis. The LD subpopulation nearly depleted of ER was able to incorporate fatty acids into triacylglycerol and phospholipids. Together, our data demonstrate that LDs in a given cell are heterogeneous in size and function, and suggest that LDs are one of cellular lipid synthetic organelles.',\n", - " 'author': ['Zhang, Shuyan',\n", - " 'Wang, Yang',\n", - " 'Cui, Liujuan',\n", - " 'Deng, Yaqin',\n", - " 'Xu, Shimeng',\n", - " 'Yu, Jinhai',\n", - " 'Cichello, Simon',\n", - " 'Serrero, Ginette',\n", - " 'Ying, Yunshu',\n", - " 'Liu, Pingsheng'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep29539\"}'],\n", - " 'title': ['Morphologically and Functionally Distinct Lipid Droplet Subpopulations']},\n", - " {'bibcode': '2013SPIE.8800E..03C',\n", - " 'abstract': 'In optoacoustic imaging absorbing structures excited with short laser pulses generate broadband ultrasound waves, which tomographically detected outside the sample enable reconstruction of initial pressure distribution. As light scatters in biological tissues, the excitation has a three-dimensional (3D) pattern allocation. Accurate reconstruction of the 3D distribution of optical absorption requires a large solid angle of detection of the ultrasonic field. Moreover, the center frequency and bandwidth of a given detector define the range of structure sizes it is able to resolve. Therefore, detectors with different frequency bandwidths record different subsets of information. A volumetric optoacoustic system using linear ultrasound arrays with different central frequencies, 6MHz and 24MHz, is introduced. By employing a novel scanning geometry that takes advantage of the high sensitivity on the transversal dimension of these linear probes, high resolution optoacoustic signals are being recorded. Resolution performance and biological capabilities are demonstrated with a 20um crossed-suture phantom and an excised mouse liver lobe.',\n", - " 'author': ['Chekkoury, Andrei',\n", - " 'Gateau, Jérôme',\n", - " 'Ntziachristos, Vasilis'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1117%2F12.2032064\"}'],\n", - " 'title': ['Multiple bandwidth volumetric optoacoustic tomography using conventional ultrasound linear arrays']},\n", - " {'bibcode': '2023FrASS..1000132S',\n", - " 'abstract': 'Introduction:RNA sequencing (RNA-seq) data from space biology experiments promise to yield invaluable insights into the effects of spaceflight on terrestrial biology. However, sample numbers from each study are low due to limited crew availability, hardware, and space. To increase statistical power, spaceflight RNA-seq datasets from different missions are often aggregated together. However, this can introduce technical variation or \"batch effects\", often due to differences in sample handling, sample processing, and sequencing platforms. Several computational methods have been developed to correct for technical batch effects, thereby reducing their impact on true biological signals.Methods:In this study, we combined 7 mouse liver RNA-seq datasets from NASA GeneLab (part of the NASA Open Science Data Repository) to evaluate several common batch effect correction methods (ComBat and ComBat-seq from the sva R package, and Median Polish, Empirical Bayes, and ANOVA from the MBatch R package). Principal component analysis (PCA) was used to identify library preparation method and mission as the primary sources of batch effect among the technical variables in the combined dataset. We next quantitatively evaluated the ability of each of the indicated methods to correct for each identified technical batch variable using the following criteria: BatchQC, PCA, dispersion separability criterion, log fold change correlation, and differential gene expression analysis. Each batch variable/correction method combination was then assessed using a custom scoring approach to identify the optimal correction method for the combined dataset, by geometrically probing the space of all allowable scoring functions to yield an aggregate volume-based scoring measure.Results and Discussion:Using the method described for the combined dataset in this study, the library preparation variable/ComBat correction method pair out ranked the other candidate pairs, suggesting that this combined dataset should be corrected for library preparation using the ComBat correction method prior to downstream analysis. We describe the GeneLab multi-study analysis and visualization portal which will allow users to access the publicly available space biology \\'omics data, select multiple studies to combine for analysis, and examine the presence or absence of batch effects using multiple metrics. If the user chooses to perform batch effect correction, the scoring approach described here can be implemented to identify the optimal correction method to use for their specific combined dataset prior to analysis.',\n", - " 'author': ['Sanders, Lauren M.',\n", - " 'Chok, Hamed',\n", - " 'Samson, Finsam',\n", - " 'Acuna, Ana Uriarte',\n", - " 'Polo, San-Huei Lai',\n", - " 'Boyko, Valery',\n", - " 'Chen, Yi-Chun',\n", - " 'Dinh, Marie',\n", - " 'Gebre, Samrawit',\n", - " 'Galazka, Jonathan M.',\n", - " 'Costes, Sylvain V.',\n", - " 'Saravia-Butler, Amanda M.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.3389%2Ffspas.2023.1200132\"}'],\n", - " 'title': ['Batch effect correction methods for NASA GeneLab transcriptomic datasets']},\n", - " {'bibcode': '1995Natur.376..167B',\n", - " 'abstract': 'NF-κB, which consists of two polypeptides, p50 (Mr 50K) and p65/RelA (Mr 65K), is thought to be a key regulator of genes involved in responses to infection, inflammation and stress1. Indeed, although developmentally normal, mice deficient in p50 display functional defects in immune responses2. Here we describe the generation of mice deficient in the RelA subunit of NF-κB. Disruption of the relA locus leads to embryonic lethality at 15-16 days of gestation, concomitant with a massive degeneration of the liver by programmed cell death or apoptosis. Embryonic fibroblasts from RelA-deficient mice are defective in the tumour necrosis factor (TNF)-mediated induction of messenger RNAs for IκBα and granulocyte/macrophage colony stimulating factor (GM-CSF), although basal levels of these transcripts are unaltered. These results indicate that RelA controls inducible, but not basal, transcription in NF-κB-regulated pathways.',\n", - " 'author': ['Beg, Amer A.',\n", - " 'Sha, William C.',\n", - " 'Bronson, Roderick T.',\n", - " 'Ghosh, Sankar',\n", - " 'Baltimore, David'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F376167a0\"}'],\n", - " 'title': ['Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-κB']},\n", - " {'bibcode': '2023PNAS..12017543L',\n", - " 'abstract': 'Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, in which the prognosis is determined by liver fibrosis. A loss-of-function variant in hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) is associated with decreased liver fibrosis, but the underlying mechanisms remain unclear. Here, we demonstrate that protection against liver fibrosis conferred by the variant in humans and by Hsd17b13 knockdown in mice is associated with decreased pyrimidine catabolism at the level of dihydropyrimidine dehydrogenase. Two common mouse models of NAFLD are characterized by a marked hepatic pyrimidine depletion. Furthermore, pharmacological inhibition of pyrimidine catabolism by a dihydropyrimidine dehydrogenase inhibitor phenocopies the protection against liver fibrosis. Our data suggest pyrimidine catabolism as a therapeutic target in NAFLD.',\n", - " 'author': ['Luukkonen, Panu K.',\n", - " 'Sakuma, Ikki',\n", - " 'Gaspar, Rafael C.',\n", - " 'Mooring, Meghan',\n", - " 'Nasiri, Ali',\n", - " 'Kahn, Mario',\n", - " 'Zhang, Xian-Man',\n", - " 'Zhang, Dongyan',\n", - " 'Sammalkorpi, Henna',\n", - " 'Penttilä, Anne K.',\n", - " 'Orho-Melander, Marju',\n", - " 'Arola, Johanna',\n", - " 'Juuti, Anne',\n", - " 'Zhang, Xuchen',\n", - " 'Yimlamai, Dean',\n", - " 'Yki-Järvinen, Hannele',\n", - " 'Petersen, Kitt Falk',\n", - " 'Shulman, Gerald I.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.2217543120\"}'],\n", - " 'title': ['Inhibition of HSD17B13 protects against liver fibrosis by inhibition of pyrimidine catabolism in nonalcoholic steatohepatitis']},\n", - " {'bibcode': '2017JMoSt1149..128A',\n", - " 'abstract': 'The goal of this study is to establish Fourier transform-infrared (FTIR) spectroscopy as a diagnostic tool for allethrin-based mosquito coil smoke inhalation induced toxicity in mice. Primarily, we confirmed mosquito coil smoke inhalation toxicity in mice via reduced the body, organ weight and major vital organ tissue morphological structure changes. Furthermore, FTIR spectra was collected from control and mosquito coil smoke inhalation (8 h per day for 30 days) mice various tissues like liver, kidney, lung, heart and brain, to investigate the functional groups and their corresponding biochemical content variations. The FTIR spectra result shown major bio macromolecules such as protein and lipid functional peaks were shifted (decreased) in the mosquito coil smoke inhalation group as compared to control. The drastic peak shift was noticed in the liver, kidney followed by lung and brain. It is therefore concluded that the FTIR spectroscopy can be a successful detection tool in mosquito coil smoke inhalation toxicity.',\n", - " 'author': ['Anusha, Chidambaram',\n", - " 'Sankar, Renu',\n", - " 'Varunkumar, Krishnamoorthy',\n", - " 'Sivasindhuja, Gnanasambantham',\n", - " 'Ravikumar, Vilwanathan'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.molstruc.2017.07.087\"}'],\n", - " 'title': ['Fourier transform-infrared spectroscopy as a diagnostic tool for mosquito coil smoke inhalation toxicity in Swiss Albino mice']},\n", - " {'bibcode': '2017NatSR...7.1359Y',\n", - " 'abstract': 'Growing evidence has shown that gut microbiome is a key factor involved in liver health. Therefore, gut microbiota modulation with probiotic bacteria, such as Saccharomyces boulardii, constitutes a promising therapy for hepatosis. In this study, we aimed to investigate the protective effects of S. boulardii on D-Galactosamine-induced liver injury in mice. Liver function test and histopathological analysis both suggested that the liver injury can be effectively attenuated by S. boulardii administration. In the meantime, S. boulardii induced dramatic changes in the gut microbial composition. At the phylum level, we found that S. boulardii significantly increased in the relative abundance of Bacteroidetes, and decreased the relative abundance of Firmicutes and Proteobacteria, which may explain the hepatic protective effects of S. boulardii. Taken together, our results demonstrated that S. boulardii administration could change the gut microbiota in mice and alleviate acute liver failure, indicating a potential protective and therapeutic role of S. boulardii.',\n", - " 'author': ['Yu, Lei',\n", - " 'Zhao, Xue-ke',\n", - " 'Cheng, Ming-liang',\n", - " 'Yang, Guo-zhen',\n", - " 'Wang, Bi',\n", - " 'Liu, Hua-juan',\n", - " 'Hu, Ya-xin',\n", - " 'Zhu, Li-li',\n", - " 'Zhang, Shuai',\n", - " 'Xiao, Zi-wen',\n", - " 'Liu, Yong-mei',\n", - " 'Zhang, Bao-fang',\n", - " 'Mu, Mao'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-017-01271-9\"}'],\n", - " 'title': ['Saccharomyces boulardii Administration Changes Gut Microbiota and Attenuates D-Galactosamine-Induced Liver Injury']},\n", - " {'bibcode': '1983PNAS...80.3845M',\n", - " 'abstract': 'Sequences from a gene coding for mouse acetylcholine receptor alpha subunit have been inserted into a recombinant plasmid and cloned in Escherichia coli. mRNAs for acetylcholine receptors occur in low abundance in vertebrate muscle. To clone the mouse alpha-subunit cDNA, we made use of (i) a cell line, BC3H-1, that overproduces the alpha-subunit mRNA and (ii) a polysome fractionation procedure that results in enrichment of alpha-subunit mRNA. Polyadenylylated RNA was used to construct a cDNA library of 750 recombinant clones. Acetylcholine receptor-specific sequences were identified by hybrid-selected translation, followed by monoclonal antibody precipitation and peptide mapping of the translation product. One clone (pA59) that fit these criteria was found in the first 80 isolates. It had a 700-base-pair insert that was excised with Pst I. Blot-hybridization experiments with nick-translated pA59 DNA showed that BC3H-1 cells contain 100-1,000 times more alpha-subunit mRNA than does newborn or adult mouse muscle. Blot hybridization of restriction digests of mouse liver DNA revealed that pA59 is homologous to a very small number (probably one) of genomic sequences.',\n", - " 'author': ['Merlie, J. P.', 'Sebbane, R.', 'Gardner, S.', 'Lindstrom, J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/80/12/3845\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/80/12/3845\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/80/12/3845\"}'],\n", - " 'title': ['cDNA Clone for the α Subunit of the Acetylcholine Receptor from the Mouse Muscle Cell Line BC3H-1']},\n", - " {'bibcode': '2016NatSR...620646G',\n", - " 'abstract': 'Cholesterol from peripheral tissue, carried by HDL, is metabolized in the liver after uptake by the HDL receptor, SR-B1. Hepatocytes have long been considered the only liver cells expressing SR-B1; however, in this study we describe two disparate immunofluorescence (IF) experiments that suggest otherwise. Using high-resolution confocal microscopy employing ultrathin (120\\u2009nm) sections of mouse liver, improving z-axis resolution, we identified the liver sinusoidal endothelial cells (LSEC), marked by FcγRIIb, as the cell within the liver expressing abundant SR-B1. In contrast, the hepatocyte, identified with β-catenin, expressed considerably weaker levels, although optical resolution of SR-B1 was inadequate. Thus, we moved to a different IF strategy, first separating dissociated liver cells by gradient centrifugation into two portions, hepatocytes (parenchymal cells) and LSEC (non-parenchymal cells). Characterizing both portions for the cellular expression of SR-B1 by flow cytometry, we found that LSEC expressed considerable amounts of SR-B1 while in hepatocytes SR-B1 expression was barely perceptible. Assessing mRNA of SR-B1 by real time PCR we found messenger expression in LSEC to be about 5 times higher than in hepatocytes.',\n", - " 'author': ['Ganesan, Latha P.',\n", - " 'Mates, Jessica M.',\n", - " 'Cheplowitz, Alana M.',\n", - " 'Avila, Christina L.',\n", - " 'Zimmerer, Jason M.',\n", - " 'Yao, Zhili',\n", - " 'Maiseyeu, Andrei',\n", - " 'Rajaram, Murugesan V. S.',\n", - " 'Robinson, John M.',\n", - " 'Anderson, Clark L.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep20646\"}'],\n", - " 'title': ['Scavenger receptor B1, the HDL receptor, is expressed abundantly in liver sinusoidal endothelial cells']},\n", - " {'bibcode': '1997PNAS...94.7239U',\n", - " 'abstract': 'The signal transducer and activator of transcription, STAT5b, has been implicated in signal transduction pathways for a number of cytokines and growth factors, including growth hormone (GH). Pulsatile but not continuous GH exposure activates liver STAT5b by tyrosine phosphorylation, leading to dimerization, nuclear translocation, and transcriptional activation of the STAT, which is proposed to play a key role in regulating the sexual dimorphism of liver gene expression induced by pulsatile plasma GH. We have evaluated the importance of STAT5b for the physiological effects of GH pulses using a mouse gene knockout model. STAT5b gene disruption led to a major loss of multiple, sexually differentiated responses associated with the sexually dimorphic pattern of pituitary GH secretion. Male-characteristic body growth rates and male-specific liver gene expression were decreased to wild-type female levels in STAT5b-/- males, while female-predominant liver gene products were increased to a level intermediate between wild-type male and female levels. Although these responses are similar to those observed in GH-deficient Little mice, STAT5b-/- mice are not GH-deficient, suggesting that they may be GH pulse-resistant. Indeed, the dwarfism, elevated plasma GH, low plasma insulin-like growth factor I, and development of obesity seen in STAT5b-/- mice are all characteristics of Laron-type dwarfism, a human GH-resistance disease generally associated with a defective GH receptor. The requirement of STAT5b to maintain sexual dimorphism of body growth rates and liver gene expression suggests that STAT5b may be the major, if not the sole, STAT protein that mediates the sexually dimorphic effects of GH pulses in liver and perhaps other target tissues. STAT5b thus has unique physiological functions for which, surprisingly, the highly homologous STAT5a is unable to substitute.',\n", - " 'author': ['Udy, Garry B.',\n", - " 'Towers, Raewyn P.',\n", - " 'Snell, Russell G.',\n", - " 'Wilkins, Richard J.',\n", - " 'Park, Soo-Hee',\n", - " 'Ram, Prabha A.',\n", - " 'Waxman, David J.',\n", - " 'Davey, Helen W.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/94/14/7239\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/94/14/7239\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/94/14/7239\"}'],\n", - " 'title': ['Requirement of STAT5b for Sexual Dimorphism of Body Growth Rates and Liver Gene Expression']},\n", - " {'bibcode': '1999Sci...284..321L',\n", - " 'author': ['Li, Qiutang',\n", - " 'van Antwerp, Daniel',\n", - " 'Mercurio, Frank',\n", - " 'Lee, Kuo-Fen',\n", - " 'Verma, Inder M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.284.5412.321\"}'],\n", - " 'title': ['Severe Liver Degeneration in Mice Lacking the IB Kinase 2 Gene']},\n", - " {'bibcode': '2005PMB....50.4225A',\n", - " 'abstract': 'The feasibility and limits in performing tomographic bioluminescence imaging with a combined optical-PET (OPET) system were explored by simulating its image formation process. A micro-MRI based virtual mouse phantom was assigned appropriate tissue optical properties to each of its segmented internal organs at wavelengths spanning the emission spectrum of the firefly luciferase at 37 °C. The TOAST finite-element code was employed to simulate the diffuse transport of photons emitted from bioluminescence sources in the mouse. OPET measurements were simulated for single-point, two-point and distributed bioluminescence sources located in different organs such as the liver, the kidneys and the gut. An expectation maximization code was employed to recover the intensity and location of these simulated sources. It was found that spectrally resolved measurements were necessary in order to perform tomographic bioluminescence imaging. The true location of emission sources could be recovered if the mouse background optical properties were known a priori. The assumption of a homogeneous optical property background proved inadequate for describing photon transport in optically heterogeneous tissues and led to inaccurate source localization in the reconstructed images. The simulation results pointed out specific methodological challenges that need to be addressed before a practical implementation of OPET-based bioluminescence tomography is achieved.',\n", - " 'author': ['Alexandrakis, George',\n", - " 'Rannou, Fernando R.',\n", - " 'Chatziioannou, Arion F.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1088%2F0031-9155%2F50%2F17%2F021\"}'],\n", - " 'title': ['Tomographic bioluminescence imaging by use of a combined optical-PET (OPET) system: a computer simulation feasibility study']},\n", - " {'bibcode': '1981Natur.294...92C',\n", - " 'abstract': 'The introduction of cloned foreign genes into cultured mammalian cells1-7 has been used to identify DNA sequences required for correct transcription in vivo8-10. It is not clear, however, to what extent these systems will be useful for an analysis of the sequences necessary for tissue-specific gene expression. A more appropriate approach for such an analysis might be the production of mice that contain a cloned foreign gene in all their cells, throughout development. This could be accomplished by the transfer of a cloned gene into germ-line cells, and the subsequent transmission of that gene to offspring. Previously, SV40 DNA sequences11 and a cloned HSV-1 thymidine kinase gene12 have been introduced into somatic tissues of mice by microinjection of the DNAs into blastocysts11 or eggs12, but germ-line transmission of these sequences has not been demonstrated. The only foreign DNA sequences which have been transferred into and transmitted by the mouse germ-line have been exogenous Moloney leukaemia virus genomes introduced by viral infection of early embryos13. We now report the introduction of a cloned rabbit DNA fragment containing the adult β-globin gene into the germ-line of mice. We have analysed 24 mice derived from eggs microinjected with this DNA. Nine mice contain the rabbit β-globin gene in liver DNA, and at least four males from this group transmit the gene to a fraction of their progeny.',\n", - " 'author': ['Costantini, Franklin', 'Lacy, Elizabeth'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F294092a0\"}'],\n", - " 'title': ['Introduction of a rabbit β-globin gene into the mouse germ line']},\n", - " {'bibcode': '2003Natur.422..897W',\n", - " 'abstract': 'Evidence suggests that haematopoietic stem cells might have unexpected developmental plasticity, highlighting therapeutic potential. For example, bone-marrow-derived hepatocytes can repopulate the liver of mice with fumarylacetoacetate hydrolase deficiency and correct their liver disease. To determine the underlying mechanism in this murine model, we performed serial transplantation of bone-marrow-derived hepatocytes. Here we show by Southern blot analysis that the repopulating hepatocytes in the liver were heterozygous for alleles unique to the donor marrow, in contrast to the original homozygous donor cells. Furthermore, cytogenetic analysis of hepatocytes transplanted from female donor mice into male recipients demonstrated 80,XXXY (diploid to diploid fusion) and 120,XXXXYY (diploid to tetraploid fusion) karyotypes, indicative of fusion between donor and host cells. We conclude that hepatocytes derived form bone marrow arise from cell fusion and not by differentiation of haematopoietic stem cells.',\n", - " 'author': ['Wang, Xin',\n", - " 'Willenbring, Holger',\n", - " 'Akkari, Yassmine',\n", - " 'Torimaru, Yumi',\n", - " 'Foster, Mark',\n", - " 'Al-Dhalimy, Muhsen',\n", - " 'Lagasse, Eric',\n", - " 'Finegold, Milton',\n", - " 'Olson, Susan',\n", - " 'Grompe, Markus'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature01531\"}'],\n", - " 'title': ['Cell fusion is the principal source of bone-marrow-derived hepatocytes']},\n", - " {'bibcode': '2005Natur.435..944L',\n", - " 'abstract': 'The specification of the vertebrate liver is thought to occur in a two-step process, beginning with the establishment of competence within the foregut endoderm for responding to organ-specific signals, followed by the induction of liver-specific genes. On the basis of expression and in vitro studies, it has been proposed that the Foxa transcription factors establish competence by opening compacted chromatin structures within liver-specific target genes. Here we show that Foxa1 and Foxa2 (forkhead box proteins A1 and A2) are required in concert for hepatic specification in mouse. In embryos deficient for both genes in the foregut endoderm, no liver bud is evident and expression of the hepatoblast marker alpha-fetoprotein (Afp) is lost. Furthermore, Foxa1/Foxa2-deficient endoderm cultured in the presence of exogenous fibroblast growth factor 2 (FGF2) fails to initiate expression of the liver markers albumin and transthyretin. Thus, Foxa1 and Foxa2 are required for the establishment of competence within the foregut endoderm and the onset of hepatogenesis.',\n", - " 'author': ['Lee, Catherine S.',\n", - " 'Friedman, Joshua R.',\n", - " 'Fulmer, James T.',\n", - " 'Kaestner, Klaus H.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature03649\"}'],\n", - " 'title': ['The initiation of liver development is dependent on Foxa transcription factors']},\n", - " {'bibcode': '2001PNAS...98.8780N',\n", - " 'abstract': 'We previously reported the disruption of the murine gene encoding the transcription factor USF2 and its consequences on glucose-dependent gene regulation in the liver. We report here a peculiar phenotype of Usf2-/- mice that progressively develop multivisceral iron overload; plasma iron overcomes transferrin binding capacity, and nontransferrin-bound iron accumulates in various tissues including pancreas and heart. In contrast, the splenic iron content is strikingly lower in knockout animals than in controls. To identify genes that may account for the abnormalities of iron homeostasis in Usf2-/- mice, we used suppressive subtractive hybridization between livers from Usf2-/- and wild-type mice. We isolated a cDNA encoding a peptide, hepcidin (also referred to as LEAP-1, for liver-expressed antimicrobial peptide), that was very recently purified from human blood ultrafiltrate and from urine as a disulfide-bonded peptide exhibiting antimicrobial activity. Accumulation of iron in the liver has been recently reported to up-regulate hepcidin expression, whereas our data clearly show that a complete defect in hepcidin expression is responsible for progressive tissue iron overload. The striking similarity of the alterations in iron metabolism between HFE knockout mice, a murine model of hereditary hemochromatosis, and the Usf2-/- hepcidin-deficient mice suggests that hepcidin may function in the same regulatory pathway as HFE. We propose that hepcidin acts as a signaling molecule that is required in conjunction with HFE to regulate both intestinal iron absorption and iron storage in macrophages.',\n", - " 'author': ['Nicolas, Gaël',\n", - " 'Bennoun, Myriam',\n", - " 'Devaux, Isabelle',\n", - " 'Beaumont, Carole',\n", - " 'Grandchamp, Bernard',\n", - " 'Kahn, Axel',\n", - " 'Vaulont, Sophie'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/98/15/8780\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/98/15/8780\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/98/15/8780\"}'],\n", - " 'title': ['From the Cover: Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice']},\n", - " {'bibcode': '1978PNAS...75..677G',\n", - " 'abstract': 'The single-stranded mitochondrial DNA (mtDNA) displacement-loop initiation sequence (7S mtDNA) is hydrogen-bonded at the origin of replication in animal cell mtDNA. Analysis of 7S mtDNA from several cell sources indicates that this initiation sequence exists as a family of fragments of relatively discrete lengths. mtDNA from both mouse L cells and mouse liver has four major sizes of 7S mtDNA fragments, ranging from 500 to 580 nucleotides in length. The 5‧-end region of each of these species is the same; thus, the size heterogeneity is due primarily to differences in length at the 3‧-end of these molecules. By contrast, 7S mtDNA from both human KB cells and human liver exists in three major forms, ranging from 555 to 615 nucleotides in length, due to differences at both terminal regions. The mtDNA initiation sequence from Xenopus laevis oocytes also exists in at least two forms, 1350 and 1510 nucleotides in length. Thus, the maintenance of multiple forms of mtDNA initiation sequence appears to be a general phenomenon of animal cells, although the precise mechanism of synthesis or processing of these forms is variable. The sequence of 42 nucleotides at the 5‧-end of 7S mtDNA from mouse L cells has been determined and found to be rich in dGuo and dThd residues, with no apparent palindromes or potential secondary structures. We thus present sequence information on the replication origin of mtDNA, as defined by the naturally occurring 7S mtDNA.',\n", - " 'author': ['Gillum, Amanda M.', 'Clayton, David A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/75/2/677\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/75/2/677\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/75/2/677\"}'],\n", - " 'title': ['Displacement-Loop Replication Initiation Sequence in Animal Mitochondrial DNA Exists as a Family of Discrete Lengths']},\n", - " {'bibcode': '2016NatSR...620484H',\n", - " 'abstract': 'Activation of the AKT/mTOR cascade and overexpression of c-Met have been implicated in the development of human hepatocellular carcinoma (HCC). To elucidate the functional crosstalk between the two pathways, we generated a model characterized by the combined expression of activated AKT and c-Met in the mouse liver. Co-expression of AKT and c-Met triggered rapid liver tumor development and mice required to be euthanized within 8 weeks after hydrodynamic injection. At the molecular level, liver tumors induced by AKT/c-Met display activation of AKT/mTOR and Ras/MAPK cascades as well as increased lipogenesis and glycolysis. Since a remarkable lipogenic phenotype characterizes liver lesions from AKT/c-Met mice, we determined the requirement of lipogenesis in AKT/c-Met driven hepatocarcinogenesis using conditional Fatty Acid Synthase (FASN) knockout mice. Of note, hepatocarcinogenesis induced by AKT/c-Met was fully inhibited by FASN ablation. In human HCC samples, coordinated expression of FASN, activated AKT, and c-Met proteins was detected in a subgroup of biologically aggressive tumors. Altogether, our study demonstrates that co-activation of AKT and c-Met induces HCC development that depends on the mTORC1/FASN pathway. Suppression of mTORC1 and/or FASN might be highly detrimental for the growth of human HCC subsets characterized by concomitant induction of the AKT and c-Met cascades.',\n", - " 'author': ['Hu, Junjie',\n", - " 'Che, Li',\n", - " 'Li, Lei',\n", - " 'Pilo, Maria G.',\n", - " 'Cigliano, Antonio',\n", - " 'Ribback, Silvia',\n", - " 'Li, Xiaolei',\n", - " 'Latte, Gavinella',\n", - " 'Mela, Marta',\n", - " 'Evert, Matthias',\n", - " 'Dombrowski, Frank',\n", - " 'Zheng, Guohua',\n", - " 'Chen, Xin',\n", - " 'Calvisi, Diego F.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep20484\"}'],\n", - " 'title': ['Co-activation of AKT and c-Met triggers rapid hepatocellular carcinoma development via the mTORC1/FASN pathway in mice']},\n", - " {'bibcode': '2007PNAS..104..979B',\n", - " 'abstract': 'The trillions of microbes that colonize our adult intestines function collectively as a metabolic organ that communicates with, and complements, our own human metabolic apparatus. Given the worldwide epidemic in obesity, there is interest in how interactions between human and microbial metabolomes may affect our energy balance. Here we report that, in contrast to mice with a gut microbiota, germ-free (GF) animals are protected against the obesity that develops after consuming a Western-style, high-fat, sugar-rich diet. Their persistently lean phenotype is associated with increased skeletal muscle and liver levels of phosphorylated AMP-activated protein kinase (AMPK) and its downstream targets involved in fatty acid oxidation (acetylCoA carboxylase; carnitine-palmitoyltransferase). Moreover, GF knockout mice lacking fasting-induced adipose factor (Fiaf), a circulating lipoprotein lipase inhibitor whose expression is normally selectively suppressed in the gut epithelium by the microbiota, are not protected from diet-induced obesity. Although GF Fiaf-/- animals exhibit similar levels of phosphorylated AMPK as their wild-type littermates in liver and gastrocnemius muscle, they have reduced expression of genes encoding the peroxisomal proliferator-activated receptor coactivator (Pgc-1α) and enzymes involved in fatty acid oxidation. Thus, GF animals are protected from diet-induced obesity by two complementary but independent mechanisms that result in increased fatty acid metabolism: (i) elevated levels of Fiaf, which induces Pgc-1α; and (ii) increased AMPK activity. Together, these findings support the notion that the gut microbiota can influence both sides of the energy balance equation, and underscore the importance of considering our metabolome in a supraorganismal context.',\n", - " 'author': ['Bäckhed, Fredrik',\n", - " 'Manchester, Jill K.',\n", - " 'Semenkovich, Clay F.',\n", - " 'Gordon, Jeffrey I.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/104/3/979\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0605374104\"}'],\n", - " 'title': ['From the Cover: Mechanisms underlying the resistance to diet-induced obesity in germ-free mice']},\n", - " {'bibcode': '1976Natur.259..224R',\n", - " 'abstract': 'IN BALB/c mice, surface immunoglobulin (Ig)-bearing B lymphocytes are first detectable by immunofluorescence at 17 d gestation in the liver and spleen1. Explants of 14-d foetal liver1 and spleen2, and 15-d bone marrow (our unpublished observations), have been shown to generate Ig-bearing B cells in vitro after 4-7 d of culture, suggesting that B lymphocytes normally develop multifocally in the haemopoietic tissues of mice. We have used direct immunofluorescence to demonstrate cells with intracellular IgM and no detectable surface Ig in mouse foetal liver as early as 12 d gestation. Our results suggest that B lymphocyte precursors synthesise IgM several days before they incorporate these molecules into their plasma membranes as cell-surface receptors for antigen.',\n", - " 'author': ['Raff, Martin C.', 'Megson, Mary'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F259224a0\"}'],\n", - " 'title': ['Early production of intracellular IgM by B-lymphocyte precursors in mouse']},\n", - " {'bibcode': '2023ScTEn.881p3382W',\n", - " 'author': ['Wang, Jing',\n", - " 'Ma, Xueqi',\n", - " 'Gao, Xiang',\n", - " 'Liu, Qing',\n", - " 'Wang, Yongfang',\n", - " 'Xia, Wangxiao',\n", - " 'Hua, Xiaoyu',\n", - " 'Yang, Jishun',\n", - " 'Höfer, Juan',\n", - " 'Pozzolini, Marina',\n", - " 'Shen, Yuxin',\n", - " 'Xiao, Liang',\n", - " 'Hao, Ruirong'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.scitotenv.2023.163382\"}'],\n", - " 'title': ['Glutathione metabolism is conserved in response to excessive copper exposure between mice liver and Aurelia coerulea polyps']},\n", - " {'bibcode': '2006Sci...313.1628F',\n", - " 'abstract': 'Liver regeneration is an orchestrated cellular response that coordinates cell activation, lipid metabolism, and cell division. We found that caveolin-1 gene-disrupted mice (cav1-/- mice) exhibited impaired liver regeneration and low survival after a partial hepatectomy. Hepatocytes showed dramatically reduced lipid droplet accumulation and did not advance through the cell division cycle. Treatment of cav1-/- mice with glucose (which is a predominant energy substrate when compared to lipids) drastically increased survival and reestablished progression of the cell cycle. Thus, caveolin-1 plays a crucial role in the mechanisms that coordinate lipid metabolism with the proliferative response occurring in the liver after cellular injury.',\n", - " 'author': ['Fernández, Manuel A.',\n", - " 'Albor, Cecilia',\n", - " 'Ingelmo-Torres, Mercedes',\n", - " 'Nixon, Susan J.',\n", - " 'Ferguson, Charles',\n", - " 'Kurzchalia, Teymuras',\n", - " 'Tebar, Francesc',\n", - " 'Enrich, Carlos',\n", - " 'Parton, Robert G.',\n", - " 'Pol, Albert'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.1130773\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.1130773\"}'],\n", - " 'title': ['Caveolin-1 Is Essential for Liver Regeneration']},\n", - " {'bibcode': '2016NatSR...623963Y',\n", - " 'abstract': 'Perfluorooctanoic acid (PFOA), a perfluoroalkyl acid, can result in hepatotoxicity and neurobehavioral effects in animals. The metabolome, which serves as a connection among transcriptome, proteome and toxic effects, provides pathway-based insights into effects of PFOA. Since understanding of changes in the metabolic profile during hepatotoxicity and neurotoxicity were still incomplete, a high-throughput targeted metabolomics approach (278 metabolites) was used to investigate effects of exposure to PFOA for 28 d on brain and liver of male Balb/c mice. Results of multivariate statistical analysis indicated that PFOA caused alterations in metabolic pathways in exposed individuals. Pathway analysis suggested that PFOA affected metabolism of amino acids, lipids, carbohydrates and energetics. Ten and 18 metabolites were identified as potential unique biomarkers of exposure to PFOA in brain and liver, respectively. In brain, PFOA affected concentrations of neurotransmitters, including serotonin, dopamine, norepinephrine, and glutamate in brain, which provides novel insights into mechanisms of PFOA-induced neurobehavioral effects. In liver, profiles of lipids revealed involvement of β-oxidation and biosynthesis of saturated and unsaturated fatty acids in PFOA-induced hepatotoxicity, while alterations in metabolism of arachidonic acid suggesting potential of PFOA to cause inflammation response in liver. These results provide insight into the mechanism and biomarkers for PFOA-induced effects.',\n", - " 'author': ['Yu, Nanyang',\n", - " 'Wei, Si',\n", - " 'Li, Meiying',\n", - " 'Yang, Jingping',\n", - " 'Li, Kan',\n", - " 'Jin, Ling',\n", - " 'Xie, Yuwei',\n", - " 'Giesy, John P.',\n", - " 'Zhang, Xiaowei',\n", - " 'Yu, Hongxia'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep23963\"}'],\n", - " 'title': ['Effects of Perfluorooctanoic Acid on Metabolic Profiles in Brain and Liver of Mouse Revealed by a High-throughput Targeted Metabolomics Approach']},\n", - " {'bibcode': '2017AngCh.129..845M',\n", - " 'abstract': 'The p300/CBP‑associated factor (PCAF) and related GCN5 bromodomain‑containing lysine acetyl transferases are members of subfamily I of the bromodomain phylogenetic tree. Iterative cycles of rational inhibitor design and biophysical characterization led to the discovery of the triazolopthalazine‑based L‑45 (dubbed L‑Moses) as the first potent, selective, and cell‑active PCAF bromodomain (Brd) inhibitor. Synthesis from readily available (1R,2S)‑(−)‑norephedrine furnished L‑45 in enantiopure form. L‑45 was shown to disrupt PCAF‑Brd histone H3.3 interaction in cells using a nanoBRET assay, and a co‑crystal structure of L‑45 with the homologous Brd PfGCN5 from Plasmodium falciparum rationalizes the high selectivity for PCAF and GCN5 bromodomains. Compound L‑45 shows no observable cytotoxicity in peripheral blood mononuclear cells (PBMC), good cell‑permeability, and metabolic stability in human and mouse liver microsomes, supporting its potential for in vivo use.',\n", - " 'author': ['Moustakim, Moses',\n", - " 'Clark, Peter G. K.',\n", - " 'Trulli, Laura',\n", - " 'Fuentes de Arriba, Angel L.',\n", - " 'Ehebauer, Matthias T.',\n", - " 'Chaikuad, Apirat',\n", - " 'Murphy, Emma J.',\n", - " 'Mendez-Johnson, Jacqui',\n", - " 'Daniels, Danette',\n", - " 'Hou, Chun-Feng D.',\n", - " 'Lin, Yu-Hui',\n", - " 'Walker, John R.',\n", - " 'Hui, Raymond',\n", - " 'Yang, Hongbing',\n", - " 'Dorrell, Lucy',\n", - " 'Rogers, Catherine M.',\n", - " 'Monteiro, Octovia P.',\n", - " 'Fedorov, Oleg',\n", - " 'Huber, Kilian V. M.',\n", - " 'Knapp, Stefan',\n", - " 'Heer, Jag',\n", - " 'Dixon, Darren J.',\n", - " 'Brennan, Paul E.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Fange.201610816\"}'],\n", - " 'title': ['Discovery of a PCAF Bromodomain Chemical Probe']},\n", - " {'bibcode': '2021NatCo..12.4219S',\n", - " 'abstract': 'Streptococcus pyogenes (Spy) Cas9 has potential as a component of gene therapeutics for incurable diseases. One of its limitations is its large size, which impedes its formulation and delivery in therapeutic applications. Smaller Cas9s are an alternative, but lack robust activity or specificity and frequently recognize longer PAMs. Here, we investigated four uncharacterized, smaller Cas9s and found three employing a \"GG\" dinucleotide PAM similar to SpyCas9. Protein engineering generated synthetic RNA-guided nucleases (sRGNs) with editing efficiencies and specificities exceeding even SpyCas9 in vitro and in human cell lines on disease-relevant targets. sRGN mRNA lipid nanoparticles displayed manufacturing advantages and high in vivo editing efficiency in the mouse liver. Finally, sRGNs, but not SpyCas9, could be packaged into all-in-one AAV particles with a gRNA and effected robust in vivo editing of non-human primate (NHP) retina photoreceptors. Human gene therapy efforts are expected to benefit from these improved alternatives to existing CRISPR nucleases.',\n", - " 'author': ['Schmidt, Moritz J.',\n", - " 'Gupta, Ashish',\n", - " 'Bednarski, Christien',\n", - " 'Gehrig-Giannini, Stefanie',\n", - " 'Richter, Florian',\n", - " 'Pitzler, Christian',\n", - " 'Gamalinda, Michael',\n", - " 'Galonska, Christina',\n", - " 'Takeuchi, Ryo',\n", - " 'Wang, Kui',\n", - " 'Reiss, Caroline',\n", - " 'Dehne, Kerstin',\n", - " 'Lukason, Michael J.',\n", - " 'Noma, Akiko',\n", - " 'Park-Windhol, Cindy',\n", - " 'Allocca, Mariacarmela',\n", - " 'Kantardzhieva, Albena',\n", - " 'Sane, Shailendra',\n", - " 'Kosakowska, Karolina',\n", - " 'Cafferty, Brian',\n", - " 'Tebbe, Jan',\n", - " 'Spencer, Sarah J.',\n", - " 'Munzer, Scott',\n", - " 'Cheng, Christopher J.',\n", - " 'Scaria, Abraham',\n", - " 'Scharenberg, Andrew M.',\n", - " 'Cohnen, André',\n", - " 'Coco, Wayne M.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41467-021-24454-5\"}'],\n", - " 'title': ['Improved CRISPR genome editing using small highly active and specific engineered RNA-guided nucleases']},\n", - " {'bibcode': '2021NatSR..1122975A',\n", - " 'author': ['AlOgayil, Najla',\n", - " 'Bauermeister, Klara',\n", - " 'Galvez, Jose Hector',\n", - " 'Venkatesh, Varun S.',\n", - " 'Zhuang, Qinwei Kim-wee',\n", - " 'Chang, Matthew L.',\n", - " 'Davey, Rachel A.',\n", - " 'Zajac, Jeffrey D.',\n", - " 'Ida, Kinuyo',\n", - " 'Kamiya, Akihide',\n", - " 'Taketo, Teruko',\n", - " 'Bourque, Guillaume',\n", - " 'Naumova, Anna K.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-021-02512-8\"}'],\n", - " 'title': ['Author Correction: Distinct roles of androgen receptor, estrogen receptor alpha, and BCL6 in the establishment of sex-biased DNA methylation in mouse liver']},\n", - " {'bibcode': '2008PNAS..105.9733L',\n", - " 'abstract': 'Inflammatory destruction of intrahepatic bile ducts is a common cause of vanishing bile duct syndrome and cholestasis, often progressing to biliary cirrhosis and liver failure. However, the molecular mechanisms underlying the pathogenesis of inflammatory biliary disease are poorly understood. Here, we show that the two IκB kinases, IKK1/IKKα and IKK2/IKKβ, display distinct collaborative and specific functions that are essential to protect the liver from cytokine toxicity and bile duct disease. Combined conditional ablation of IKK1 and IKK2, but not of each kinase alone, sensitized the liver to in vivo LPS challenge, uncovering a redundant function of the two IκB kinases in mediating canonical NF-κB signaling in hepatocytes and protecting the liver from TNF-induced failure. Unexpectedly, mice with combined ablation of IKK1 and IKK2 or IKK1 and NEMO spontaneously developed severe jaundice and fatal cholangitis characterized by inflammatory destruction of small portal bile ducts. This bile duct disease was caused by the combined impairment of canonical NF-κB signaling together with inhibition of IKK1-specific functions affecting the bile-blood barrier. These results reveal a novel function of the two IκB kinases in cooperatively regulating liver immune homeostasis and bile duct integrity and suggest that IKK signaling may be implicated in human biliary diseases.',\n", - " 'author': ['Luedde, Tom',\n", - " 'Heinrichsdorff, Jan',\n", - " 'de Lorenzi, Rossana',\n", - " 'De Vos, Rita',\n", - " 'Roskams, Tania',\n", - " 'Pasparakis, Manolis'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/105/28/9733\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/105/28/9733.full.pdf\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0800198105\"}'],\n", - " 'title': ['From the Cover: IKK1 and IKK2 cooperate to maintain bile duct integrity in the liver']},\n", - " {'bibcode': '2022Natur.612..141X',\n", - " 'abstract': 'The heterogeneity of the tumour immune microenvironment (TIME), organized by various immune and stromal cells, is a major contributing factor of tumour metastasis, relapse and drug resistance1-3, but how different TIME subtypes are connected to the clinical relevance in liver cancer remains unclear. Here we performed single-cell RNA-sequencing (scRNA-seq) analysis of 189 samples collected from 124 patients and 8 mice with liver cancer. With more than 1 million cells analysed, we stratified patients into five TIME subtypes, including immune activation, immune suppression mediated by myeloid or stromal cells, immune exclusion and immune residence phenotypes. Different TIME subtypes were spatially organized and associated with chemokine networks and genomic features. Notably, tumour-associated neutrophil (TAN) populations enriched in the myeloid-cell-enriched subtype were associated with an unfavourable prognosis. Through in vitro induction of TANs and ex vivo analyses of patient TANs, we showed that CCL4+ TANs can recruit macrophages and that PD-L1+ TANs can suppress T cell cytotoxicity. Furthermore, scRNA-seq analysis of mouse neutrophil subsets revealed that they are largely conserved with those of humans. In vivo neutrophil depletion in mouse models attenuated tumour progression, confirming the pro-tumour phenotypes of TANs. With this detailed cellular heterogeneity landscape of liver cancer, our study illustrates diverse TIME subtypes, highlights immunosuppressive functions of TANs and sheds light on potential immunotherapies targeting TANs.',\n", - " 'author': ['Xue, Ruidong',\n", - " 'Zhang, Qiming',\n", - " 'Cao, Qi',\n", - " 'Kong, Ruirui',\n", - " 'Xiang, Xiao',\n", - " 'Liu, Hengkang',\n", - " 'Feng, Mei',\n", - " 'Wang, Fangyanni',\n", - " 'Cheng, Jinghui',\n", - " 'Li, Zhao',\n", - " 'Zhan, Qimin',\n", - " 'Deng, Mi',\n", - " 'Zhu, Jiye',\n", - " 'Zhang, Zemin',\n", - " 'Zhang, Ning'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"data\", \"url\": \"http://meta-cancer.cn:3838/scplc\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"data\", \"url\": \"https://asia.ensembl.org/\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"data\", \"url\": \"https://portal.gdc.cancer.gov/\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"data\", \"url\": \"https://www.ncbi.nlm.nih.gov/bioproject/?term=prjca007744\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41586-022-05400-x\"}'],\n", - " 'title': ['Liver tumour immune microenvironment subtypes and neutrophil heterogeneity']},\n", - " {'bibcode': '2019SPIE10882E..1BH',\n", - " 'abstract': 'Intravital multiphoton microscopy was used to study hepatobiliary metabolism in chronic pathologies of the liver. Through the use of the probe molecule 6-carboxyfluorescein diacetate (6-CFDA), the effects of liver fibrosis, fatty liver, and hepatocellular carcinoma on the metabolic capabilities of mouse liver were investigated. After the acquisition of time lapse images, a first order kinetic model was used to calculate rate constant resolved images of various pathologies. It was found the ability of the liver to metabolically process the probe molecules varies among different pathologies, with liver fibrosis and fatty liver disease negatively impacted the uptake, processing, and excretion of molecules.',\n", - " 'author': ['Huang, Hsu-Cheng',\n", - " 'Lin, Chih-Ju',\n", - " 'Lee, Sheng-Lin',\n", - " 'Wang, Wei-Hsiang',\n", - " 'Hovhannisyan, Vladimir A.',\n", - " 'Huang, Yao-De',\n", - " 'Lee, Hsuan-Shu',\n", - " 'Dong, Chen-Yuan'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1117%2F12.2507345\"}'],\n", - " 'title': ['In vivo multiphoton dynamic imaging of the hepatobiliary metabolism in chronic hepatic diseases']},\n", - " {'bibcode': '2000Sci...287.1253R',\n", - " 'abstract': \"Accelerated telomere loss has been proposed to be a factor leading to end-stage organ failure in chronic diseases of high cellular turnover such as liver cirrhosis. To test this hypothesis directly, telomerase-deficient mice, null for the essential telomerase RNA (mTR) gene, were subjected to genetic, surgical, and chemical ablation of the liver. Telomere dysfunction was associated with defects in liver regeneration and accelerated the development of liver cirrhosis in response to chronic liver injury. Adenoviral delivery of mTR into the livers of mTR-/- mice with short dysfunctional telomeres restored telomerase activity and telomere function, alleviated cirrhotic pathology, and improved liver function. These studies indicate that telomere dysfunction contributes to chronic diseases of continual cellular loss-replacement and encourage the evaluation of ``telomerase therapy'' for such diseases.\",\n", - " 'author': ['Rudolph, Karl Lenhard',\n", - " 'Chang, Sandy',\n", - " 'Millard, Melissa',\n", - " 'Schreiber-Agus, Nicole',\n", - " 'DePinho, Ronald A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.287.5456.1253\"}'],\n", - " 'title': ['Inhibition of Experimental Liver Cirrhosis in Mice by Telomerase Gene Delivery']},\n", - " {'bibcode': '1997PNAS...94.1441Y',\n", - " 'abstract': 'The mechanisms that initiate liver regeneration after resection of liver tissue are not known. To determine whether cytokines are involved in the initiation of liver growth, we studied the regeneration of the liver after partial hepatectomy (PH) in mice lacking type I tumor necrosis factor receptor (TNFR-I). DNA synthesis after PH was severely impaired in these animals, and the expected increases in the binding of the NF-κB and STAT3 transcription factors shortly after PH failed to occur. Binding of AP-1 after PH was decreased in TNFR-I knockout mice compared with animals with the intact receptor whereas C/EBP binding was not modified. Injection of interleukin 6 in TNFR-I-deficient animals 30 min before PH corrected the defect in DNA synthesis and restored STAT3 and AP-1 binding to normal levels but had no effect on NF-κB binding in the regenerating liver. The results indicate that TNF, signaling through the TNFR-I, can initiate liver regeneration and acts by activating an interleukin 6-dependent pathway that involves the STAT3 transcription factor.',\n", - " 'author': ['Yamada, Yasuhiro',\n", - " 'Kirillova, Irina',\n", - " 'Peschon, Jacques J.',\n", - " 'Fausto, Nelson'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/94/4/1441\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/94/4/1441\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/94/4/1441\"}'],\n", - " 'title': ['Initiation of Liver Growth by Tumor Necrosis Factor: Deficient Liver Regeneration in Mice Lacking Type I Tumor Necrosis Factor Receptor']},\n", - " {'bibcode': '2011NRL.....6....8W',\n", - " 'abstract': \"Herein, we report the effects of graphene oxides on human fibroblast cells and mice with the aim of investigating graphene oxides' biocompatibility. The graphene oxides were prepared by the modified Hummers method and characterized by high-resolution transmission electron microscope and atomic force microscopy. The human fibroblast cells were cultured with different doses of graphene oxides for day 1 to day 5. Thirty mice divided into three test groups (low, middle, high dose) and one control group were injected with 0.1, 0.25, and 0.4 mg graphene oxides, respectively, and were raised for 1 day, 7 days, and 30 days, respectively. Results showed that the water-soluble graphene oxides were successfully prepared; graphene oxides with dose less than 20 μg/mL did not exhibit toxicity to human fibroblast cells, and the dose of more than 50 μg/mL exhibits obvious cytotoxicity such as decreasing cell adhesion, inducing cell apoptosis, entering into lysosomes, mitochondrion, endoplasm, and cell nucleus. Graphene oxides under low dose (0.1 mg) and middle dose (0.25 mg) did not exhibit obvious toxicity to mice and under high dose (0.4 mg) exhibited chronic toxicity, such as 4/9 mice death and lung granuloma formation, mainly located in lung, liver, spleen, and kidney, almost could not be cleaned by kidney. In conclusion, graphene oxides exhibit dose-dependent toxicity to cells and animals, such as inducing cell apoptosis and lung granuloma formation, and cannot be cleaned by kidney. When graphene oxides are explored for in vivo applications in animal or human body, its biocompatibility must be considered.\",\n", - " 'author': ['Wang, Kan',\n", - " 'Ruan, Jing',\n", - " 'Song, Hua',\n", - " 'Zhang, Jiali',\n", - " 'Wo, Yan',\n", - " 'Guo, Shouwu',\n", - " 'Cui, Daxiang'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1007%2Fs11671-010-9751-6\"}'],\n", - " 'title': ['Biocompatibility of Graphene Oxide']},\n", - " {'bibcode': '2016NatSR...634382G',\n", - " 'abstract': 'Anti-CD20 monoclonal antibodies (mAbs) represent an effective treatment for a number of B cell malignancies and autoimmune disorders. Glycoengineering of anti-CD20mAb may contribute to increased anti-tumor efficacy through enhanced antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADP) as reported by in vitro studies. However, where and how glycoengineered Ab may potentiate therapeutic responses in vivo is yet to be elucidated. Here, we have performed mouse liver transplants to demonstrate that the liver is sufficient to mediate systemic B cells depletion after anti-CD20 treatment. Relying on intravital two-photon imaging of human CD20-expressing mice, we provide evidence that ADP by Kupffer cells (KC) is a major mechanism for rituximab-mediated B cell depletion. Notably, a glycoengineered anti-mouse CD20 Ab but not its wild-type counterpart triggered potent KC-mediated B cell depletion at low doses. Finally, distinct thresholds for KC phagocytosis were also observed for GA101 (obinutuzumab), a humanized glycoengineered type II anti-CD20 Ab and rituximab. Thus, we propose that enhanced phagocytosis of circulating B cells by KC represents an important in vivo mechanism underlying the improved activity of glycoengineered anti-CD20 mAbs.',\n", - " 'author': ['Grandjean, Capucine L.',\n", - " 'Montalvao, Fabricio',\n", - " 'Celli, Susanna',\n", - " 'Michonneau, David',\n", - " 'Breart, Beatrice',\n", - " 'Garcia, Zacarias',\n", - " 'Perro, Mario',\n", - " 'Freytag, Olivier',\n", - " 'Gerdes, Christian A.',\n", - " 'Bousso, Philippe'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep34382\"}'],\n", - " 'title': ['Intravital imaging reveals improved Kupffer cell-mediated phagocytosis as a mode of action of glycoengineered anti-CD20 antibodies']},\n", - " {'bibcode': '1987PNAS...84.5242L',\n", - " 'abstract': 'Peroxisome proliferators (PP) induce a highly predictable pleiotropic response in rat and mouse liver that is characterized by hepatomegaly, increase in peroxisome number in hepatocytes, and induction of certain peroxisomal enzymes. The PP-binding protein (PPbP) was purified from rat liver cytosol by a two-step procedure involving affinity chromatography and ion-exchange chromatography. Three PP, nafenopin and its structural analogs clofibric acid and ciprofibrate, were used as affinity ligands and eluting agents. This procedure yields a major protein with an apparent Mr of 70,000 on NaDodSO4/PAGE in the presence of reducing agent and Mr 140,000 (Mr 140,000-160,000) on gel filtration and polyacrylamide gradient gel electrophoresis under nondenaturing conditions, indicating that the active protein is a dimer. This protein has an acidic pI of 4.2 under nondenaturing conditions, which rises to 5.6 under denaturing conditions. The isolation of the same Mr 70,000 protein with three different, but structurally related, agents as affinity ligands and the immunological identity of the isolated proteins constitute strong evidence that this protein is the PPbP capable of recognizing PP that are structurally related to clofibrate. The PPbP probably plays an important role in the regulation of PP-induced pleiotropic response.',\n", - " 'author': ['Lalwani, Narendra D.',\n", - " 'Alvares, Keith',\n", - " 'Kumudavalli Reddy, M.',\n", - " 'Narahari Reddy, M.',\n", - " 'Parikh, Indu',\n", - " 'Reddy, Janardan K.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/84/15/5242\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/84/15/5242\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/84/15/5242\"}'],\n", - " 'title': ['Peroxisome proliferator-binding protein: identification and partial characterization of nafenopin-, clofibric acid-, and ciprofibrate-binding proteins from rat liver.']},\n", - " {'bibcode': '2001Natur.409..729A',\n", - " 'abstract': 'The earliest defect in developing type 2 diabetes is insulin resistance, characterized by decreased glucose transport and metabolism in muscle and adipocytes. The glucose transporter GLUT4 mediates insulin-stimulated glucose uptake in adipocytes and muscle by rapidly moving from intracellular storage sites to the plasma membrane. In insulin-resistant states such as obesity and type 2 diabetes, GLUT4 expression is decreased in adipose tissue but preserved in muscle. Because skeletal muscle is the main site of insulin-stimulated glucose uptake, the role of adipose tissue GLUT4 downregulation in the pathogenesis of insulin resistance and diabetes is unclear. To determine the role of adipose GLUT4 in glucose homeostasis, we used Cre/loxP DNA recombination to generate mice with adipose-selective reduction of GLUT4 (G4A-/-). Here we show that these mice have normal growth and adipose mass despite markedly impaired insulin-stimulated glucose uptake in adipocytes. Although GLUT4 expression is preserved in muscle, these mice develop insulin resistance in muscle and liver, manifested by decreased biological responses and impaired activation of phosphoinositide-3-OH kinase. G4A-/- mice develop glucose intolerance and hyperinsulinaemia. Thus, downregulation of GLUT4 and glucose transport selectively in adipose tissue can cause insulin resistance and thereby increase the risk of developing diabetes.',\n", - " 'author': ['Abel, E. Dale',\n", - " 'Peroni, Odile',\n", - " 'Kim, Jason K.',\n", - " 'Kim, Young-Bum',\n", - " 'Boss, Olivier',\n", - " 'Hadro, Ed',\n", - " 'Minnemann, Timo',\n", - " 'Shulman, Gerald I.',\n", - " 'Kahn, Barbara B.'],\n", - " 'title': ['Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver']},\n", - " {'bibcode': '1982PNAS...79.7619D',\n", - " 'abstract': \"Eighteen cDNA clones containing inserts specific for the third component of complement (C3) have been derived from high molecular weight mouse liver mRNA. The inserts span 4,600 nucleotides of the C3 coding sequence, including the 3' end of C3 mRNA. The length of C3 mRNA was determined to be 5,100 +/- 200 nucleotides, including a poly(A)-containing tail of mean length 170 nucleotides. From cDNA sequence analysis of the 5'-proximal region of C3 mRNA, the NH2-terminal amino acid sequence of the mature C3 beta chain was predicted to be Ile-Pro-Met-Tyr-Ser-Ile-Ile-Thr-Pro-Asn-Val-Leu-Arg-Leu-Glu. This sequence is in good agreement with the reported amino acid sequences of human and guinea pig C3 beta chains. These data position the C3 beta subunit to the NH2-terminal portion of the precursor C3 molecule (pro-C3) and establish the order of subunits in pro-C3 to be NH2-beta-alpha-COOH. In addition, the cDNA sequence indicates that an NH2-terminal extension peptide precedes the beta chain in pro-C3. The amino acid sequence of the mouse C3a fragment and its flanking regions was determined. The data indicate the presence of four arginine residues located between the COOH terminus of the C3 beta and the NH2 terminus of the C3 alpha subunits in pro-C3. The coding sequences of the amino acids that constitute the internal thioester domain in C3 were determined. Unexpectedly, the glutamyl residue that has been shown to participate in the thioester bond in native C3 was found to be encoded as a glutamine.\",\n", - " 'author': ['Domdey, Horst',\n", - " 'Wiebauer, Karin',\n", - " 'Kazmaier, Michael',\n", - " 'Muller, Verena',\n", - " 'Odink, Karel',\n", - " 'Fey, George'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/79/24/7619\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/79/24/7619\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/79/24/7619\"}'],\n", - " 'title': ['Characterization of the mRNA and cloned cDNA specifying the third component of mouse complement.']},\n", - " {'bibcode': '2006PNAS..10311294L',\n", - " 'abstract': 'Islet transplantation offers a potential therapy to restore glucose homeostasis in type 1 diabetes patients. However, islet transplantation is not routinely successful because most islet recipients gradually lose graft function. Furthermore, serological markers of islet function are insensitive to islet loss until the latter stages of islet graft rejection. A noninvasive method of monitoring islet grafts would aid in the assessment of islet graft survival and the evaluation of interventions designed to prolong graft survival. Here, we show that recombinant adenovirus can engineer isolated islets to express a positron-emission tomography (PET) reporter gene and that these islets can be repeatedly imaged by using microPET after transplantation into mice. The magnitude of signal from engineered islets implanted into the axillary cavity was directly related to the implanted islet mass. PET signals attenuated over the following weeks because of the transient nature of adenovirus-mediated gene expression. Because the liver is the preferred site for islet implantation in humans, we also tested whether islets could be imaged after transfusion into the mouse liver. Control studies revealed that both intrahepatic islet transplantation and hyperglycemia altered the biodistribution kinetics of the PET probe systemically. Although transplanted islets were dispersed throughout the liver, clear signals from the liver region of mice receiving PET reporter-expressing islets were detectable for several weeks. Viral transduction, PET reporter expression, and repeated microPET imaging had no apparent deleterious effects on islet function after implantation. These studies lay a foundation for noninvasive quantitative assessments of islet graft survival using PET. diabetes | transplantation',\n", - " 'author': ['Lu, Yuxin',\n", - " 'Dang, Hoa',\n", - " 'Middleton, Blake',\n", - " 'Zhang, Zesong',\n", - " 'Washburn, Lorraine',\n", - " 'Stout, David B.',\n", - " 'Campbell-Thompson, Martha',\n", - " 'Atkinson, Mark A.',\n", - " 'Phelps, Michael',\n", - " 'Gambhir, Sanjiv Sam',\n", - " 'Tian, Jide',\n", - " 'Kaufman, Daniel L.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/103/30/11294\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/103/30/11294\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/full/103/30/11294\"}'],\n", - " 'title': ['Noninvasive imaging of islet grafts using positron-emission tomography']},\n", - " {'bibcode': '1995Sci...270..985W',\n", - " 'abstract': 'The role of the cell-surface molecule CTLA-4 in the regulation of T cell activation has been controversial. Here, lymph nodes and spleens of CTLA-4-deficient mice accumulated T cell blasts with up-regulated activation markers. These blast cells also infiltrated liver, heart, lung, and pancreas tissue, and amounts of serum immunoglobulin were elevated. The mice invariably became moribund by 3 to 4 weeks of age. Although CTLA-4-deficient T cells proliferated spontaneously and strongly when stimulated through the T cell receptor, they were sensitive to cell death induced by cross-linking of the Fas receptor and by gamma irradiation. Thus, CTLA-4 acts as a negative regulator of T cell activation and is vital for the control of lymphocyte homeostasis.',\n", - " 'author': ['Waterhouse, Paul',\n", - " 'Penninger, Josef M.',\n", - " 'Timms, Emma',\n", - " 'Wakeham, Andrew',\n", - " 'Shahinian, Arda',\n", - " 'Lee, Kelvin P.',\n", - " 'Thompson, Craig B.',\n", - " 'Griesser, Henrik',\n", - " 'Mak, Tak W.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.270.5238.985\"}'],\n", - " 'title': ['Lymphoproliferative Disorders with Early Lethality in Mice Deficient in Ctla-4']},\n", - " {'bibcode': '2021SPIE11630E..1QM',\n", - " 'abstract': 'A three-dimensional multi-contrast tissue dynamics imaging method based on polarization-sensitive optical coherence tomography is presented to visualize microvascular tissue activity of mouse livers. Temporal variance of birefringence, temporal polarization uniformity and logarithmic OCT intensity variance are used to access the tissue dynamics. These methods are applied to time-course microvasculature activity visualization of dissected normal and inflammatory mouse liver. Multi-contrast projection images are generated to visualize vascular network of the liver. Cross-sectional and en face dynamics images show high activity around the periportal region of mouse liver at initial time point. Degradation of tissue activity is demonstrated by time-lapse imaging.',\n", - " 'author': ['Mukherjee, P.',\n", - " 'Miyazawa, A.',\n", - " 'Shen, L. T. W.',\n", - " 'Fukuda, S.',\n", - " 'Yamashita, T.',\n", - " 'Oka, Y.',\n", - " 'Abd El-Sadek, I. G.',\n", - " 'Makita, S.',\n", - " 'Matsusaka, S.',\n", - " 'Oshika, T.',\n", - " 'Kano, H.',\n", - " 'Yasuno, Y.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"video\", \"url\": \"https://doi.org/10.1117/12.2577994\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1117%2F12.2577994\"}'],\n", - " 'title': ['Volumetric multi-contrast dynamics imaging for ex vivo liver microvasculature activity visualization using Jones matrix optical coherence tomography']},\n", - " {'bibcode': '1992EnvMM..19....1S',\n", - " 'abstract': 'Non‑isotopic in situ hybridization using a mouse gamma (major) satellite probe DNA was applied to detect centromeres in micronuclei, which were induced in vitro in mouse liver cells by ionizing radiation and by vinblastine sulfate. In a cytokinesis‑blocked micronucleus assay a dose‑dependent induction of micronuclei was found for both agents. After vinblastine exposure the observed micronuclei showed centromere‑positive hybridization signals in an order of magnitude of 70–90%, but after radiation exposure the magnitude was only 10–20%. Since the in situ hybridization technique detects centromeric DNA directly, it can be used in a cytokinesis‑blocked micronucleus assay for a rapid and reliable discrimination between aneuploidy‑inducing and clastogenic agents.',\n", - " 'author': ['Salassidis, K.',\n", - " 'Huber, R.',\n", - " 'Zitzelsberger, H.',\n", - " 'Bauchinger, M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Fem.2850190102\"}'],\n", - " 'title': ['Centromere detection in vinblastine‑ and radiation‑induced micronuclei of cytokinesis‑blocked mouse cells by using in situ hybridization with a mouse gamma (Major) satellite DNA probe']},\n", - " {'bibcode': '2005Natur.438..685K',\n", - " 'abstract': \"MicroRNAs (miRNAs) are an abundant class of non-coding RNAs that are believed to be important in many biological processes through regulation of gene expression. The precise molecular function of miRNAs in mammals is largely unknown and a better understanding will require loss-of-function studies in vivo. Here we show that a novel class of chemically engineered oligonucleotides, termed `antagomirs', are efficient and specific silencers of endogenous miRNAs in mice. Intravenous administration of antagomirs against miR-16, miR-122, miR-192 and miR-194 resulted in a marked reduction of corresponding miRNA levels in liver, lung, kidney, heart, intestine, fat, skin, bone marrow, muscle, ovaries and adrenals. The silencing of endogenous miRNAs by this novel method is specific, efficient and long-lasting. The biological significance of silencing miRNAs with the use of antagomirs was studied for miR-122, an abundant liver-specific miRNA. Gene expression and bioinformatic analysis of messenger RNA from antagomir-treated animals revealed that the 3' untranslated regions of upregulated genes are strongly enriched in miR-122 recognition motifs, whereas downregulated genes are depleted in these motifs. Analysis of the functional annotation of downregulated genes specifically predicted that cholesterol biosynthesis genes would be affected by miR-122, and plasma cholesterol measurements showed reduced levels in antagomir-122-treated mice. Our findings show that antagomirs are powerful tools to silence specific miRNAs in vivo and may represent a therapeutic strategy for silencing miRNAs in disease.\",\n", - " 'author': ['Krützfeldt, Jan',\n", - " 'Rajewsky, Nikolaus',\n", - " 'Braich, Ravi',\n", - " 'Rajeev, Kallanthottathil G.',\n", - " 'Tuschl, Thomas',\n", - " 'Manoharan, Muthiah',\n", - " 'Stoffel, Markus'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature04303\"}'],\n", - " 'title': [\"Silencing of microRNAs in vivo with `antagomirs'\"]},\n", - " {'bibcode': '1997PNAS...94..569Z',\n", - " 'abstract': 'Transcription factors are master regulatory switches of differentiation, including the development of specific hematopoietic lineages from stem cells. Here we show that mice with targeted disruption of the CCAAT enhancer binding protein α gene (C/EBPα) demonstrate a selective block in differentiation of neutrophils. Mature neutrophils and eosinophils are not observed in the blood or fetal liver of mutant animals, while other hematopoietic lineages, including monocytes, are not affected. Instead, most of the white cells in the peripheral blood of mutant mice had the appearance of myeloid blasts. We also observed a selective loss of expression of a critical gene target of CCAAT enhancer binding protein α, the granulocyte colony-stimulating factor receptor. As a result, multipotential myeloid progenitors from the mutant fetal liver are unable to respond to granulocyte colony-stimulating factor signaling, although they are capable of forming granulocyte-macrophage and macrophage colonies in methylcellulose in response to other growth factors. Finally, we demonstrate that the lack of granulocyte development results from a defect intrinsic to the hematopoietic system; transplanted fetal liver from mutant mice can reconstitute lymphoid but not neutrophilic cells in irradiated recipients. These studies suggest a model by which transcription factors can direct the differentiation of multipotential precursors through activation of expression of a specific growth factor receptor, allowing proliferation and differentiation in response to a specific extracellular signal. In addition, the c/ebpα-/- mice may be useful in understanding the mechanisms involved in acute myelogenous leukemia, in which a block in differentiation of myeloid precursors is a key feature of the disease.',\n", - " 'author': ['Zhang, Dong-Er',\n", - " 'Zhang, Pu',\n", - " 'Wang, Nai-dy',\n", - " 'Hetherington, Christopher J.',\n", - " 'Darlington, Gretchen J.',\n", - " 'Tenen, Daniel G.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/94/2/569\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/94/2/569\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/94/2/569\"}'],\n", - " 'title': ['Absence of Granulocyte Colony-Stimulating Factor Signaling and Neutrophil Development in CCAAT Enhancer Binding Protein α -deficient Mice']},\n", - " {'bibcode': '1974Natur.249..361O',\n", - " 'abstract': \"THERE is good evidence that in birds a haemopoietic stem cells of yolk sac origin1,2 differentiate into immunoglobulin-bearing lymphocytes in the bursa of Fabricius3. The differentiated lymphocytes then migrate to the peripheral lymphoid tissues4,5, where they constitute the bursa-derived B lymphocyte population. The primary site(s) of B lymphocyte development in mammals, however, has remained a mystery, with gastrointestinal associated lymphoid tissues6 (including appendix7, tonsils8 and Peyer's patches9) and haemopoietic tissues10-12 generally considered the main candidates for mammalian `bursa equivalent'. Here we report the development of IgM, IgG and probably IgA-bearing lymphocytes in organ cultures of mouse foetal liver removed at 14 d gestation, a time well before immunoglobulin-bearing cells or cells of lymphoid morphology could be detected in the intact animal. These studies indicate that foetal liver is a bursa equivalent in mice and that gastrointestinal lymphoid tissues are not a sine qua non for the initial development of B cells. In addition, they provide evidence that IgG and probablv IgA-bearing B lymphocytes can develop in the absence of T lymphocytes.\",\n", - " 'author': ['Owen, John J. T.', 'Cooper, Max D.', 'Raff, Martin C.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F249361a0\"}'],\n", - " 'title': [\"In vitro generation of B lymphocytes in mouse foetal liver, a mammalian `bursa equivalent'\"]},\n", - " {'bibcode': '1977PNAS...74.3528L',\n", - " 'abstract': 'Messenger RNAs for antibody heavy (γ) and light (κ) chains were isolated from the polysomes of an IgG-producing mouse myeloma cell line. Polysomes engaged in heavy or light chain synthesis were separated by immunoprecipitation using rabbit antibodies specific for the mouse IgG formed. The mRNAs obtained, more than 85% specifying IgG [Legler, M. & Cohen, E. P. (1976) Biochemistry 15, 4390-4399], were used as \"probes\" in hybridization experiments with sheared mouse liver DNA. To determine whether mRNAs for Ig heavy and light chains contained covalently bound transcripts of unique and reiterated DNA, hybrids were isolated with or without treatment with ribonuclease (RNase) prior to fractionation and the apparent rates of hybridization were compared. A monophasic Cot (DNA concentration × incubation time) curve with a C0t1/2 of 4000 moles of nucleotide per liter × sec, corresponding to less than five hybridization sites per haploid genome, was obtained whether or not RNase was used in the isolation protocol. With a similar experimental design, the apparent hybridization rates of heterogeneous nuclear RNA from the same cell source were clearly different. The \"stringency\" of the reaction was reduced by incubating the hybridization mixtures at lower temperatures in a further attempt to detect a large class of repetitive sequences that would form hybrids with the IgG mRNA used, if such sequences were present. The results, however, were the same; i.e., the apparent rates of hybridization of mRNAs for mouse antibody γ and κ chains with sheared mouse liver DNA were essentially the same whether or not RNase was used in the isolation procedure. Reiteration of genes in mouse liver DNA for mouse IgG could not be detected.',\n", - " 'author': ['Legler, Mary K.', 'Cohen, Edward P.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/74/8/3528\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/74/8/3528\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/74/8/3528\"}'],\n", - " 'title': ['Hybridization Properties of Immunoglobulin mRNA: Failure to Detect Covalently Associated IgG mRNA Transcripts of Reiterated and Unique Mouse DNA']},\n", - " {'bibcode': '1995Sci...268..722F',\n", - " 'abstract': 'The aryl hydrocarbon (Ah) receptor (AHR) mediates many carcinogenic and teratogenic effects of environmentally toxic chemicals such as dioxin. An AHR-deficient (Ahr-/-) mouse line was constructed by homologous recombination in embryonic stem cells. Almost half of the mice died shortly after birth, whereas survivors reached maturity and were fertile. The Ahr-/- mice showed decreased accumulation of lymphocytes in the spleen and lymph nodes, but not in the thymus. The livers of Ahr-/- mice were reduced in size by 50 percent and showed bile duct fibrosis. Ahr-/- mice were also nonresponsive with regard to dioxin-mediated induction of genes encoding enzymes that catalyze the metabolism of foreign compounds. Thus, the AHR plays an important role in the development of the liver and the immune system.',\n", - " 'author': ['Fernandez-Salguero, Pedro',\n", - " 'Pineau, Thierry',\n", - " 'Hilbert, David M.',\n", - " 'McPhail, Timothy',\n", - " 'Lee, Susanna S. T.',\n", - " 'Kimura, Shioko',\n", - " 'Nebert, Daniel W.',\n", - " 'Rudikoff, Stuart',\n", - " 'Ward, Jerrold M.',\n", - " 'Gonzalez, Frank J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.7732381\"}'],\n", - " 'title': ['Immune System Impairment and Hepatic Fibrosis in Mice Lacking the Dioxin- Binding Ah Receptor']},\n", - " {'bibcode': '2000PNAS...97.5498T',\n", - " 'abstract': 'Natural killer T (NKT) cells constitute a distinct subpopulation of T cells with a unique antigen specificity, prompt effector functions, and an unusual tissue distribution. NKT cells are especially abundant in the liver, but their physiological function in this organ remains unclear. In the present study, we examined the possible contribution of NKT cells to a murine model of hepatitis induced by i.v. injection of Con A. CD1-deficient mice lacking NKT cells were highly resistant to Con A-induced hepatitis. Adoptive transfer of hepatic NKT cells isolated from wild-type mice, but not from FasL-deficient gld mice, sensitized CD1-deficient mice to Con A-induced hepatitis. Furthermore, adoptive transfer of hepatic mononuclear cells from wild-type mice, but not from CD1-deficient mice, sensitized gld mice to Con A-induced hepatitis. Upon Con A administration, hepatic NKT cells rapidly up-regulated cell surface FasL expression and FasL-mediated cytotoxicity. At the same time, NKT cells underwent apoptosis leading to their rapid disappearance in the liver. These results implicated FasL expression on liver NKT cells in the pathogenesis of Con A-induced hepatitis, suggesting a similar pathogenic role in human liver diseases such as autoimmune hepatitis.',\n", - " 'author': ['Takeda, Kazuyoshi',\n", - " 'Hayakawa, Yoshihiro',\n", - " 'Van Kaer, Luc',\n", - " 'Matsuda, Hironori',\n", - " 'Yagita, Hideo',\n", - " 'Okumura, Ko'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/97/10/5498\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/97/10/5498\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/97/10/5498\"}'],\n", - " 'title': ['Critical contribution of liver natural killer T cells to a murine model of hepatitis']},\n", - " {'bibcode': '2023ApOpt..62.3310Y',\n", - " 'abstract': 'Ultraviolet (UV) hyperspectral imaging technology is commonly used in the field of atmospheric remote sensing. In recent years, some in-laboratory research has been carried out for substance detection and identification. In this paper, UV hyperspectral imaging technology is introduced into microscopy to better utilize the obvious absorption characteristics of components, such as proteins and nucleic acids in biological tissues in the ultraviolet band. A deep UV microscopic hyperspectral imager based on the Offner structure with F# 2.5, low spectral keystone and smile is designed and developed. A 0.68 numerical aperture microscope objective is designed. The spectral range of the system is from 200 nm to 430 nm; the spectral resolution is better than 0.5 nm; and the spatial resolution is better than 1.3 µm. The K562 cells can be distinguished by transmission spectrum of nucleus. The UV microscopic hyperspectral image of the unstained mouse liver slices showed similar results to the microscopic image after hematoxylin and eosin staining, which could help to simplify the pathological examination process. Both results show a great performance in spatial and spectral detecting capabilities of our instrument, which has the potential for biomedical research and diagnosis.',\n", - " 'author': ['Yang, Jingyao',\n", - " 'Xue, Qingsheng',\n", - " 'Li, Jinze',\n", - " 'Han, Bing',\n", - " 'Wang, Youpeng',\n", - " 'Bai, Haoxuan'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1364%2FAO.485387\"}'],\n", - " 'title': ['Deep ultraviolet high-resolution microscopic hyperspectral imager and its biological tissue detection']},\n", - " {'bibcode': '1996Radcb..38..347L',\n", - " 'abstract': 'We have studied DNA adduction with14C-labeled nicotine and nicotine-derived nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), by accelerator mass spectrometry (AMS) in mouse liver at doses equivalent to low-level exposure of humans. The dose ranges of nicotine and NNK administered were from 0.4 μg to 4.0×102μg kg b.w.-1, and from 0.1 μg to 2.0×104μg kg b.w.-1, respectively. In the exposure of mice to either nicotine or NNK, the number of DNA adducts increased linearly with increasing dose. The detection limit of DNA adducts was 1 adduct per 1011nucleotide molecules. This limit is 1–4 orders of magnitude lower than that of other techniques used for quantification of DNA adducts. The results of our animal experiments enabled us to speculate that nicotine is a potential carcinogen. According to the procedure for14C-labeled-NNK synthesis, we discuss the ultimate chemical speciation of NNK bound to DNA. From the animal tests we derived a directly perceivable relation between tobacco consumption and DNA adduction as the carcinogenic risk assessment.',\n", - " 'author': ['Li, X. S.',\n", - " 'Wang, H. F.',\n", - " 'Shi, J. Y.',\n", - " 'Wang, X. Y.',\n", - " 'Liu, Y. F.',\n", - " 'Li, K.',\n", - " 'Lu, X. Y.',\n", - " 'Wang, J. J.',\n", - " 'Liu, K. X.',\n", - " 'Guo, Z. Y.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1017%2FS0033822200017677\"}'],\n", - " 'title': ['Genotoxicity Study on Nicotine and Nicotine-Derived Nitrosamine by Accelerator Mass Spectrometry']},\n", - " {'bibcode': '1966Natur.209.1241M',\n", - " 'abstract': 'SINCE the 1962 report by Bucha et al.1, who described the herbicidal activity of certain uracils substituted in the 3 and 6 positions, one of this class of chemicals, 5-bromo-3-sec-butyl-6-methyluracil (bromacil), has gained wide acceptance as an industrial herbicide. Investigations of the mode of action of this herbicide2,3 have shown that it is a potent direct inhibitor of photosynthesis acting at the chloroplast level. The chemical analogy between 5-bromouracil and the foregoing 3,6-substituted 5-bromouracil suggested the possibility that it might be incorporated into DNA and thereby act as a mutagen. McGahen and Hoffmann4,5 were unable to demonstrate incorporation of 5-bromo-3-sec-butyl-6-methyluracil (IV) either into the DNA of a thymineless Escherichia coli (15T-) or into mouse liver DNA under conditions in which 5-bromouracil (5-BU) was incorporated. Their investigations, however, did not rule out the possibility of indirect mutagenic activity. The subject of this report is a comparison of the effects of 5-BU and 5-bromouracils with several different alkyl substituents at the 3 and/or 6 positions on the back-mutation of an aminopurine-induced rII mutant of coliphage T4.',\n", - " 'author': ['McGahen, J. W.', 'Hoffmann, C. E.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F2091241a0\"}'],\n", - " 'title': ['Absence of Mutagenic Effects of 3- and 6-Alkyl-5-bromouracil Herbicides on a Bacteriophage']},\n", - " {'bibcode': '2016NatSR...621598W',\n", - " 'abstract': 'The roles of miRNAs as important post-transcriptional regulators in the circadian clock have been suggested in several studies. But the search for circadian miRNAs has led to disparate results. Here we demonstrated that at least 57 miRNA primary transcripts are rhythmically transcribed in mouse liver. Most of these transcripts are under the regulation of circadian transcription factors such as BMAL1/CLOCK and REV-ERBα/β. However, the mature miRNAs derived from these transcripts are either not oscillating or oscillating at low amplitudes, which could explain the inconsistency of different circadian miRNA studies. In order to show that these circadian primary transcripts can give rise to miRNAs with circadian functions, we over-expressed one of them, miR-378, in mouse by adenovirus injection. We found a significant over-representation of circadian oscillating genes under-expressed by miR-378 over-expression in liver. In particular, we observed that miR-378 modulates the oscillation amplitudes of Cdkn1a in the control of cell cycle and Por in the regulation of oxidation reduction by forming partnership with different circadian transcription factors. Our study suggests that circadian transcription of miRNA at primary transcript level can be a good indicator for circadian miRNA functions.',\n", - " 'author': ['Wang, Haifang',\n", - " 'Fan, Zenghua',\n", - " 'Zhao, Meng',\n", - " 'Li, Juan',\n", - " 'Lu, Minghua',\n", - " 'Liu, Wei',\n", - " 'Ying, Hao',\n", - " 'Liu, Mofang',\n", - " 'Yan, Jun'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep21598\"}'],\n", - " 'title': ['Oscillating primary transcripts harbor miRNAs with circadian functions']},\n", - " {'bibcode': '2021ScTEn.778n6322C',\n", - " 'author': ['Cui, Shixuan',\n", - " 'Yu, Yang',\n", - " 'Zhan, Tingjie',\n", - " 'Zhang, Chunlong',\n", - " 'Zhuang, Shulin'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.scitotenv.2021.146322\"}'],\n", - " 'title': ['2,6-Di-tert-butylphenol and its quinone metabolite trigger aberrant transcriptional responses in C57BL/6 mice liver']},\n", - " {'bibcode': '2022Chmsp.288m2504C',\n", - " 'author': ['Chen, Mei-Hong',\n", - " 'Zhang, Sheng-Hu',\n", - " 'Jia, Shi-Ming',\n", - " 'Wang, Li-Jun',\n", - " 'Ma, Wan-Li'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.chemosphere.2021.132504\"}'],\n", - " 'title': ['In vitro biotransformation of tris(1,3-dichloro-2-propyl) phosphate and triphenyl phosphate by mouse liver microsomes: Kinetics and key CYP isoforms']},\n", - " {'bibcode': '2013EnvMM..54..659B',\n", - " 'abstract': 'Furan is a rodent liver carcinogen, but the mode of action for furan hepatocarcinogenicity is unclear. H‑ras codon 61 mutations have been detected in spontaneous liver tumors of B6C3F1 mice, and the fraction of liver tumors carrying H‑ras codon 61 CAA to AAA mutation increased in furan‑treated mice. Allele‑specific competitive blocker PCR (ACB‑PCR) has been used previously to quantify early, carcinogen‑induced increases in tumor‑associated mutations. The present pilot study investigated whether furan drives clonal expansion of pre‑existing H‑ras mutant cells in B6C3F1 mouse liver. H‑ras codon 61 CAA to CTA and CAA to AAA mutations were measured in DNA isolated from liver tissue of female mice treated with 0, 1, 2, 4, or 8 mg furan/kg body weight, five days per week for three weeks, using five mice per treatment group. Spontaneous levels of mutation were low, with two of five control mice having an H‑ras codon 61 CTA or AAA mutant fraction (MF) greater than 10−5. Several furan‑treated mice had H‑ras codon 61 AAA or CTA MFs greater than those measured in control mice and lower bound estimates of induced MF were calculated. However, no statistically‑significant differences were observed between treatment groups. Therefore, while sustained exposure to furan is carcinogenic, at the early stage of carcinogenesis examined in this study (three weeks), there was not a significant expansion of H‑ras mutant cells. Environ. Mol. Mutagen. 54:659–667, 2013.',\n", - " 'author': ['Banda, Malathi', 'Recio, Leslie', 'Parsons, Barbara L.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Fem.21808\"}'],\n", - " 'title': ['ACB‑PCR measurement of spontaneous and furan‑induced H‑ras Codon 61 CAA to CTA and CAA to AAA mutation in B6C3F1 mouse liver']},\n", - " {'bibcode': '1988PNAS...85..836B',\n", - " 'abstract': 'Experiments were designed to test the effect of introns on gene expression in transgenic mice. Four different pairs of gene constructs, which were identical except that one member of each pair lacked all introns, were compared for expression of mRNA after introduction into the murine germ line by microinjection of fertilized eggs. The expression of two chimeric genes, made by fusing either the mouse metallothionein I or the rat elastase 1 promoter/enhancer to the rat growth hormone gene, was assayed in fetal liver or pancreas, respectively, while two natural genes, an oligonucleotide-marked mouse metallothionein I gene and the human beta-globin gene, were assayed in fetal liver. In each case there was, on average, 10- to 100-fold more mRNA produced from the intron-containing construct. Moreover, mRNA levels were proportional to the relative rates of transcription that were measured in isolated nuclei. However, when the expression of the two mouse metallothionein I gene-based constructs was tested after transfection into cultured cells, little difference was observed. These observations suggest that introns play a role in facilitating transcription of microinjected genes and that this effect may be manifest only on genes exposed to developmental influences.',\n", - " 'author': ['Brinster, Ralph L.',\n", - " 'Allen, James M.',\n", - " 'Behringer, Richard R.',\n", - " 'Gelinas, Richard E.',\n", - " 'Palmiter, Richard D.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/85/3/836\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/85/3/836\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/85/3/836\"}'],\n", - " 'title': ['Introns increase transcriptional efficiency in transgenic mice.']},\n", - " {'bibcode': '2022NatCo..13..437L',\n", - " 'abstract': 'Analysis of off-target editing is an important aspect of the development of safe nuclease-based genome editing therapeutics. in vivo assessment of nuclease off-target activity has primarily been indirect (based on discovery in vitro, in cells or via computational prediction) or through ChIP-based detection of double-strand break (DSB) DNA repair factors, which can be cumbersome. Herein we describe GUIDE-tag, which enables one-step, off-target genome editing analysis in mouse liver and lung. The GUIDE-tag system utilizes tethering between the Cas9 nuclease and the DNA donor to increase the capture rate of nuclease-mediated DSBs and UMI incorporation via Tn5 tagmentation to avoid PCR bias. These components can be delivered as SpyCas9-mSA ribonucleoprotein complexes and biotin-dsDNA donor for in vivo editing analysis. GUIDE-tag enables detection of off-target sites where editing rates are ≥ 0.2%. UDiTaS analysis utilizing the same tagmented genomic DNA detects low frequency translocation events with off-target sites and large deletions in vivo. The SpyCas9-mSA and biotin-dsDNA system provides a method to capture DSB loci in vivo in a variety of tissues with a workflow that is amenable to analysis of gross genomic alterations that are associated with genome editing.',\n", - " 'author': ['Liang, Shun-Qing',\n", - " 'Liu, Pengpeng',\n", - " 'Smith, Jordan L.',\n", - " 'Mintzer, Esther',\n", - " 'Maitland, Stacy',\n", - " 'Dong, Xiaolong',\n", - " 'Yang, Qiyuan',\n", - " 'Lee, Jonathan',\n", - " 'Haynes, Cole M.',\n", - " 'Zhu, Lihua Julie',\n", - " 'Watts, Jonathan K.',\n", - " 'Sontheimer, Erik J.',\n", - " 'Wolfe, Scot A.',\n", - " 'Xue, Wen'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41467-022-28135-9\"}'],\n", - " 'title': ['Genome-wide detection of CRISPR editing in vivo using GUIDE-tag']},\n", - " {'bibcode': '1966RSPSB.165...61C',\n", - " 'abstract': \"Hitherto the only sources of 'Bacillus piliformis' available for experimental study of Tyzzer's disease have been infected mouse liver and brain and the sole evidence that this organism is the aetiological agent has been its constant association with the typical liver lesions of the disease. The isolation and serial propagation of B. piliformis in embryonated eggs is described in the preceding paper (Craigie 1966) and this communication reports results obtained when infected yolk sac and chick embryo liver were injected into mice. B. piliformis did not lose its capacity to infect hepatic cells of the mouse and produce typical liver lesions when subjected to serial passage in embryonated eggs. A non-sporing variant proved as pathogenic as the parent sporing strain and produced hepatic lesions in rats and hamsters. In general, suspensions prepared from infected yolk sac and chick embryo liver were sufficiently potent to produce liver infection when injected intraperitoneally and with a number of preparations fatal infection was obtained by intraperitoneal injection of adult mice not treated with cortisone. With active preparations the enhancing effect of cortisone was confirmed. Penicillin was found effective in checking experimental and naturally occurring infection. An increase in the severity of infection was demonstrated in mice implanted with a transplantable sarcoma, in which the organism multiplied. B. piliformis was also found to survive in the Krebs 2 ascites tumour preserved at -75 degrees C.\",\n", - " 'author': ['Craigie, J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1098%2Frspb.1966.0058\"}'],\n", - " 'title': [\"'Bacillus piliformis' (Tyzzer) and Tyzzer's Disease of the Laboratory Mouse. II. Mouse Pathogenicity of B. piliformis Grown in Embryonated Eggs\"]},\n", - " {'bibcode': '2021NatSR..1111307K',\n", - " 'abstract': 'Frozen section analysis is a frequently used method for examination of tissue samples, especially for tumour detection. In the majority of cases, the aim is to identify characteristic tissue morphologies or tumour margins. Depending on the type of tissue, a high number of misdiagnoses are associated with this process. In this work, a fast spectroscopic measurement device and workflow was developed that significantly improves the speed of whole frozen tissue section analyses and provides sufficient information to visualize tissue structures and tumour margins, dependent on their lipid and protein molecular vibrations. That optical and non-destructive method is based on selected wavenumbers in the mid-infrared (MIR) range. We present a measuring system that substantially outperforms a commercially available Fourier Transform Infrared (FT-IR) Imaging system, since it enables acquisition of reduced spectral information at a scan field of 1 cm2 in 3 s, with a spatial resolution of 20 µm. This allows fast visualization of segmented structure areas with little computational effort. For the first time, this multiphotometric MIR system is applied to biomedical tissue sections. We are referencing our novel MIR scanner on cryopreserved murine sagittal and coronal brain sections, especially focusing on the hippocampus, and show its usability for rapid identification of primary hepatocellular carcinoma (HCC) in mouse liver.',\n", - " 'author': ['Kümmel, Tim',\n", - " 'van Marwick, Björn',\n", - " 'Rittel, Miriam',\n", - " 'Ramallo Guevara, Carina',\n", - " 'Wühler, Felix',\n", - " 'Teumer, Tobias',\n", - " 'Wängler, Björn',\n", - " 'Hopf, Carsten',\n", - " 'Rädle, Matthias'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-021-90777-4\"}'],\n", - " 'title': ['Rapid brain structure and tumour margin detection on whole frozen tissue sections by fast multiphotometric mid-infrared scanning']},\n", - " {'bibcode': '2016NatNa..11..986Z',\n", - " 'abstract': \"Until now, the Food and Drug Administration (FDA)-approved iron supplement ferumoxytol and other iron oxide nanoparticles have been used for treating iron deficiency, as contrast agents for magnetic resonance imaging and as drug carriers. Here, we show an intrinsic therapeutic effect of ferumoxytol on the growth of early mammary cancers, and lung cancer metastases in liver and lungs. In vitro, adenocarcinoma cells co-incubated with ferumoxytol and macrophages showed increased caspase-3 activity. Macrophages exposed to ferumoxytol displayed increased mRNA associated with pro-inflammatory Th1-type responses. In vivo, ferumoxytol significantly inhibited growth of subcutaneous adenocarcinomas in mice. In addition, intravenous ferumoxytol treatment before intravenous tumour cell challenge prevented development of liver metastasis. Fluorescence-activated cell sorting (FACS) and histopathology studies showed that the observed tumour growth inhibition was accompanied by increased presence of pro-inflammatory M1 macrophages in the tumour tissues. Our results suggest that ferumoxytol could be applied 'off label' to protect the liver from metastatic seeds and potentiate macrophage-modulating cancer immunotherapies.\",\n", - " 'author': ['Zanganeh, Saeid',\n", - " 'Hutter, Gregor',\n", - " 'Spitler, Ryan',\n", - " 'Lenkov, Olga',\n", - " 'Mahmoudi, Morteza',\n", - " 'Shaw, Aubie',\n", - " 'Pajarinen, Jukka Sakari',\n", - " 'Nejadnik, Hossein',\n", - " 'Goodman, Stuart',\n", - " 'Moseley, Michael',\n", - " 'Coussens, Lisa Marie',\n", - " 'Daldrup-Link, Heike Elisabeth'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnnano.2016.168\"}'],\n", - " 'title': ['Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues']},\n", - " {'bibcode': '2012Sci...335.1503C',\n", - " 'abstract': 'Alzheimer’s disease (AD) is associated with impaired clearance of β-amyloid (Aβ) from the brain, a process normally facilitated by apolipoprotein E (apoE). ApoE expression is transcriptionally induced through the action of the nuclear receptors peroxisome proliferator-activated receptor gamma and liver X receptors in coordination with retinoid X receptors (RXRs). Oral administration of the RXR agonist bexarotene to a mouse model of AD resulted in enhanced clearance of soluble Aβ within hours in an apoE-dependent manner. Aβ plaque area was reduced more than 50% within just 72 hours. Furthermore, bexarotene stimulated the rapid reversal of cognitive, social, and olfactory deficits and improved neural circuit function. Thus, RXR activation stimulates physiological Aβ clearance mechanisms, resulting in the rapid reversal of a broad range of Aβ-induced deficits.',\n", - " 'author': ['Cramer, Paige E.',\n", - " 'Cirrito, John R.',\n", - " 'Wesson, Daniel W.',\n", - " 'Lee, C. Y. Daniel',\n", - " 'Karlo, J. Colleen',\n", - " 'Zinn, Adriana E.',\n", - " 'Casali, Brad T.',\n", - " 'Restivo, Jessica L.',\n", - " 'Goebel, Whitney D.',\n", - " 'James, Michael J.',\n", - " 'Brunden, Kurt R.',\n", - " 'Wilson, Donald A.',\n", - " 'Landreth, Gary E.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.1217697\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.1217697\"}'],\n", - " 'title': ['ApoE-Directed Therapeutics Rapidly Clear β-Amyloid and Reverse Deficits in AD Mouse Models']},\n", - " {'bibcode': '2008PNAS..10514017S',\n", - " 'abstract': 'Infection of mice with sporozoites of Plasmodium berghei or Plasmodium yoelii has been used extensively to evaluate liver-stage protection by candidate preerythrocytic malaria vaccines. Unfortunately, repeated success of such vaccines in mice has not translated readily to effective malaria vaccines in humans. Thus, mice may be used better as models to dissect basic parameters required for immunity to Plasmodium-infection than as preclinical vaccine models. In turn, this basic information may aid in the rational design of malaria vaccines. Here, we describe a model of circumsporozoite-specific memory CD8 T cell generation that protects mice against multiple P. berghei sporozoite challenges for at least 19 months. Using this model we defined a threshold frequency of memory CD8 T cells in the blood that predicts long-term sterilizing immunity against liver-stage infection. Importantly, the number of Plasmodium-specific memory CD8 T cells required for immunity greatly exceeds the number required for resistance to other pathogens. In addition, this model allowed us to identify readily individual immunized mice that exceed or fall below the protective threshold before infection, information that should greatly facilitate studies to dissect basic mechanisms of protective CD8 T cell memory against liver-stage Plasmodium infection. Furthermore, the extremely large threshold in memory CD8 T cell frequencies required for long-term protection in mice may have important implications for development of effective malaria vaccines.',\n", - " 'author': ['Schmidt, Nathan W.',\n", - " 'Podyminogin, Rebecca L.',\n", - " 'Butler, Noah S.',\n", - " 'Badovinac, Vladimir P.',\n", - " 'Tucker, Brad J.',\n", - " 'Bahjat, Keith S.',\n", - " 'Lauer, Peter',\n", - " 'Reyes-Sandoval, Arturo',\n", - " 'Hutchings, Claire L.',\n", - " 'Moore, Anne C.',\n", - " 'Gilbert, Sarah C.',\n", - " 'Hill, Adrian V.',\n", - " 'Bartholomay, Lyric C.',\n", - " 'Harty, John T.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/105/37/14017\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/105/37/14017.full.pdf\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0805452105\"}'],\n", - " 'title': ['Memory CD8 T cell responses exceeding a large but definable threshold provide long-term immunity to malaria']},\n", - " {'bibcode': '2014Natur.506..382L',\n", - " 'abstract': 'Recombinant adeno-associated viral (rAAV) vectors have shown early promise in clinical trials. The therapeutic transgene cassette can be packaged in different AAV capsid pseudotypes, each having a unique transduction profile. At present, rAAV capsid serotype selection for a specific clinical trial is based on effectiveness in animal models. However, preclinical animal studies are not always predictive of human outcome. Here, in an attempt to further our understanding of these discrepancies, we used a chimaeric human-murine liver model to compare directly the relative efficiency of rAAV transduction in human versus mouse hepatocytes in vivo. As predicted from preclinical and clinical studies, rAAV2 vectors functionally transduced mouse and human hepatocytes at equivalent but relatively low levels. However, rAAV8 vectors, which are very effective in many animal models, transduced human hepatocytes rather poorly--approximately 20 times less efficiently than mouse hepatocytes. In light of the limitations of the rAAV vectors currently used in clinical studies, we used the same murine chimaeric liver model to perform serial selection using a human-specific replication-competent viral library composed of DNA-shuffled AAV capsids. One chimaeric capsid composed of five different parental AAV capsids was found to transduce human primary hepatocytes at high efficiency in vitro and in vivo, and provided species-selected transduction in primary liver, cultured cells and a hepatocellular carcinoma xenograft model. This vector is an ideal clinical candidate and a reagent for gene modification of human xenotransplants in mouse models of human diseases. More importantly, our results suggest that humanized murine models may represent a more precise approach for both selecting and evaluating clinically relevant rAAV serotypes for gene therapeutic applications.',\n", - " 'author': ['Lisowski, Leszek',\n", - " 'Dane, Allison P.',\n", - " 'Chu, Kirk',\n", - " 'Zhang, Yue',\n", - " 'Cunningham, Sharon C.',\n", - " 'Wilson, Elizabeth M.',\n", - " 'Nygaard, Sean',\n", - " 'Grompe, Markus',\n", - " 'Alexander, Ian E.',\n", - " 'Kay, Mark A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature12875\"}'],\n", - " 'title': ['Selection and evaluation of clinically relevant AAV variants in a xenograft liver model']},\n", - " {'bibcode': '1981PNAS...78.3659F',\n", - " 'abstract': 'Fetal mouse liver hepatocytes proliferate on a substrate of irradiated pigskin epidermis scored with scalpel blade slits to permit cell access to the basement membrane. At the time the cells are explanted, fetal genes, such as those responsible for production of alpha-fetoprotein (AFP) and gamma-glutamyltransferase (GGTase), are strongly expressed. The levels of GGTase decrease rapidly and become undetectable within 2 weeks. The levels of AFP decrease more gradually but become undetectable after 3-5 weeks in culture. As the AFP levels decrease, there is a concomitant increase in albumin production. Hydrocortisone prolongs production of AFP (for up to 8 weeks) but not of GGTase, and it decreases albumin production for up to 8 weeks. Once cells lose AFP expression, addition of hydrocortisone does not restart it. Based on these data, fetal mouse liver hepatocytes, cultured on pigskin, seem to be an excellent in vitro model for liver cell maturation.',\n", - " 'author': ['Freeman, Aaron E.',\n", - " 'Engvall, Eva',\n", - " 'Hirata, Koichi',\n", - " 'Yoshida, Yutaka',\n", - " 'Kottel, Randall H.',\n", - " 'Hilborn, Virginia',\n", - " 'Ruoslahti, Erkki'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/78/6/3659\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/78/6/3659\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/78/6/3659\"}'],\n", - " 'title': ['Differentiation of fetal liver cells in vitro.']},\n", - " {'bibcode': '1991Natur.351..317K',\n", - " 'abstract': 'THE exact role of hepatitis B virus in the development of liver cancer is not known. The recent identification of a viral regulatory gene HBx suggests a possible direct involvement of the virus whereby the HBx protein, acting as a transcriptional transactivator of viral genes, may alter host gene expression and lead to the development of hepatocellular carcinoma. We have tested this possibility by placing the entire HBx gene under its own regulatory elements directly into the germline of mice. Transgenic animals harbouring this viral gene succumbed to progressive histopathological changes specifically in the liver, beginning with multifocal areas of altered hepatocytes, followed by the appearance of benign adenomas, and proceeding to the development of malignant carcinomas. Male mice developed disease and died much earlier than females. This transgenic animal model appears ideal for defining the molecular events that follow the expression of the viral HBx gene and are responsible for the development of liver cancer.',\n", - " 'author': ['Kim, Chang-Min',\n", - " 'Koike, Kazuhiko',\n", - " 'Saito, Izumu',\n", - " 'Miyamura, Tatsuo',\n", - " 'Jay, Gilbert'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F351317a0\"}'],\n", - " 'title': ['HBx gene of hepatitis B virus induces liver cancer in transgenic mice']},\n", - " {'bibcode': '2001PNAS...98.7522K',\n", - " 'abstract': 'Insulin resistance in skeletal muscle and liver may play a primary role in the development of type 2 diabetes mellitus, and the mechanism by which insulin resistance occurs may be related to alterations in fat metabolism. Transgenic mice with muscle- and liver-specific overexpression of lipoprotein lipase were studied during a 2-h hyperinsulinemic-euglycemic clamp to determine the effect of tissue-specific increase in fat on insulin action and signaling. Muscle-lipoprotein lipase mice had a 3-fold increase in muscle triglyceride content and were insulin resistant because of decreases in insulin-stimulated glucose uptake in skeletal muscle and insulin activation of insulin receptor substrate-1-associated phosphatidylinositol 3-kinase activity. In contrast, liver-lipoprotein lipase mice had a 2-fold increase in liver triglyceride content and were insulin resistant because of impaired ability of insulin to suppress endogenous glucose production associated with defects in insulin activation of insulin receptor substrate-2-associated phosphatidylinositol 3-kinase activity. These defects in insulin action and signaling were associated with increases in intracellular fatty acid-derived metabolites (i.e., diacylglycerol, fatty acyl CoA, ceramides). Our findings suggest a direct and causative relationship between the accumulation of intracellular fatty acid-derived metabolites and insulin resistance mediated via alterations in the insulin signaling pathway, independent of circulating adipocyte-derived hormones.',\n", - " 'author': ['Kim, Jason K.',\n", - " 'Fillmore, Jonathan J.',\n", - " 'Chen, Yan',\n", - " 'Yu, Chunli',\n", - " 'Moore, Irene K.',\n", - " 'Pypaert, Marc',\n", - " 'Lutz, E. Peer',\n", - " 'Kako, Yuko',\n", - " 'Velez-Carrasco, Wanda',\n", - " 'Goldberg, Ira J.',\n", - " 'Breslow, Jan L.',\n", - " 'Shulman, Gerald I.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/98/13/7522\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/98/13/7522\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/98/13/7522\"}'],\n", - " 'title': ['Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance']},\n", - " {'bibcode': '2000PNAS...9710442L',\n", - " 'abstract': 'A physiological examination of mice harboring a null allele at the aryl hydrocarbon (Ah) locus revealed that the encoded aryl hydrocarbon receptor plays a role in the resolution of fetal vascular structures during development. Although the aryl hydrocarbon receptor is more commonly studied for its role in regulating xenobiotic metabolism and dioxin toxicity, a developmental role of this protein is supported by the observation that Ah null mice display smaller livers, reduced fecundity, and decreased body weights. Upon investigating the liver phenotype, we found that the decrease in liver size is directly related to a reduction in hepatocyte size. We also found that smaller hepatocyte size is the result of massive portosystemic shunting in null animals. Colloidal carbon uptake and microsphere perfusion studies indicated that 56% of portal blood flow bypasses the liver sinusoids. Latex corrosion casts and angiography demonstrated that shunting is consistent with the existence of a patent ductus venosus in adult animals. Importantly, fetal vascular structures were also observed at other sites. Intravital microscopy demonstrated an immature sinusoidal architecture in the liver and persistent hyaloid arteries in the eyes of adult Ah null mice, whereas corrosion casting experiments described aberrations in kidney vascular patterns.',\n", - " 'author': ['Lahvis, Garet P.',\n", - " 'Lindell, Susanne L.',\n", - " 'Thomas, Russell S.',\n", - " 'McCuskey, Robert S.',\n", - " 'Murphy, Christopher',\n", - " 'Glover, Edward',\n", - " 'Bentz, Michael',\n", - " 'Southard, James',\n", - " 'Bradfield, Christopher A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/97/19/10442\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/97/19/10442\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/97/19/10442\"}'],\n", - " 'title': ['Portosystemic shunting and persistent fetal vascular structures in aryl hydrocarbon receptor-deficient mice']},\n", - " {'bibcode': '2017NatSR...715167K',\n", - " 'abstract': 'Cell-based assays are growing in importance for screening drugs and investigating their mechanisms of action. Most of the assays use so-called \"normal\" cell strain because it is difficult to produce cell lines in which the disease conditions are reproduced. In this study, we used a cell-resealing technique, which reversibly permeabilizes the plasma membrane, to develop diabetic (Db) model hepatocytes into which cytosol from diabetic mouse liver had been introduced. Db model hepatocytes showed several disease-specific phenotypes, namely disturbance of insulin-induced repression of gluconeogenic gene expression and glucose secretion. Quantitative image analysis and principal component analysis revealed that the ratio of phosphorylated Akt (pAkt) to Akt was the best index to describe the difference between wild-type and Db model hepatocytes. By performing image-based drug screening, we found pioglitazone, a PPARγ agonist, increased the pAkt/Akt ratio, which in turn ameliorated the insulin-induced transcriptional repression of the gluconeogenic gene phosphoenolpyruvate carboxykinase 1. The disease-specific model cells coupled with image-based quantitative analysis should be useful for drug development, enabling the reconstitution of disease conditions at the cellular level and the discovery of disease-specific markers.',\n", - " 'author': ['Kano, Fumi', 'Noguchi, Yoshiyuki', 'Murata, Masayuki'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-017-15443-0\"}'],\n", - " 'title': ['Establishment and phenotyping of disease model cells created by cell-resealing technique']},\n", - " {'bibcode': '2021NatCo..12.5204K',\n", - " 'abstract': 'Secretory proteins are an essential component of interorgan communication networks that regulate animal physiology. Current approaches for identifying secretory proteins from specific cell and tissue types are largely limited to in vitro or ex vivo models which often fail to recapitulate in vivo biology. As such, there is mounting interest in developing in vivo analytical tools that can provide accurate information on the origin, identity, and spatiotemporal dynamics of secretory proteins. Here, we describe iSLET (in situ Secretory protein Labeling via ER-anchored TurboID) which selectively labels proteins that transit through the classical secretory pathway via catalytic actions of Sec61b-TurboID, a proximity labeling enzyme anchored in the ER lumen. To validate iSLET in a whole-body system, we express iSLET in the mouse liver and demonstrate efficient labeling of liver secretory proteins which could be tracked and identified within circulating blood plasma. Furthermore, proteomic analysis of the labeled liver secretome enriched from liver iSLET mouse plasma is highly consistent with previous reports of liver secretory protein profiles. Taken together, iSLET is a versatile and powerful tool for studying spatiotemporal dynamics of secretory proteins, a valuable class of biomarkers and therapeutic targets.',\n", - " 'author': ['Kim, Kwang-eun',\n", - " 'Park, Isaac',\n", - " 'Kim, Jeesoo',\n", - " 'Kang, Myeong-Gyun',\n", - " 'Choi, Won Gun',\n", - " 'Shin, Hyemi',\n", - " 'Kim, Jong-Seo',\n", - " 'Rhee, Hyun-Woo',\n", - " 'Suh, Jae Myoung'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41467-021-25546-y\"}'],\n", - " 'title': ['Dynamic tracking and identification of tissue-specific secretory proteins in the circulation of live mice']},\n", - " {'bibcode': '2020NatSR..10.7083Y',\n", - " 'abstract': 'Spatial transcriptomics is useful for understanding the molecular organization of a tissue and providing insights into cellular function in a morphological context. In order to obtain reproducible results in spatial transcriptomics, we have to maintain tissue morphology and RNA molecule stability during the image acquisition and biomolecule collection processes. Here, we developed a tissue processing method for robust and reproducible RNA-seq from tissue microdissection samples. In this method, we suppressed RNA degradation in fresh-frozen tissue specimens by dehydration fixation and effectively collected a small amount of RNA molecules from microdissection samples by magnetic beads. We demonstrated the spatial transcriptome analysis of the mouse liver and brain in serial microdissection samples (100 μm in a diameter and 10 μm in thickness) produced by a microdissection punching system. Using our method, we could prevent RNA degradation at room temperature and effectively produce a sequencing library with Smart-seq2. This resulted in reproducible sequence read mapping in exon regions and the detection of more than 2000 genes compared to non-fixed samples in the RNA-seq analysis. Our method would be applied to various transcriptome analyses, providing the information for region specific gene expression in tissue specimens.',\n", - " 'author': ['Yamazaki, Miki',\n", - " 'Hosokawa, Masahito',\n", - " 'Arikawa, Koji',\n", - " 'Takahashi, Kiyofumi',\n", - " 'Sakanashi, Chikako',\n", - " 'Yoda, Takuya',\n", - " 'Matsunaga, Hiroko',\n", - " 'Takeyama, Haruko'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-020-63495-6\"}'],\n", - " 'title': ['Effective microtissue RNA extraction coupled with Smart-seq2 for reproducible and robust spatial transcriptome analysis']},\n", - " {'bibcode': '2017NatSR...7..174S',\n", - " 'abstract': 'Diet plays a crucial role in shaping human health and disease. Diets promoting obesity and insulin resistance can lead to severe metabolic diseases, while calorie-restricted (CR) diets can improve health and extend lifespan. In this work, we fed mice either a chow diet (CD), a 16 week high-fat diet (HFD), or a CR diet to compare and contrast the effects of these diets on mouse liver biology. We collected transcriptomic and epigenomic datasets from these mice using RNA-Seq and DNase-Seq. We found that both CR and HFD induce extensive transcriptional changes, in some cases altering the same genes in the same direction. We used our epigenomic data to infer transcriptional regulatory proteins bound near these genes that likely influence their expression levels. In particular, we found evidence for critical roles played by PPARα and RXRα. We used ChIP-Seq to profile the binding locations for these factors in HFD and CR livers. We found extensive binding of PPARα near genes involved in glycolysis/gluconeogenesis and uncovered a role for this factor in regulating anaerobic glycolysis. Overall, we generated extensive transcriptional and epigenomic datasets from livers of mice fed these diets and uncovered new functions and gene targets for PPARα.',\n", - " 'author': ['Soltis, Anthony R.',\n", - " 'Motola, Shmulik',\n", - " 'Vernia, Santiago',\n", - " 'Ng, Christopher W.',\n", - " 'Kennedy, Norman J.',\n", - " 'Dalin, Simona',\n", - " 'Matthews, Bryan J.',\n", - " 'Davis, Roger J.',\n", - " 'Fraenkel, Ernest'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-017-00267-9\"}'],\n", - " 'title': ['Hyper- and hypo- nutrition studies of the hepatic transcriptome and epigenome suggest that PPARα regulates anaerobic glycolysis']},\n", - " {'bibcode': '2017NatSR...712480F',\n", - " 'abstract': 'Nucleic acids, which constitute the genetic material of all organisms, are continuously exposed to endogenous and exogenous damaging agents, representing a significant challenge to genome stability and genome integrity over the life of a cell or organism. Unrepaired DNA lesions, such as single- and double-stranded DNA breaks (SSBs and DSBs), and single-stranded gaps can block progression of the DNA replication fork, causing replicative stress and/or cell cycle arrest. However, translesion synthesis (TLS) DNA polymerases, such as Rev1, have the ability to bypass some DNA lesions, which can circumvent the process leading to replication fork arrest and minimize replicative stress. Here, we show that Rev1-deficiency in mouse embryo fibroblasts or mouse liver tissue is associated with replicative stress and mitochondrial dysfunction. In addition, Rev1-deficiency is associated with high poly(ADP) ribose polymerase 1 (PARP1) activity, low endogenous NAD+, low expression of SIRT1 and PGC1α and low adenosine monophosphate (AMP)-activated kinase (AMPK) activity. We conclude that replication stress via Rev1-deficiency contributes to metabolic stress caused by compromized mitochondrial function via the PARP-NAD+-SIRT1-PGC1α axis.',\n", - " 'author': ['Fakouri, Nima Borhan',\n", - " 'Durhuus, Jon Ambæk',\n", - " 'Regnell, Christine Elisabeth',\n", - " 'Angleys, Maria',\n", - " 'Desler, Claus',\n", - " 'Hasan-Olive, Md Mahdi',\n", - " 'Martín-Pardillos, Ana',\n", - " 'Tsaalbi-Shtylik, Anastasia',\n", - " 'Thomsen, Kirsten',\n", - " 'Lauritzen, Martin',\n", - " 'Bohr, Vilhelm A.',\n", - " 'de Wind, Niels',\n", - " 'Bergersen, Linda Hildegard',\n", - " 'Rasmussen, Lene Juel'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-017-12662-3\"}'],\n", - " 'title': ['Rev1 contributes to proper mitochondrial function via the PARP-NAD+-SIRT1-PGC1α axis']},\n", - " {'bibcode': '2010PNAS..107..264P',\n", - " 'abstract': 'MicroRNA (miRNAs) are negative regulators of gene expression and can function as tumor suppressors or oncogenes. Expression patterns of miRNAs and their role in the pathogenesis of hepatocellular carcinoma (HCC) are still poorly understood. We profiled miRNA expression in tissue samples (104 HCC, 90 adjacent cirrhotic livers, 21 normal livers) as well as in 35 HCC cell lines. A set of 12 miRNAs (including miR-21, miR-221/222, miR-34a, miR-519a, miR-93, miR-96, and let-7c) was linked to disease progression from normal liver through cirrhosis to full-blown HCC. miR-221/222, the most up-regulated miRNAs in tumor samples, are shown to target the CDK inhibitor p27 and to enhance cell growth in vitro. Conversely, these activities can be efficiently inhibited by an antagomiR specific for miR-221. In addition, we show, using a mouse model of liver cancer, that miR-221 overexpression stimulates growth of tumorigenic murine hepatic progenitor cells. Finally, we identified DNA damage-inducible transcript 4 (DDIT4), a modulator of mTOR pathway, as a bona fide target of miR-221. Taken together, these data reveal an important contribution for miR-221 in hepatocarcinogenesis and suggest a role for DDIT4 dysregulation in this process. Thus, the use of synthetic inhibitors of miR-221 may prove to be a promising approach to liver cancer treatment.',\n", - " 'author': ['Pineau, Pascal',\n", - " 'Volinia, Stefano',\n", - " 'McJunkin, Katherine',\n", - " 'Marchio, Agnès',\n", - " 'Battiston, Carlo',\n", - " 'Terris, Benoît',\n", - " 'Mazzaferro, Vincenzo',\n", - " 'Lowe, Scott W.',\n", - " 'Croce, Carlo M.',\n", - " 'Dejean, Anne'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/107/1/264\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0907904107\"}'],\n", - " 'title': ['miR-221 overexpression contributes to liver tumorigenesis']},\n", - " {'bibcode': '2018AdM....3005308C',\n", - " 'abstract': 'mRNA‑mediated protein replacement represents a promising concept for the treatment of liver disorders. Children born with fumarylacetoacetate hydrolase (FAH) mutations suffer from Hepatorenal Tyrosinemia Type 1 (HT‑1) resulting in renal dysfunction, liver failure, neurological impairments, and cancer. Protein replacement therapy using FAH mRNA offers tremendous potential to cure HT‑1, but is currently hindered by the development of effective mRNA carriers that can function in diseased livers. Structure‑guided, rational optimization of 5A2‑SC8 mRNA‑loaded dendrimer lipid nanoparticles (mDLNPs) increases delivery potency of FAH mRNA, resulting in functional FAH protein and sustained normalization of body weight and liver function in FAH−/− knockout mice. Optimization using luciferase mRNA produces DLNP carriers that are efficacious at mRNA doses as low as 0.05 mg kg−1 in vivo. mDLNPs transfect > 44% of all hepatocytes in the liver, yield high FAH protein levels (0.5 mg kg−1 mRNA), and are well tolerated in a knockout mouse model with compromised liver function. Genetically engineered FAH−/− mice treated with FAH mRNA mDLNPs have statistically equivalent levels of TBIL, ALT, and AST compared to wild type C57BL/6 mice and maintain normal weight throughout the month‑long course of treatment. This study provides a framework for the rational optimization of LNPs to improve delivery of mRNA broadly and introduces a specific and viable DLNP carrier with translational potential to treat genetic diseases of the liver.',\n", - " 'author': ['Cheng, Qiang',\n", - " 'Wei, Tuo',\n", - " 'Jia, Yuemeng',\n", - " 'Farbiak, Lukas',\n", - " 'Zhou, Kejin',\n", - " 'Zhang, Shuyuan',\n", - " 'Wei, Yonglong',\n", - " 'Zhu, Hao',\n", - " 'Siegwart, Daniel J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Fadma.201805308\"}'],\n", - " 'title': ['Dendrimer‑Based Lipid Nanoparticles Deliver Therapeutic FAH mRNA to Normalize Liver Function and Extend Survival in a Mouse Model of Hepatorenal Tyrosinemia Type I']},\n", - " {'bibcode': '2006Natur.441..537G',\n", - " 'abstract': 'RNA interference (RNAi) is a universal and evolutionarily conserved phenomenon of post-transcriptional gene silencing by means of sequence-specific mRNA degradation, triggered by small double-stranded RNAs. Because this mechanism can be efficiently induced in vivo by expressing target-complementary short hairpin RNA (shRNA) from non-viral and viral vectors, RNAi is attractive for functional genomics and human therapeutics. Here we systematically investigate the long-term effects of sustained high-level shRNA expression in livers of adult mice. Robust shRNA expression in all the hepatocytes after intravenous infusion was achieved with an optimized shRNA delivery vector based on duplex-DNA-containing adeno-associated virus type 8 (AAV8). An evaluation of 49 distinct AAV/shRNA vectors, unique in length and sequence and directed against six targets, showed that 36 resulted in dose-dependent liver injury, with 23 ultimately causing death. Morbidity was associated with the downregulation of liver-derived microRNAs (miRNAs), indicating possible competition of the latter with shRNAs for limiting cellular factors required for the processing of various small RNAs. In vitro and in vivo shRNA transfection studies implied that one such factor, shared by the shRNA/miRNA pathways and readily saturated, is the nuclear karyopherin exportin-5. Our findings have fundamental consequences for future RNAi-based strategies in animals and humans, because controlling intracellular shRNA expression levels will be imperative. However, the risk of oversaturating endogenous small RNA pathways can be minimized by optimizing shRNA dose and sequence, as exemplified here by our report of persistent and therapeutic RNAi against human hepatitis B virus in vivo.',\n", - " 'author': ['Grimm, Dirk',\n", - " 'Streetz, Konrad L.',\n", - " 'Jopling, Catherine L.',\n", - " 'Storm, Theresa A.',\n", - " 'Pandey, Kusum',\n", - " 'Davis, Corrine R.',\n", - " 'Marion, Patricia',\n", - " 'Salazar, Felix',\n", - " 'Kay, Mark A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature04791\"}'],\n", - " 'title': ['Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways']},\n", - " {'bibcode': '2021NatCo..12.7172D',\n", - " 'abstract': 'Complement receptor of immunoglobulin superfamily (CRIg) is expressed on liver macrophages and directly binds complement component C3b or Gram-positive bacteria to mediate phagocytosis. CRIg plays important roles in several immune-mediated diseases, but it is not clear how its pathogen recognition and phagocytic functions maintain homeostasis and prevent disease. We previously associated cytolysin-positive Enterococcus faecalis with severity of alcohol-related liver disease. Here, we demonstrate that CRIg is reduced in liver tissues from patients with alcohol-related liver disease. CRIg-deficient mice developed more severe ethanol-induced liver disease than wild-type mice; disease severity was reduced with loss of toll-like receptor 2. CRIg-deficient mice were less efficient than wild-type mice at clearing Gram-positive bacteria such as Enterococcus faecalis that had translocated from gut to liver. Administration of the soluble extracellular domain CRIg-Ig protein protected mice from ethanol-induced steatohepatitis. Our findings indicate that ethanol impairs hepatic clearance of translocated pathobionts, via decreased hepatic CRIg, which facilitates progression of liver disease.',\n", - " 'author': ['Duan, Yi',\n", - " 'Chu, Huikuan',\n", - " 'Brandl, Katharina',\n", - " 'Jiang, Lu',\n", - " 'Zeng, Suling',\n", - " 'Meshgin, Nairika',\n", - " 'Papachristoforou, Eleni',\n", - " 'Argemi, Josepmaria',\n", - " 'Mendes, Beatriz G.',\n", - " 'Wang, Yanhan',\n", - " 'Su, Hua',\n", - " 'Sun, Weizhong',\n", - " 'Llorente, Cristina',\n", - " 'Hendrikx, Tim',\n", - " 'Liu, Xiao',\n", - " 'Hosseini, Mojgan',\n", - " 'Kisseleva, Tatiana',\n", - " 'Brenner, David A.',\n", - " 'Bataller, Ramon',\n", - " 'Ramachandran, Prakash',\n", - " 'Karin, Michael',\n", - " 'Fu, Wenxian',\n", - " 'Schnabl, Bernd'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41467-021-27385-3\"}'],\n", - " 'title': ['CRIg on liver macrophages clears pathobionts and protects against alcoholic liver disease']},\n", - " {'bibcode': '2010PNAS..107..844I',\n", - " 'abstract': 'TGF-β-activated kinase 1 (TAK1) is a MAP3K family member that activates NF-κB and JNK via Toll-like receptors and the receptors for IL-1, TNF-α, and TGF-β. Because the TAK1 downstream molecules NF-κB and JNK have opposite effects on cell death and carcinogenesis, the role of TAK1 in the liver is unpredictable. To address this issue, we generated hepatocyte-specific Tak1-deficient (Tak1ΔHEP) mice. The Tak1ΔHEP mice displayed spontaneous hepatocyte death, compensatory proliferation, inflammatory cell infiltration, and perisinusoidal fibrosis at age 1 month. Older Tak1ΔHEP mice developed multiple cancer nodules characterized by increased expression of fetal liver genes including α-fetoprotein. Cultures of primary hepatocytes deficient in Tak1 exhibited spontaneous cell death that was further increased in response to TNF-α. TNF-α increased caspase-3 activity but activated neither NF-κB nor JNK in Tak1-deficient hepatocytes. Genetic abrogation of TNF receptor type I (TNFRI) in Tak1ΔHEP mice reduced liver damage, inflammation, and fibrosis compared with unmodified Tak1ΔHEP mice. In conclusion, hepatocyte-specific deletion of TAK1 in mice resulted in spontaneous hepatocyte death, inflammation, fibrosis, and carcinogenesis that was partially mediated by TNFR signaling, indicating that TAK1 is an essential component for cellular homeostasis in the liver.',\n", - " 'author': ['Inokuchi, Sayaka',\n", - " 'Aoyama, Tomonori',\n", - " 'Miura, Kouichi',\n", - " 'Österreicher, Christoph H.',\n", - " 'Kodama, Yuzo',\n", - " 'Miyai, Katsumi',\n", - " 'Akira, Shizuo',\n", - " 'Brenner, David A.',\n", - " 'Seki, Ekihiro'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/107/2/844\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0909781107\"}'],\n", - " 'title': ['Disruption of TAK1 in hepatocytes causes hepatic injury, inflammation, fibrosis, and carcinogenesis']},\n", - " {'bibcode': '2004PNAS..10110422U',\n", - " 'abstract': 'Insulin resistance, obesity, diabetes, dyslipidemia, and nonalcoholic fatty liver are components of the metabolic syndrome, a disease complex that is increasing at epidemic rates in westernized countries. Although proinflammatory cytokines have been suggested to contribute to the development of these disorders, the molecular mechanism is poorly understood. Here we show that overexpression of suppressors of cytokine signaling (SOCS)-1 and SOCS-3 in liver causes insulin resistance and an increase in the key regulator of fatty acid synthesis in liver, sterol regulatory element-binding protein (SREBP)-1c. Conversely, inhibition of SOCS-1 and -3 in obese diabetic mice improves insulin sensitivity, normalizes the increased expression of SREBP-1c, and dramatically ameliorates hepatic steatosis and hypertriglyceridemia. In obese animals, increased SOCS proteins enhance SREBP-1c expression by antagonizing STAT3-mediated inhibition of SREBP-1c promoter activity. Thus, SOCS proteins play an important role in pathogenesis of the metabolic syndrome by concordantly modulating insulin signaling and cytokine signaling.',\n", - " 'author': ['Ueki, Kohjiro',\n", - " 'Kondo, Tatsuya',\n", - " 'Tseng, Yu-Hua',\n", - " 'Kahn, C. Ronald'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/101/28/10422\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0402511101\"}'],\n", - " 'title': ['Central role of suppressors of cytokine signaling proteins in hepatic steatosis, insulin resistance, and the metabolic syndrome in the mouse']},\n", - " {'bibcode': '1950Natur.166..783C',\n", - " 'abstract': \"APPLYING histochemical techniques devised by Friedenwald and Becker1, it was found2 that in normal male mouse liver (Fig. 1) and kidney, β-glucuronidase activity is mainly confined to the mitochondria. It was considered that the rise in glucuronidase activity shown by biochemical methods to occur in these organs when repair has commenced subsequent to damage3 might be reflected in a change in the cytochemical picture. This has been found to be the case in experiments with frozen sections of mouse liver regenerating after partial hepatectomy or carbon-tetrachloride poisoning, using 8-hydroxyquinoline glucuronide as substrate. In contrast to the mitochondrial site in normal liver, β-glucuronidase activity as detected by this method now appears to correspond in situation to the nucleus (Fig. 2). This did not result from aggregation of the mitochondria, which were seen to be normally situated in sequent sections stained with Iron Hæmatoxylin after fixation in Regaud's fluid. On the other hand, Feulgen staining in regenerating liver gave a similar picture to that obtained by the glucuronidase method. Normal liver sections stained by the Feulgen method did not in any way resemble those obtained histochemically.\",\n", - " 'author': ['Campbell, J. G.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F166783a0\"}'],\n", - " 'title': ['Cytochemical Localization of β-Glucuronidase']},\n", - " {'bibcode': '1975Natur.258..726J',\n", - " 'abstract': 'THEORIES of the development of mammalian hepatic haemopoiesis have polarised around two viewpoints. One hypothesis suggests that multipotential haemopoietic stem cells (HSC) migrate from the yolk sac and colonise the developing hepatic primordia1. According to the other view, hepatic haemopoietic tissue arises from the transformation of liver mesenchyme cells and thus has no direct relationship with vitelline haemopoiesis2. To solve this developmental problem, it is necessary to establish techniques, either in vivo or in vitro, to maintain hepatic tissue in a foetal state. In vitro studies have demonstrated that hepatic haemopoietic tissue can develop if tissues are explanted after the 28-somite stage3. Thus, these experiments did not verify the inductive model2 of hepatic haemopoiesis, although the in vitro conditions may have curtailed haemopoietic induction without altering hepatic differentiation. With an exogenous source of yolk-sac-derived HSC attempts have been made to colonise pre-28-somite hepatic explants in vitro, using the appearance of granulopoiesis as an indication of successful recombination. These experiments were not conclusive since granulopoiesis was observed with yolk sac cells in vitro in the absence of hepatic tissue (G.R.J., unpublished).',\n", - " 'author': ['Johnson, G. R.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F258726a0\"}'],\n", - " 'title': ['Role of stem cell migration in initiation of mouse foetal liver haemopoiesis']},\n", - " {'bibcode': '2018NatSR...816070C',\n", - " 'abstract': 'Exosomes are small extracellular membrane vesicles released from endosomes of various cells and could be found in most body fluids. The main functions of exosomes have been recognized as important mediators of intercellular communication and as potential biomarkers of various disease states. This study investigated whether exogenous exosomes from mice with acetaminophen (APAP)-induced liver injury can damage the recipient hepatic cells or promote hepatotoxicity in mice. We observed that exogenous exosomes derived from APAP-exposed mice were internalized into the primary mouse hepatocytes or HepG2 hepatoma cells and significantly decreased the viability of these recipient cells. They also elevated mRNA transcripts and proteins associated with the cell death signaling pathways in primary hepatocytes or HepG2 cells via exosomes-to-cell communications. In addition, confocal microscopy of ex vivo liver section showed that exogenously added exosomes were accumulated in recipient hepatocytes. Furthermore, plasma reactive oxygen species and hepatic TNF-α/IL-1β production were elevated in APAP-exosomes recipient mice compared to control-exosomes recipient mice. The levels of apoptosis-related proteins such as phospho-JNK/JNK, Bax, and cleaved caspase-3 were increased in mouse liver received APAP-exosomes. These results demonstrate that exogenous exosomes from APAP-exposed mice with acute liver injury are functional and stimulate cell death or toxicity of the recipient hepatocytes and mice.',\n", - " 'author': ['Cho, Young-Eun',\n", - " 'Seo, Wonhyo',\n", - " 'Kim, Do-Kyun',\n", - " 'Moon, Pyong-Gon',\n", - " 'Kim, Sang-Hyun',\n", - " 'Lee, Byung-Heon',\n", - " 'Song, Byoung-Joon',\n", - " 'Baek, Moon-Chang'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-018-34309-7\"}'],\n", - " 'title': ['Exogenous exosomes from mice with acetaminophen-induced liver injury promote toxicity in the recipient hepatocytes and mice']},\n", - " {'bibcode': '2010Natur.468.1100S',\n", - " 'abstract': 'The multi-component mechanistic target of rapamycin complex 1 (mTORC1) kinase is the central node of a mammalian pathway that coordinates cell growth with the availability of nutrients, energy and growth factors. Progress has been made in the identification of mTORC1 pathway components and in understanding their functions in cells, but there is relatively little known about the role of the pathway in vivo. Specifically, we have little knowledge regarding the role mTOCR1 has in liver physiology. In fasted animals, the liver performs numerous functions that maintain whole-body homeostasis, including the production of ketone bodies for peripheral tissues to use as energy sources. Here we show that mTORC1 controls ketogenesis in mice in response to fasting. We find that liver-specific loss of TSC1 (tuberous sclerosis 1), an mTORC1 inhibitor, leads to a fasting-resistant increase in liver size, and to a pronounced defect in ketone body production and ketogenic gene expression on fasting. The loss of raptor (regulatory associated protein of mTOR, complex 1) an essential mTORC1 component, has the opposite effects. In addition, we find that the inhibition of mTORC1 is required for the fasting-induced activation of PPARα (peroxisome proliferator activated receptor α), the master transcriptional activator of ketogenic genes, and that suppression of NCoR1 (nuclear receptor co-repressor 1), a co-repressor of PPARα, reactivates ketogenesis in cells and livers with hyperactive mTORC1 signalling. Like livers with activated mTORC1, livers from aged mice have a defect in ketogenesis, which correlates with an increase in mTORC1 signalling. Moreover, we show that the suppressive effects of mTORC1 activation and ageing on PPARα activity and ketone production are not additive, and that mTORC1 inhibition is sufficient to prevent the ageing-induced defect in ketogenesis. Thus, our findings reveal that mTORC1 is a key regulator of PPARα function and hepatic ketogenesis and suggest a role for mTORC1 activity in promoting the ageing of the liver.',\n", - " 'author': ['Sengupta, Shomit',\n", - " 'Peterson, Timothy R.',\n", - " 'Laplante, Mathieu',\n", - " 'Oh, Stephanie',\n", - " 'Sabatini, David M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature09584\"}'],\n", - " 'title': ['mTORC1 controls fasting-induced ketogenesis and its modulation by ageing']},\n", - " {'bibcode': '2018Sci...359.1156M',\n", - " 'abstract': 'Despite multiple associations between the microbiota and immune diseases, their role in autoimmunity is poorly understood. We found that translocation of a gut pathobiont, Enterococcus gallinarum, to the liver and other systemic tissues triggers autoimmune responses in a genetic background predisposing to autoimmunity. Antibiotic treatment prevented mortality in this model, suppressed growth of E. gallinarum in tissues, and eliminated pathogenic autoantibodies and T cells. Hepatocyte-E. gallinarum cocultures induced autoimmune-promoting factors. Pathobiont translocation in monocolonized and autoimmune-prone mice induced autoantibodies and caused mortality, which could be prevented by an intramuscular vaccine targeting the pathobiont. E. gallinarum-specific DNA was recovered from liver biopsies of autoimmune patients, and cocultures with human hepatocytes replicated the murine findings; hence, similar processes apparently occur in susceptible humans. These discoveries show that a gut pathobiont can translocate and promote autoimmunity in genetically predisposed hosts.',\n", - " 'author': ['Manfredo Vieira, S.',\n", - " 'Hiltensperger, M.',\n", - " 'Kumar, V.',\n", - " 'Zegarra-Ruiz, D.',\n", - " 'Dehner, C.',\n", - " 'Khan, N.',\n", - " 'Costa, F. R. C.',\n", - " 'Tiniakou, E.',\n", - " 'Greiling, T.',\n", - " 'Ruff, W.',\n", - " 'Barbieri, A.',\n", - " 'Kriegel, C.',\n", - " 'Mehta, S. S.',\n", - " 'Knight, J. R.',\n", - " 'Jain, D.',\n", - " 'Goodman, A. L.',\n", - " 'Kriegel, M. A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.aar7201\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.aar7201\"}'],\n", - " 'title': ['Translocation of a gut pathobiont drives autoimmunity in mice and humans']},\n", - " {'bibcode': '2017LSSR...13....1C',\n", - " 'abstract': \"In this paper we describe revisions to the NASA Space Cancer Risk (NSCR) model focusing on updates to probability distribution functions (PDF) representing the uncertainties in the radiation quality factor (QF) model parameters and the dose and dose-rate reduction effectiveness factor (DDREF). We integrate recent heavy ion data on liver, colorectal, intestinal, lung, and Harderian gland tumors with other data from fission neutron experiments into the model analysis. In an earlier work we introduced distinct QFs for leukemia and solid cancer risk predictions, and here we consider liver cancer risks separately because of the higher RBE's reported in mouse experiments compared to other tumors types, and distinct risk factors for liver cancer for astronauts compared to the U.S. population. The revised model is used to make predictions of fatal cancer and circulatory disease risks for 1-year deep space and International Space Station (ISS) missions, and a 940 day Mars mission. We analyzed the contribution of the various model parameter uncertainties to the overall uncertainty, which shows that the uncertainties in relative biological effectiveness (RBE) factors at high LET due to statistical uncertainties and differences across tissue types and mouse strains are the dominant uncertainty. NASA's exposure limits are approached or exceeded for each mission scenario considered. Two main conclusions are made: 1) Reducing the current estimate of about a 3-fold uncertainty to a 2-fold or lower uncertainty will require much more expansive animal carcinogenesis studies in order to reduce statistical uncertainties and understand tissue, sex and genetic variations. 2) Alternative model assumptions such as non-targeted effects, increased tumor lethality and decreased latency at high LET, and non-cancer mortality risks from circulatory diseases could significantly increase risk estimates to several times higher than the NASA limits.\",\n", - " 'author': ['Cucinotta, Francis A.', 'To, Khiet', 'Cacao, Eliedonna'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.lssr.2017.01.005\"}'],\n", - " 'title': ['Predictions of space radiation fatality risk for exploration missions']},\n", - " {'bibcode': '2021JPhCS1912a2046S',\n", - " 'abstract': 'The present research aimed to investigate the acute toxicity effects of eel (Anguilla bicolor bicolor) oil on liver and kidney function after oral administration in mice. Eel is one of marine biodiversity and fish consumed in many countries, especially Japan, China, and Indonesia. Toxic effect symptoms were observed for 14 days. On the 15th day, the level of alanine aminotransferase (ALT), histology profile of liver, creatinine, and histology profile of kidney were measured. The current result showed the LD50 value of eel oil was > 15 g/kg b.w, which categorized practically nontoxic. Eel oil didn’t affect the toxic effect symptoms on ALT level, lever histology profile, and creatinine level. Histology profile observation showed that eel oil effects on the histological profile of mice kidney with moderate injury level (26-50%).',\n", - " 'author': ['Sasongko, H.',\n", - " 'Sugiantoro, R. S. W.',\n", - " 'Advaita, N.',\n", - " 'Sugiyarto'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1088%2F1742-6596%2F1912%2F1%2F012046\"}'],\n", - " 'title': ['Acute Oral Toxicity Test of Eel (Anguilla bicolor bicolor) Oil in Mice Liver and Kidney Cells']},\n", - " {'bibcode': '2019DIB....2504112A',\n", - " 'abstract': 'Resistin is an adipokine produced in white adipose tissue that is thought to modulate insulin sensitivity in peripheral tissues (such as liver, skeletal muscle or adipose tissue). Human and murine resistin molecules share only about 60% sequence homology. [1] Contrary to humans, in which resistin is secreted mostly by macrophages, Park and Ahima 2013 resistin in rodents is produced primarily by the mature adipocytes of the white adipose tissue. Although resistin can bind to toll-like receptor 4 (TLF4) activating proinflammatory responses in human and rodents, [3-8] the inflammatory actions of resistin in human monocytes were found to be mediated by resistin binding to adenylyl cyclase-associated protein 1 (CAP1). [9] In this study, we aimed to investigate the in vitro effects of resistin on the expression of various genes related to insulin resistance in mouse liver cells. Using BNL CL.2 cells, we investigated the effect of resistin in untransfected or CAP1 siRNA-transfected cells on the expression of 84 key genes involved in insulin resistance.',\n", - " 'author': ['Avtanski, Dimiter', 'Chen, Karin', 'Poretsky, Leonid'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.dib.2019.104112\"}'],\n", - " 'title': ['Resistin and adenylyl cyclase-associated protein 1 (CAP1) regulate the expression of genes related to insulin resistance in BNL CL.2 mouse liver cells']},\n", - " {'bibcode': '1973PNAS...70.3899B',\n", - " 'abstract': 'In tumors and embryoid bodies of mouse teratoma a correlation has been established between specific activity of alkaline phosphatase (EC 3.1.3.1) and content of embryonal carcinoma, the stem cell of the tumor. A histochemical study of embryoid bodies has shown that high levels of the enzyme are confined to embryonal carcinoma. Fifteen tissue culture lines could be classified into three groups: (a) lines identifiable as pluripotential embryonal carcinoma by their morphology, tumorigenicity, and capacity to differentiate in vivo; (b) nullipotential embryonal carcinoma, resembling pluripotential embryonal carcinoma in morphology and malignancy but giving rise to undifferentiated tumors; and (c) lines of apparently nonmalignant somatic cells. Both types of embryonal carcinoma possess levels of alkaline phosphatase 5- to a 100-fold higher than the somatic cell lines. The embryonal carcinoma enzyme resembles the enzymes from kidney and placenta in kinetics of thermal inactivation and sensitivity to the inhibitor L-phenylalanine, but is distinguishable from the alkaline phosphatases of liver and intestine. These findings are discussed in relation to the use of teratoma for the study of cell differentiation.',\n", - " 'author': ['Bernstine, Edward G.',\n", - " 'Hooper, Martin L.',\n", - " 'Grandchamp, Simone',\n", - " 'Ephrussi, Boris'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/70/12/3899\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/70/12/3899\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/70/12/3899\"}'],\n", - " 'title': ['Alkaline Phosphatase Activity in Mouse Teratoma']},\n", - " {'bibcode': '2015Natur.524..180W',\n", - " 'abstract': 'The source of new hepatocytes in the uninjured liver has remained an open question. By lineage tracing using the Wnt-responsive gene Axin2 in mice, we identify a population of proliferating and self-renewing cells adjacent to the central vein in the liver lobule. These pericentral cells express the early liver progenitor marker Tbx3, are diploid, and thereby differ from mature hepatocytes, which are mostly polyploid. The descendants of pericentral cells differentiate into Tbx3-negative, polyploid hepatocytes, and can replace all hepatocytes along the liver lobule during homeostatic renewal. Adjacent central vein endothelial cells provide Wnt signals that maintain the pericentral cells, thereby constituting the niche. Thus, we identify a cell population in the liver that subserves homeostatic hepatocyte renewal, characterize its anatomical niche, and identify molecular signals that regulate its activity.',\n", - " 'author': ['Wang, Bruce',\n", - " 'Zhao, Ludan',\n", - " 'Fish, Matt',\n", - " 'Logan, Catriona Y.',\n", - " 'Nusse, Roel'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"data\", \"url\": \"http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse68806\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature14863\"}'],\n", - " 'title': ['Self-renewing diploid Axin2+ cells fuel homeostatic renewal of the liver']},\n", - " {'bibcode': '1979PNAS...76.1373W',\n", - " 'abstract': 'In this report, we demonstrate the feasibility of transforming mouse cells deficient in adenine phosphoribosyltransferase (aprt; AMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.7) to the aprt+ phenotype by means of DNA-mediated gene transfer. Transformation was effected by using unfractionated high molecular weight genomic DNA from Chinese hamster, human, and mouse cells and restriction endonuclease-digested DNA from rabbit liver. The transformation frequency observed was between 1 and 10 colonies per 10(6) cells per 20 microgram of donor DNA. Transformants displayed enzymatic activity that was donor derived as demonstrated by isoelectric focusing of cytoplasmic extracts. These transformants fall into two classes: those that are phenotypically stable when grown in the absence of selective pressure and those that are phenotypically unstable under the same conditions.',\n", - " 'author': ['Wigler, Michael',\n", - " 'Pellicer, Angel',\n", - " 'Silverstein, Saul',\n", - " 'Axel, Richard',\n", - " 'Urlaub, Gail',\n", - " 'Chasin, Lawrence'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/76/3/1373\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/76/3/1373\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/76/3/1373\"}'],\n", - " 'title': ['DNA-mediated transfer of the adenine phosphoribosyltransferase locus into mammalian cells.']},\n", - " {'bibcode': '2017INL.....7..221K',\n", - " 'abstract': 'Nanotechnology has revolutionized gene therapy, diagnostics and environmental remediation. Their bulk production, uses and disposal have posed threat to the environment. With the appearance of these nanoparticles in the environment, their toxicity assessment is an immediate concern. This review is an attempt to summarize the major techniques used in cytotoxity determination. The review also presents a detailed and elaborative discussion on the toxicity imposed by different types of nanoparticles including carbon nanotubes, gold nanoparticles, silver nanoparticles, quantum dots, fullerenes, aluminium nanoparticles, zinc nanoparticles, iron nanoparticles, titanium nanoparticles and silica nanoparticles. It discusses the in vitro and in vivo toxological effects of nanoparticles on bacteria, microalgae, zebrafish, crustacean, fish, rat, mouse, pig, guinea pig, human cell lines and human. It also discusses toxological effects on organs such as liver, kidney, spleen, sperm, neural tissues, liver lysosomes, spleen macrophages, glioblastoma cells, hematoma cells and various mammalian cell lines. It provides information about the effects of nanoparticles on the gene-expression, growth and reproduction of the organisms.',\n", - " 'author': ['Kumar, Vinay', 'Sharma, Neha', 'Maitra, S. S.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1007%2Fs40089-017-0221-3\"}'],\n", - " 'title': ['In vitro and in vivo toxicity assessment of nanoparticles']},\n", - " {'bibcode': '2001PNAS...9813266P',\n", - " 'abstract': 'The mouse has become an indispensable and versatile model organism for the study of development, genetics, behavior, and disease. The application of comprehensive gene expression profiling technologies to compare normal and diseased tissues or to assess molecular alterations resulting from various experimental interventions has the potential to provide highly detailed qualitative and quantitative descriptions of these processes. Ideally, to interpret experimental data, the magnitude and diversity of gene expression for the system under study should be well characterized, yet little is known about the normal variation of mouse gene expression in vivo. To assess natural differences in murine gene expression, we used a 5406-clone spotted cDNA microarray to quantitate transcript levels in the kidney, liver, and testis from each of 6 normal male C57BL6 mice. We used ANOVA to compare the variance across the six mice to the variance among four replicate experiments performed for each mouse tissue. For the 6 kidney samples, 102 of 3,088 genes (3.3%) exhibited a statistically significant mouse variance at a level of 0.05. In the testis, 62 of 3,252 genes (1.9%) showed statistically significant variance, and in the liver, there were 21 of 2,514 (0.8%) genes with significantly variable expression. Immune-modulated, stress-induced, and hormonally regulated genes were highly represented among the transcripts that were most variable. The expression levels of several genes varied significantly in more than one tissue. These studies help to define the baseline level of variability in mouse gene expression and emphasize the importance of replicate microarray experiments.',\n", - " 'author': ['Pritchard, Colin C.',\n", - " 'Hsu, Li',\n", - " 'Delrow, Jeffrey',\n", - " 'Nelson, Peter S.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/98/23/13266\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/98/23/13266\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/98/23/13266\"}'],\n", - " 'title': ['Project normal: Defining normal variance in mouse gene expression']},\n", - " {'bibcode': '2002PNAS...99.4596N',\n", - " 'abstract': 'We recently reported the hemochromatosis-like phenotype observed in our Usf2 knockout mice. In these mice, as in murine models of hemochromatosis and patients with hereditary hemochromatosis, iron accumulates in parenchymal cells (in particular, liver and pancreas), whereas the reticuloendothelial system is spared from this iron loading. We suggested that this phenotypic trait could be attributed to the absence, in the Usf2 knockout mice, of a secreted liver-specific peptide, hepcidin. We conjectured that the reverse situation, namely overexpression of hepcidin, might result in phenotypic traits of iron deficiency. This question was addressed by generating transgenic mice expressing hepcidin under the control of the liver-specific transthyretin promoter. We found that the majority of the transgenic mice were born with a pale skin and died within a few hours after birth. These transgenic animals had decreased body iron levels and presented severe microcytic hypochromic anemia. So far, three mosaic transgenic animals have survived. They were unequivocally identified by physical features, including reduced body size, pallor, hairless and crumpled skin. These pleiotropic effects were found to be associated with erythrocyte abnormalities, with marked anisocytosis, poikylocytosis and hypochromia, which are features characteristic of iron-deficiency anemia. These results strongly support the proposed role of hepcidin as a putative iron-regulatory hormone. The animal models devoid of hepcidin (the Usf2 knockout mice) or overexpressing the peptide (the transgenic mice presented in this paper) represent valuable tools for investigating iron homeostasis in vivo and for deciphering the molecular mechanisms of hepcidin action.',\n", - " 'author': ['Nicolas, Gaël',\n", - " 'Bennoun, Myriam',\n", - " 'Porteu, Arlette',\n", - " 'Mativet, Sandrine',\n", - " 'Beaumont, Carole',\n", - " 'Grandchamp, Bernard',\n", - " 'Sirito, Mario',\n", - " 'Sawadogo, Michèle',\n", - " 'Kahn, Axel',\n", - " 'Vaulont, Sophie'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/99/7/4596\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/99/7/4596\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/99/7/4596\"}'],\n", - " 'title': ['Severe iron deficiency anemia in transgenic mice expressing liver hepcidin']},\n", - " {'bibcode': '1995PNAS...9210302M',\n", - " 'abstract': 'Thy-1loSca-1+Lin-Mac-1+CD4- cells have been isolated from the livers of C57BL-Thy-1.1 fetuses. This population appears to be an essentially pure population of hematopoietic stem cells (HSC), in that injection of only six cells into lethally irradiated adult recipients yields a limit dilution frequency of donor cell-reconstituted mice. Sixty-seven to 77% of clones in this population exhibit long-term multilineage progenitor activity. This population appears to include all long-term multilineage reconstituting progenitors in the fetal liver. A high proportion of cells are in cycle, and the absolute number of cells in this population doubles daily in the fetal liver until 14.5 days postcoitum. At 15.5 days postcoitum, the frequency of this population falls dramatically. Long-term reconstituting HSC clones from the fetal liver give rise to higher levels of reconstitution in lethally irradiated mice than long-term reconstituting HSC from the bone marrow. The precise phenotypic and functional characteristics of HSC vary according to tissue and time during ontogeny.',\n", - " 'author': ['Morrison, Sean J.',\n", - " 'Hemmati, Houman D.',\n", - " 'Wandycz, Antoni M.',\n", - " 'Weissman, Irving L.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/92/22/10302\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/92/22/10302\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/92/22/10302\"}'],\n", - " 'title': ['The purification and characterization of fetal liver hematopoietic stem cells.']},\n", - " {'bibcode': '2004PNAS..10117216C',\n", - " 'abstract': 'Although inappropriate activation of the Wnt/β-catenin pathway has been implicated in the development of hepatocellular carcinoma (HCC), the role of this signaling in liver carcinogenesis remains unclear. To investigate this issue, we constructed a mutant mouse strain, Apclox/lox, in which exon 14 of the tumor-suppressor gene adenomatous polyposis coli (Apc) is flanked by loxP sequences. i.v. injection of adenovirus encoding Cre recombinase (AdCre) at high multiplicity [109 plaque-forming units (pfu) per mouse] inactivated the Apc gene in the liver and resulted in marked hepatomegaly, hepatocyte hyperplasia, and rapid mortality. β-Catenin signaling activation was demonstrated by nuclear and cytoplasmic accumulation of β-catenin in the hepatocytes and by the induction of β-catenin target genes (glutamine synthetase, glutamate transporter 1, ornithine aminotransferase, and leukocyte cell-derived chemotaxin 2) in the liver. To test a long-term oncogenic effect, we inoculated mice with lower doses of AdCre (0.5 × 109 pfu per mouse), compatible with both survival and persistence of β-catenin-activated cells. In these conditions, 67% of mice developed HCC. β-Catenin signaling was strongly activated in these Apc-inactivated HCCs. The HCCs were well, moderately, or poorly differentiated. Indeed, their histological and molecular features mimicked human HCC. Thus, deletion of Apc in the liver provides a valuable model of human HCC, and, in this model, activation of the Wnt/β-catenin pathway by invalidation of Apc is required for liver tumorigenesis.',\n", - " 'author': ['Colnot, S.',\n", - " 'Decaens, T.',\n", - " 'Niwa-Kawakita, M.',\n", - " 'Godard, C.',\n", - " 'Hamard, G.',\n", - " 'Kahn, A.',\n", - " 'Giovannini, M.',\n", - " 'Perret, C.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/101/49/17216\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0404761101\"}'],\n", - " 'title': ['Liver-targeted disruption of Apc in mice activates β-catenin signaling and leads to hepatocellular carcinomas']},\n", - " {'bibcode': '2008Sci...322..945S',\n", - " 'abstract': 'Pluripotent stem cells have been generated from mouse and human somatic cells by viral expression of the transcription factors Oct4, Sox2, Klf4, and c-Myc. A major limitation of this technology is the use of potentially harmful genome-integrating viruses. We generated mouse induced pluripotent stem (iPS) cells from fibroblasts and liver cells by using nonintegrating adenoviruses transiently expressing Oct4, Sox2, Klf4, and c-Myc. These adenoviral iPS (adeno-iPS) cells show DNA demethylation characteristic of reprogrammed cells, express endogenous pluripotency genes, form teratomas, and contribute to multiple tissues, including the germ line, in chimeric mice. Our results provide strong evidence that insertional mutagenesis is not required for in vitro reprogramming. Adenoviral reprogramming may provide an improved method for generating and studying patient-specific stem cells and for comparing embryonic stem cells and iPS cells.',\n", - " 'author': ['Stadtfeld, Matthias',\n", - " 'Nagaya, Masaki',\n", - " 'Utikal, Jochen',\n", - " 'Weir, Gordon',\n", - " 'Hochedlinger, Konrad'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.1162494\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.1162494\"}'],\n", - " 'title': ['Induced Pluripotent Stem Cells Generated Without Viral Integration']},\n", - " {'bibcode': '2009Sci...326..437L',\n", - " 'abstract': 'Circadian clocks coordinate behavioral and physiological processes with daily light-dark cycles by driving rhythmic transcription of thousands of genes. Whereas the master clock in the brain is set by light, pacemakers in peripheral organs, such as the liver, are reset by food availability, although the setting, or “entrainment,” mechanisms remain mysterious. Studying mouse fibroblasts, we demonstrated that the nutrient-responsive adenosine monophosphate-activated protein kinase (AMPK) phosphorylates and destabilizes the clock component cryptochrome 1 (CRY1). In mouse livers, AMPK activity and nuclear localization were rhythmic and inversely correlated with CRY1 nuclear protein abundance. Stimulation of AMPK destabilized cryptochromes and altered circadian rhythms, and mice in which the AMPK pathway was genetically disrupted showed alterations in peripheral clocks. Thus, phosphorylation by AMPK enables cryptochrome to transduce nutrient signals to circadian clocks in mammalian peripheral organs.',\n", - " 'author': ['Lamia, Katja A.',\n", - " 'Sachdeva, Uma M.',\n", - " 'DiTacchio, Luciano',\n", - " 'Williams, Elliot C.',\n", - " 'Alvarez, Jacqueline G.',\n", - " 'Egan, Daniel F.',\n", - " 'Vasquez, Debbie S.',\n", - " 'Juguilon, Henry',\n", - " 'Panda, Satchidananda',\n", - " 'Shaw, Reuben J.',\n", - " 'Thompson, Craig B.',\n", - " 'Evans, Ronald M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.1172156\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.1172156\"}'],\n", - " 'title': ['AMPK Regulates the Circadian Clock by Cryptochrome Phosphorylation and Degradation']},\n", - " {'bibcode': '2008Sci...320.1492L',\n", - " 'abstract': 'Dietary carbohydrates regulate hepatic lipogenesis by controlling the expression of critical enzymes in glycolytic and lipogenic pathways. We found that the transcription factor XBP1, a key regulator of the unfolded protein response, is required for the unrelated function of normal fatty acid synthesis in the liver. XBP1 protein expression in mice was elevated after feeding carbohydrates and corresponded with the induction of critical genes involved in fatty acid synthesis. Inducible, selective deletion of XBP1 in the liver resulted in marked hypocholesterolemia and hypotriglyceridemia, secondary to a decreased production of lipids from the liver. This phenotype was not accompanied by hepatic steatosis or compromise in protein secretory function. The identification of XBP1 as a regulator of lipogenesis has important implications for human dyslipidemias.',\n", - " 'author': ['Lee, Ann-Hwee',\n", - " 'Scapa, Erez F.',\n", - " 'Cohen, David E.',\n", - " 'Glimcher, Laurie H.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.1158042\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.1158042\"}'],\n", - " 'title': ['Regulation of Hepatic Lipogenesis by the Transcription Factor XBP1']},\n", - " {'bibcode': '1997Radcb..39..293W',\n", - " 'abstract': 'Based on the study of DNA adduction with nicotine, we have measured the mouse hepatic histone adduction with14C-labeled nicotinein vivoby bio-accelerator mass spectrometry (bio-AMS). In the exposure of mice to nicotine, the dose range administered was from 0.2 μg to 6.0 μg kg b.w.-1, which was equivalent to a very low level of human exposure to cigarette smoke. The adducts of either histone 1 (H1) or histone 3 (H3) with nicotine in mouse liver increased markedly with increasing nicotine dose. Our results have demonstrated that in the study of protein adduction with toxic xenobiotics as a biomarker, the AMS method achieves the highest sensitivity, 4.6 × 10-17mol (46 amol) adducts per mg H1 protein, compared to all the other methods used previously.',\n", - " 'author': ['Wu, X. H.',\n", - " 'Wang, H. F.',\n", - " 'Liu, Y. F.',\n", - " 'Lu, X. Y.',\n", - " 'Wang, J. J.',\n", - " 'Li, K.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1017%2FS0033822200053273\"}'],\n", - " 'title': ['Histone Adduction with Nicotine: A Bio-Ams Study']},\n", - " {'bibcode': '2017NatSR...716112K',\n", - " 'abstract': 'The mechanistic target of rapamycin complex 1 (mTORC1) is a central regulator of cell growth that is often aberrantly activated in cancer. However, mTORC1 inhibitors, such as rapamycin, have limited effectiveness as single agent cancer therapies, with feedback mechanisms inherent to the signaling network thought to diminish the anti-tumor effects of mTORC1 inhibition. Here, we identify the protein kinase and proto-oncogene PIM3 as being repressed downstream of mTORC1 signaling. PIM3 expression is suppressed in cells with loss of the tuberous sclerosis complex (TSC) tumor suppressors, which exhibit growth factor-independent activation of mTORC1, and in the mouse liver upon feeding-induced activation of mTORC1. Inhibition of mTORC1 with rapamycin induces PIM3 transcript and protein levels in a variety of settings. Suppression of PIM3 involves the sterol regulatory element-binding (SREBP) transcription factors SREBP1 and 2, whose activation and mRNA expression are stimulated by mTORC1 signaling. We find that PIM3 repression is mediated by miR-33, an intronic microRNA encoded within the SREBP loci, the expression of which is decreased with rapamycin. These results demonstrate that PIM3 is induced upon mTORC1 inhibition, with potential implications for the effects of mTORC1 inhibitors in TSC, cancers, and the many other disease settings influenced by aberrant mTORC1 signaling.',\n", - " 'author': ['Kelsey, Ilana',\n", - " 'Zbinden, Marie',\n", - " 'Byles, Vanessa',\n", - " 'Torrence, Margaret',\n", - " 'Manning, Brendan D.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-017-16398-y\"}'],\n", - " 'title': ['mTORC1 suppresses PIM3 expression via miR-33 encoded by the SREBP loci']},\n", - " {'bibcode': '2022PLSCB..18E9653V',\n", - " 'abstract': 'Biliary ducts collect bile from liver lobules, the smallest functional and anatomical units of liver, and carry it to the gallbladder. Disruptions in this process caused by defective embryonic development, or through ductal reaction in liver disease have a major impact on life quality and survival of patients. A deep understanding of the processes underlying bile duct lumen formation is crucial to identify intervention points to avoid or treat the appearance of defective bile ducts. Several hypotheses have been proposed to characterize the biophysical mechanisms driving initial bile duct lumen formation during embryogenesis. Here, guided by the quantification of morphological features and expression of genes in bile ducts from embryonic mouse liver, we sharpened these hypotheses and collected data to develop a high resolution individual cell-based computational model that enables to test alternative hypotheses in silico. This model permits realistic simulations of tissue and cell mechanics at sub-cellular scale. Our simulations suggest that successful bile duct lumen formation requires a simultaneous contribution of directed cell division of cholangiocytes, local osmotic effects generated by salt excretion in the lumen, and temporally-controlled differentiation of hepatoblasts to cholangiocytes, with apical constriction of cholangiocytes only moderately affecting luminal size.',\n", - " 'author': ['Van Liedekerke, Paul',\n", - " 'Gannoun, Lila',\n", - " 'Loriot, Axelle',\n", - " 'Johann, Tim',\n", - " 'Lemaigre, Frédéric P.',\n", - " 'Drasdo, Dirk'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pcbi.1009653\"}'],\n", - " 'title': ['Quantitative modeling identifies critical cell mechanics driving bile duct lumen formation']},\n", - " {'bibcode': '2017NatSR...7.6122K',\n", - " 'abstract': 'Complete removal of hepatitis B virus (HBV) DNA from nuclei is difficult by the current therapies. Recent reports have shown that a novel genome-editing tool using Cas9 with a single-guide RNA (sgRNA) system can cleave the HBV genome in vitro and in vivo. However, induction of a double-strand break (DSB) on the targeted genome by Cas9 risks undesirable off-target cleavage on the host genome. Nickase-Cas9 cleaves a single strand of DNA, and thereby two sgRNAs are required for inducing DSBs. To avoid Cas9-induced off-target mutagenesis, we examined the effects of the expressions of nickase-Cas9 and nuclease dead Cas9 (d-Cas9) with sgRNAs on HBV replication. The expression of nickase-Cas9 with a pair of sgRNAs cleaved the target HBV genome and suppressed the viral-protein expression and HBV replication in vitro. Moreover, nickase-Cas9 with the sgRNA pair cleaved the targeted HBV genome in mouse liver. Interestingly, d-Cas9 expression with the sgRNAs also suppressed HBV replication in vitro without cleaving the HBV genome. These results suggest the possible use of nickase-Cas9 and d-Cas9 with a pair of sgRNAs for eliminating HBV DNA from the livers of chronic hepatitis B patients with low risk of undesirable off-target mutation on the host genome.',\n", - " 'author': ['Kurihara, Takeshi',\n", - " 'Fukuhara, Takasuke',\n", - " 'Ono, Chikako',\n", - " 'Yamamoto, Satomi',\n", - " 'Uemura, Kentaro',\n", - " 'Okamoto, Toru',\n", - " 'Sugiyama, Masaya',\n", - " 'Motooka, Daisuke',\n", - " 'Nakamura, Shota',\n", - " 'Ikawa, Masato',\n", - " 'Mizokami, Masashi',\n", - " 'Maehara, Yoshihiko',\n", - " 'Matsuura, Yoshiharu'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-017-05905-w\"}'],\n", - " 'title': ['Suppression of HBV replication by the expression of nickase- and nuclease dead-Cas9']},\n", - " {'bibcode': '2018NatSR...8.8896G',\n", - " 'abstract': 'Abscisic acid (ABA) is an ancient stress hormone and is detectable in a wide variety of organisms where it regulates innate immunity and inflammation. Previously, we showed that oral supplementation with ABA decreased parasitemia in a mouse model of malaria, decreased liver and spleen pathology and reduced parasite transmission to mosquitoes. Here, we report that higher circulating ABA levels were associated with a reduced risk of symptomatic malaria in a cohort of Plasmodium falciparum-infected Ugandan children. To understand possible mechanisms of ABA protection in malaria, we returned to our mouse model to show that ABA effects on Plasmodium yoelii 17XNL infection were accompanied by minimal effects on complete blood count and blood chemistry analytes, suggesting a benefit to host health. In addition, orally delivered ABA induced patterns of gene expression in mouse liver and spleen that suggested enhancement of host anti-parasite defenses. To test these inferences, we utilized passive immunization and knockout mice to demonstrate that ABA supplementation increases circulating levels of protective, parasite-specific IgG and requires caspase-1 to reduce parasitemia. Collectively, ABA induces host responses that ameliorate infection and disease in an animal model and suggest that further studies of ABA in the context of human malaria are warranted.',\n", - " 'author': ['Glennon, Elizabeth K. K.',\n", - " 'Megawati, Dewi',\n", - " 'Torrevillas, Brandi K.',\n", - " 'Ssewanyana, Isaac',\n", - " 'Huang, Liusheng',\n", - " 'Aweeka, Fran',\n", - " 'Greenhouse, Bryan',\n", - " 'Adams, L. Garry',\n", - " 'Luckhart, Shirley'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-018-27073-1\"}'],\n", - " 'title': ['Elevated plasma abscisic acid is associated with asymptomatic falciparum malaria and with IgG-/caspase-1-dependent immunity in Plasmodium yoelii-infected mice']},\n", - " {'bibcode': '2016NatSR...636926D',\n", - " 'abstract': 'Emerging evidence implies a key role of angiopoietin-like protein 8 (Angptl8) in the metabolic transition between fasting and feeding, whereas much less is known about the mechanism of its own expression. Here we show that hepatic Angptl8 is rhythmically expressed, which involving the liver X receptor alpha (LXRα) and glucocorticoid receptor (GR) modulation during feeding and fasting periods, respectively. In addition, Angptl8 mRNA is very unstable, which contributes to the nature of its daily rhythmicity by rapidly responding to fasting/feeding transition. To explore its pathological function in dexamethasone (DEX)-induced fatty liver, we reversed its suppression by glucocorticoids through adenoviral delivery of Angptl8 gene in mouse liver. Surprisingly, hepatic overexpression of Angptl8 dramatically elevated plasma triglyceride (TG) and non-esterified fatty acid (NEFA) levels in DEX-treated mice, suggesting a metabolic interaction between Angptl8 and glucocorticoid signaling. Moreover, intracellular hepatic Angptl8 is implicated in the regulation of lipid homeostasis by the experiments with ectopic expression of a nonsecreted Angptl8 mutant (Δ25-Angptl8). Altogether, our data demonstrate the molecular mechanism of the diurnal rhythm of Angptl8 expression regulated by glucocorticoid signaling and LXRα pathway, and provide new evidence to understand the role of Angptl8 in maintaining plasma TG homeostasis.',\n", - " 'author': ['Dang, Fabin',\n", - " 'Wu, Rong',\n", - " 'Wang, Pengfei',\n", - " 'Wu, Yuting',\n", - " 'Azam, Md. Shofiul',\n", - " 'Xu, Qian',\n", - " 'Chen, Yaqiong',\n", - " 'Liu, Yi'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep36926\"}'],\n", - " 'title': ['Fasting and Feeding Signals Control the Oscillatory Expression of Angptl8 to Modulate Lipid Metabolism']},\n", - " {'bibcode': '2005PNAS..102.5374R',\n", - " 'abstract': 'PCSK9 encodes proprotein convertase subtilisin/kexin type 9a (PCSK9), a member of the proteinase K subfamily of subtilases. Missense mutations in PCSK9 cause an autosomal dominant form of hypercholesterolemia in humans, likely due to a gain-of-function mechanism because overexpression of either WT or mutant PCSK9 reduces hepatic LDL receptor protein (LDLR) in mice. Here, we show that livers of knockout mice lacking PCSK9 manifest increased LDLR protein but not mRNA. Increased LDLR protein led to increased clearance of circulating lipoproteins and decreased plasma cholesterol levels (46 mg/dl in Pcsk9-/- mice versus 96 mg/dl in WT mice). Statins, a class of drugs that inhibit cholesterol synthesis, increase expression of sterol regulatory element-binding protein-2 (SREBP-2), a transcription factor that activates both the Ldlr and Pcsk9 genes. Statin administration to Pcsk9-/- mice produced an exaggerated increase in LDLRs in liver and enhanced LDL clearance from plasma. These data demonstrate that PCSK9 regulates the amount of LDLR protein in liver and suggest that inhibitors of PCSK9 may act synergistically with statins to enhance LDLRs and reduce plasma cholesterol.',\n", - " 'author': ['Rashid, Shirya',\n", - " 'Curtis, David E.',\n", - " 'Garuti, Rita',\n", - " 'Anderson, Norma N.',\n", - " 'Bashmakov, Yuriy',\n", - " 'Ho, Y. K.',\n", - " 'Hammer, Robert E.',\n", - " 'Moon, Young-Ah',\n", - " 'Horton, Jay D.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/102/15/5374\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0501652102\"}'],\n", - " 'title': ['Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9']},\n", - " {'bibcode': '2010Natur.468..310D',\n", - " 'abstract': 'During embryogenesis, endothelial cells induce organogenesis before the development of circulation. These findings suggest that endothelial cells not only form passive conduits to deliver nutrients and oxygen, but also establish an instructive vascular niche, which through elaboration of paracrine trophogens stimulates organ regeneration, in a manner similar to endothelial-cell-derived angiocrine factors that support haematopoiesis. However, the precise mechanism by which tissue-specific subsets of endothelial cells promote organogenesis in adults is unknown. Here we demonstrate that liver sinusoidal endothelial cells (LSECs) constitute a unique population of phenotypically and functionally defined VEGFR3+CD34-VEGFR2+VE-cadherin+FactorVIII+CD45- endothelial cells, which through the release of angiocrine trophogens initiate and sustain liver regeneration induced by 70% partial hepatectomy. After partial hepatectomy, residual liver vasculature remains intact without experiencing hypoxia or structural damage, which allows study of physiological liver regeneration. Using this model, we show that inducible genetic ablation of vascular endothelial growth factor (VEGF)-A receptor-2 (VEGFR2) in the LSECs impairs the initial burst of hepatocyte proliferation (days 1-3 after partial hepatectomy) and subsequent reconstitution of the hepatovascular mass (days 4-8 after partial hepatectomy) by inhibiting upregulation of the endothelial-cell-specific transcription factor Id1. Accordingly, Id1-deficient mice also manifest defects throughout liver regeneration, owing to diminished expression of LSEC-derived angiocrine factors, including hepatocyte growth factor (HGF) and Wnt2. Notably, in in vitro co-cultures, VEGFR2-Id1 activation in LSECs stimulates hepatocyte proliferation. Indeed, intrasplenic transplantation of Id1+/+ or Id1-/- LSECs transduced with Wnt2 and HGF (Id1-/-Wnt2+HGF+ LSECs) re-establishes an inductive vascular niche in the liver sinusoids of the Id1-/- mice, initiating and restoring hepatovascular regeneration. Therefore, in the early phases of physiological liver regeneration, VEGFR2-Id1-mediated inductive angiogenesis in LSECs through release of angiocrine factors Wnt2 and HGF provokes hepatic proliferation. Subsequently, VEGFR2-Id1-dependent proliferative angiogenesis reconstitutes liver mass. Therapeutic co-transplantation of inductive VEGFR2+Id1+Wnt2+HGF+ LSECs with hepatocytes provides an effective strategy to achieve durable liver regeneration.',\n", - " 'author': ['Ding, Bi-Sen',\n", - " 'Nolan, Daniel J.',\n", - " 'Butler, Jason M.',\n", - " 'James, Daylon',\n", - " 'Babazadeh, Alexander O.',\n", - " 'Rosenwaks, Zev',\n", - " 'Mittal, Vivek',\n", - " 'Kobayashi, Hideki',\n", - " 'Shido, Koji',\n", - " 'Lyden, David',\n", - " 'Sato, Thomas N.',\n", - " 'Rabbany, Sina Y.',\n", - " 'Rafii, Shahin'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature09493\"}'],\n", - " 'title': ['Inductive angiocrine signals from sinusoidal endothelium are required for liver regeneration']},\n", - " {'bibcode': '1980Natur.283..397R',\n", - " 'abstract': 'Several drugs, including clofibrate (ethyl-a-p-chlorophenoxyisobutyrate)1, are now available for the treatment of hyperlipidaemias2,3 and others are in the process of preclinical or clinical evaluation4,5. Clofibrate, the most widely used hypo-lipidaemic drug in Europe and the US2, as well as other potent hypolipidaemic agents, cause massive hepatomegaly when administered to rats6-8, mice7,8 or hamsters (J.K.R., unpublished). This hepatomegaly is characteristically associated with a marked increase of peroxisomes (Fig. 1) in the liver cells of all three species6-8. These ubiquitous cytoplasmic organelles9,10contain catalase, several hydrogen peroxide-generating oxi-dases, carnitine acetyltransferase11 as well as enzymes involved in the β-oxidation of long-chain fatty acids12. The activities of these enzymes in liver are elevated in association with peroxisome proliferation8,13. As hepatomegaly and peroxisome proliferation persist for as long as these drugs are administered to the animals, we initiated chronic toxicity studies with selected hepatic peroxisome proliferators in CSb mice and F344 rats. Liver tumours were observed in both rats and mice fed nafeno-pin (2-methyl-2[p-(l,2,3,4-tetrahydro-l-naphthyl)phenoxy]-propionic acid)14-16 or Wy-14,643 ([4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid)17, two structurally unrelated compounds (Fig. 2, compounds 2 and 3) which are several times more potent than clofibrate in inducing peroxisome proliferation and hypolipidaemia8. Recent evidence indicates that clofibrate (Fig. 2, compound 1) is also carcinogenic when fed to rats at a concentration of 0.5% in the diet18,19. We report here that BR-931 ([4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio(N-β-hydroxyethyl)-acetamide])20 and tibric acid(2-chloro-5-(3,5-dimethylpiperidinosulphonyl)benzoic acid)8, two potent hypolipidaemic hepatic peroxisome proliferators (Fig. 2, compounds 4 and 5) induce hepatocellular carcinomas in CSb mice and/or F344 rats. Thus, the development of liver tumours, in animals fed five structually diverse hypolipidaemic compounds (Fig. 2) supports our hypothesis that potent hepatic peroxisome proliferators as a class are carcinogenic.',\n", - " 'author': ['Reddy, J. K.', 'Azarnoff, D. L.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F283397a0\"}'],\n", - " 'title': ['Hypolipidaemic hepatic peroxisome proliferators form a novel class of chemical carcinogens']},\n", - " {'bibcode': '2018NatSR...8.9281E',\n", - " 'abstract': 'The liver X receptors (LXRs), LXRα and LXRβ, are nuclear receptors that regulate lipid homeostasis. LXRs also regulate inflammatory responses in cultured macrophages. However, the role of LXRs in hepatic immune cells remains poorly characterized. We investigated the role of LXRs in regulation of inflammatory responses of hepatic mononuclear cells (MNCs) in mice. Both LXRα and LXRβ were expressed in mouse hepatic MNCs and F4/80+ Kupffer cells/macrophages. LXRα/β-knockout (KO) mice had an increased number of hepatic MNCs and elevated expression of macrophage surface markers and inflammatory cytokines compared to wild-type (WT) mice. Among MNCs, F4/80+CD11b+ cells, not F4/80+CD11b- or F4/80+CD68+ cells, were increased in LXRα/β-KO mice more than WT mice. Isolated hepatic MNCs and F4/80+CD11b+ cells of LXRα/β-KO mice showed enhanced production of inflammatory cytokines after stimulation by lipopolysaccharide or CpG-DNA compared to WT cells, and LXR ligand treatment suppressed lipopolysaccharide-induced cytokine expression in hepatic MNCs. Lipopolysaccharide administration also stimulated inflammatory cytokine production in LXRα/β-KO mice more effectively than WT mice. Thus, LXR deletion enhances recruitment of F4/80+CD11b+ Kupffer cells/macrophages and acute immune responses in the liver. LXRs regulate the Kupffer cell/macrophage population and innate immune and inflammatory responses in mouse liver.',\n", - " 'author': ['Endo-Umeda, Kaori',\n", - " 'Nakashima, Hiroyuki',\n", - " 'Komine-Aizawa, Shihoko',\n", - " 'Umeda, Naoki',\n", - " 'Seki, Shuhji',\n", - " 'Makishima, Makoto'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-018-27615-7\"}'],\n", - " 'title': ['Liver X receptors regulate hepatic F4/80+CD11b+ Kupffer cells/macrophages and innate immune responses in mice']},\n", - " {'bibcode': '2016NatSR...623781S',\n", - " 'abstract': 'Irreversible electroporation is a fast-growing liver ablation technique. Although safety has been well documented in small ablations, our aim is to assess its safety and feasibility when a large portion of liver is ablated. Eighty-seven mice were subjected to high voltage pulses directly delivered across parallel plate electrodes comprising around 40% of mouse liver. One group consisted in 55 athymic-nude, in which a tumor from the KM12C cell line was grown and the other thirty-two C57-Bl6 non-tumoral mice. Both groups were subsequently divided into subsets according to the delivered field strength (1000\\u2009V/cm, 2000\\u2009V/cm) and whether or not they received anti-hyperkalemia therapy. Early mortality (less than 24\\u2009hours post-IRE) in the 2000\\u2009V/cm group was observed and revealed considerably higher mean potassium levels. In contrast, the animals subjected to a 2000\\u2009V/cm field treated with the anti-hyperkalemia therapy had higher survival rates (OR\\u2009=\\u20090.1, 95%CI\\u2009=\\u20090.02-0.32, p\\u2009<\\u20090.001). Early mortality also depended on the electric field magnitude of the IRE protocol, as mice given 1000\\u2009V/cm survived longer than those given 2000\\u2009V/cm (OR\\u2009=\\u20094.7, 95%CI\\u2009=\\u20091.8-11.8, p\\u2009=\\u20090.001). Our findings suggest that ionic disturbances, mainly due to potassium alterations, should be warned and envisioned when large volume ablations are performed by IRE.',\n", - " 'author': ['Sánchez-Velázquez, P.',\n", - " 'Castellví, Q.',\n", - " 'Villanueva, A.',\n", - " 'Quesada, R.',\n", - " 'Pañella, C.',\n", - " 'Cáceres, M.',\n", - " 'Dorcaratto, D.',\n", - " 'Andaluz, A.',\n", - " 'Moll, X.',\n", - " 'Trujillo, M.',\n", - " 'Burdío, J. M.',\n", - " 'Berjano, E.',\n", - " 'Grande, L.',\n", - " 'Ivorra, A.',\n", - " 'Burdío, F.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep23781\"}'],\n", - " 'title': ['Irreversible electroporation of the liver: is there a safe limit to the ablation volume?']},\n", - " {'bibcode': '2009SPIE.7262E..0PD',\n", - " 'abstract': 'High-frequency (> 20 MHz) ultrasound images of preclinical tumor models are sensitive to changes in tissue microstructure that accompany tumor progression and treatment responses, but the relationships between tumor microanatomy and high-frequency ultrasound backscattering are incompletely understood. Computational models of tissue microstructure can be employed with ultrasound propagation simulators to investigate these relationships. This paper introduces a three-dimensional microanatomical model in which tissue is treated as a population of stochastically positioned spherical cells embedded in a homogeneous extracellular matrix, where each cell consists of a spherical nucleus surrounded by homogeneous cytoplasm. The model is used to represent the microstructure of both healthy mouse liver and experimental liver metastasis. Normal and cancerous tissue specimens stained with DAPI and H&E are digitized at 20× magnification and analyzed to specify values of the model parameters. Simulated healthy and tumor tissues are initialized based on the ratio of cell to nucleus diameter and the nuclear volume fraction and size distribution estimated by stereological analysis of the normal and cancerous liver specimens, respectively. For each simulated tissue, the spatial organization of cells is controlled by a Gibbs-Markov point process. The parameters of the Gibbs-Markov process are tuned to accurately reproduce the number density and distribution of center-to-center spacing of nuclei in the DAPI-stained slides of the corresponding experimental tissue specimen. The morphological variations that can be produced by changing the model parameters are expected to be sufficient to represent the microstructural changes during tumor progression that are the most significant determinants of high-frequency ultrasound backscattering.',\n", - " 'author': ['Daoud, Mohammad I.', 'Lacefield, James C.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1117%2F12.812938\"}'],\n", - " 'title': ['Stochastic modeling of tissue microstructure for high-frequency ultrasound imaging simulations']},\n", - " {'bibcode': '2021ApPhL.118x4102R',\n", - " 'abstract': \"Ultrasound is playing an emerging role in molecular and cellular imaging thanks to new micro- and nanoscale contrast agents and reporter genes. Acoustic methods for the selective in vivo detection of these imaging agents are needed to maximize their impact in biology and medicine. Existing ultrasound pulse sequences use the nonlinearity in contrast agents' response to acoustic pressure to distinguish them from mostly linear tissue scattering. However, such pulse sequences typically scan the sample using focused transmissions, resulting in a limited frame rate and restricted field of view. Meanwhile, existing wide-field scanning techniques based on plane wave transmissions suffer from limited sensitivity or nonlinear artifacts. To overcome these limitations, we introduce an ultrafast nonlinear imaging modality combining amplitude-modulated pulses, multiplane wave transmissions, and selective coherent compounding. This technique achieves contrast imaging sensitivity comparable to much slower gold-standard amplitude modulation sequences and enables the acquisition of larger and deeper fields of view, while providing a much faster imaging framerate of 3.2 kHz. Additionally, it enables simultaneous nonlinear and linear image formation and allows concurrent monitoring of phenomena accessible only at ultrafast framerates, such as blood volume variations. We demonstrate the performance of this ultrafast amplitude modulation technique by imaging gas vesicles, an emerging class of genetically encodable biomolecular contrast agents, in several in vitro and in vivo contexts. These demonstrations include the rapid discrimination of moving contrast agents and the real-time monitoring of phagolysosomal function in the mouse liver.\",\n", - " 'author': ['Rabut, Claire',\n", - " 'Wu, Di',\n", - " 'Ling, Bill',\n", - " 'Jin, Zhiyang',\n", - " 'Malounda, Dina',\n", - " 'Shapiro, Mikhail G.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1063%2F5.0050807\"}'],\n", - " 'title': ['Ultrafast amplitude modulation for molecular and hemodynamic ultrasound imaging']},\n", - " {'bibcode': '2003EnTox..18..176B',\n", - " 'abstract': 'The freshwater cyanobacterium Cylindrospermopsis raciborskii is known to produce toxic effects in several countries. Acute and chronic exposures to C. raciborskii in Australia have been linked to liver damage (hepatotoxicity) with concomitant effects on the kidneys, adrenal glands, small intestine, lungs, thymus, and heart. The alkaloid cylindrospermopsin, which produces these toxic effects, is thought to be a potent inhibitor of protein synthesis. C. raciborskii strains producing cylindrospermopsin or analogue alkaloids have also been reported in Florida, USA, and Thailand. Brazilian isolates of C. raciborskii are also toxic but act by a different mechanism, causing acute death in mice with neurotoxic symptoms similar to those induced by the saxitoxins. In this article we compare the toxicity in the mouse of a C. raciborskii French strain with C. raciborskii strains from various other sources (Australia, Brazil, Mexico, and Hungary). We tested the toxicity of cell extracts by a mouse bioassay. Acute, fatal neurotoxicity was produced by the Brazilian strain, which was confirmed by liquid chromatography with fluorescence detection of the cell extracts, which revealed the presence of saxitoxin, neosaxitoxin, and decarbamoylsaxitoxin, along with two unidentified compounds. Acute hepatotoxicity with severe liver, kidney, and thymus damage was observed with the Australian cylindrospermopsin‑producing strain. The Mexican and Hungarian strains were not found to be toxic to mice in our experimental conditions. No animals died after exposure to the extracts of the French C. raciborskii strain. Histological examination of the liver revealed moderate, multifocal necrosis characterized by small areas of hepatocellular necrosis, combined with disorganization of the parenchyma and congestion of the inner sinusoid. These symptoms and lesions resembled those induced by cylindrospermopsin, but the chemical analysis performed by liquid chromatography coupled with either a diode array detector or a mass spectrometer demonstrated that this toxin was not present in our culture extract.',\n", - " 'author': ['Bernard, C.',\n", - " 'Harvey, M.',\n", - " 'Briand, J. F.',\n", - " 'Biré, R.',\n", - " 'Krys, S.',\n", - " 'Fontaine, J. J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Ftox.10112\"}'],\n", - " 'title': ['Toxicological comparison of diverse Cylindrospermopsis raciborskii strains: Evidence of liver damage caused by a French C. raciborskii strain']},\n", - " {'bibcode': '2012AcAC..717...67J',\n", - " 'abstract': 'OATP1B1, OATP1B3 and OATP2B1 are important members of the organic anion transporting polypeptides (OATP) family and are implicated in the hepatic disposition of endobiotics and xenobiotics. Quantitating the expression levels of human OATP1B1, OATP1B3 and OATP2B1 in in vitro systems and tissue samples could significantly improve attempts to scale up in vitro data and result in more effective in vitro-in vivo correlation of transporter-mediated effects on drug disposition, such as hepatic clearance. In the present study, a quantification method was developed, characterized, and implemented for simultaneous determination of human OATP1B1, OATP1B3 and OATP2B1 in HEK cells transfected with OATP-expressing plasmid vectors (SLCO1B1, SLCO1B3, and SLCO2B1, respectively), human hepatocytes, human brain capillary endothelial cells, and humanized mouse liver tissue using UPLC-MRM MS. Purified membrane protein standards prepared and characterized as previously reported (Protein Expr. Purif. 2008, 57, 163-71) were first used as standards for absolute quantification of the expression levels of the three human OATP membrane proteins. The specificity of the optimized MRM transitions were characterized by analyzing the tryptic digests of the membrane protein fraction of wild type HEK cells and control mouse liver tissue using the herein reported UPLC-MRM MS method. The linearity of the calibration curve spanned from 0.2 μg mL-1 (0.040 μg mg-1) to 20 μg mL-1 (4.0 μg mg-1), with accuracy (% RE) within 15% at all concentrations examined for all three OATPs of interest in this study. The intra- and inter-day assay accuracy (% RE) and coefficient of variations (% CV) of triplicates are all within 15% for all levels of quality control samples prepared by mixing the membrane fraction of control mouse liver tissue with the required amount of purified human OATP1B1, OATP1B3 and OATP2B1.',\n", - " 'author': ['Ji, Chengjie',\n", - " 'Tschantz, William R.',\n", - " 'Pfeifer, Nathan D.',\n", - " 'Ullah, Mohammed',\n", - " 'Sadagopan, Nalini'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.aca.2011.12.005\"}'],\n", - " 'title': ['Development of a multiplex UPLC-MRM MS method for quantification of human membrane transport proteins OATP1B1, OATP1B3 and OATP2B1 in in vitro systems and tissues']},\n", - " {'bibcode': '2020ApEnM..86E3004K',\n", - " 'abstract': 'This study investigated the effect of Akkermansia muciniphila on fatty liver disease. Although some research about the effects of A. muciniphila on host health has been published, study of the relationship between A. muciniphila administration and fatty liver, as well as changes in the gut microbiota, has not been conducted. In this study, we demonstrated that A. muciniphila prevented fatty liver disease by regulation of the expression of genes that regulate fat synthesis and inflammation in the liver. ABSTRACT The objective of this study was to elucidate the effect of intestinal Akkermansia muciniphila bacteria on fatty liver disease. Five-week-old C57BL/6N mice were administered either phosphate-buffered saline (PBS; control) or A. muciniphila at 10 8 to 10 9 CFU/ml, and were fed either a 45% fat diet (high-fat diet [HFD]) or a 10% fat diet (normal diet [ND]) for 10 weeks. After 10 weeks, the mice were euthanized, and blood and tissue samples, including adipose tissue, cecum, liver, and brain, were immediately collected. Biochemical and histological analyses were conducted, and the expression levels of related factors were compared to determine the antiobesity effects of Akkermansia muciniphila . The gut microbiome was analyzed in fecal samples. Oral administration of A. muciniphila significantly ( P < 0.05) lowered serum triglyceride (TG) and alanine aminotransferase (ALT) levels in obese mice. Compared to the non- A. muciniphila -treated group, the expression of SREBP (regulator of TG synthesis in liver tissue) was decreased in the A. muciniphila -treated group. The expression of IL-6 in the liver of obese mice was decreased following the administration of A. muciniphila . Furthermore, alterations in the ratio of Firmicutes to Bacteroidetes and the decrease in bacterial diversity caused by the HFD were restored upon the administration of A. muciniphila . These results indicate that A. muciniphila prevents fatty liver disease in obese mice by regulating TG synthesis in the liver and maintaining gut homeostasis. IMPORTANCE This study investigated the effect of Akkermansia muciniphila on fatty liver disease. Although some research about the effects of A. muciniphila on host health has been published, study of the relationship between A. muciniphila administration and fatty liver, as well as changes in the gut microbiota, has not been conducted. In this study, we demonstrated that A. muciniphila prevented fatty liver disease by regulation of the expression of genes that regulate fat synthesis and inflammation in the liver.',\n", - " 'author': ['Kim, Sejeong',\n", - " 'Lee, Yewon',\n", - " 'Kim, Yujin',\n", - " 'Seo, Yeongeun',\n", - " 'Lee, Heeyoung',\n", - " 'Ha, Jimyeong',\n", - " 'Lee, Jeeyeon',\n", - " 'Choi, Yukyung',\n", - " 'Oh, Hyemin',\n", - " 'Yoon, Yohan'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1128%2FAEM.03004-19\"}'],\n", - " 'title': ['Akkermansia muciniphila Prevents Fatty Liver Disease, Decreases Serum Triglycerides, and Maintains Gut Homeostasis']},\n", - " {'bibcode': '2019EnTox..34..878S',\n", - " 'abstract': 'Perfluorooctanoic acid (PFOA) is an octanoic acid and is found in wildlife and humans. We have investigated mitochondrial toxicity in isolated mitochondria from, placenta, brain, liver, and heart after oral exposure with PFOA in mice during gestational days (7‑15). Histopathological examination and mitochondrial toxicity parameters were assayed. Results indicated that PFOA decreased the weight of the fetus and placenta, the length of the fetus and the diameter of the placenta, dead fetuses and dead macerated fetuses in treated mice with 25 mg/kg. Histopathological examination showed that PFOA induced pathological abnormalities in liver, brain, heart, and placenta. Also, PFOA induced mitochondria toxicity in brain, liver, heart of mouse fetus. Our results indicate that PFOA up to 20 mg/kg exposure adversely affect embryofetal/developmental because for mitochondria dysfunction. These results suggested that mitochondrial dysfunction induced by PFOA in liver, heart, and brain lead to developmental toxicity and abnormality in tissues.',\n", - " 'author': ['Salimi, Ahmad',\n", - " 'Nikoosiar Jahromi, Mahnia',\n", - " 'Pourahmad, Jalal'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Ftox.22760\"}'],\n", - " 'title': ['Maternal exposure causes mitochondrial dysfunction in brain, liver, and heart of mouse fetus: An explanation for perfluorooctanoic acid induced abortion and developmental toxicity']},\n", - " {'bibcode': '2000PNAS...97.1206Y',\n", - " 'abstract': 'We have imaged, in real time, fluorescent tumors growing and metastasizing in live mice. The whole-body optical imaging system is external and noninvasive. It affords unprecedented continuous visual monitoring of malignant growth and spread within intact animals. We have established new human and rodent tumors that stably express very high levels of the Aequorea victoria green fluorescent protein (GFP) and transplanted these to appropriate animals. B16F0-GFP mouse melanoma cells were injected into the tail vein or portal vein of 6-week-old C57BL/6 and nude mice. Whole-body optical images showed metastatic lesions in the brain, liver, and bone of B16F0-GFP that were used for real time, quantitative measurement of tumor growth in each of these organs. The AC3488-GFP human colon cancer was surgically implanted orthotopically into nude mice. Whole-body optical images showed, in real time, growth of the primary colon tumor and its metastatic lesions in the liver and skeleton. Imaging was with either a trans-illuminated epifluorescence microscope or a fluorescence light box and thermoelectrically cooled color charge-coupled device camera. The depth to which metastasis and micrometastasis could be imaged depended on their size. A 60-μm diameter tumor was detectable at a depth of 0.5 mm whereas a 1,800-μm tumor could be visualized at 2.2-mm depth. The simple, noninvasive, and highly selective imaging of growing tumors, made possible by strong GFP fluorescence, enables the detailed imaging of tumor growth and metastasis formation. This should facilitate studies of modulators of cancer growth including inhibition by potential chemotherapeutic agents.',\n", - " 'author': ['Yang, Meng',\n", - " 'Baranov, Eugene',\n", - " 'Jiang, Ping',\n", - " 'Sun, Fang-Xian',\n", - " 'Li, Xiao-Ming',\n", - " 'Li, Lingna',\n", - " 'Hasegawa, Satoshi',\n", - " 'Bouvet, Michael',\n", - " 'Al-Tuwaijri, Maraya',\n", - " 'Chishima, Takashi',\n", - " 'Shimada, Hiroshi',\n", - " 'Moossa, A. R.',\n", - " 'Penman, Sheldon',\n", - " 'Hoffman, Robert M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/97/3/1206\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/97/3/1206\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/97/3/1206\"}'],\n", - " 'title': ['Whole-body optical imaging of green fluorescent protein-expressing tumors and metastases']},\n", - " {'bibcode': '2007PNAS..10417081N',\n", - " 'abstract': 'Mice lacking the EGF receptor (EGFR) die between midgestation and postnatal day 20 with various defects in neural and epithelial organs. Here, we generated mice carrying a floxed EGFR allele to inactivate the EGFR in fetal and adult liver. Perinatal deletion of EGFR in hepatocytes resulted in decreased body weight, whereas deletion in the adult liver did not affect body mass. Although liver function was not affected, after partial hepatectomy mice lacking EGFR in the liver showed increased mortality accompanied by increased levels of serum transaminases indicating liver damage. Liver regeneration was delayed in the mutants because of reduced hepatocyte proliferation. Analysis of cell cycle progression in EGFR-deficient livers indicated a defective G1-S phase entry with delayed transcriptional activation and reduced protein expression of cyclin D1 followed by reduced cdk2 and cdk1 expression. Impaired liver regeneration was accompanied by compensatory up-regulation of TNFα in the serum and prolonged activation of c-Jun. Moreover, p38α and NF-κB activation was reduced in regenerating mutant livers, indicating an impaired stress response after hepatectomy. Our studies demonstrate that EGFR is a critical regulator of hepatocyte proliferation in the initial phases of liver regeneration.',\n", - " 'author': ['Natarajan, Anuradha', 'Wagner, Bettina', 'Sibilia, Maria'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/104/43/17081\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0704126104\"}'],\n", - " 'title': ['The EGF receptor is required for efficient liver regeneration']},\n", - " {'bibcode': '2020Natur.583..127A',\n", - " 'abstract': 'Cellular senescence is characterized by stable cell-cycle arrest and a secretory program that modulates the tissue microenvironment1,2. Physiologically, senescence serves as a tumour-suppressive mechanism that prevents the expansion of premalignant cells3,4 and has a beneficial role in wound-healing responses5,6. Pathologically, the aberrant accumulation of senescent cells generates an inflammatory milieu that leads to chronic tissue damage and contributes to diseases such as liver and lung fibrosis, atherosclerosis, diabetes and osteoarthritis1,7. Accordingly, eliminating senescent cells from damaged tissues in mice ameliorates the symptoms of these pathologies and even promotes longevity1,2,8-10. Here we test the therapeutic concept that chimeric antigen receptor (CAR) T cells that target senescent cells can be effective senolytic agents. We identify the urokinase-type plasminogen activator receptor (uPAR)11 as a cell-surface protein that is broadly induced during senescence and show that uPAR-specific CAR T cells efficiently ablate senescent cells in vitro and in vivo. CAR T cells that target uPAR extend the survival of mice with lung adenocarcinoma that are treated with a senescence-inducing combination of drugs, and restore tissue homeostasis in mice in which liver fibrosis is induced chemically or by diet. These results establish the therapeutic potential of senolytic CAR T cells for senescence-associated diseases.',\n", - " 'author': ['Amor, Corina',\n", - " 'Feucht, Judith',\n", - " 'Leibold, Josef',\n", - " 'Ho, Yu-Jui',\n", - " 'Zhu, Changyu',\n", - " 'Alonso-Curbelo, Direna',\n", - " 'Mansilla-Soto, Jorge',\n", - " 'Boyer, Jacob A.',\n", - " 'Li, Xiang',\n", - " 'Giavridis, Theodoros',\n", - " 'Kulick, Amanda',\n", - " 'Houlihan, Shauna',\n", - " 'Peerschke, Ellinor',\n", - " 'Friedman, Scott L.',\n", - " 'Ponomarev, Vladimir',\n", - " 'Piersigilli, Alessandra',\n", - " 'Sadelain, Michel',\n", - " 'Lowe, Scott W.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41586-020-2403-9\"}'],\n", - " 'title': ['Senolytic CAR T cells reverse senescence-associated pathologies']},\n", - " {'bibcode': '2012PNAS..109.2003J',\n", - " 'abstract': 'A critical regulator of autophagy is the Class III PI3K Vps34 (also called PIK3C3). Although Vps34 is known to play an essential role in autophagy in yeast, its role in mammals remains elusive. To elucidate the physiological function of Vps34 and to determine its precise role in autophagy, we have generated Vps34f/f mice, in which expression of Cre recombinase results in a deletion of exon 4 of Vps34 and a frame shift causing a deletion of 755 of the 887 amino acids of Vps34. Acute ablation of Vps34 in MEFs upon adenoviral Cre infection results in a diminishment of localized generation of phosphatidylinositol 3-phosphate and blockade of both endocytic and autophagic degradation. Starvation-induced autophagosome formation is blocked in both Vps34-null MEFs and liver. Liver-specific Albumin-Cre;Vps34f/f mice developed hepatomegaly and hepatic steatosis, and impaired protein turnover. Ablation of Vps34 in the heart of muscle creatine kinase-Cre;Vps34f/f mice led to cardiomegaly and decreased contractility. In addition, while amino acid-stimulated mTOR activation was suppressed in the absence of Vps34, the steady-state level of mTOR signaling was not affected in Vps34-null MEFs, liver, or cardiomyocytes. Taken together, our results indicate that Vps34 plays an essential role in regulating functional autophagy and is indispensable for normal liver and heart function.',\n", - " 'author': ['Jaber, Nadia',\n", - " 'Dou, Zhixun',\n", - " 'Chen, Juei-Suei',\n", - " 'Catanzaro, Joseph',\n", - " 'Jiang, Ya-Ping',\n", - " 'Ballou, Lisa M.',\n", - " 'Selinger, Elzbieta',\n", - " 'Ouyang, Xiaosen',\n", - " 'Lin, Richard Z.',\n", - " 'Zhang, Jianhua',\n", - " 'Zong, Wei-Xing'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/109/6/2003\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1112848109\"}'],\n", - " 'title': ['Class III PI3K Vps34 plays an essential role in autophagy and in heart and liver function']},\n", - " {'bibcode': '2020Natur.583..133Y',\n", - " 'abstract': \"Neutrophil extracellular traps (NETs), which consist of chromatin DNA filaments coated with granule proteins, are released by neutrophils to trap microorganisms1-3. Recent studies have suggested that the DNA component of NETs (NET-DNA) is associated with cancer metastasis in mouse models4-6. However, the functional role and clinical importance of NET-DNA in metastasis in patients with cancer remain unclear. Here we show that NETs are abundant in the liver metastases of patients with breast and colon cancers, and that serum NETs can predict the occurrence of liver metastases in patients with early-stage breast cancer. NET-DNA acts as a chemotactic factor to attract cancer cells, rather than merely acting as a `trap' for them; in several mouse models, NETs in the liver or lungs were found to attract cancer cells to form distant metastases. We identify the transmembrane protein CCDC25 as a NET-DNA receptor on cancer cells that senses extracellular DNA and subsequently activates the ILK-β-parvin pathway to enhance cell motility. NET-mediated metastasis is abrogated in CCDC25-knockout cells. Clinically, we show that the expression of CCDC25 on primary cancer cells is closely associated with a poor prognosis for patients. Overall, we describe a transmembrane DNA receptor that mediates NET-dependent metastasis, and suggest that targeting CCDC25 could be an appealing therapeutic strategy for the prevention of cancer metastasis.\",\n", - " 'author': ['Yang, Linbin',\n", - " 'Liu, Qiang',\n", - " 'Zhang, Xiaoqian',\n", - " 'Liu, Xinwei',\n", - " 'Zhou, Boxuan',\n", - " 'Chen, Jianing',\n", - " 'Huang, Di',\n", - " 'Li, Jiaqian',\n", - " 'Li, Heliang',\n", - " 'Chen, Fei',\n", - " 'Liu, Jiang',\n", - " 'Xing, Yue',\n", - " 'Chen, Xueman',\n", - " 'Su, Shicheng',\n", - " 'Song, Erwei'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41586-020-2394-6\"}'],\n", - " 'title': ['DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25']},\n", - " {'bibcode': '2001Chaos..11...98H',\n", - " 'abstract': 'High-density DNA arrays allow measurements of gene expression levels (messenger RNA abundance) for thousands of genes simultaneously. We analyze arrays with spotted cDNA used in monitoring of expression profiles. A dilution series of a mouse liver probe is deployed to quantify the reproducibility of expression measurements. Saturation effects limit the accessible signal range at high intensities. Additive noise and outshining from neighboring spots dominate at low intensities. For repeated measurements on the same filter and filter-to-filter comparisons correlation coefficients of 0.98 are found. Next we consider the clustering of gene expression time series from stimulated human fibroblasts which aims at finding co-regulated genes. We analyze how preprocessing, the distance measure, and the clustering algorithm affect the resulting clusters. Finally we discuss algorithms for the identification of transcription factor binding sites from clusters of co-regulated genes.',\n", - " 'author': ['Herzel, Hanspeter',\n", - " 'Beule, Dieter',\n", - " 'Kielbasa, Szymon',\n", - " 'Korbel, Jan',\n", - " 'Sers, Christine',\n", - " 'Malik, Arif',\n", - " 'Eickhoff, Holger',\n", - " 'Lehrach, Hans',\n", - " 'Schuchhardt, Johannes'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1063%2F1.1336843\"}'],\n", - " 'title': ['Extracting information from cDNA arrays']},\n", - " {'bibcode': '2021NatCo..12.2621Z',\n", - " 'abstract': 'Cullin-RING E3 ligases (CRLs) regulate the turnover of approximately 20% of mammalian cellular proteins. Neddylation of individual cullin proteins is essential for the activation of each CRL. We report herein the discovery of DI-1548 and DI-1859 as two potent, selective and covalent DCN1 inhibitors. These inhibitors selectively inhibit neddylation of cullin 3 in cells at low nanomolar concentrations and are 2-3 orders of magnitude more potent than our previously reported reversible DCN1 inhibitor. Mass spectrometric analysis and co-crystal structures reveal that these compounds employ a unique mechanism of covalent bond formation with DCN1. DI-1859 induces a robust increase of NRF2 protein, a CRL3 substrate, in mouse liver and effectively protects mice from acetaminophen-induced liver damage. Taken together, this study demonstrates the therapeutic potential of selective inhibition of cullin neddylation.',\n", - " 'author': ['Zhou, Haibin',\n", - " 'Lu, Jianfeng',\n", - " 'Chinnaswamy, Krishnapriya',\n", - " 'Stuckey, Jeanne A.',\n", - " 'Liu, Liu',\n", - " 'McEachern, Donna',\n", - " 'Yang, Chao-Yie',\n", - " 'Bernard, Denzil',\n", - " 'Shen, Hong',\n", - " 'Rui, Liangyou',\n", - " 'Sun, Yi',\n", - " 'Wang, Shaomeng'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41467-021-22924-4\"}'],\n", - " 'title': ['Selective inhibition of cullin 3 neddylation through covalent targeting DCN1 protects mice from acetaminophen-induced liver toxicity']},\n", - " {'bibcode': '1974Natur.251..627K',\n", - " 'abstract': 'CELL surface antigens have been isolated by solubilisation and fractionation of membranes1-3. Here we present data on the membrane antigens of mouse liver cells soluble in the nonionic detergent Triton X-100.',\n", - " 'author': ['Khramkova, N. I.', 'Beloshapkina, T. D.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F251627a0\"}'],\n", - " 'title': ['Antigen of mouse bile capillaries and cuticle of intestinal mucosa']},\n", - " {'bibcode': '2015NatSR...513079M',\n", - " 'abstract': 'Liver synthetic and metabolic function can only be optimised by the growth of cells within a supportive liver matrix. This can be achieved by the utilisation of decellularised human liver tissue. Here we demonstrate complete decellularization of whole human liver and lobes to form an extracellular matrix scaffold with a preserved architecture. Decellularized human liver cubic scaffolds were repopulated for up to 21 days using human cell lines hepatic stellate cells (LX2), hepatocellular carcinoma (Sk-Hep-1) and hepatoblastoma (HepG2), with excellent viability, motility and proliferation and remodelling of the extracellular matrix. Biocompatibility was demonstrated by either omental or subcutaneous xenotransplantation of liver scaffold cubes (5\\u2009×\\u20095\\u2009×\\u20095\\u2009mm) into immune competent mice resulting in absent foreign body responses. We demonstrate decellularization of human liver and repopulation with derived human liver cells. This is a key advance in bioartificial liver development.',\n", - " 'author': ['Mazza, Giuseppe',\n", - " 'Rombouts, Krista',\n", - " 'Rennie Hall, Andrew',\n", - " 'Urbani, Luca',\n", - " 'Vinh Luong, Tu',\n", - " 'Al-Akkad, Walid',\n", - " 'Longato, Lisa',\n", - " 'Brown, David',\n", - " 'Maghsoudlou, Panagiotis',\n", - " 'Dhillon, Amar P.',\n", - " 'Fuller, Barry',\n", - " 'Davidson, Brian',\n", - " 'Moore, Kevin',\n", - " 'Dhar, Dipok',\n", - " 'de Coppi, Paolo',\n", - " 'Malago, Massimo',\n", - " 'Pinzani, Massimo'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep13079\"}'],\n", - " 'title': ['Decellularized human liver as a natural 3D-scaffold for liver bioengineering and transplantation']},\n", - " {'bibcode': '1994Sci...263.1600G',\n", - " 'abstract': 'Injectable nanoparticulate carriers have important potential applications such as site-specific drug delivery or medical imaging. Conventional carriers, however, cannot generally be used because they are eliminated by the reticulo-endothelial system within seconds or minutes after intravenous injection. To address these limitations, monodisperse biodegradable nanospheres were developed from amphiphilic copolymers composed of two biocompatible blocks. The nanospheres exhibited dramatically increased blood circulation times and reduced liver accumulation in mice. Furthermore, they entrapped up to 45 percent by weight of the drug in the dense core in a one-step procedure and could be freeze-dried and easily redispersed without additives in aqueous solutions.',\n", - " 'author': ['Gref, Ruxandra',\n", - " 'Minamitake, Yoshiharu',\n", - " 'Peracchia, Maria Teresa',\n", - " 'Trubetskoy, Vladimir',\n", - " 'Torchilin, Vladimir',\n", - " 'Langer, Robert'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.8128245\"}'],\n", - " 'title': ['Biodegradable Long-Circulating Polymeric Nanospheres']},\n", - " {'bibcode': '1999PNAS...96.7088S',\n", - " 'abstract': 'The body growth of animals is regulated by growth hormone and IGF-I. The classical theory of this regulation is that most IGF-I in the blood originates in the liver and that body growth is controlled by the concentration of IGF-I in the blood. We have abolished IGF-I production in the livers of mice by using the Cre/loxP recombination system. These mice demonstrated complete inactivation of the IGF-I gene in the hepatocytes. Although the liver accounts for less than 5% of body mass, the concentration of IGF-I in the serum was reduced by 75%. This finding confirms that the liver is the principal source of IGF-I in the blood. However, the reduction in serum IGF-I concentration had no discernible effect on postnatal body growth. We conclude that postnatal body growth is preserved despite complete absence of IGF-I production by the hepatocytes.',\n", - " 'author': ['Sjögren, Klara',\n", - " 'Liu, Jun-Li',\n", - " 'Blad, Kristina',\n", - " 'Skrtic, Stanko',\n", - " 'Vidal, Olle',\n", - " 'Wallenius, Ville',\n", - " 'LeRoith, Derek',\n", - " 'Törnell, Jan',\n", - " 'Isaksson, Olle G. P.',\n", - " 'Jansson, John-Olov',\n", - " 'Ohlsson, Claes'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/96/12/7088\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/96/12/7088\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/96/12/7088\"}'],\n", - " 'title': ['Liver-Derived Insulin-Like Growth Factor I (IGF-I) Is the Principal Source of IGF-I in Blood but Is Not Required for Postnatal Body Growth in Mice']},\n", - " {'bibcode': '2012PNAS..109.3510S',\n", - " 'abstract': \"A 30-d course of oral administration of a semipurified extract of the root of Withania somnifera consisting predominantly of withanolides and withanosides reversed behavioral deficits, plaque pathology, accumulation of β-amyloid peptides (Aβ) and oligomers in the brains of middle-aged and old APP/PS1 Alzheimer's disease transgenic mice. It was similarly effective in reversing behavioral deficits and plaque load in APPSwInd mice (line J20). The temporal sequence involved an increase in plasma Aβ and a decrease in brain Aβ monomer after 7 d, indicating increased transport of Aβ from the brain to the periphery. Enhanced expression of low-density lipoprotein receptor-related protein (LRP) in brain microvessels and the Aβ-degrading protease neprilysin (NEP) occurred 14-21 d after a substantial decrease in brain Aβ levels. However, significant increase in liver LRP and NEP occurred much earlier, at 7 d, and were accompanied by a rise in plasma sLRP, a peripheral sink for brain Aβ. In WT mice, the extract induced liver, but not brain, LRP and NEP and decreased plasma and brain Aβ, indicating that increase in liver LRP and sLRP occurring independent of Aβ concentration could result in clearance of Aβ. Selective down-regulation of liver LRP, but not NEP, abrogated the therapeutic effects of the extract. The remarkable therapeutic effect of W. somnifera mediated through up-regulation of liver LRP indicates that targeting the periphery offers a unique mechanism for Aβ clearance and reverses the behavioral deficits and pathology seen in Alzheimer's disease models.\",\n", - " 'author': ['Sehgal, Neha',\n", - " 'Gupta, Alok',\n", - " 'Valli, Rupanagudi Khader',\n", - " 'Joshi, Shanker Datt',\n", - " 'Mills, Jessica T.',\n", - " 'Hamel, Edith',\n", - " 'Khanna, Pankaj',\n", - " 'Jain, Subhash Chand',\n", - " 'Thakur, Suman S.',\n", - " 'Ravindranath, Vijayalakshmi'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/109/9/3510\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1112209109\"}'],\n", - " 'title': [\"From the Cover: Withania somnifera reverses Alzheimer's disease pathology by enhancing low-density lipoprotein receptor-related protein in liver\"]},\n", - " {'bibcode': '2001PNAS...9810469H',\n", - " 'abstract': \"The levels of 8-oxo-2-deoxyguanosine (oxo8dG) in DNA isolated from tissues of rodents (male F344 rats, male B6D2F1 mice, male C57BL/6 mice, and female C57BL/6 mice) of various ages were measured using sodium iodide to prevent oxidative damage to DNA during DNA isolation. Oxo8dG was measured in nuclear DNA (nDNA) isolated from liver, heart, brain, kidney, skeletal muscle, and spleen and in mitochondrial DNA (mtDNA) isolated from liver. We observed a significant increase in oxo8dG levels in nDNA with age in all tissues and strains of rodents studied. The age-related increase in oxo8dG in nDNA from old mice was shown not to the result of the tissue's reduced ability to remove the oxo8dG lesion. Rather, the increase in oxo8dG levels appears to arise from an age-related increase in the sensitivity of these tissues to oxidative stress. We also observed an age-related increase in oxo8dG in mtDNA isolated from the livers of the rats and mice. Dietary restriction, which is known to retard aging and increase the lifespan of rodents, was shown to significantly reduce the age-related accumulation of oxo8dG levels in nDNA in all tissues of male B6D23F1 mice and in most tissues of male F344 rats. Our study also showed that dietary restriction prevented the age-related increase in oxo8dG levels in mtDNA isolated from the livers of both rats and mice.\",\n", - " 'author': ['Hamilton, Michelle L.',\n", - " 'Van Remmen, Holly',\n", - " 'Drake, Jessica A.',\n", - " 'Yang, Hong',\n", - " 'Guo, Zhong Mao',\n", - " 'Kewitt, Kristen',\n", - " 'Walter, Christi A.',\n", - " 'Richardson, Arlan'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/98/18/10469\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/98/18/10469\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/98/18/10469\"}'],\n", - " 'title': ['Does oxidative damage to DNA increase with age?']},\n", - " {'bibcode': '2011NatNa...6..321Y',\n", - " 'abstract': 'The increasing use of nanomaterials has raised concerns about their potential risks to human health. Recent studies have shown that nanoparticles can cross the placenta barrier in pregnant mice and cause neurotoxicity in their offspring, but a more detailed understanding of the effects of nanoparticles on pregnant animals remains elusive. Here, we show that silica and titanium dioxide nanoparticles with diameters of 70 nm and 35 nm, respectively, can cause pregnancy complications when injected intravenously into pregnant mice. The silica and titanium dioxide nanoparticles were found in the placenta, fetal liver and fetal brain. Mice treated with these nanoparticles had smaller uteri and smaller fetuses than untreated controls. Fullerene molecules and larger (300 and 1,000 nm) silica particles did not induce these complications. These detrimental effects are linked to structural and functional abnormalities in the placenta on the maternal side, and are abolished when the surfaces of the silica nanoparticles are modified with carboxyl and amine groups.',\n", - " 'author': ['Yamashita, Kohei',\n", - " 'Yoshioka, Yasuo',\n", - " 'Higashisaka, Kazuma',\n", - " 'Mimura, Kazuya',\n", - " 'Morishita, Yuki',\n", - " 'Nozaki, Masatoshi',\n", - " 'Yoshida, Tokuyuki',\n", - " 'Ogura, Toshinobu',\n", - " 'Nabeshi, Hiromi',\n", - " 'Nagano, Kazuya',\n", - " 'Abe, Yasuhiro',\n", - " 'Kamada, Haruhiko',\n", - " 'Monobe, Youko',\n", - " 'Imazawa, Takayoshi',\n", - " 'Aoshima, Hisae',\n", - " 'Shishido, Kiyoshi',\n", - " 'Kawai, Yuichi',\n", - " 'Mayumi, Tadanori',\n", - " 'Tsunoda, Shin-Ichi',\n", - " 'Itoh, Norio',\n", - " 'Yoshikawa, Tomoaki',\n", - " 'Yanagihara, Itaru',\n", - " 'Saito, Shigeru',\n", - " 'Tsutsumi, Yasuo'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnnano.2011.41\"}'],\n", - " 'title': ['Silica and titanium dioxide nanoparticles cause pregnancy complications in mice']},\n", - " {'bibcode': '1984CPL...111..449L',\n", - " 'abstract': 'The results of recent experiments which indicate that surface-enhanced Raman scattering from molecules adsorbed on coldly evaporated silver films is associated with cavity sites is interpreted as an electromagnetic field enhancement in regions enclosed by several silver grains. No such enhancement is obtained for a wedge geometry. Cavity sites are seen to be also strong enhancement centers for resonance optical phenomena such as fluorescence and photochemical yield.',\n", - " 'author': ['Liver, Naomi', 'Nitzan, Abraham', 'Gersten, J. I.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2F0009-2614%2884%2985539-6\"}'],\n", - " 'title': ['Local fields in cavity sites of rough dielectric surfaces']},\n", - " {'bibcode': '2015Sci...349..500Y',\n", - " 'abstract': 'The association between inflammation and endoplasmic reticulum (ER) stress has been observed in many diseases. However, if and how chronic inflammation regulates the unfolded protein response (UPR) and alters ER homeostasis in general, or in the context of chronic disease, remains unknown. Here, we show that, in the setting of obesity, inflammatory input through increased inducible nitric oxide synthase (iNOS) activity causes S-nitrosylation of a key UPR regulator, IRE1α, which leads to a progressive decline in hepatic IRE1α-mediated XBP1 splicing activity in both genetic (ob/ob) and dietary (high-fat diet-induced) models of obesity. Finally, in obese mice with liver-specific IRE1α deficiency, reconstitution of IRE1α expression with a nitrosylation-resistant variant restored IRE1α-mediated XBP1 splicing and improved glucose homeostasis in vivo. Taken together, these data describe a mechanism by which inflammatory pathways compromise UPR function through iNOS-mediated S-nitrosylation of IRE1α, which contributes to defective IRE1α activity, impaired ER function, and prolonged ER stress in obesity.',\n", - " 'author': ['Yang, Ling',\n", - " 'Calay, Ediz S.',\n", - " 'Fan, Jason',\n", - " 'Arduini, Alessandro',\n", - " 'Kunz, Ryan C.',\n", - " 'Gygi, Steven P.',\n", - " 'Yalcin, Abdullah',\n", - " 'Fu, Suneng',\n", - " 'Hotamisligil, Gökhan S.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.aaa0079\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.aaa0079\"}'],\n", - " 'title': ['S-Nitrosylation links obesity-associated inflammation to endoplasmic reticulum dysfunction']},\n", - " {'bibcode': '1980BuECT..25...34M',\n", - " 'author': ['Morales, Nydia M.', 'Matthews, H. B.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1007%2FBF01985482\"}'],\n", - " 'title': ['In vivo binding of the flame retardantsTris(2,3-dibromopropyl) phosphate andTris(1,3-dichloro-2-propyl) phosphate to macromolecules of mouse liver, kidney and muscle']},\n", - " {'bibcode': '2009NRL.....4..858C',\n", - " 'abstract': 'The environmental impact of nanoparticles is evident; however, their toxicity due to their nanosize is rarely discussed. Gold nanoparticles (GNPs) may serve as a promising model to address the size-dependent biological response to nanoparticles because they show good biocompatibility and their size can be controlled with great precision during their chemical synthesis. Naked GNPs ranging from 3 to 100 nm were injected intraperitoneally into BALB/C mice at a dose of 8 mg/kg/week. GNPs of 3, 5, 50, and 100 nm did not show harmful effects; however, GNPs ranging from 8 to 37 nm induced severe sickness in mice. Mice injected with GNPs in this range showed fatigue, loss of appetite, change of fur color, and weight loss. Starting from day 14, mice in this group exhibited a camel-like back and crooked spine. The majority of mice in these groups died within 21 days. Injection of 5 and 3 nm GNPs, however, did not induce sickness or lethality in mice. Pathological examination of the major organs of the mice in the diseased groups indicated an increase of Kupffer cells in the liver, loss of structural integrity in the lungs, and diffusion of white pulp in the spleen. The pathological abnormality was associated with the presence of gold particles at the diseased sites, which were verified by ex vivo Coherent anti-Stoke Raman scattering microscopy. Modifying the surface of the GNPs by incorporating immunogenic peptides ameliorated their toxicity. This reduction in the toxicity is associated with an increase in the ability to induce antibody response. The toxicity of GNPs may be a fundamental determinant of the environmental toxicity of nanoparticles.',\n", - " 'author': ['Chen, Yu-Shiun',\n", - " 'Hung, Yao-Ching',\n", - " 'Liau, Ian',\n", - " 'Huang, G. Steve'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1007%2Fs11671-009-9334-6\"}'],\n", - " 'title': ['Assessment of the In Vivo Toxicity of Gold Nanoparticles']},\n", - " {'bibcode': '2017NRL....12..478J',\n", - " 'abstract': 'Nanoscale titanium dioxide (nano-TiO2) has been widely used in industry and medicine. However, the safety of nano-TiO2 exposure remains unclear. In this study, we evaluated the liver, brain, and embryo toxicity and the underlying mechanism of nano-TiO2 using mice models. The results showed that titanium was distributed to and accumulated in the heart, brain, spleen, lung, and kidney of mice after intraperitoneal (i.p.) nano-TiO2 exposure, in a dose-dependent manner. The organ/body weight ratios of the heart, spleen, and kidney were significantly increased, and those of the brain and lung were decreased. High doses of nano-TiO2 significantly damaged the functions of liver and kidney and glucose and lipid metabolism, as showed in the blood biochemistry tests. Nano-TiO2 caused damages in mitochondria and apoptosis of hepatocytes, generation of reactive oxygen species, and expression disorders of protective genes in the liver of mice. We found ruptured and cracked nerve cells and inflammatory cell infiltration in the brain. We also found that the activities of constitutive nitric oxide synthases (cNOS), inducible NOS (iNOS), and acetylcholinesterase, and the levels of nitrous oxide and glutamic acid were changed in the brain after nano-TiO2 exposure. Ex vivo mouse embryo models exhibited developmental and genetic toxicity after high doses of nano-TiO2. The size of nano-TiO2 particles may affect toxicity, larger particles producing higher toxicity. In summary, nano-TiO2 exhibited toxicity in multiple organs in mice after exposure through i.p. injection and gavage. Our study may provide data for the assessment of the risk of nano-TiO2 exposure on human health.',\n", - " 'author': ['Jia, Xiaochuan', 'Wang, Shuo', 'Zhou, Lei', 'Sun, Li'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1186%2Fs11671-017-2242-2\"}'],\n", - " 'title': ['The Potential Liver, Brain, and Embryo Toxicity of Titanium Dioxide Nanoparticles on Mice']},\n", - " {'bibcode': '2021Sci...373..662L',\n", - " 'abstract': 'The functional role of long noncoding RNAs (lncRNAs) in inherited metabolic disorders, including phenylketonuria (PKU), is unknown. Here, we demonstrate that the mouse lncRNA Pair and human HULC associate with phenylalanine hydroxylase (PAH). Pair-knockout mice exhibited excessive blood phenylalanine (Phe), musty odor, hypopigmentation, growth retardation, and progressive neurological symptoms including seizures, which faithfully models human PKU. HULC depletion led to reduced PAH enzymatic activities in human induced pluripotent stem cell–differentiated hepatocytes. Mechanistically, HULC modulated the enzymatic activities of PAH by facilitating PAH-substrate and PAH-cofactor interactions. To develop a therapeutic strategy for restoring liver lncRNAs, we designed GalNAc-tagged lncRNA mimics that exhibit liver enrichment. Treatment with GalNAc-HULC mimics reduced excessive Phe in Pair−/− and PahR408W/R408W mice and improved the Phe tolerance of these mice.',\n", - " 'author': ['Li, Yajuan',\n", - " 'Tan, Zhi',\n", - " 'Zhang, Yaohua',\n", - " 'Zhang, Zhao',\n", - " 'Hu, Qingsong',\n", - " 'Liang, Ke',\n", - " 'Jun, Yao',\n", - " 'Ye, Youqiong',\n", - " 'Li, Yi-Chuan',\n", - " 'Li, Chunlai',\n", - " 'Liao, Lan',\n", - " 'Xu, Jianming',\n", - " 'Xing, Zhen',\n", - " 'Pan, Yinghong',\n", - " 'Chatterjee, Sujash S.',\n", - " 'Nguyen, Tina K.',\n", - " 'Hsiao, Heidi',\n", - " 'Egranov, Sergey D.',\n", - " 'Putluri, Nagireddy',\n", - " 'Coarfa, Cristian',\n", - " 'Hawke, David H.',\n", - " 'Gunaratne, Preethi H.',\n", - " 'Tsai, Kuang-Lei',\n", - " 'Han, Leng',\n", - " 'Hung, Mien-Chie',\n", - " 'Calin, George A.',\n", - " 'Namour, Fares',\n", - " 'Guéant, Jean-Louis',\n", - " 'Muntau, Ania C.',\n", - " 'Blau, Nenad',\n", - " 'Sutton, V. Reid',\n", - " 'Schiff, Manuel',\n", - " 'Feillet, François',\n", - " 'Zhang, Shuxing',\n", - " 'Lin, Chunru',\n", - " 'Yang, Liuqing'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.aba4991\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.aba4991\"}'],\n", - " 'title': ['A noncoding RNA modulator potentiates phenylalanine metabolism in mice']},\n", - " {'bibcode': '2012JESHA..47.1948E',\n", - " 'author': ['El-Demerdash, Fatma', 'Attia, Azza A.', 'Elmazoudy, Reda H.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1080%2F03601234.2012.676513\"}'],\n", - " 'title': ['Biochemical and histopathological changes induced by different time intervals of methomyl treatment in mice liver']},\n", - " {'bibcode': '1996Natur.382..635N',\n", - " 'abstract': 'THE chemokines are a large family of small, structurally related cytokines1,2. The physiological importance of most members of this family has yet to be elucidated, although some are inducible inflammatory mediators that determine leukocyte chemotaxis1-5. Pre-B-cell growth-stimulating factor/stromal cell-derived factor-1 (PBSF/SDF-1) is a member of the CXC group of chemokines6,7. PBSF/SDF-1 stimulates proliferation of B-cell progenitors in vitro6 and is constitutively expressed in bone-marrow-derived stromal cells6,7. Here we investigate the physiological roles of PBSF/SDF-1 by generating mutant mice with a targeted disruption of the gene encoding PBSF/SDF-1. We found that mice lacking PBSF/SDF-1 died perinatally and that although the numbers of B-cell progenitors in mutant embryos were severely reduced in fetal liver and bone marrow, myeloid progenitors were reduced only in the bone marrow but not in the fetal liver, indicating that PBSF/SDF-1 is responsible for B-cell lymphopoiesis and bone-marrow myelopoiesis. In addition, the mutants had a cardiac ventricular septal defect. Hence, we have shown that the chemokine PBSF/SDF-1 has several essential functions in development.',\n", - " 'author': ['Nagasawa, Takashi',\n", - " 'Hirota, Seiichi',\n", - " 'Tachibana, Kazunobu',\n", - " 'Takakura, Nobuyuki',\n", - " 'Nishikawa, Shin-Ichi',\n", - " 'Kitamura, Yukihiko',\n", - " 'Yoshida, Nobuaki',\n", - " 'Kikutani, Hitoshi',\n", - " 'Kishimoto, Tadamitsu'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F382635a0\"}'],\n", - " 'title': ['Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1']},\n", - " {'bibcode': '2008Sci...322.1250I',\n", - " 'abstract': 'Metabolic regulation in mammals requires communication between multiple organs and tissues. The rise in the incidence of obesity and associated metabolic disorders, including type 2 diabetes, has renewed interest in interorgan communication. We used mouse models to explore the mechanism whereby obesity enhances pancreatic β cell mass, pathophysiological compensation for insulin resistance. We found that hepatic activation of extracellular regulated kinase (ERK) signaling induced pancreatic β cell proliferation through a neuronal-mediated relay of metabolic signals. This metabolic relay from the liver to the pancreas is involved in obesity-induced islet expansion. In mouse models of insulin-deficient diabetes, liver-selective activation of ERK signaling increased β cell mass and normalized serum glucose levels. Thus, interorgan metabolic relay systems may serve as valuable targets in regenerative treatments for diabetes.',\n", - " 'author': ['Imai, Junta',\n", - " 'Katagiri, Hideki',\n", - " 'Yamada, Tetsuya',\n", - " 'Ishigaki, Yasushi',\n", - " 'Suzuki, Toshinobu',\n", - " 'Kudo, Hirohito',\n", - " 'Uno, Kenji',\n", - " 'Hasegawa, Yutaka',\n", - " 'Gao, Junhong',\n", - " 'Kaneko, Keizo',\n", - " 'Ishihara, Hisamitsu',\n", - " 'Niijima, Akira',\n", - " 'Nakazato, Masamitsu',\n", - " 'Asano, Tomoichiro',\n", - " 'Minokoshi, Yasuhiko',\n", - " 'Oka, Yoshitomo'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.1163971\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.1163971\"}'],\n", - " 'title': ['Regulation of Pancreatic β Cell Mass by Neuronal Signals from the Liver']},\n", - " {'bibcode': '2021NatSR..11.3961N',\n", - " 'abstract': 'Simultaneous expression of multiplex guide RNAs (gRNAs) is valuable for knockout of multiple genes and also for effective disruption of a gene by introducing multiple deletions. We developed a method of Tetraplex-guide Tandem for construction of cosmids containing four and eight multiplex gRNA-expressing units in one step utilizing lambda in vitro packaging. Using this method, we produced an adenovirus vector (AdV) containing four multiplex-gRNA units for two double-nicking sets. Unexpectedly, the AdV could stably be amplified to the scale sufficient for animal experiments with no detectable lack of the multiplex units. When the AdV containing gRNAs targeting the H2-Aa gene and an AdV expressing Cas9 nickase were mixed and doubly infected to mouse embryonic fibroblast cells, deletions were observed in more than 80% of the target gene even using double-nicking strategy. Indels were also detected in about 20% of the target gene at two sites in newborn mouse liver cells by intravenous injection. Interestingly, when one double-nicking site was disrupted, the other was simultaneously disrupted, implying that two genes in the same cell may simultaneously be disrupted in the AdV system. The AdVs expressing four multiplex gRNAs could offer simultaneous knockout of four genes or two genes by double-nicking cleavages with low off-target effect.',\n", - " 'author': ['Nakanishi, Tomoko',\n", - " 'Maekawa, Aya',\n", - " 'Suzuki, Mariko',\n", - " 'Tabata, Hirotaka',\n", - " 'Sato, Kumiko',\n", - " 'Mori, Mai',\n", - " 'Saito, Izumu'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-021-83259-0\"}'],\n", - " 'title': ['Construction of adenovirus vectors simultaneously expressing four multiplex, double-nicking guide RNAs of CRISPR/Cas9 and in vivo genome editing']},\n", - " {'bibcode': '2017NatSR...7.8267V',\n", - " 'abstract': 'Antiviral treatment options for chronic Hepatitis E Virus (HEV) infections are limited and immunological determinants of viral persistence remain largely unexplored. We studied the antiviral potency of pegylated interferon-α (pegIFNα) against HEV infections in humanized mice and modelled intrahepatic interferon stimulated gene (ISG) responses. Human gene expression levels in humanized mouse livers were analyzed by qPCR and Nanostring. Human CXCL10 was measured in mouse serum. HEV genotype 3 (gt3) infections were cleared from liver and feces within 8 pegIFNα doses in all mice and relapsed after a single pegIFNα injection in only half of treated animals. Rapid viral clearance by pegIFNα was confirmed in HEV gt1, but not in Hepatitis B Virus infected animals. No ISG induction was observed in untreated HEV gt3 and gt1 infected humanized livers compared to control chimeric mice, irrespective of the human hepatocyte donor, viral isolate or HEV infection duration. Human specific ISG transcript levels in mouse liver increased significantly after pegIFNα treatment and induced high circulating human CXCL10 in mouse serum. In conclusion, HEV gt1 and gt3 infections do not elicit innate intrahepatic immune responses and remain highly sensitive to pegIFNα in immunocompromised humanized mice.',\n", - " 'author': ['van de Garde, Martijn D. B.',\n", - " 'Pas, Suzan D.',\n", - " 'van Oord, Gertine W.',\n", - " 'Gama, Lucio',\n", - " 'Choi, Youkyung',\n", - " 'de Man, Robert A.',\n", - " 'Boonstra, Andre',\n", - " 'Vanwolleghem, Thomas'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-017-07434-y\"}'],\n", - " 'title': ['Interferon-alpha treatment rapidly clears Hepatitis E virus infection in humanized mice']},\n", - " {'bibcode': '2013ToxIH..29..888M',\n", - " 'abstract': 'The present study was carried out to determine histopathological effects of nicotine, one of the most significant components of tobacco, on mouse liver and ameliorative effect of melatonin on liver damage. A total of 140 mature Swiss Albino mice ( Mus musculus) were divided into four experimental groups: control group, nicotine group, melatonin group and nicotine + melatonin group. Each group was further subdivided into seven groups (five mice each) according to the time of killing (12 h and days 1, 3, 5, 7, 14 and 21 after drug administration). In nicotine and nicotine + melatonin groups, 3 mg/kg of nicotine was injected intraperitoneally every day until killing. The nicotine + melatonin group was additionally injected with 10 mg/kg of melatonin after 30 min of nicotine injection. The melatonin group was injected only with 10 mg/kg of melatonin every day until killing. All the treatments were given 2 h before sunset, when melatonin receptors were active. After the last injection, five mice from each group were killed at 12th hour and on days 1, 3, 5, 7, 14 and 21; the livers were removed for histopathological processing by light microscopy. The histopathological results revealed time-dependent degeneration in the livers of mice in nicotine group. Regenerative changes in the nicotine and melatonin groups were observed when compared with nicotine groups.',\n", - " 'author': ['Mercan, Sevcan', 'Eren, Banu'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1177%2F0748233712446725\"}'],\n", - " 'title': ['Protective role of melatonin supplementation against nicotine-induced liver damage in mouse']},\n", - " {'bibcode': '2012JMagR.214..352M',\n", - " 'abstract': 'Detection and quantification of total choline-containing metabolites (CCMs) in tissues by magnetic resonance spectroscopy (MRS) has received considerable attention as a biomarker of cancer. Tissue CCMs are mainly choline (Cho), phosphocholine (PCho), and glycerophosphocholine (GPCho). Because the methyl 1H resonances of tissue CCMs exhibit small chemical shift differences and overlap significantly in 1D 1H MRS, quantification of individual components is precluded. Development of a MRS method capably of resolving individual components of tissue CCMs would be a significant advance. Herein, a modification of the 2D 1H- 14N HSQC technique is targeted on the two methylene 1H in the CH 2O group ( 3J1H14N = 2.7 Hz) and applied to ex vivo mouse and human liver samples at physiological temperature (37 °C). Specifically, the 1H- 14N HSQC technique is modified into a 2D 1H- 14N three-bond correlation (HN3BC) experiment, which selectively detects the 1H of CH 2O coupled to 14N in CCMs. Separate signals from Cho, PCho, and GPCho components are resolved with high detection sensitivity. A 2D HN3BC spectrum can be recorded from mouse liver in only 1.5 min and from human carcinoma liver tissue in less than 3 min with effective sample volume of 0.2 ml at 14.1 T.',\n", - " 'author': ['Mao, Xi-an',\n", - " 'Li, Ning',\n", - " 'Mao, Jiezhen',\n", - " 'Li, Qiurong',\n", - " 'Xiao, Nan',\n", - " 'Jiang, Bin',\n", - " 'Jiang, Ling',\n", - " 'Wang, Xu-xia',\n", - " 'Liu, Maili'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.jmr.2011.11.019\"}'],\n", - " 'title': ['Fast detection of choline-containing metabolites in liver using 2D 1H- 14N three-bond correlation (HN3BC) spectroscopy']},\n", - " {'bibcode': '2010NatCo...1....3H',\n", - " 'abstract': 'Genetic overexpression of protein deacetylase Sir2 increases longevity in a variety of lower organisms, and this has prompted interest in the effects of its closest mammalian homologue, Sirt1, on ageing and cancer. We have generated transgenic mice moderately overexpressing Sirt1 under its own regulatory elements (Sirt1-tg). Old Sirt1-tg mice present lower levels of DNA damage, decreased expression of the ageing-associated gene p16Ink4a, a better general health and fewer spontaneous carcinomas and sarcomas. These effects, however, were not sufficiently potent to affect longevity. To further extend these observations, we developed a metabolic syndrome-associated liver cancer model in which wild-type mice develop multiple carcinomas. Sirt1-tg mice show a reduced susceptibility to liver cancer and exhibit improved hepatic protection from both DNA damage and metabolic damage. Together, these results provide direct proof of the anti-ageing activity of Sirt1 in mammals and of its tumour suppression activity in ageing- and metabolic syndrome-associated cancer.',\n", - " 'author': ['Herranz, Daniel',\n", - " 'Muñoz-Martin, Maribel',\n", - " 'Cañamero, Marta',\n", - " 'Mulero, Francisca',\n", - " 'Martinez-Pastor, Barbara',\n", - " 'Fernandez-Capetillo, Oscar',\n", - " 'Serrano, Manuel'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fncomms1001\"}'],\n", - " 'title': ['Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer']},\n", - " {'bibcode': '2011PNAS..10811842C',\n", - " 'abstract': '\"Humanized\" mice offer a window into aspects of human physiology that are otherwise inaccessible. The best available methods for liver humanization rely on cell transplantation into immunodeficient mice with liver injury but these methods have not gained widespread use due to the duration and variability of hepatocyte repopulation. In light of the significant progress that has been achieved in clinical cell transplantation through tissue engineering, we sought to develop a humanized mouse model based on the facile and ectopic implantation of a tissue-engineered human liver. These human ectopic artificial livers (HEALs) stabilize the function of cryopreserved primary human hepatocytes through juxtacrine and paracrine signals in polymeric scaffolds. In contrast to current methods, HEALs can be efficiently established in immunocompetent mice with normal liver function. Mice transplanted with HEALs exhibit humanized liver functions persistent for weeks, including synthesis of human proteins, human drug metabolism, drug-drug interaction, and drug-induced liver injury. Here, mice with HEALs are used to predict the disproportionate metabolism and toxicity of \"major\" human metabolites using multiple routes of administration and monitoring. These advances may enable manufacturing of reproducible in vivo models for diverse drug development and research applications.',\n", - " 'author': ['Chen, Alice A.',\n", - " 'Thomas, David K.',\n", - " 'Ong, Luvena L.',\n", - " 'Schwartz, Robert E.',\n", - " 'Golub, Todd R.',\n", - " 'Bhatia, Sangeeta N.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/108/29/11842\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1101791108\"}'],\n", - " 'title': ['Humanized mice with ectopic artificial liver tissues']},\n", - " {'bibcode': '1989PNAS...86.2903S',\n", - " 'abstract': \"Docosahexaenoic acid [22:6 omega 3; 22:6(4, 7, 10, 13, 16, 19)] is concentrated in phospholipids of cellular membranes from brain and retina. Although linolenic acid [18:3 omega 3; 18:3(9, 12, 15)] is the major omega 3 fatty acid of mouse dams' milk, 22:6 is the prevalent omega 3 fatty acid in serum and tissues. Intraperitoneal injection of [1-14C]18:3 into 3-day-old mouse pups resulted in liver and serum lipid labeling that was initially high, followed by a rapid decline. In contrast, labeling of brain and retinal lipids were initially low and increased with time. Labeled 22:6 first appeared in liver 2 hr after injection and later in brain and retina. We suggest that 22:6 synthesized from 18:3 by the liver is secreted into the bloodstream in lipoproteins, taken up by brain and retina, and incorporated into cell membranes. We hypothesize that the 22:6 requirements of membranes (e.g., during synaptogenesis, photoreceptor membrane biogenesis, or repair after ischemic injury or neurodegenerative disorders) are met by a signal that is sent by the appropriate tissues to the liver to evoke the secretion of 22:6-containing lipoproteins.\",\n", - " 'author': ['Scott, Burton L.', 'Bazan, Nicolas G.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/86/8/2903\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/86/8/2903\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/86/8/2903\"}'],\n", - " 'title': ['Membrane docosahexaenoate is supplied to the developing brain and retina by the liver.']},\n", - " {'bibcode': '2018JPhCS1025a2043J',\n", - " 'abstract': 'Neem has been known as herb contraceptive plant which shows an antifertility effect both in male and female rats. The anti-fertility compound of Neem has the same potencies to interfere with or affect the function of several organs. The Hepato-somatic index (HSI) reflects the value of toxic compounds that enter the animal body also. HSI values can also be used to assess animal health levels. A study to examine the effect of ethanolic extract of Neem as an herb contraceptive to the hepato-somatic index of male mice has been done. Neem leaf was collected from the campus area, dried, mashed then extracted with ethanol 70%. Mature male Swiss Webster mice with 25-30 grams in weight were used as laboratory animals. Mice were divided into 4 groups: P0 (given distilled water), P1, P2, and P3 were given Neem leaf extract with 8.4, 11.2 and 14 mg/KgBW/day respectively. Each treatment group had six replications. Treatment was given orally for 21 days. The body weight was measured every week until the end of treatment. The mice were anesthetized with chloroform at the end of treatment, continued by dissecting and isolating liver isolation. The isolated liver is then weighed to determine the HSI value. Data were analyzed with ANOVA followed by DMRT test. The results showed that the body weight of control group showed a significant difference (p<0.05) to the treatment group. The hepatic weights and HSI values of the control group showed nonsignificant differences (p>0.05) with the P1 and P2 treatment groups but showed a significant difference (p<0.05) with the P3 treatment group. It can be concluded that the exposure of ethanolic Neem leaves extract as herb contraceptive affects liver function which causes the increase of hepatic weight and HSI value.',\n", - " 'author': ['Janika Sitasiwi, Agung',\n", - " 'Isdadiyanto, Sri',\n", - " 'Muflichatun Mardiati, Siti'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1088%2F1742-6596%2F1025%2F1%2F012043\"}'],\n", - " 'title': ['Effect of ethanolic Neem (Azadirachta indica) leaf extract as an herb contraceptive on Hepato-somatic Index of the male mice (Mus musculus)']},\n", - " {'bibcode': '2004PNAS..101.7088P',\n", - " 'abstract': 'In obese humans and rodents there is increased expression of the key glucocorticoid (GC) regenerating enzyme, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), in adipose tissue. This increased expression appears to be of pathogenic importance because transgenic mice overexpressing 11β-HSD1 selectively in adipose tissue exhibit a full metabolic syndrome with visceral obesity, dyslipidemia, insulin-resistant diabetes, and hypertension. In this model, while systemic plasma GC levels are unaltered, GC delivery to the liver via the portal vein is increased. 11β-HSD1 is most highly expressed in liver where inhibition or deficiency of its activity improves glucose and lipid homeostasis. To determine the potential contribution of elevated intrahepatic GCs alone toward development of insulin-resistant syndromes we generated transgenic mice expressing increased 11β-HSD1 activity selectively in the liver under transcriptional control of hepatic regulatory sequences derived from the human apoE gene (apoE-HSD1). Transgenic lines with 2- and 5-fold-elevated 11β-HSD1 activity exhibited mild insulin resistance without altered fat depot mass. ApoE-HSD1 transgenic mice exhibited fatty liver and dyslipidemia with increased hepatic lipid synthesis/flux associated with elevated hepatic LXRα and PPARα mRNA levels as well as impaired hepatic lipid clearance. Further, apoE-HSD1 transgenic mice have a marked, transgene-dose-associated hypertension paralleled by incrementally increased liver angiotensinogen expression. These data suggest that elevated hepatic expression of 11β-HSD1 may relate to the pathogenesis of specific fatty liver, insulin-resistant, and hypertensive syndromes without obesity in humans as may occur in, for example, myotonic dystrophy, and possibly, the metabolically obese, normal-weight individual.',\n", - " 'author': ['Paterson, Janice M.',\n", - " 'Morton, Nicholas M.',\n", - " 'Fievet, Catherine',\n", - " 'Kenyon, Christopher J.',\n", - " 'Holmes, Megan C.',\n", - " 'Staels, Bart',\n", - " 'Seckl, Jonathan R.',\n", - " 'Mullins, John J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/101/18/7088\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0305524101\"}'],\n", - " 'title': ['Metabolic syndrome without obesity: Hepatic overexpression of 11β-hydroxysteroid dehydrogenase type 1 in transgenic mice']},\n", - " {'bibcode': '2012Natur.483..350I',\n", - " 'abstract': 'Free fatty acids provide an important energy source as nutrients, and act as signalling molecules in various cellular processes. Several G-protein-coupled receptors have been identified as free-fatty-acid receptors important in physiology as well as in several diseases. GPR120 (also known as O3FAR1) functions as a receptor for unsaturated long-chain free fatty acids and has a critical role in various physiological homeostasis mechanisms such as adipogenesis, regulation of appetite and food preference. Here we show that GPR120-deficient mice fed a high-fat diet develop obesity, glucose intolerance and fatty liver with decreased adipocyte differentiation and lipogenesis and enhanced hepatic lipogenesis. Insulin resistance in such mice is associated with reduced insulin signalling and enhanced inflammation in adipose tissue. In human, we show that GPR120 expression in adipose tissue is significantly higher in obese individuals than in lean controls. GPR120 exon sequencing in obese subjects reveals a deleterious non-synonymous mutation (p.R270H) that inhibits GPR120 signalling activity. Furthermore, the p.R270H variant increases the risk of obesity in European populations. Overall, this study demonstrates that the lipid sensor GPR120 has a key role in sensing dietary fat and, therefore, in the control of energy balance in both humans and rodents.',\n", - " 'author': ['Ichimura, Atsuhiko',\n", - " 'Hirasawa, Akira',\n", - " 'Poulain-Godefroy, Odile',\n", - " 'Bonnefond, Amélie',\n", - " 'Hara, Takafumi',\n", - " 'Yengo, Loïc',\n", - " 'Kimura, Ikuo',\n", - " 'Leloire, Audrey',\n", - " 'Liu, Ning',\n", - " 'Iida, Keiko',\n", - " 'Choquet, Hélène',\n", - " 'Besnard, Philippe',\n", - " 'Lecoeur, Cécile',\n", - " 'Vivequin, Sidonie',\n", - " 'Ayukawa, Kumiko',\n", - " 'Takeuchi, Masato',\n", - " 'Ozawa, Kentaro',\n", - " 'Tauber, Maithé',\n", - " 'Maffeis, Claudio',\n", - " 'Morandi, Anita',\n", - " 'Buzzetti, Raffaella',\n", - " 'Elliott, Paul',\n", - " 'Pouta, Anneli',\n", - " 'Jarvelin, Marjo-Riitta',\n", - " 'Körner, Antje',\n", - " 'Kiess, Wieland',\n", - " 'Pigeyre, Marie',\n", - " 'Caiazzo, Roberto',\n", - " 'van Hul, Wim',\n", - " 'van Gaal, Luc',\n", - " 'Horber, Fritz',\n", - " 'Balkau, Beverley',\n", - " 'Lévy-Marchal, Claire',\n", - " 'Rouskas, Konstantinos',\n", - " 'Kouvatsi, Anastasia',\n", - " 'Hebebrand, Johannes',\n", - " 'Hinney, Anke',\n", - " 'Scherag, Andre',\n", - " 'Pattou, François',\n", - " 'Meyre, David',\n", - " 'Koshimizu, Taka-Aki',\n", - " 'Wolowczuk, Isabelle',\n", - " 'Tsujimoto, Gozoh',\n", - " 'Froguel, Philippe'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature10798\"}'],\n", - " 'title': ['Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human']},\n", - " {'bibcode': '2011Sci...334..475E',\n", - " 'abstract': 'Our goal is to develop a vaccine that sustainably prevents Plasmodium falciparum (Pf) malaria in ≥80% of recipients. Pf sporozoites (PfSPZ) administered by mosquito bites are the only immunogens shown to induce such protection in humans. Such protection is thought to be mediated by CD8+ T cells in the liver that secrete interferon-γ (IFN-γ). We report that purified irradiated PfSPZ administered to 80 volunteers by needle inoculation in the skin was safe, but suboptimally immunogenic and protective. Animal studies demonstrated that intravenous immunization was critical for inducing a high frequency of PfSPZ-specific CD8+, IFN-γ-producing T cells in the liver (nonhuman primates, mice) and conferring protection (mice). Our results suggest that intravenous administration of this vaccine will lead to the prevention of infection with Pf malaria.',\n", - " 'author': ['Epstein, J. E.',\n", - " 'Tewari, K.',\n", - " 'Lyke, K. E.',\n", - " 'Sim, B. K. L.',\n", - " 'Billingsley, P. F.',\n", - " 'Laurens, M. B.',\n", - " 'Gunasekera, A.',\n", - " 'Chakravarty, S.',\n", - " 'James, E. R.',\n", - " 'Sedegah, M.',\n", - " 'Richman, A.',\n", - " 'Velmurugan, S.',\n", - " 'Reyes, S.',\n", - " 'Li, M.',\n", - " 'Tucker, K.',\n", - " 'Ahumada, A.',\n", - " 'Ruben, A. J.',\n", - " 'Li, T.',\n", - " 'Stafford, R.',\n", - " 'Eappen, A. G.',\n", - " 'Tamminga, C.',\n", - " 'Bennett, J. W.',\n", - " 'Ockenhouse, C. F.',\n", - " 'Murphy, J. R.',\n", - " 'Komisar, J.',\n", - " 'Thomas, N.',\n", - " 'Loyevsky, M.',\n", - " 'Birkett, A.',\n", - " 'Plowe, C. V.',\n", - " 'Loucq, C.',\n", - " 'Edelman, R.',\n", - " 'Richie, T. L.',\n", - " 'Seder, R. A.',\n", - " 'Hoffman, S. L.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.1211548\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.1211548\"}'],\n", - " 'title': ['Live Attenuated Malaria Vaccine Designed to Protect Through Hepatic CD8+ T Cell Immunity']},\n", - " {'bibcode': '1991PNAS...88.5533W',\n", - " 'abstract': 'The receptor for mouse hepatitis virus (MHV), a murine coronavirus, is a 110- to 120-kDa glycoprotein on intestinal brush border membranes and hepatocyte membranes. The N-terminal 25-amino acid sequence of immunoaffinity-purified MHV receptor was identical to the predicted mature N termini of two mouse genes related to human carcinoembryonic antigen (CEA) and was strongly homologous to the N termini of members of the CEA family in humans and rats. Polyclonal antibodies to human CEA recognized the immunoaffinity-purified MHV receptor and the MHV receptor in liver membranes and intestinal brush border membranes from MHV-susceptible mouse strains. In membranes from MHV-resistant SJL/J mice, the anti-CEA antibodies recognized a homologous glycoprotein that failed to bind MHV. The MHV receptor glycoprotein was detected in membranes of BALB/c colon, small intestine, and liver, which are the principal targets for MHV replication in vivo. The MHV receptor glycoprotein resembled members of the human CEA family in molecular weight, acidic pI, extensive glycosylation, solubility in perchloric acid, and tissue distribution. Thus, the MHV receptor is, to our knowledge, the first member of the CEA family of glycoproteins to be identified as a virus receptor.',\n", - " 'author': ['Williams, Richard K.', 'Jiang, Gui-Sen', 'Holmes, Kathryn V.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/88/13/5533\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/88/13/5533\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/88/13/5533\"}'],\n", - " 'title': ['Receptor for mouse hepatitis virus is a member of the carcinoembryonic antigen family of glycoproteins.']},\n", - " {'bibcode': '2011PNAS..108.7890S',\n", - " 'abstract': 'Transporters at the hepatic canalicular membrane are essential for the formation of bile and the prevention of cholestatic liver disease. One such example is ATP8B1, a P4-type ATPase disrupted in three inherited forms of intrahepatic cholestasis. Mutation of the X-linked mouse gene Atp11c, which encodes a paralogous P4-type ATPase, precludes B-cell development in the adult bone marrow, but also causes hyperbilirubinemia. Here we explore this hyperbilirubinemia in two independent Atp11c mutant mouse lines, and find that it originates from an effect on nonhematopoietic cells. Liver function tests and histology revealed only minor pathology, although cholic acid was elevated in the serum of mutant mice, and became toxic to mutant mice when given as a dietary supplement. The majority of homozygous mutant females also died of dystocia in a maternal genotype-specific manner. ATP11C therefore represents a multifunctional transporter, essential for adult B-cell development, the prevention of intrahepatic cholestasis, and parturition, and is a new candidate for genetically undiagnosed cases of cholestasis and dystocia in humans.',\n", - " 'author': ['Siggs, Owen M.',\n", - " 'Schnabl, Bernd',\n", - " 'Webb, Bill',\n", - " 'Beutler, Bruce'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/108/19/7890\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1104631108\"}'],\n", - " 'title': ['X-linked cholestasis in mouse due to mutations of the P4-ATPase ATP11C']},\n", - " {'bibcode': '1982PNAS...79.2172H',\n", - " 'abstract': 'Thymosin beta 4, recently isolated from calf thymus, is present in a number of rat and mouse tissues, including spleen, thymus, brain, lung, liver, and heart muscle. High concentrations are found in peritoneal macrophages, suggesting that its occurrence in other tissues may be related to the presence of macrophages or macrophage-like cells in these tissues. The conclusion that \"thymosin\" beta 4 does not originate solely in the thymus gland is supported by the high concentrations found in tissues of athymic (nu/nu) mice.',\n", - " 'author': ['Hannappel, Ewald',\n", - " 'Xu, -Jun, , Gen',\n", - " 'Morgan, James',\n", - " 'Hempstead, James',\n", - " 'Horecker, B. L.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/79/7/2172\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/79/7/2172\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/79/7/2172\"}'],\n", - " 'title': ['Thymosin β 4: A Ubiquitous Peptide in Rat and Mouse Tissues']},\n", - " {'bibcode': '1966Sci...152..352R',\n", - " 'abstract': 'The histochemical localization of glucose-6-phosphatase activity in neonatal mouse liver was studied under electron microscopy. The activity was demonstrated in the tubular endoplasmic reticulum, which pervades the glycogen areas of the cell during glycogenolysis. Activity was also demonstrated in the nuclear envelope and ergastoplasm.',\n", - " 'author': ['Rosen, Sidney I.', 'Kelly, George W.', 'Peters, Virginia B.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.jstor.org/stable/1718318?origin=ads\"}'],\n", - " 'title': ['Glucose-6-Phosphatase in Tubular Endoplasmic Reticulum of Hepatocytes']},\n", - " {'bibcode': '1985PNAS...82.1746L',\n", - " 'abstract': 'Mouse liver cDNA clones related to the C4 and C4-Slp isoforms of the fourth component of complement differ by few nucleotide changes within a region of substantial divergence from human C4. It is suggested that the mouse C4 gene duplication is an evolutionarily recent event with respect to the time of mammalian radiation. This conclusion is reinforced by the presence of a single C4 gene in the Syrian hamster. Most H-2 haplotypes, including those characterized by an undetectable C4-Slp protein, possess two C4 gene copies which, in contrast to the neighboring factor B, show a marked restriction site polymorphism. The genetic variation of this region is emphasized by the presence in the mouse of a rare \"polymorphism\" for C4 gene number. Multiple C4-related gene copies characterize those exceptional wild-derived H-2 haplotypes, H-2w7, H-2w16, and H-2w19, that determine the expression of the C4-Slp protein in female animals.',\n", - " 'author': ['Levi-Strauss, Matthieu',\n", - " 'Tosi, Mario',\n", - " 'Steinmetz, Michael',\n", - " 'Klein, Jan',\n", - " 'Meo, Tommaso'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/82/6/1746\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/82/6/1746\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/82/6/1746\"}'],\n", - " 'title': ['Multiple duplications of complement C4 gene correlate with H-2-controlled testosterone-independent expression of its sex-limited isoform, C4-Slp.']},\n", - " {'bibcode': '1978Sci...200..785G',\n", - " 'abstract': \"A flame retardant used in children's sleepwear, tris-(1,3-dichloro-2-propyl)phosphate (Fyrol FR2) is a mutagen in the Salmonella-mammalian tissue homogenate test after it has been activated by mouse or rat liver homogenate. The expected enzymatic hydrolysis product, 1,3-dichloro-2-propanol, is similarly a mutagen after activation by liver homogenate. A proposed metabolite of the flame retardant, 1,3-dichloro-2-propanone, is a potent mutagen in the absence of such activation. A flame retardant with similar structure, tris-(2,3-dibromopropyl)phosphate (tris-BP), was shown previously to be a mutagen, to cause sterility in animals, to be a carcinogen, and to be absorbed through human skin. These and other flame retardants have characteristic nuclear magnetic resonance spectra that can be used to determine which flame retardant is present in commercially purchased sleepwear. Sleepwear treated with tris-BP, Fyrol FR2, and other chemical additives was being sold in late 1977.\",\n", - " 'author': ['Gold, Marian Deborah', 'Blum, Arlene', 'Ames, Bruce N.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.347576\"}'],\n", - " 'title': ['Another Flame Retardant, Tris-(1,3-Dichloro-2-Propyl)-Phosphate, and Its Expected Metabolites Are Mutagens']},\n", - " {'bibcode': '2022AcAC.120439697P',\n", - " 'abstract': 'In this study, a strategy of improving imprinting performance was developed using an enhanced cooperation effect of functional monomers based on deep eutectic solvents (DESs) monomer for the specific enrichment of benzoylation modified peptides. Zinc acrylate and DESs monomers were used as binary functional monomers, and ethylene glycol dimethacrylate was used as the cross-linking agent with SGRGKbz as template to prepare an imprinted monolith. It was observed that the use of DESs monomer significantly improveed the affinity of benzoylation imprinted monolith and increased the adsorption capacity. Under optimal conditions, the recovery and imprinting factor (IF) of the imprinted monolith for SGRGKbz can reach 93.0% and 10.58, respectively. The average recovery of SGRGKbz extracted from the spiked histone digestion solution can reach 88.4% (n = 5, RSD = 3.4%). After treatment with the benzoylation imprinted monolith, 12 benzoylation modified peptides, 13 benzoylation modified sites and 12 benzoylation proteins could be identified in the digestion of mouse liver protein, while only one of each benzoylation modified peptide, benzoylation modified site and benzoylation protein could be identified in the untreated digestion of mouse liver protein. The results indicated that the prepared imprinted monolith using DESs-based functional monomer was an effective method to increase the affinity of the resulting MIP.',\n", - " 'author': ['Pu, Wan-Rong',\n", - " 'An, Dong-Yu',\n", - " 'Wang, Yang',\n", - " 'Zhang, Xue',\n", - " 'Huang, Yan-Ping',\n", - " 'Liu, Zhao-Sheng'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.aca.2022.339697\"}'],\n", - " 'title': ['Improving identification of molecularly imprinted monolith to benzoylation modified peptides by a deep eutectic solvents monomer-induced cooperation']},\n", - " {'bibcode': '2004PNAS..101.6409D',\n", - " 'abstract': 'Stearoyl-CoA desaturase (SCD) catalyzes the rate-limiting step in the biosynthesis of monounsaturated fatty acids. Mice with a targeted disruption of the SCD1 isoform have reduced body adiposity, increased energy expenditure, and up-regulated expression of several genes encoding enzymes of fatty acid β-oxidation in liver. The mechanisms by which SCD deficiency leads to these metabolic changes are presently unknown. Here we show that the phosphorylation and activity of AMP-activated protein kinase (AMPK), a metabolic sensor that regulates lipid metabolism during increased energy expenditure is significantly increased (≈40%, P < 0.01) in liver of SCD1 knockout mice (SCD1-/-). In parallel with the activation of AMPK, the phosphorylation of acetyl-CoA carboxylase at Ser-79 was increased and enzymatic activity was decreased (≈35%, P < 0.001), resulting in decreased intracellular levels of malonyl-CoA (≈47%, P < 0.001). An SCD1 mutation also increased AMPK phosphorylation and activity and increased acetyl-CoA carboxylase phosphorylation in leptin-deficient ob/ob mice. Lower malonyl-CoA concentrations are known to derepress carnitine palmitoyltransferase 1 (CPT1). In SCD1-/- mice, CPT1 and CPT2 activities were significantly increased (in both cases ≈60%, P < 0.001) thereby stimulating the oxidation of mitochondrial palmitoyl-CoA. Our results identify AMPK as a mediator of increased fatty acid oxidation in liver of SCD1-deficient mice.',\n", - " 'author': ['Dobrzyn, Pawel',\n", - " 'Dobrzyn, Agnieszka',\n", - " 'Miyazaki, Makoto',\n", - " 'Cohen, Paul',\n", - " 'Asilmaz, Esra',\n", - " 'Hardie, D. Grahame',\n", - " 'Friedman, Jeffrey M.',\n", - " 'Ntambi, James M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/101/17/6409\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0401627101\"}'],\n", - " 'title': ['Stearoyl-CoA desaturase 1 deficiency increases fatty acid oxidation by activating AMP-activated protein kinase in liver']},\n", - " {'bibcode': '2012PNAS..109E2165S',\n", - " 'abstract': 'Chronic infection with hepatitis B virus (HBV) is a major risk factor for the development of hepatocellular carcinoma (HCC). The pathogenesis of HBV-associated HCC involves both viral and host factors. The latter include a functionally inefficient CD8+ T-cell response that fails to clear the infection from the liver but sustains a chronic necroinflammatory process that contributes to the development of HCC. According to this scenario, amelioration of immune-mediated chronic liver injury may prevent HCC. Because platelets facilitate immune-mediated liver injury by promoting the hepatic accumulation of virus-specific CD8+ T cells, we evaluated the long-term consequences of antiplatelet therapy in an HBV transgenic mouse model of chronic immune-mediated necroinflammatory liver disease that progresses to HCC. Treatment with aspirin and clopidogrel during the chronic phase of the disease diminished the number of intrahepatic HBV-specific CD8+ T cells and HBV-nonspecific inflammatory cells, the severity of liver fibrosis, and the development of HCC. Antiplatelet therapy improved overall survival without causing significant side effects. In contrast, the same antiplatelet regimen had no antitumor effect when HCC was induced nonimmunologically by chronic exposure to a hepatotoxic chemical. The unprecedented observation that antiplatelet therapy inhibits or delays immune-mediated hepatocarcinogenesis suggests that platelets may be key players in the pathogenesis of HBV-associated liver cancer and supports the notion that immune-mediated necroinflammatory reactions are an important cause of hepatocellular transformation during chronic hepatitis.',\n", - " 'author': ['Sitia, Giovanni',\n", - " 'Aiolfi, Roberto',\n", - " 'Di Lucia, Pietro',\n", - " 'Mainetti, Marta',\n", - " 'Fiocchi, Amleto',\n", - " 'Mingozzi, Francesca',\n", - " 'Esposito, Antonio',\n", - " 'Ruggeri, Zaverio M.',\n", - " 'Chisari, Francis V.',\n", - " 'Iannacone, Matteo',\n", - " 'Guidotti, Luca G.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/109/32/E2165\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1209182109\"}'],\n", - " 'title': ['From the Cover: PNAS Plus: Antiplatelet therapy prevents hepatocellular carcinoma and improves survival in a mouse model of chronic hepatitis B']},\n", - " {'bibcode': '2008PNAS..10514342R',\n", - " 'abstract': 'Antigen specific T cell migration to sites of infection or cancer is critical for an effective immune response. In mouse models of cancer, the number of lymphocytes reaching the tumor is typically only a few hundred, yet technology capable of imaging these cells using bioluminescence has yet to be achieved. A combination of codon optimization, removal of cryptic splice sites and retroviral modification was used to engineer an enhanced firefly luciferase (ffLuc) vector. Compared with ffLuc, T cells expressing our construct generated >100 times more light, permitting detection of as few as three cells implanted s.c. while maintaining long term coexpression of a reporter gene (Thy1.1). Expression of enhanced ffLuc in mouse T cells permitted the tracking of <3 × 104 adoptively transferred T cells infiltrating sites of vaccination and preestablished tumors. Penetration of light through deep tissues, including the liver and spleen, was also observed. Finally, we were able to enumerate infiltrating mouse lymphocytes constituting <0.3% of total tumor cellularity, representing a significant improvement over standard methods of quantitation including flow cytometry.',\n", - " 'author': ['Rabinovich, Brian A.',\n", - " 'Ye, Yang',\n", - " 'Etto, Tamara',\n", - " 'Chen, Jie Qing',\n", - " 'Levitsky, Hyam I.',\n", - " 'Overwijk, Willem W.',\n", - " 'Cooper, Laurence J. N.',\n", - " 'Gelovani, Juri',\n", - " 'Hwu, Patrick'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/105/38/14342\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/105/38/14342.full.pdf\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0804105105\"}'],\n", - " 'title': ['Visualizing fewer than 10 mouse T cells with an enhanced firefly luciferase in immunocompetent mouse models of cancer']},\n", - " {'bibcode': '2020Sci...369..167H',\n", - " 'abstract': 'Reversing brain aging may be possible through systemic interventions such as exercise. We found that administration of circulating blood factors in plasma from exercised aged mice transferred the effects of exercise on adult neurogenesis and cognition to sedentary aged mice. Plasma concentrations of glycosylphosphatidylinositol (GPI)–specific phospholipase D1 (Gpld1), a GPI-degrading enzyme derived from liver, were found to increase after exercise and to correlate with improved cognitive function in aged mice, and concentrations of Gpld1 in blood were increased in active, healthy elderly humans. Increasing systemic concentrations of Gpld1 in aged mice ameliorated age-related regenerative and cognitive impairments by altering signaling cascades downstream of GPI-anchored substrate cleavage. We thus identify a liver-to-brain axis by which blood factors can transfer the benefits of exercise in old age.',\n", - " 'author': ['Horowitz, Alana M.',\n", - " 'Fan, Xuelai',\n", - " 'Bieri, Gregor',\n", - " 'Smith, Lucas K.',\n", - " 'Sanchez-Diaz, Cesar I.',\n", - " 'Schroer, Adam B.',\n", - " 'Gontier, Geraldine',\n", - " 'Casaletto, Kaitlin B.',\n", - " 'Kramer, Joel H.',\n", - " 'Williams, Katherine E.',\n", - " 'Villeda, Saul A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.aaw2622\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.aaw2622\"}'],\n", - " 'title': ['Blood factors transfer beneficial effects of exercise on neurogenesis and cognition to the aged brain']},\n", - " {'bibcode': '2017Natur.542..450T',\n", - " 'abstract': 'Adipose tissue is a major site of energy storage and has a role in the regulation of metabolism through the release of adipokines. Here we show that mice with an adipose-tissue-specific knockout of the microRNA (miRNA)-processing enzyme Dicer (ADicerKO), as well as humans with lipodystrophy, exhibit a substantial decrease in levels of circulating exosomal miRNAs. Transplantation of both white and brown adipose tissue—brown especially—into ADicerKO mice restores the level of numerous circulating miRNAs that are associated with an improvement in glucose tolerance and a reduction in hepatic Fgf21 mRNA and circulating FGF21. This gene regulation can be mimicked by the administration of normal, but not ADicerKO, serum exosomes. Expression of a human-specific miRNA in the brown adipose tissue of one mouse in vivo can also regulate its 3‧ UTR reporter in the liver of another mouse through serum exosomal transfer. Thus, adipose tissue constitutes an important source of circulating exosomal miRNAs, which can regulate gene expression in distant tissues and thereby serve as a previously undescribed form of adipokine.',\n", - " 'author': ['Thomou, Thomas',\n", - " 'Mori, Marcelo A.',\n", - " 'Dreyfuss, Jonathan M.',\n", - " 'Konishi, Masahiro',\n", - " 'Sakaguchi, Masaji',\n", - " 'Wolfrum, Christian',\n", - " 'Rao, Tata Nageswara',\n", - " 'Winnay, Jonathon N.',\n", - " 'Garcia-Martin, Ruben',\n", - " 'Grinspoon, Steven K.',\n", - " 'Gorden, Phillip',\n", - " 'Kahn, C. Ronald'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature21365\"}'],\n", - " 'title': ['Adipose-derived circulating miRNAs regulate gene expression in other tissues']},\n", - " {'bibcode': '2017NatSR...746687D',\n", - " 'abstract': 'Microplastics (MPs) are a significant environmental health issue and increasingly greater source of concern. MPs have been detected in oceans, rivers, sediments, sewages, soil and even table salts. MPs exposure on marine organisms and humans has been documented, but information about the toxicity of MPs in mammal is limited. Here we used fluorescent and pristine polystyrene microplastics (PS-MPs) particles with two diameters (5\\u2009μm and 20\\u2009μm) to investigate the tissue distribution, accumulation, and tissue-specific health risk of MPs in mice. Results indicated that MPs accumulated in liver, kidney and gut, with a tissue-accumulation kinetics and distribution pattern that was strongly depended on the MPs particle size. In addition, analyses of multiple biochemical biomarkers and metabolomic profiles suggested that MPs exposure induced disturbance of energy and lipid metabolism as well as oxidative stress. Interestingly, blood biomarkers of neurotoxicity were also altered. Our results uncovered the distribution and accumulation of MPs across mice tissues and revealed significant alteration in several biomarkers that indicate potential toxicity from MPs exposure. Collectively, our data provided new evidence for the adverse consequences of MPs.',\n", - " 'author': ['Deng, Yongfeng',\n", - " 'Zhang, Yan',\n", - " 'Lemos, Bernardo',\n", - " 'Ren, Hongqiang'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep46687\"}'],\n", - " 'title': ['Tissue accumulation of microplastics in mice and biomarker responses suggest widespread health risks of exposure']},\n", - " {'bibcode': '2002Sci...296..340E',\n", - " 'abstract': 'Although humans and their closest evolutionary relatives, the chimpanzees, are 98.7% identical in their genomic DNA sequences, they differ in many morphological, behavioral, and cognitive aspects. The underlying genetic basis of many of these differences may be altered gene expression. We have compared the transcriptome in blood leukocytes, liver, and brain of humans, chimpanzees, orangutans, and macaques using microarrays, as well as protein expression patterns of humans and chimpanzees using two-dimensional gel electrophoresis. We also studied three mouse species that are approximately as related to each other as are humans, chimpanzees, and orangutans. We identified species-specific gene expression patterns indicating that changes in protein and gene expression have been particularly pronounced in the human brain.',\n", - " 'author': ['Enard, Wolfgang',\n", - " 'Khaitovich, Philipp',\n", - " 'Klose, Joachim',\n", - " 'Zöllner, Sebastian',\n", - " 'Heissig, Florian',\n", - " 'Giavalisco, Patrick',\n", - " 'Nieselt-Struwe, Kay',\n", - " 'Muchmore, Elaine',\n", - " 'Varki, Ajit',\n", - " 'Ravid, Rivka',\n", - " 'Doxiadis, Gaby M.',\n", - " 'Bontrop, Ronald E.',\n", - " 'Pääbo, Svante'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.1068996\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.1068996\"}'],\n", - " 'title': ['Intra- and Interspecific Variation in Primate Gene Expression Patterns']},\n", - " {'bibcode': '2020NatSR..1017593T',\n", - " 'abstract': 'Excessive intake of fat causes accumulation of fat in liver, leading to non-alcoholic fatty liver disease (NAFLD). High-fat diet (HFD) upregulates the expression of Factor D, a complement pathway component, in the liver of mice. However, the functions of Factor D in liver are not well known. Therefore, the current study investigated the relationship between Factor D and hepatic lipid accumulation using CRISPR/Cas9-mediated Factor D knockout (FD-KO) mice. Factor D deficiency downregulated expression of genes related to fatty acid uptake and de novo lipogenesis in the liver. Furthermore, Factor D deficiency reduced the expression of inflammatory factors (Tnf and Ccl2) and fibrosis markers and decreased accumulation of F4/80-positive macrophages. These data suggest that the Factor D deficiency improved hepatic lipid accumulation and hepatic inflammation in HFD-fed mice.',\n", - " 'author': ['Tsuru, Hiromi',\n", - " 'Osaka, Mizuko',\n", - " 'Hiraoka, Yuichi',\n", - " 'Yoshida, Masayuki'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-020-74617-5\"}'],\n", - " 'title': ['HFD-induced hepatic lipid accumulation and inflammation are decreased in Factor D deficient mouse']},\n", - " {'bibcode': '2018Natur.562...69S',\n", - " 'abstract': 'Primary liver cancer represents a major health problem. It comprises hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), which differ markedly with regards to their morphology, metastatic potential and responses to therapy. However, the regulatory molecules and tissue context that commit transformed hepatic cells towards HCC or ICC are largely unknown. Here we show that the hepatic microenvironment epigenetically shapes lineage commitment in mosaic mouse models of liver tumorigenesis. Whereas a necroptosis-associated hepatic cytokine microenvironment determines ICC outgrowth from oncogenically transformed hepatocytes, hepatocytes containing identical oncogenic drivers give rise to HCC if they are surrounded by apoptotic hepatocytes. Epigenome and transcriptome profiling of mouse HCC and ICC singled out Tbx3 and Prdm5 as major microenvironment-dependent and epigenetically regulated lineage-commitment factors, a function that is conserved in humans. Together, our results provide insight into lineage commitment in liver tumorigenesis, and explain molecularly why common liver-damaging risk factors can lead to either HCC or ICC.',\n", - " 'author': ['Seehawer, Marco',\n", - " 'Heinzmann, Florian',\n", - " \"D'Artista, Luana\",\n", - " 'Harbig, Jule',\n", - " 'Roux, Pierre-François',\n", - " 'Hoenicke, Lisa',\n", - " 'Dang, Hien',\n", - " 'Klotz, Sabrina',\n", - " 'Robinson, Lucas',\n", - " 'Doré, Grégory',\n", - " 'Rozenblum, Nir',\n", - " 'Kang, Tae-Won',\n", - " 'Chawla, Rishabh',\n", - " 'Buch, Thorsten',\n", - " 'Vucur, Mihael',\n", - " 'Roth, Mareike',\n", - " 'Zuber, Johannes',\n", - " 'Luedde, Tom',\n", - " 'Sipos, Bence',\n", - " 'Longerich, Thomas',\n", - " 'Heikenwälder, Mathias',\n", - " 'Wang, Xin Wei',\n", - " 'Bischof, Oliver',\n", - " 'Zender, Lars'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41586-018-0519-y\"}'],\n", - " 'title': ['Necroptosis microenvironment directs lineage commitment in liver cancer']},\n", - " {'bibcode': '2014EnvMM..55..500L',\n", - " 'abstract': 'Titanium dioxide (TiO2) nanomaterials (NMs) are widely used in a diversity of products including cosmetics, pharmaceuticals, food, and inks, despite uncertainties surrounding the potential health risks that they pose to humans and the environment. Previous studies on the genotoxicity of TiO2 have reported discrepant or inconclusive findings in both in vitro and in vivo systems. This study explores the in vivo genotoxic potential of a well‑characterized uncoated TiO2 NM with an average diameter of 22 nm (NM‑102, from JRC repository) using several genotoxicity endpoints in the LacZ plasmid‑based transgenic mouse model. Mice were exposed by intravenous injection to two daily doses of NM‑102: 10 and 15 mg/kg of body weight/day. Micronuclei were analyzed in peripheral blood reticulocytes 42 hr after the last treatment. DNA strand breaks (comet assay) and gene mutations were determined in the spleens and livers of the same animals 28 days after the last treatment. Histopathological and cytological analyses were also performed in liver samples. Genotoxic effects were not detected in mice exposed to the nanosized TiO2 under the experimental conditions used, despite a moderate inflammatory response that was observed in the liver. Considering the biopersistence of TiO2 in mouse liver and the moderate inflammatory response, the possibility of a secondary genotoxic effect at higher doses and in conditions that result in a stronger inflammatory response, for example, within a longer time window, should be investigated further. Environ. Mol. Mutagen. 55:500–509, 2014.',\n", - " 'author': ['Louro, Henriqueta',\n", - " 'Tavares, Ana',\n", - " 'Vital, Nádia',\n", - " 'Costa, Pedro M.',\n", - " 'Alverca, Elsa',\n", - " 'Zwart, Edwin',\n", - " 'de Jong, Wim H.',\n", - " 'Fessard, Valérie',\n", - " 'Lavinha, João',\n", - " 'Silva, Maria J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Fem.21864\"}'],\n", - " 'title': ['Integrated approach to the in vivo genotoxic effects of a titanium dioxide nanomaterial using LacZ plasmid‑based transgenic mice']},\n", - " {'bibcode': '2017NatSR...741888V',\n", - " 'abstract': 'This study clarified the role of Cygb, the fourth globin in mammals originally discovered in rat hepatic stellate cells (HSCs), in cholestatic liver disease. Bile duct ligation (BDL) augmented inflammatory reactions as revealed by increased infiltrating neutrophils, CD68+-macrophages, and chemokine expression in Cygb-/- mice. In these mice, impairment of bile canalicular indicated by the loss of CD10 expression, down-regulation of bile salt transporters, increased total bile acid, and massive apoptotic and necrotic hepatocytes occurred with the release of cytochrome c, activation of caspase 3, resulting in reduced animal survival compared to wild-type mice. In Cygb-/- mouse liver, all of NO metabolites and oxidative stress were increased. Treatment with NO inhibitor restrained all above phenotypes and restored CD10 expression in BDL Cygb-/- mice, while administration of NO donor aggravated liver damage in BDL-wild type mice to the same extent of BDL-Cygb-/- mice. N-acetylcysteine administration had a negligible effect in all groups. In mice of BDL for 1-3 weeks, expression of all fibrosis-related markers was significantly increased in Cygb-/- mice compared with wild-type mice. Thus, Cygb deficiency in HSCs enhances hepatocyte damage and inflammation in early phase and fibrosis development in late phase in mice subjected to BDL, presumably via altered NO metabolism.',\n", - " 'author': ['van Thuy, Tuong Thi',\n", - " 'Thuy, Le Thi Thanh',\n", - " 'Yoshizato, Katsutoshi',\n", - " 'Kawada, Norifumi'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep41888\"}'],\n", - " 'title': ['Possible Involvement of Nitric Oxide in Enhanced Liver Injury and Fibrogenesis during Cholestasis in Cytoglobin-deficient Mice']},\n", - " {'bibcode': '2016HETox..35.1093X',\n", - " 'abstract': 'Tri- ortho–cresyl phosphate (TOCP) has been widely used as plasticizers, plastic softeners, and flame retardants in industry and reported to have delayed neurotoxicity and reproductive toxicology in animals. However, it remains to be elusive whether TOCP induces liver injury. In this study, male mice were orally administered different concentrations of TOCP (100, 200, or 400 mg/kg/day) for 28 days. Histological examination showed that TOCP led to serious hepatocellular injury. In addition, administration of TOCP induced a marked elevation in the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in mice. The content of malondialdehyde (MDA) was increased significantly in the liver after the mice were treated with TOCP; while there was a dramatic decrease in the content of glutathione (GSH) and the activities of antioxidative enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX). TOCP inhibited viability of mouse liver cancer Hepa 1-6 cells in a dose-dependent manner. Meanwhile, TOCP significantly increased MDA content and inhibited GSH content and the activities of SOD and GSH-PX in the cells, respectively. Oxidative stress dramatically inhibited viability of Hepa 1-6 cells; while inhibition of oxidative stress by N-acetyl-l-cysteine could rescue the cell viability inhibited by TOCP to a certain extent. In summary, oxidative stress might be involved in TOCP-induced hepatocellular injury in male mice.',\n", - " 'author': ['Xu, LL', 'Long, CY', 'Wang, JL', 'Yu, M.', 'Chen, JX'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1177%2F0960327115621363\"}'],\n", - " 'title': ['Involvement of oxidative stress in tri-ortho–cresyl phosphate-induced liver injury in male mice']},\n", - " {'bibcode': '2023SPIE12367E..0GZ',\n", - " 'abstract': 'Full field optical coherence tomography (FF-OCT) utilizes low coherence gate to suppress the out-of-focus scattering light. The spatial resolution remains limited by numerical aperture of objective and bandwidth of light source. Structured illumination microscopy not only is a wide-field three-dimensional imaging modality which shift high spatial frequency components to optical transfer function of system, but also enables optical sectioning in biological tissue. Thus, we propose a structured illumination based FF-OCT(SI-FF-OCT) to realize three-dimensional sub-cellular resolution using parallel coded digital micromirror device (DMD). First, the principle of SI-FF-OCT was introduced in terms of point spread function (PSF) of the standard FF-OCT optical system. Second, a 1D illumination pattern of SI-FF-OCT for imaging random tissue was simulated for both of lateral resolution enhancement and optical sectioning capacity in the same configuration. The results of onion cells and mouse liver tissue suggested that the proposed white-light structured illumination approach in FF-OCT demonstrates tomographic imaging for thick transparent samples with a higher lateral resolution and better contrast than standard FF-OCT. As a benefit of the fringe projection and low-coherence gate filtering, SI-FF-OCT also has optical sectioning capability in free of speckle-noise in sub-pixel accuracy way.',\n", - " 'author': ['Zhu, Yue', 'Zhou, Yuan', 'Guo, Zhenyan', 'Tian, Haoying'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"video\", \"url\": \"https://doi.org/10.1117/12.2641988\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1117%2F12.2641988\"}'],\n", - " 'title': ['DMD-based structured illumination full-field optical coherence tomography']},\n", - " {'bibcode': '2020NatCo..11.6215M',\n", - " 'abstract': 'A distinct 12-hour clock exists in addition to the 24-hour circadian clock to coordinate metabolic and stress rhythms. Here, we show that liver-specific ablation of X-box binding protein 1 (XBP1) disrupts the hepatic 12-hour clock and promotes spontaneous non-alcoholic fatty liver disease (NAFLD). We show that hepatic XBP1 predominantly regulates the 12-hour rhythmicity of gene transcription in the mouse liver and demonstrate that perturbation of the 12-hour clock, but not the core circadian clock, is associated with the onset and progression of this NAFLD phenotype. Mechanistically, we provide evidence that the spliced form of XBP1 (XBP1s) binds to the hepatic 12-hour cistrome to directly regulate the 12-hour clock, with a periodicity paralleling the harmonic activation of the 12-hour oscillatory transcription of many rate-limiting metabolic genes known to have perturbations in human metabolic disease. Functionally, we show that Xbp1 ablation significantly reduces cellular membrane fluidity and impairs lipid homeostasis via rate-limiting metabolic processes in fatty acid monounsaturated and phospholipid remodeling pathways. These findings reveal that genetic disruption of the hepatic 12-hour clock links to the onset and progression of NAFLD development via transcriptional regulator XBP1, and demonstrate a role for XBP1 and the 12-hour clock in the modulation of phospholipid composition and the maintenance of lipid homeostasis.',\n", - " 'author': ['Meng, Huan',\n", - " 'Gonzales, Naomi M.',\n", - " 'Lonard, David M.',\n", - " 'Putluri, Nagireddy',\n", - " 'Zhu, Bokai',\n", - " 'Dacso, Clifford C.',\n", - " 'York, Brian',\n", - " \"O'Malley, Bert W.\"],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41467-020-20028-z\"}'],\n", - " 'title': ['XBP1 links the 12-hour clock to NAFLD and regulation of membrane fluidity and lipid homeostasis']},\n", - " {'bibcode': '2018ScTEn.626..147P',\n", - " 'author': ['Pardo, Michal',\n", - " 'Xu, Fanfan',\n", - " 'Qiu, Xinghua',\n", - " 'Zhu, Tong',\n", - " 'Rudich, Yinon'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.scitotenv.2018.01.017\"}'],\n", - " 'title': ['Seasonal variations in fine particle composition from Beijing prompt oxidative stress response in mouse lung and liver']},\n", - " {'bibcode': '2023NatCo..14.3304G',\n", - " 'abstract': 'Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by chronic inflammation and progressive fibrosis of the biliary tree. The majority of PSC patients suffer from concomitant inflammatory bowel disease (IBD), which has been suggested to promote disease development and progression. However, the molecular mechanisms by which intestinal inflammation may aggravate cholestatic liver disease remain incompletely understood. Here, we employ an IBD-PSC mouse model to investigate the impact of colitis on bile acid metabolism and cholestatic liver injury. Unexpectedly, intestinal inflammation and barrier impairment improve acute cholestatic liver injury and result in reduced liver fibrosis in a chronic colitis model. This phenotype is independent of colitis-induced alterations of microbial bile acid metabolism but mediated via hepatocellular NF-κB activation by lipopolysaccharide (LPS), which suppresses bile acid metabolism in-vitro and in-vivo. This study identifies a colitis-triggered protective circuit suppressing cholestatic liver disease and encourages multi-organ treatment strategies for PSC.',\n", - " 'author': ['Gui, Wenfang',\n", - " 'Hole, Mikal Jacob',\n", - " 'Molinaro, Antonio',\n", - " 'Edlund, Karolina',\n", - " 'Jørgensen, Kristin K.',\n", - " 'Su, Huan',\n", - " 'Begher-Tibbe, Brigitte',\n", - " 'Gaßler, Nikolaus',\n", - " 'Schneider, Carolin V.',\n", - " 'Muthukumarasamy, Uthayakumar',\n", - " 'Mohs, Antje',\n", - " 'Liao, Lijun',\n", - " 'Jaeger, Julius',\n", - " 'Mertens, Christian J.',\n", - " 'Bergheim, Ina',\n", - " 'Strowig, Till',\n", - " 'Hengstler, Jan G.',\n", - " 'Hov, Johannes R.',\n", - " 'Marschall, Hanns-Ulrich',\n", - " 'Trautwein, Christian',\n", - " 'Schneider, Kai Markus'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41467-023-38840-8\"}'],\n", - " 'title': ['Colitis ameliorates cholestatic liver disease via suppression of bile acid synthesis']},\n", - " {'bibcode': '2004Natur.432..173S',\n", - " 'abstract': \"RNA interference (RNAi) holds considerable promise as a therapeutic approach to silence disease-causing genes, particularly those that encode so-called `non-druggable' targets that are not amenable to conventional therapeutics such as small molecules, proteins, or monoclonal antibodies. The main obstacle to achieving in vivo gene silencing by RNAi technologies is delivery. Here we show that chemically modified short interfering RNAs (siRNAs) can silence an endogenous gene encoding apolipoprotein B (apoB) after intravenous injection in mice. Administration of chemically modified siRNAs resulted in silencing of the apoB messenger RNA in liver and jejunum, decreased plasma levels of apoB protein, and reduced total cholesterol. We also show that these siRNAs can silence human apoB in a transgenic mouse model. In our in vivo study, the mechanism of action for the siRNAs was proven to occur through RNAi-mediated mRNA degradation, and we determined that cleavage of the apoB mRNA occurred specifically at the predicted site. These findings demonstrate the therapeutic potential of siRNAs for the treatment of disease.\",\n", - " 'author': ['Soutschek, Jürgen',\n", - " 'Akinc, Akin',\n", - " 'Bramlage, Birgit',\n", - " 'Charisse, Klaus',\n", - " 'Constien, Rainer',\n", - " 'Donoghue, Mary',\n", - " 'Elbashir, Sayda',\n", - " 'Geick, Anke',\n", - " 'Hadwiger, Philipp',\n", - " 'Harborth, Jens',\n", - " 'John, Matthias',\n", - " 'Kesavan, Venkitasamy',\n", - " 'Lavine, Gary',\n", - " 'Pandey, Rajendra K.',\n", - " 'Racie, Timothy',\n", - " 'Rajeev, Kallanthottathil G.',\n", - " 'Röhl, Ingo',\n", - " 'Toudjarska, Ivanka',\n", - " 'Wang, Gang',\n", - " 'Wuschko, Silvio',\n", - " 'Bumcrot, David',\n", - " 'Koteliansky, Victor',\n", - " 'Limmer, Stefan',\n", - " 'Manoharan, Muthiah',\n", - " 'Vornlocher, Hans-Peter'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature03121\"}'],\n", - " 'title': ['Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs']},\n", - " {'bibcode': '2007PNAS..10414771T',\n", - " 'abstract': 'We used several of the genetic lesions commonly associated with human liver tumors to reconstruct genetic progression to hepatocellular carcinoma and adenoma in mouse models. We initiated tumorigenesis with a transgene of the protooncogene MET or by hydrodynamic transfection of MET in combination with other genes into the livers of adult animals. Hepatocellular carcinoma in both instances arose from cooperation between MET and constitutively active versions of β-catenin. In contrast, adenomas were produced by cooperation between MET and defective signaling through the transcription factor HNF1α. Prompted by these findings, we uncovered a coincidence between activation of the protein-tyrosine kinase encoded by MET and activating mutations of β-catenin in a subset of human hepatocellular carcinomas. Inactivation of MET transgenes led to regression of hepatocellular carcinomas despite the persistence of activated β-catenin. The tumors eventually recurred in the absence of MET expression, however, presumably after the occurrence of one or more events that cooperated with activated β-catenin in lieu of MET. These results offer insight into hepatic tumorigenesis, provide mouse models that should be useful in the further study of hepatic tumorigenesis and for preclinical testing, and identify a subset of human hepatocellular carcinomas that may be susceptible to combination therapy directed against Met and the Wnt signaling pathway.',\n", - " 'author': ['Tward, Aaron D.',\n", - " 'Jones, Kirk D.',\n", - " 'Yant, Stephen',\n", - " 'Cheung, Siu Tim',\n", - " 'Fan, Sheung Tat',\n", - " 'Chen, Xin',\n", - " 'Kay, Mark A.',\n", - " 'Wang, Rong',\n", - " 'Bishop, J. Michael'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/104/37/14771\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0706578104\"}'],\n", - " 'title': ['Distinct pathways of genomic progression to benign and malignant tumors of the liver']},\n", - " {'bibcode': '2021Natur.595..730J',\n", - " 'abstract': 'Hepatocellular carcinoma (HCC)—the most common form of liver cancer—is an aggressive malignancy with few effective treatment options1. Lenvatinib is a small-molecule inhibitor of multiple receptor tyrosine kinases that is used for the treatment of patients with advanced HCC, but this drug has only limited clinical benefit2. Here, using a kinome-centred CRISPR-Cas9 genetic screen, we show that inhibition of epidermal growth factor receptor (EGFR) is synthetic lethal with lenvatinib in liver cancer. The combination of the EGFR inhibitor gefitinib and lenvatinib displays potent anti-proliferative effects in vitro in liver cancer cell lines that express EGFR and in vivo in xenografted liver cancer cell lines, immunocompetent mouse models and patient-derived HCC tumours in mice. Mechanistically, inhibition of fibroblast growth factor receptor (FGFR) by lenvatinib treatment leads to feedback activation of the EGFR-PAK2-ERK5 signalling axis, which is blocked by EGFR inhibition. Treatment of 12 patients with advanced HCC who were unresponsive to lenvatinib treatment with the combination of lenvatinib plus gefitinib (trial identifier NCT04642547) resulted in meaningful clinical responses. The combination therapy identified here may represent a promising strategy for the approximately 50% of patients with advanced HCC who have high levels of EGFR.',\n", - " 'author': ['Jin, Haojie',\n", - " 'Shi, Yaoping',\n", - " 'Lv, Yuanyuan',\n", - " 'Yuan, Shengxian',\n", - " 'Ramirez, Christel F. A.',\n", - " 'Lieftink, Cor',\n", - " 'Wang, Liqin',\n", - " 'Wang, Siying',\n", - " 'Wang, Cun',\n", - " 'Dias, Matheus Henrique',\n", - " 'Jochems, Fleur',\n", - " 'Yang, Yuan',\n", - " 'Bosma, Astrid',\n", - " 'Hijmans, E. Marielle',\n", - " 'de Groot, Marnix H. P.',\n", - " 'Vegna, Serena',\n", - " 'Cui, Dan',\n", - " 'Zhou, Yangyang',\n", - " 'Ling, Jing',\n", - " 'Wang, Hui',\n", - " 'Guo, Yuchen',\n", - " 'Zheng, Xingling',\n", - " 'Isima, Nikita',\n", - " 'Wu, Haiqiu',\n", - " 'Sun, Chong',\n", - " 'Beijersbergen, Roderick L.',\n", - " 'Akkari, Leila',\n", - " 'Zhou, Weiping',\n", - " 'Zhai, Bo',\n", - " 'Qin, Wenxin',\n", - " 'Bernards, ReneÌ\\x81'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"data\", \"url\": \"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse157905\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41586-021-03741-7\"}'],\n", - " 'title': ['EGFR activation limits the response of liver cancer to lenvatinib']},\n", - " {'bibcode': '2022EnTox..37.2515G',\n", - " 'abstract': '1,3-Dichloro-2-propanol (1,3-DCP) is a representative chloropropane environmental contaminant with multiple toxicities. Ferroptosis is a novel iron-dependent form of regulated cell death that is closely associated with the accumulation of lipid peroxides, Fe2+ and reactive oxygen species (ROS). In this study, we found that 1,3-DCP could induce mouse liver injury via ferroptosis. Administrating of C57BL/6J mice with 12.5, 25, and 50 mg/kg 1,3-DCP for 4 weeks via oral gavage, the data showed that 1,3-DCP exposure led to the pathological changes in mouse livers, remarkably induced accumulation of malondialdehyde (MDA) and Iron, reduction of glutathione (GSH), and changed in the expression of ferroptosis marker proteins glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase-4 (ACSL4). Then, we also proved the results with HepG2 cells in vitro. The data showed that treatment 1,3-DCP significantly triggered the ferroptosis in vitro. Furthermore, we found that the ferroptosis-related signal pathways were significantly activated in mice livers and HepG2 cells in response to 1,3-DCP exposure. The data showed that 1,3-DCP induced ferroptosis by inhibiting nuclear factor erythroid 2-related factor 2 (Nrf2) translocation into nuclear and thereby suppressing the expression of its downstream target proteins including GPX4, ferritin heavy chain (FTH), ferroportin (FPN), cystine/glutamate transporter xCT (SLC7A11), and heme oxygenase 1 (HO-1). Taken together, our findings confirmed that 1,3-DCP induced ferroptosis via the Nrf2/ARE signaling pathway in hepatocytes. Our works provide new toxicity mechanisms of 1,3-DCP with ferroptosis on hepatocytes injury.',\n", - " 'author': ['Guan, Shuang',\n", - " 'Zhang, Ranran',\n", - " 'Zhao, Yanan',\n", - " 'Meng, Zhuoqun',\n", - " 'Lu, Jing'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Ftox.23615\"}'],\n", - " 'title': ['1,3-Dichloro-2-propanol induced ferroptosis through Nrf2/ ARE signaling pathway in hepatocytes']},\n", - " {'bibcode': '1991PNAS...88.8870B',\n", - " 'abstract': 'Observations of patients deficient in the steroidogenic enzyme 3 beta-hydroxy-delta 5-steroid dehydrogenase/isomerase (3 beta HSD) have suggested the presence of distinct 3 beta HSD structural gene(s) that are expressed at peripheral sites, possibly the liver. We now report the isolation of cDNA clones representing three forms of 3 beta HSD from mouse Leydig cell and liver libraries. The three forms share significant identify but differ from each other by 5-10% within their coding regions. RNA that hybridizes to radiolabeled 3 beta HSD probes is present in the gonads, adrenal glands, liver, and kidneys of both sexes. Ribonuclease protection analysis using antisense probes derived from each of the three forms demonstrates that one form, 3 beta HSD I, is restricted to steroidogenic tissues. Two other forms, 3 beta HSD II and III, are expressed in liver and kidney but are not detected in steroidogenic tissues. A polyclonal antibody raised against the human placental form of 3 beta HSD recognizes a 42-kDa protein in gonadal and adrenal tissue and a 45-kDa protein in liver. The antibody recognizes a 42-kDa protein in kidney only weakly. 3 beta HSD enzyme activity is present in testicular, adrenal, hepatic, and renal tissue, with adrenal tissue possessing the highest specific activity. When expressed as total 3 beta HSD activity for whole organ mass, activity is greatest in the liver. The results demonstrate that the mouse liver is a significant site of 3 beta HSD activity and demonstrate the existence of multiple 3 beta HSD structural genes in the mouse.',\n", - " 'author': ['Bain, Paul A.',\n", - " 'Yoo, Min',\n", - " 'Clarke, Trent',\n", - " 'Hammond, Sarah H.',\n", - " 'Payne, Anita H.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/88/20/8870\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/88/20/8870\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/88/20/8870\"}'],\n", - " 'title': ['Multiple Forms of Mouse 3β-Hydroxysteroid Dehydrogenase/Δ^5 - Δ^4 Isomerase and Differential Expression in Gonads, Adrenal Glands, Liver, and Kidneys of Both Sexes']},\n", - " {'bibcode': '2020Sci...367..652Z',\n", - " 'abstract': 'Liver cell death has an essential role in nonalcoholic steatohepatitis (NASH). The activity of the energy sensor adenosine monophosphate (AMP)–activated protein kinase (AMPK) is repressed in NASH. Liver-specific AMPK knockout aggravated liver damage in mouse NASH models. AMPK phosphorylated proapoptotic caspase-6 protein to inhibit its activation, keeping hepatocyte apoptosis in check. Suppression of AMPK activity relieved this inhibition, rendering caspase-6 activated in human and mouse NASH. AMPK activation or caspase-6 inhibition, even after the onset of NASH, improved liver damage and fibrosis. Once phosphorylation was decreased, caspase-6 was activated by caspase-3 or -7. Active caspase-6 cleaved Bid to induce cytochrome c release, generating a feedforward loop that leads to hepatocyte death. Thus, the AMPK–caspase-6 axis regulates liver damage in NASH, implicating AMPK and caspase-6 as therapeutic targets.',\n", - " 'author': ['Zhao, Peng',\n", - " 'Sun, Xiaoli',\n", - " 'Chaggan, Cynthia',\n", - " 'Liao, Zhongji',\n", - " 'in Wong, Kai',\n", - " 'He, Feng',\n", - " 'Singh, Seema',\n", - " 'Loomba, Rohit',\n", - " 'Karin, Michael',\n", - " 'Witztum, Joseph L.',\n", - " 'Saltiel, Alan R.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.aay0542\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.aay0542\"}'],\n", - " 'title': ['An AMPK–caspase-6 axis controls liver damage in nonalcoholic steatohepatitis']},\n", - " {'bibcode': '2017NatSR...742959A',\n", - " 'abstract': 'Neuregulin1 is an epidermal growth factor (EGF)-like domain-containing protein that has multiple isoforms and functions as a local mediator in the control of various cellular functions. Here we show that type I isoform of neuregulin1 with an α-type EGF-like domain (Nrg1α) is the major isoform in mouse liver and regulates hepatic glucose production. Forced expression of Nrg1α in mouse liver enhanced systemic glucose disposal and decreased hepatic glucose production with reduced fasting blood glucose levels. Nuclear forkhead box protein O1 (FoxO1) and its downstream targets, PEPCK and G6Pase, were suppressed in liver and isolated hepatocytes by Nrg1α overexpression. In contrast, silencing of Nrg1α enhanced glucose production with increased PEPCK and G6Pase expressions in cAMP/dexamethasone-stimulated hepatocytes. Mechanistically, the recombinant α-type EGF-like domain of NRG1α (rNRG1α) stimulated the ERBB3 signalling pathway in hepatocytes, resulting in decreased nuclear FoxO1 accumulation via activation of both the AKT and ERK pathways. In addition, acute treatment with rNRG1α also suppressed elevation of blood glucose levels after both glucose and pyruvate challenge. Although a liver-specific deletion of Nrg1 gene in mice showed little effect on systemic glucose metabolism, these results suggest that NRG1α have a novel regulatory function in hepatic gluconeogenesis by regulating the ERBB3-AKT/ERK-FoxO1 cascade.',\n", - " 'author': ['Arai, Takatomo',\n", - " 'Ono, Yumika',\n", - " 'Arimura, Yujiro',\n", - " 'Sayama, Keimon',\n", - " 'Suzuki, Tomohiro',\n", - " 'Shinjo, Satoko',\n", - " 'Kanai, Mai',\n", - " 'Abe, Shin-Ichi',\n", - " 'Semba, Kentaro',\n", - " 'Goda, Nobuhito'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep42959\"}'],\n", - " 'title': ['Type I neuregulin1α is a novel local mediator to suppress hepatic gluconeogenesis in mice']},\n", - " {'bibcode': '2005HETox..24..325W',\n", - " 'abstract': 'Comparisons on a linear and the Rozman logarithmic scale for dosage versus carcinogenicity in rodents are presented for methyl eugenol (ME), nitrosodiethylamine (NDEA), ethyl carbamate (EC) and 2-acetylaminofluorene (AAF). Each of these chemicals has been shown to be carcinogenic in experimental animals and, in addition, humans are regularly exposed to at least three of these compounds (ME, NDEA, EC) in foods. Although the source of adducts from AAF is not known, the aminofluorene (AF) adduct is present in humans. Plotted on the same graphs are either some doses from common foods (ME, NDEA, EC) or adducts (AF) on human haemoglobin, for perspective, with their thresholds for carcinogenesis in animals. Use of a linear scale when comparing doses administered to animals in studies of carcinogenicity with doses of those same chemicals to which humans are exposed does not provide useful, comparative information. On the other hand, the Rozman logarithmic scale for dose allows one to put these relative doses in perspective. It is also evident that forcing a linear extrapolation through the zero, zero origin does not agree with the experimental data. Further analyses for goodness of fit for these dose responses reveal that the dose response for three of these compounds (ME, NDEA, EC) appears to be linear with the logarithm of the dose. However, AAF appears to be linear with the logarithm of the dose for bladder, but not for liver. It is suggested that the high background incidence of tumours in the BALB/c StCrlfC3Hf/Nctr mouse liver may confound the interpretation of dose response from AAF carcinogenesis in mouse liver.',\n", - " 'author': ['Waddell, William J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1191%2F0960327105ht525oa\"}'],\n", - " 'title': ['Comparisons of thresholds for carcinogenicity on linear and logarithmic dosage scales']},\n", - " {'bibcode': '2011PNAS..10821075F',\n", - " 'abstract': 'Diabetes mellitus is the most common metabolic disorder worldwide and a major risk factor for cardiovascular disease. MicroRNAs are negative regulators of gene expression that have been implicated in many biological processes, including metabolism. Here we show that the Let-7 family of microRNAs regulates glucose metabolism in multiple organs. Global and pancreas-specific overexpression of Let-7 in mice resulted in impaired glucose tolerance and reduced glucose-induced pancreatic insulin secretion. Mice overexpressing Let-7 also had decreased fat mass and body weight, as well as reduced body size. Global knockdown of the Let-7 family with an antimiR was sufficient to prevent and treat impaired glucose tolerance in mice with diet-induced obesity, at least in part by improving insulin sensitivity in liver and muscle. AntimiR treatment of mice on a high-fat diet also resulted in increased lean and muscle mass, but not increased fat mass, and prevented ectopic fat deposition in the liver. These findings demonstrate that Let-7 regulates multiple aspects of glucose metabolism and suggest antimiR-induced Let-7 knockdown as a potential treatment for type 2 diabetes mellitus. Furthermore, our Cre-inducible Let-7-transgenic mice provide a unique model for studying tissue-specific aspects of body growth and type 2 diabetes.',\n", - " 'author': ['Frost, Robert J. A.', 'Olson, Eric N.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/108/52/21075\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1118922109\"}'],\n", - " 'title': ['Control of glucose homeostasis and insulin sensitivity by the Let-7 family of microRNAs']},\n", - " {'bibcode': '2004Natur.432.1027W',\n", - " 'abstract': 'The regulation of fat and glucose metabolism in the liver is controlled primarily by insulin and glucagon. Changes in the circulating concentrations of these hormones signal fed or starvation states and elicit counter-regulatory responses that maintain normoglycaemia. Here we show that in normal mice, plasma insulin inhibits the forkhead transcription factor Foxa2 by nuclear exclusion and that in the fasted (low insulin) state Foxa2 activates transcriptional programmes of lipid metabolism and ketogenesis. In insulin-resistant or hyperinsulinaemic mice, Foxa2 is inactive and permanently located in the cytoplasm of hepatocytes. In these mice, adenoviral expression of Foxa2T156A, a nuclear, constitutively active Foxa2 that cannot be inhibited by insulin, decreases hepatic triglyceride content, increases hepatic insulin sensitivity, reduces glucose production, normalizes plasma glucose and significantly lowers plasma insulin. These changes are associated with increased expression of genes encoding enzymes of fatty acid oxidation, ketogenesis and glycolysis. Chronic hyperinsulinaemia in insulin-resistant syndromes results in the cytoplasmic localization and inactivation of Foxa2, thereby promoting lipid accumulation and insulin resistance in the liver. Pharmacological intervention to inhibit phosphorylation of Foxa2 may be an effective treatment for type 2 diabetes.',\n", - " 'author': ['Wolfrum, Christian',\n", - " 'Asilmaz, Esra',\n", - " 'Luca, Edlira',\n", - " 'Friedman, Jeffrey M.',\n", - " 'Stoffel, Markus'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature03047\"}'],\n", - " 'title': ['Foxa2 regulates lipid metabolism and ketogenesis in the liver during fasting and in diabetes']},\n", - " {'bibcode': '2006PNAS..103.5723K',\n", - " 'abstract': 'We originally identified senescence marker protein 30 (SMP30) as a distinctive protein whose expression decreases in an androgen-independent manner with aging. Here, we report its sequence homology found in two kinds of bacterial gluconolactonases (GNLs) by using the blast search. Then, through a biochemical study, we identify SMP30 as the lactone-hydrolyzing enzyme GNL of animal species. SMP30 purified from the rat liver had lactonase activity toward various aldonolactones, such as d- and l-glucono-δ-lactone, d- and l-gulono-γ-lactone, and d- and l-galactono-γ-lactone, with a requirement for Zn2+ or Mn2+ as a cofactor. Furthermore, in SMP30 knockout mice, no GNL activity was detectable in the liver. Thus, we conclude that SMP30 is a unique GNL in the liver. The lactonase reaction with l-gulono-γ-lactone is the penultimate step in l-ascorbic acid (AA) biosynthesis, and the essential role of SMP30 in this synthetic process was verified here by a nutritional study using SMP30 knockout mice. These knockout mice (n = 6), fed a vitamin C-deficient diet, did not thrive; i.e., they displayed symptoms of scurvy such as bone fracture and rachitic rosary and then died by 135 days after the start of receiving the deficient diet. The AA levels in their livers and kidneys at the time of death were <1.6% of those in WT control mice. In addition, by using the SMP30 knockout mouse, we demonstrate that the alternative pathway of AA synthesis involving d-glucurono-γ-lactone operates in vivo, although its flux is fairly small.',\n", - " 'author': ['Kondo, Yoshitaka',\n", - " 'Inai, Yoko',\n", - " 'Sato, Yasunori',\n", - " 'Handa, Setsuko',\n", - " 'Kubo, Sachiho',\n", - " 'Shimokado, Kentaro',\n", - " 'Goto, Sataro',\n", - " 'Nishikimi, Morimitsu',\n", - " 'Maruyama, Naoki',\n", - " 'Ishigami, Akihito'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/103/15/5723\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/103/15/5723\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/full/103/15/5723\"}'],\n", - " 'title': ['Senescence marker protein 30 functions as gluconolactonase in L-ascorbic acid biosynthesis, and its knockout mice are prone to scurvy']},\n", - " {'bibcode': '2008OptCo.281.5480L',\n", - " 'abstract': 'We report on the design, test and Monte Carlo simulations of a non-descanned (NDS) collection port that we compare to a descanned (DS) port implemented on the same confocal microscope to carry out two-photon excitation fluorescence (TPEF) imaging. Our optical concept provides compactness, a wide field of view to the NDS port and allows the usage of small-area photosensors. The collection efficiency of the NDS port was measured with respect to those of the DS port as function of the imaging depth within a tissue-like optical phantom, for two high numerical aperture objectives. A NDS-to-DS collection ratio as high as about 30 was found for an imaging depth of 500 μm, corresponding to four mean scattering paths of the collected photons within the turbid medium. Measurements were fully interpreted by Monte Carlo simulations of light scattering through the turbid medium and collection by the spatio-angular apertured DS and NDS ports. Comparison of XZ cross-sectional views of mice liver samples imaged with the two ports emphasized the advantage of our NDS device for imaging deeply inside biological samples using TPEF microscopy.',\n", - " 'author': ['Le Grand, Y.', 'Leray, A.', 'Guilbert, T.', 'Odin, C.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.optcom.2008.07.027\"}'],\n", - " 'title': ['Non-descanned versus descanned epifluorescence collection in two-photon microscopy: Experiments and Monte Carlo simulations']},\n", - " {'bibcode': '2005PNAS..102.3022M',\n", - " 'abstract': 'Plasmodium parasites of mammals, including the species that cause malaria in humans, infect the liver first and develop there into clinically silent liver stages. Liver stages grow and ultimately produce thousands of first-generation merozoites, which initiate the erythrocytic cycles causing malaria pathology. Here, we present a Plasmodium protein with a critical function for complete liver stage development. UIS4 (up-regulated in infective sporozoites gene 4) is expressed exclusively in infective sporozoites and developing liver stages, where it localizes to the parasitophorous vacuole membrane. Targeted gene disruption of UIS4 in the rodent model malaria parasite Plasmodium berghei generated knockout parasites that progress through the malaria life cycle until after hepatocyte invasion but are severely impaired in further liver stage development. Immunization with UIS4 knockout sporozoites completely protects mice against subsequent infectious WT sporozoite challenge. Genetically attenuated liver stages may thus induce immune responses, which inhibit subsequent infection of the liver with WT parasites.',\n", - " 'author': ['Mueller, Ann-Kristin',\n", - " 'Camargo, Nelly',\n", - " 'Kaiser, Karine',\n", - " 'Andorfer, Cathy',\n", - " 'Frevert, Ute',\n", - " 'Matuschewski, Kai',\n", - " 'Kappe, Stefan H. I.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/102/8/3022\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0408442102\"}'],\n", - " 'title': ['Plasmodium liver stage developmental arrest by depletion of a protein at the parasite-host interface']},\n", - " {'bibcode': '2001PNAS...98.5560L',\n", - " 'abstract': 'Liver-specific and nonliver-specific methionine adenosyltransferases (MATs) are products of two genes, MAT1A and MAT2A, respectively, that catalyze the formation of S-adenosylmethionine (AdoMet), the principal biological methyl donor. Mature liver expresses MAT1A, whereas MAT2A is expressed in extrahepatic tissues and is induced during liver growth and dedifferentiation. To examine the influence of MAT1A on hepatic growth, we studied the effects of a targeted disruption of the murine MAT1A gene. MAT1A mRNA and protein levels were absent in homozygous knockout mice. At 3 months, plasma methionine level increased 776% in knockouts. Hepatic AdoMet and glutathione levels were reduced by 74 and 40%, respectively, whereas S-adenosylhomocysteine, methylthioadenosine, and global DNA methylation were unchanged. The body weight of 3-month-old knockout mice was unchanged from wild-type littermates, but the liver weight was increased 40%. The Affymetrix GENECHIP system and Northern and Western blot analyses were used to analyze differential expression of genes. The expression of many acute phase-response and inflammatory markers, including orosomucoid, amyloid, metallothionein, Fas antigen, and growth-related genes, including early growth response 1 and proliferating cell nuclear antigen, is increased in the knockout animal. At 3 months, knockout mice are more susceptible to choline-deficient diet-induced fatty liver. At 8 months, knockout mice developed spontaneous macrovesicular steatosis and predominantly periportal mononuclear cell infiltration. Thus, absence of MAT1A resulted in a liver that is more susceptible to injury, expresses markers of an acute phase response, and displays increased proliferation.',\n", - " 'author': ['Lu, Shelly C.',\n", - " 'Alvarez, Luis',\n", - " 'Huang, Zong-Zhi',\n", - " 'Chen, Lixin',\n", - " 'An, Wei',\n", - " 'Corrales, Fernando J.',\n", - " 'Avila, Matías A.',\n", - " 'Kanel, Gary',\n", - " 'Mato, José M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/98/10/5560\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/98/10/5560\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/98/10/5560\"}'],\n", - " 'title': ['Methionine adenosyltransferase 1A knockout mice are predisposed to liver injury and exhibit increased expression of genes involved in proliferation']},\n", - " {'bibcode': '2012PNAS..109.3826D',\n", - " 'abstract': 'Cyclin-dependent kinase 1 (Cdk1) is an archetypical kinase and a central regulator that drives cells through G2 phase and mitosis. Knockouts of Cdk2, Cdk3, Cdk4, or Cdk6 have resulted in viable mice, but the in vivo functions of Cdk1 have not been fully explored in mammals. Here we have generated a conditional-knockout mouse model to study the functions of Cdk1 in vivo. Ablation of Cdk1 leads to arrest of embryonic development around the blastocyst stage. Interestingly, liver-specific deletion of Cdk1 is well tolerated, and liver regeneration after partial hepatectomy is not impaired, indicating that regeneration can be driven by cell growth without cell division. The loss of Cdk1 does not affect S phase progression but results in DNA re-replication because of an increase in Cdk2/cyclin A2 activity. Unlike other Cdks, loss of Cdk1 in the liver confers complete resistance against tumorigenesis induced by activated Ras and silencing of p53.',\n", - " 'author': ['Diril, M. Kasim',\n", - " 'Ratnacaram, Chandrahas Koumar',\n", - " 'Padmakumar, V. C.',\n", - " 'Du, Tiehua',\n", - " 'Wasser, Martin',\n", - " 'Coppola, Vincenzo',\n", - " 'Tessarollo, Lino',\n", - " 'Kaldis, Philipp'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1115201109\"}'],\n", - " 'title': ['Cyclin-dependent kinase 1 (Cdk1) is essential for cell division and suppression of DNA re-replication but not for liver regeneration']},\n", - " {'bibcode': '2021AIPC.2353c0095J',\n", - " 'abstract': 'Non-alcoholic fatty liver disease (NAFLD) occurs when triglycerides inside hepatocytes are swollen. A single bulb garlic extract containing allicin components, S-allyl-l-cysteine, Ajoene (E-Ajoene and Z-Ajoene) are thought to inhibit fat biosynthesis and reduce triglycerides in blood serum. This study aimed to analyze single bulb garlic extract in NAFLD due to a high-fat diet (HFD) in mice. Twenty male Balb/C mice were divided into five groups: normal, HFD, HFD + Single Bulb Garlic Extract (SBGE) 100 mg kg BW−1, HFD + SBGE 200 mg kg BW−1, and HFD + SBGE 400 mg kg BW−1. The administration of SBGE orally altogether with HFD for 30 days. On the last day of treatment, the mice were sacrificed. The liver was collected to make a micro-anatomic slide and stained by Hematoxylin Eosin. Liver microanatomy slides were observed under a light microscope and scoring to count fatty liver cells. The results of this study indicated that administration of SBGE affected the average liver weight (p < 0.05). Treating SBGE with dose of 100 mg kg BW−1, 200 mg kg BW−1, and 400 mg kg BW−1 decreased hepatic steatosis (p < 0.05). SBGE could prevent non-alcoholic fatty liver disease in mice fed with HFD.',\n", - " 'author': ['Jannah, Fita Nur',\n", - " 'Anggraini, Putri Diyah',\n", - " 'Gofur, Abdul',\n", - " 'Lestari, Sri Rahayu'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1063%2F5.0052672\"}'],\n", - " 'title': ['The prevention of single bulb garlic extract on non-alcoholic fatty liver disease (NAFLD) in high fat mice (Mus musculus) model']},\n", - " {'bibcode': '2006PNAS..10317862H',\n", - " 'abstract': 'An animal model for human hepatitis B virus (HBV) tolerance is needed to investigate the mechanisms. This model will also facilitate therapeutic strategies for the existing 350 million patients with chronic hepatitis B. We established a mouse model by hydrodynamic injection of an engineered, replication-competent HBV DNA into the tail veins of C57BL/6 mice. In 40% of the injected mice, HBV surface antigenemia persisted for >6 months. Viral replication intermediates, transcripts, and proteins were detected in the liver tissues of the injected mice for up to 1 year. The tolerance toward HBV surface antigen in this model was shown to be due to an insufficient cellular immunity against hepatitis B core antigen, as was documented in humans. This animal model will accelerate further genetic and mechanistic studies of human chronic hepatitis B infection.',\n", - " 'author': ['Huang, Li-Rung',\n", - " 'Wu, Hui-Lin',\n", - " 'Chen, Pei-Jer',\n", - " 'Chen, Ding-Shinn'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/103/47/17862\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0608578103\"}'],\n", - " 'title': ['An immunocompetent mouse model for the tolerance of human chronic hepatitis B virus infection']},\n", - " {'bibcode': '2016PNAS..113E..71N',\n", - " 'abstract': 'Patients with intrahepatic cholangiocellular carcinoma (ICC) and combined hepatocellular and cholangiocarcinoma (cHC-CC) have worse prognoses than those with hepatocellular carcinoma and rarely show clinical responses to drugs. Our analyses of mice with liver-specific deletions of Mps One Binder Kinase Activator (MOB)1A/1B reveal that MOB1A/1B constitute the most important hub of Hippo signaling in mammalian liver. MOB1A/1B maintain hepatocyte stem/progenitor cell quiescence and are potent tumor suppressors, especially in cHC-CCs and ICCs. Because these functions depend on the Hippo target Yap1/Taz and the Yap1/Taz targets Tgfbs, our data point to a new therapeutic approach for liver cancer based on inhibition of MOB1-YAP1/TAZ and/or TGF-βs-SMADs signaling. Our demonstration that well-tolerated and already-approved antiparasitic drugs inhibit YAP1 signaling may point to a new route of treatment for these cancers that can be rapidly tested and implemented.',\n", - " 'author': ['Nishio, Miki',\n", - " 'Sugimachi, Keishi',\n", - " 'Goto, Hiroki',\n", - " 'Wang, Jia',\n", - " 'Morikawa, Takumi',\n", - " 'Miyachi, Yosuke',\n", - " 'Takano, Yusuke',\n", - " 'Hikasa, Hiroki',\n", - " 'Itoh, Tohru',\n", - " 'Suzuki, Satoshi O.',\n", - " 'Kurihara, Hiroki',\n", - " 'Aishima, Shinichi',\n", - " 'Leask, Andrew',\n", - " 'Sasaki, Takehiko',\n", - " 'Nakano, Toru',\n", - " 'Nishina, Hiroshi',\n", - " 'Nishikawa, Yuji',\n", - " 'Sekido, Yoshitaka',\n", - " 'Nakao, Kazuwa',\n", - " 'Shin-ya, Kazuo',\n", - " 'Mimori, Koshi',\n", - " 'Suzuki, Akira'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/113/1/E71\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1517188113\"}'],\n", - " 'title': ['Dysregulated YAP1/TAZ and TGF-β signaling mediate hepatocarcinogenesis in Mob1a/1b-deficient mice']},\n", - " {'bibcode': '1995Natur.375..316N',\n", - " 'abstract': 'ERYTHROID Krüppel-like factor (EKLF) was originally isolated from erythroid cell RNA by differential screening and shown to be erythroid-specific, although a low level of EKLF was found in mast cell lines1,2. EKLF contains three zinc-fingers homologous to those found in the Kriippel family of transcription factors. Because it binds the sequence CCACACCCT, EKLF may affect erythroid development as a result of its ability to bind to the CAC box in the promoter of the β-globin gene1,2. Mutation of this element leads to reduced pβ-globin expression3-5 and it appears to mediate the effect of the globin locus control region on the promoter6. Here we inactivate the EKLF gene through insertion of a lacZ reporter gene by homologous recombination in embryonic stem (ES) cells. Heterozygous EKLF+/- mice show that the reporter gene is expressed in a developmental!) specific manner in all types of erythroblasts in the fetal liver and adult bone marrow. Homo-zygous EKLF-/- mice appear normal during the embryonic stage of haematopoiesis in the yolk sac, but develop a fatal anaemia during early fetal life when haematopoiesis has switched to the fetal liver. Enucleated erythrocytes are formed but these do not contain the proper amount of haemoglobin. We conclude that the transcription factor EKLF is essential for the final steps of definitive erythropoiesis in fetal liver.',\n", - " 'author': ['Nuez, Beatriz',\n", - " 'Michalovich, Dave',\n", - " 'Bygrave, Anne',\n", - " 'Ploemacher, Rob',\n", - " 'Grosveld, Frank'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F375316a0\"}'],\n", - " 'title': ['Defective haematopoiesis in fetal liver resulting from inactivation of the EKLF gene']},\n", - " {'bibcode': '2015SciBu..60..336M',\n", - " 'abstract': 'Abnormal hepatic lipid metabolism is a key component of fatty liver development with excess fat deposition in the liver through steatosis. Cystathionine gamma-lyase (CSE) is one of the enzymes that catalyze hydrogen sulfide (H2S) production in the liver. The aim of the present study was to investigate the role of CSE/H2S in hepatic regulation of cholesterol and fatty acid metabolism. Wild-type (WT) and CSE knockout (CSE-KO) mice fed with high-fat diet (HFD) were analyzed for liver morphological and biochemical changes. HFD feeding of CSE-KO mice, not WT mice, markedly increased cholesterol levels in plasma and livers, and the sizes of the liver and gall bladder. Typical histological and biochemical changes of fatty liver disease were found in CSE-KO mice with damaged liver functions. The levels of plasma and liver triglyceride were significantly lower in HFD-fed CSE-KO mice than in HFD-fed WT mice. Moreover, the expression of nuclear receptors transcriptional factors, especially LXRα, in the liver was decreased in both control diet- or HFD-fed CSE-KO mice. Decreased expression of CYP7A1, an LXRα targeted gene, halted catabolism of cholesterol into bile and subsequently led to cholesterol accumulation in the liver and gall bladder. Since deficiency in CSE/H2S pathway results in high susceptibility to HFD-induced fatty liver, targeting at CSE/H2S pathway in the liver may represent a novel strategy against the development of fatty liver damage.',\n", - " 'author': ['Mani, Sarathi',\n", - " 'Li, Hongzhu',\n", - " 'Yang, Guangdong',\n", - " 'Wu, Lingyun',\n", - " 'Wang, Rui'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1007%2Fs11434-014-0722-7\"}'],\n", - " 'title': ['Deficiency of cystathionine gamma-lyase and hepatic cholesterol accumulation during mouse fatty liver development']},\n", - " {'bibcode': '2017JaJAP..56e5002S',\n", - " 'abstract': 'Magnetic liposomes containing Fe3O4 nanoparticles were prepared using colipids [1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC8,9PC)] and mixtures of the colipids with an anionic lipid [1,2-dioleoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt (DOPG)] or a cationic lipid [cetyltrimethylammonium bromide (CTAB)]. Transmission electron microscopy (TEM) and small-angle X-ray scattering (SAXS) analysis showed that the magnetic liposomes containing DC8,9PC and DOPC were tubular and spherical in structure, respectively. The effects of an external magnetic field and the structure of the liposomes on cellular association were investigated. The external magnetic field increased cellular association and uptake levels independent of the structure both in vitro and in vivo. Although the level of in vitro cellular association for the tubular liposomes was higher than that for the spherical liposomes, there was no significant difference in the level of in vivo uptake of fluorescent Fe3O4 nanoparticles in the mouse liver. Finally, the magnetic liposomes were found to be biocompatible by haematological and serum chemical analyses.',\n", - " 'author': ['Sakuragi, Mina', 'Taguchi, Kazuaki', 'Kusakabe, Katsuki'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.7567%2FJJAP.56.055002\"}'],\n", - " 'title': ['Structural and biological characterization of Fe3O4-loaded spherical and tubular liposomes for use in drug delivery systems']},\n", - " {'bibcode': '1987PNAS...84.7051T',\n", - " 'abstract': 'Mouse alkaline phosphatase [ALP; orthophosphoric-monoester phosphohydrolase (alkaline optimum), EC 3.1.3.1] was partially purified from placenta. Data obtained by immunoblotting analysis suggested that the primary structure of this enzyme has a much greater homology to that of human and bovine liver ALPs than to the human placental isozyme. Therefore, a full-length cDNA encoding human liver-type ALP was used as a probe to isolate the mouse placental ALP cDNA. The cloned mouse cDNA is 2459 base pairs long and is composed of an open reading frame encoding a 524-amino acid polypeptide that contains a putative signal peptide of 17 amino acids. Homology at the amino acid level of the mouse placental ALP is 90% to the human liver isozyme but only 55% to the human placental counterpart. RNA blot hybridization results indicate that the mouse placental ALP is encoded by a gene identical to the gene expressed in mouse liver, kidney, and teratocarcinoma stem cells. This gene is therefore evolutionarily highly conserved in mouse and human.',\n", - " 'author': ['Terao, Mineko', 'Mintz, Beatrice'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/84/20/7051\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/84/20/7051\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/84/20/7051\"}'],\n", - " 'title': ['Cloning and characterization of a cDNA coding for mouse placental alkaline phosphatase.']},\n", - " {'bibcode': '2010JSFA...90..329L',\n", - " 'abstract': 'BACKGROUND: Acetaminophen (AAP)‑induced oxidative stress can cause cell death to induce liver damage. The antioxidant effect of Hibiscus sabdariffa L. (HS) was shown in previous studies. In this study the effect of HS extract (HSE) on AAP‑induced liver injury in BALB/c mice was investigated.RESULTS: In vivo, BALB/c mice were fed orally with 200, 400 or 600 mg kg−1 HSE for 2 weeks and then injected with 1000 mg kg−1 AAP. Pretreatment with HSE decreased lipid peroxidation and increased catalase activity and glutathione level. It also decreased AAP‑induced liver injury, accompanied by decreased expression of pJNK, Bax and tBid in the liver. Additionally, HSE protected BALB/c normal liver cells from AAP‑induced damage in vitro.CONCLUSION: It has been demonstrated that HSE can protect the mouse liver from AAP‑induced injury and that the protective mechanism might involve decreasing oxidative stress and reducing cell death. Copyright',\n", - " 'author': ['Liu, Liang-Chih',\n", - " 'Wang, Chau-Jong',\n", - " 'Lee, Ching-Chih',\n", - " 'Su, Sheng-Chi',\n", - " 'Chen, Huei-Lin',\n", - " 'Hsu, Jen-Dong',\n", - " 'Lee, Huei-Jane'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Fjsfa.3821\"}'],\n", - " 'title': ['Aqueous extract of Hibiscus sabdariffa L. decelerates acetaminophen‑induced acute liver damage by reducing cell death and oxidative stress in mouse experimental models']},\n", - " {'bibcode': '2019NatCo..10.3882M',\n", - " 'abstract': 'The β-catenin mutation is frequently observed in hepatoblastoma (HB), but the underlying mechanism by which Wnt/β-catenin signaling induces HB tumor formation is unknown. Here we show that expression of growth regulation by estrogen in breast cancer 1 (GREB1) depends on Wnt/β-catenin signaling in HB patients. GREB1 is localized to the nucleus where it binds Smad2/3 in a competitive manner with p300 and inhibits TGFβ signaling, thereby promoting HepG2 HB cell proliferation. Forced expression of β-catenin, YAP, and c-Met induces HB-like mouse liver tumor (BYM mice), with an increase in GREB1 expression and HB markers. Depletion of GREB1 strongly suppresses marker gene expression and HB-like liver tumorigenesis, and instead enhances TGFβ signaling in BYM mice. Furthermore, antisense oligonucleotides for GREB1 suppress the formation of HepG2 cell-induced tumors and HB-like tumors in vivo. We propose that GREB1 is a target molecule of Wnt/β-catenin signaling and required for HB progression.',\n", - " 'author': ['Matsumoto, Shinji',\n", - " 'Yamamichi, Taku',\n", - " 'Shinzawa, Koei',\n", - " 'Kasahara, Yuuya',\n", - " 'Nojima, Satoshi',\n", - " 'Kodama, Takahiro',\n", - " 'Obika, Satoshi',\n", - " 'Takehara, Tetsuo',\n", - " 'Morii, Eiichi',\n", - " 'Okuyama, Hiroomi',\n", - " 'Kikuchi, Akira'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41467-019-11533-x\"}'],\n", - " 'title': ['GREB1 induced by Wnt signaling promotes development of hepatoblastoma by suppressing TGFβ signaling']},\n", - " {'bibcode': '2017NatSR...7.7190S',\n", - " 'abstract': 'Hypoxia-inducible factors (HIFs) play a central role in the transcriptional response to changes in oxygen availability. Stability of HIFs is regulated by multi-step reactions including recognition by the von Hippel-Lindau tumour suppressor protein (pVHL) in association with an E3 ligase complex. Here we show that pVHL physically interacts with fatty acid synthase (FASN), displacing the E3 ubiquitin ligase complex. This results in HIF-α protein stabilization and activation of HIF target genes even in normoxia such as during adipocyte differentiation. 25-hydroxycholesterol (25-OH), an inhibitor of FASN expression, also inhibited HIF target gene expression in cultured cells and in mouse liver. Clinically, FASN is frequently upregulated in a broad variety of cancers and has been reported to have an oncogenic function. We found that upregulation of FASN correlated with induction of many HIF target genes, notably in a malignant subtype of prostate tumours. Therefore, pVHL-FASN interaction plays a regulatory role for HIFs and their target gene expression.',\n", - " 'author': ['Sun, Wendi',\n", - " 'Kato, Hiroyuki',\n", - " 'Kitajima, Shojiro',\n", - " 'Lee, Kian Leong',\n", - " 'Gradin, Katarina',\n", - " 'Okamoto, Takashi',\n", - " 'Poelllinger, Lorenz'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-017-05685-3\"}'],\n", - " 'title': ['Interaction between von Hippel-Lindau Protein and Fatty Acid Synthase Modulates Hypoxia Target Gene Expression']},\n", - " {'bibcode': '2006PNAS..10312093T',\n", - " 'abstract': 'The phosphoinositide 3-kinase (PI3K) pathway is central to the metabolic actions of insulin on liver. Here, we show that mice with a liver-specific deletion of the p85α regulatory subunit of PI3K (L-Pik3r1KO) exhibit a paradoxical improvement of hepatic and peripheral insulin sensitivity. Although PI3K enzymatic activity is diminished in L-Pik3r1KO livers because of a reduced level of regulatory and catalytic subunits of PI3K, insulin-stimulated Akt activity is actually increased. This increased Akt activity correlates with increased phosphatidylinositol (3,4,5)-trisphosphate levels which are due, at least in part, to diminished activity of the (3,4,5)-trisphosphate phosphatase PTEN. Thus, the regulatory subunit p85α is a critical modulator of insulin sensitivity in vivo not only because of its effects on PI3K activation, but also as a regulator of PTEN activity.',\n", - " 'author': ['Taniguchi, Cullen M.',\n", - " 'Tran, Thien T.',\n", - " 'Kondo, Tatsuya',\n", - " 'Luo, Ji',\n", - " 'Ueki, Kohjiro',\n", - " 'Cantley, Lewis C.',\n", - " 'Kahn, C. Ronald'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/103/32/12093\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/103/32/12093\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/full/103/32/12093\"}'],\n", - " 'title': ['Phosphoinositide 3-kinase regulatory subunit p85α suppresses insulin action via positive regulation of PTEN']},\n", - " {'bibcode': '2007Natur.445..886S',\n", - " 'abstract': 'The determinants of vertebrate organ size are poorly understood, but the process is thought to depend heavily on growth factors and other environmental cues. In the blood and central nervous system, for example, organ mass is determined primarily by growth-factor-regulated cell proliferation and apoptosis to achieve a final target size. Here, we report that the size of the mouse pancreas is constrained by an intrinsic programme established early in development, one that is essentially not subject to growth compensation. Specifically, final pancreas size is limited by the size of the progenitor cell pool that is set aside in the developing pancreatic bud. By contrast, the size of the liver is not constrained by reductions in the progenitor cell pool. These findings show that progenitor cell number, independently of regulation by growth factors, can be a key determinant of organ size.',\n", - " 'author': ['Stanger, Ben Z.', 'Tanaka, Akemi J.', 'Melton, Douglas A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature05537\"}'],\n", - " 'title': ['Organ size is limited by the number of embryonic progenitor cells in the pancreas but not the liver']},\n", - " {'bibcode': '1991PNAS...88.7595A',\n", - " 'abstract': 'We describe preliminary studies of the pharmacokinetics, biodistribution, and excretion of an oligodeoxy-nucleotide phosphorothioate ([S]oligonucleotide) in mice. After either intravenous or intraperitoneal administration of a single dose (30 mg/kg of body weight), [S]oligonucleotide (35S-labeled at each internucleotide linkage) was found in most of the tissues for up to 48 hr. About 30% of the dose was excreted in urine within 24 hr, irrespective of the mode of administration; the excreted [S]oligonucleotide was found to be extensively degraded. In plasma, stomach, heart, and intestine, the [S]oligonucleotide was degraded by only 15%, whereas in the kidney and liver degradation was about 50% in 48 hr. The surprising observation was made that chain length extension of administered [S]oligonucleotide occurred in kidney, liver, and intestine. These results provide an initial definition of parameters for the pharmaceutical development of antisense oligonucleotides.',\n", - " 'author': ['Agrawal, Sudhir', 'Temsamani, Jamal', 'Tang, Jin Yan'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/88/17/7595\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/88/17/7595\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/88/17/7595\"}'],\n", - " 'title': ['Pharmacokinetics, biodistribution, and stability of oligodeoxynucleotide phosphorothioates in mice.']},\n", - " {'bibcode': '2014cosp...40E1902L',\n", - " 'author': ['Lv, Ke', 'Qu, Lina'],\n", - " 'title': ['Influence of simulated microgravity on clock genes expression rhythmicity and underlying blood circulating miRNAs-mRNA co-expression regulatory mechanism in C57BL/6J mice'],\n", - " 'abstract': \"Purpose: It is vital for astronauts to maintain the optimal alertness and neurobehavioral function. Among various factors that exist in the space flight and long-duration mission environment, gravity changes may probably an essential environmental factor to interfere with internal circadian rhythms homeostasis and sleep quality, but the underlying mechanism is unclear. Mammals' biological clock is controlled by the suprachiasmatic nucleus (SCN), and peripheral organs adjust their own rhythmicity with the central signals. Nevertheless the mechanism underlying this synchronizition process is still unknown. microRNAs (miRNAs) are about 19∼22nt long regulatory RNAs that serve as critical modulators of post-transcriptional gene regulation. Recently, circulating miRNAs were found to have the regulatory role between cells and peripheral tissues, besides its function inside the cells. This study aims to investigate the regulatory signal transduction role of miRNAs between SCN and peripheral biological clock effecter tissues and to further decipher the mechanism of circadian disturbance under microgravity. Method: Firstly, based on the assumption that severe alterations in the expression of genes known to be involved in circadian rhythms may affect the expression of other genes, the labeled cDNA from liver and suprachiasmatic nucleus (SCN) of clock-knockout mice and control mice in different time points were cohybridized to microarrays. The fold change exceeding 2 (FC>2) was used to identify genes with altered expression levels in the knockout mice compared with control mice. Secondly, male C57BL/6J mice at 8 weeks of age were individually caged and acclimatized to the laboratory conditions (12h light/dark cycle) before being used for continuous core body temperature and activity monitoring. The mice were individually caged and tail suspended using a strip of adhesive surgical tape attached to a chain hanging from a pulley. Peripheral blood and liver tissues collection were consecutively performed. Blood samples and liver tissues were collected from tail-suspended and control mice under LD 12:12h and DD conditions during the 12th, 13th and 14th testing days at 4h intervals. Melatonin and corticosterone in mice plasma at different time points were assayed. NIH-3T3 cells were plated in culture dish for 22h before the experiment. For ground-based simulation of weightlessness, the medium was exchanged with DMEM containing 50% horse serum to synchronization, after 2 h, this medium was replaced with DMEM and 10% FBS. Then, at various time point (0, 6, 12, 18, 24, 30, 36, 42, 48h), cells were cultured on the roating clinostat at 30r/min. Total RNA was extracted from liver and NIH-3T3 cells and subsequently reverse-transcribed. The SYBR green I real-time quantitative PCR system was conducted to examine the mRNA expression level of clock, bmal1, per1, per2, cry1 and cry2 in mice and NIH-3T3 cells, respectively. Paired comparisons of the circadian genes expression between period, peak values, amplitude and mesor (midline estimating statistic of rhythm) were examined for evidence of circadian variation using Chronos-Fit software in mice and Cosine analyses in NIH-3T3 cells. Statistical analysis: All numerical data were expressed as the mean ± standard deviation (SD). Statistical differences among groups were analyzed by one-way analysis of variance (ANOVA) to determine time points differences in the study parameters. Statistical differences between two groups were determined by the Student's t test. Results: (1) Circadian rhythm of clock and bmal1 mRNA expression was found in each testing day with similar peak phase in both tail suspension group and control group. Compared with control group, tail suspension group showed that the peak phase of clock gene mRNA level advanced approximately 4 hours and the amplitude of bmal1 gene mRNA level significantly reduced at ZT2 and ZT6. (2) The expression of circadian genes in NIH-3T3 cells demonstrated that the maximum and minimum value of mRNA relative expression levels of clock and bmal1 during clinorotation were both found approximately at the time points 6h and 18h, respectively. The period length of experimental group was about 16h longer than control group. The peak phase and peak time of clock and bmal1 with simulated weightlessness group were ahead of control group. (3) At the Zeitgeber time 2 (ZT2), we found that 23 miRNAs in the SCN and 60 miRNAs in liver were significantly altered on the basis of an adjusted FC>2 among 611 miRNAs. At the ZT14, 23 miRNAs in the SCN and 57 miRNAs in liver were altered compared with the control group (FC>2). (a) Effects of clock knock out altered expression of miRNA. We analyzed the miRNA profile in SCN and liver of clock knonck out and WT mouse at two different time points using miRNA microarray. Of these, miR-122,miR-144, miR-210 and miR-669b at ZT2, miR-200a, miR-200b, miR-429, miR-455, miR-669d and miR-96 at ZT14 were both changed in SCN and liver, respectively. Interestingly, the miR-122, a tissue specific miRNA of liver was also changed in SCN at ZT2. (b) Effects of light altered expression of miRNA: Light is an important environmental factors to regulate circadian genes expression. In clock mutant mice, all altered miRNAs except miR-144 were down-regulated in SCN while up-regulated in liver at ZT14 compared to ZT2. Interestingly, the miRNAs expression profiling in SCN and liver were opposite of WT mice at ZT14 compared to ZT2. (c) Effects of clock mutant on mRNA expression: To test whether the alteration in expression of miRNAs correlates with the gene expression pattern, cDNA microarray of SCN were assayed. The results revealed that the expression of nearly 1285 genes was altered substantially with at least 1 fold change absolute in the absence of clock. Among these altered genes, we chose the mRNAs with at least 4 fold changes to further study. Only 23 genes were altered in clock knockout compared with WT at ZT2, but 67 genes at ZT14. (d) Effects of light on mRNA expression. To evaluate the light effecting on genes expression in SCN, the cDNA microarrays in SCN at ZT2 and ZT14 were tested. 21 genes were over expression and 12 genes were down regulation ZT14 compared with ZT2 in WT. The number of altered genes in clock-/- mice was 67. (e) Direct interaction between altered miRNAs and mRNAs. To identify the interaction between regulatory miRNAs and altered mRNAs in the absence of clock, we predicted the target genes of miRNAs by TargetScan. The genes both the target genes of miRNAs and altered in cDNA microarray were unravelled. The exploration of functional interaction between miRNAs and clock genes mRNA is ongoing. Conclusion: Taken together, these results indicate that ground-based simulated weightlessness could alter the molecular biological rhythm patterns, which may preliminarily present the biological regulatory mechanism of circadian rhythm systems under spaceflight-related gravity. The potential underlying functional miRNAs could serve as targets to interfere with for interaction between central and peripheral circadian organs under simulated microgravity. This preliminary study may facilitate the exploration of circadian rhythm characteristics in space and the detailed process of signal transduction and circadian gene regulation. Key words: circadian rhythms, tail-suspension, simulated microgravity, clock genes, miRNAs Acknowledgments: This study was supported by the National Basic Research Program of China (Grant NO. 2011CB707704) and the Foundation of State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center (Grant NO. SMFA13B02, SMFA09A06 and SMFA12B05).\"},\n", - " {'bibcode': '2017NatCo...8..837L',\n", - " 'abstract': 'Chronic liver disease is rising in western countries and liver cirrhosis is the 12th leading cause of death worldwide. Simultaneously, use of gastric acid suppressive medications is increasing. Here, we show that proton pump inhibitors promote progression of alcoholic liver disease, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis in mice by increasing numbers of intestinal Enterococcus spp. Translocating enterococci lead to hepatic inflammation and hepatocyte death. Expansion of intestinal Enterococcus faecalis is sufficient to exacerbate ethanol-induced liver disease in mice. Proton pump inhibitor use increases the risk of developing alcoholic liver disease among alcohol-dependent patients. Reduction of gastric acid secretion therefore appears to promote overgrowth of intestinal Enterococcus, which promotes liver disease, based on data from mouse models and humans. Recent increases in the use of gastric acid-suppressive medications might contribute to the increasing incidence of chronic liver disease.',\n", - " 'author': ['Llorente, Cristina',\n", - " 'Jepsen, Peter',\n", - " 'Inamine, Tatsuo',\n", - " 'Wang, Lirui',\n", - " 'Bluemel, Sena',\n", - " 'Wang, Hui J.',\n", - " 'Loomba, Rohit',\n", - " 'Bajaj, Jasmohan S.',\n", - " 'Schubert, Mitchell L.',\n", - " 'Sikaroodi, Masoumeh',\n", - " 'Gillevet, Patrick M.',\n", - " 'Xu, Jun',\n", - " 'Kisseleva, Tatiana',\n", - " 'Ho, Samuel B.',\n", - " 'DePew, Jessica',\n", - " 'Du, Xin',\n", - " 'Sørensen, Henrik T.',\n", - " 'Vilstrup, Hendrik',\n", - " 'Nelson, Karen E.',\n", - " 'Brenner, David A.',\n", - " 'Fouts, Derrick E.',\n", - " 'Schnabl, Bernd'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41467-017-00796-x\"}'],\n", - " 'title': ['Gastric acid suppression promotes alcoholic liver disease by inducing overgrowth of intestinal Enterococcus']},\n", - " {'bibcode': '2017NatSR...744754K',\n", - " 'abstract': 'Non-alcoholic steatohepatitis (NASH) is characterized by steatosis with lobular inflammation and hepatocyte injury. Pirfenidone (PFD) is an orally bioavailable pyridone derivative that has been clinically used for the treatment of idiopathic pulmonary fibrosis. However, it remains unknown whether PFD improves liver fibrosis in a mouse model with human NASH-like phenotypes. In this study, we employed melanocortin 4 receptor-deficient (MC4R-KO) mice as a mouse model with human NASH-like phenotypes to elucidate the effect and action mechanisms of PFD on the development of NASH. PFD markedly attenuated liver fibrosis in western diet (WD)-fed MC4R-KO mice without affecting metabolic profiles or steatosis. PFD prevented liver injury and fibrosis associated with decreased apoptosis of liver cells in WD-fed MC4R-KO mice. Pretreatment of PFD inhibited the tumor necrosis factor-α (TNF-α)-induced liver injury and fibrogenic responses associated with decreased apoptosis of liver cells in wild-type mice. PFD also prevented TNF-α-induced hepatocyte apoptosis in vitro with reduced activation of caspase-8 and -3. This study provides evidence for the antifibrotic effect of PFD in a mouse model of human NASH. The data of this study highlight hepatocyte apoptosis as a potential therapeutic target, and suggest that PFD can be repositioned as an antifibrotic drug for human NASH.',\n", - " 'author': ['Komiya, Chikara',\n", - " 'Tanaka, Miyako',\n", - " 'Tsuchiya, Kyoichiro',\n", - " 'Shimazu, Noriko',\n", - " 'Mori, Kentaro',\n", - " 'Furuke, Shunsaku',\n", - " 'Miyachi, Yasutaka',\n", - " 'Shiba, Kumiko',\n", - " 'Yamaguchi, Shinobu',\n", - " 'Ikeda, Kenji',\n", - " 'Ochi, Kozue',\n", - " 'Nakabayashi, Kazuhiko',\n", - " 'Hata, Ken-Ichiro',\n", - " 'Itoh, Michiko',\n", - " 'Suganami, Takayoshi',\n", - " 'Ogawa, Yoshihiro'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep44754\"}'],\n", - " 'title': ['Antifibrotic effect of pirfenidone in a mouse model of human nonalcoholic steatohepatitis']},\n", - " {'bibcode': '2021Natur.592..444D',\n", - " 'abstract': 'Nonalcoholic steatohepatitis (NASH) is a manifestation of systemic metabolic disease related to obesity, and causes liver disease and cancer1,2. The accumulation of metabolites leads to cell stress and inflammation in the liver3, but mechanistic understandings of liver damage in NASH are incomplete. Here, using a preclinical mouse model that displays key features of human NASH (hereafter, NASH mice), we found an indispensable role for T cells in liver immunopathology. We detected the hepatic accumulation of CD8 T cells with phenotypes that combined tissue residency (CXCR6) with effector (granzyme) and exhaustion (PD1) characteristics. Liver CXCR6+ CD8 T cells were characterized by low activity of the FOXO1 transcription factor, and were abundant in NASH mice and in patients with NASH. Mechanistically, IL-15 induced FOXO1 downregulation and CXCR6 upregulation, which together rendered liver-resident CXCR6+ CD8 T cells susceptible to metabolic stimuli (including acetate and extracellular ATP) and collectively triggered auto-aggression. CXCR6+ CD8 T cells from the livers of NASH mice or of patients with NASH had similar transcriptional signatures, and showed auto-aggressive killing of cells in an MHC-class-I-independent fashion after signalling through P2X7 purinergic receptors. This killing by auto-aggressive CD8 T cells fundamentally differed from that by antigen-specific cells, which mechanistically distinguishes auto-aggressive and protective T cell immunity.',\n", - " 'author': ['Dudek, Michael',\n", - " 'Pfister, Dominik',\n", - " 'Donakonda, Sainitin',\n", - " 'Filpe, Pamela',\n", - " 'Schneider, Annika',\n", - " 'Laschinger, Melanie',\n", - " 'Hartmann, Daniel',\n", - " 'Hüser, Norbert',\n", - " 'Meiser, Philippa',\n", - " 'Bayerl, Felix',\n", - " 'Inverso, Donato',\n", - " 'Wigger, Jennifer',\n", - " 'Sebode, Marcial',\n", - " 'Öllinger, Rupert',\n", - " 'Rad, Roland',\n", - " 'Hegenbarth, Silke',\n", - " 'Anton, Martina',\n", - " 'Guillot, Adrien',\n", - " 'Bowman, Andrew',\n", - " 'Heide, Danijela',\n", - " 'Müller, Florian',\n", - " 'Ramadori, Pierluigi',\n", - " 'Leone, Valentina',\n", - " 'Garcia-Caceres, Cristina',\n", - " 'Gruber, Tim',\n", - " 'Seifert, Gabriel',\n", - " 'Kabat, Agnieszka M.',\n", - " 'Malm, Jan-Philipp',\n", - " 'Reider, Simon',\n", - " 'Effenberger, Maria',\n", - " 'Roth, Susanne',\n", - " 'Billeter, Adrian T.',\n", - " 'Müller-Stich, Beat',\n", - " 'Pearce, Edward J.',\n", - " 'Koch-Nolte, Friedrich',\n", - " 'Käser, Rafael',\n", - " 'Tilg, Herbert',\n", - " 'Thimme, Robert',\n", - " 'Böttler, Tobias',\n", - " 'Tacke, Frank',\n", - " 'Dufour, Jean-Francois',\n", - " 'Haller, Dirk',\n", - " 'Murray, Peter J.',\n", - " 'Heeren, Ron',\n", - " 'Zehn, Dietmar',\n", - " 'Böttcher, Jan P.',\n", - " 'Heikenwälder, Mathias',\n", - " 'Knolle, Percy A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"data\", \"url\": \"https://ega-archive.org/access/data-access\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"data\", \"url\": \"http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse145104\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"data\", \"url\": \"http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse159977\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41586-021-03233-8\"}'],\n", - " 'title': ['Auto-aggressive CXCR6+ CD8 T cells cause liver immune pathology in NASH']},\n", - " {'bibcode': '2009Natur.457..882P',\n", - " 'abstract': 'Hepatitis C virus (HCV) is a leading cause of liver disease worldwide. The development of much needed specific antiviral therapies and an effective vaccine has been hampered by the lack of a convenient small animal model. The determinants restricting HCV tropism to human and chimpanzee hosts are unknown. Replication of the viral RNA has been demonstrated in mouse cells, but these cells are not infectable with either lentiviral particles bearing HCV glycoproteins (HCVpp) or HCV produced in cell culture (HCVcc) (A.P., M.E. and C.M.R., unpublished observations), suggesting that there is a block at the level of entry. Here we show, using an iterative complementary DNA library screening approach, that human occludin (OCLN) is an essential HCV cell entry factor that is able to render murine cells infectable with HCVpp. Similarly, OCLN is required for the HCV-susceptibility of human cells, because its overexpression in uninfectable cells specifically enhanced HCVpp uptake, whereas its silencing in permissive cells impaired both HCVpp and HCVcc infection. In addition to OCLN, HCVpp infection of murine cells required expression of the previously identified HCV entry factors CD81 (ref. 4), scavenger receptor class B type I (SR-BI, also known as SCARB1) and claudin-1 (CLDN1). Although the mouse versions of SR-BI and CLDN1 function at least as well as the human proteins in promoting HCV entry, both OCLN and CD81 must be of human origin to allow efficient infection. The species-specific determinants of OCLN were mapped to its second extracellular loop. The identification of OCLN as a new HCV entry factor further highlights the importance of the tight junction complex in the viral entry process, and provides an important advance towards efforts to develop small animal models for HCV.',\n", - " 'author': ['Ploss, Alexander',\n", - " 'Evans, Matthew J.',\n", - " 'Gaysinskaya, Valeriya A.',\n", - " 'Panis, Maryline',\n", - " 'You, Hana',\n", - " 'de Jong, Ype P.',\n", - " 'Rice, Charles M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature07684\"}'],\n", - " 'title': ['Human occludin is a hepatitis C virus entry factor required for infection of mouse cells']},\n", - " {'bibcode': '1990PNAS...87.5729S',\n", - " 'abstract': 'To examine the amino acid sequence requirements for the biphasic association of Drosophila melanogaster apocytochrome c with mouse liver mitochondria in vitro, recombinant constructs of the protein were prepared. Removal of the C-terminal sequence to residue 58 had little influence, but truncation to residue 50 decreased the association to low levels and removal to residue 36 was even more effective. However, a mutant missing the segment between residues 35 and 66 was fully functional, but, when the C-terminal segment from residue 36 was replaced with a noncytochrome c sequence, the high-affinity phase of the association was lost. A mutant in which residues 90, 91, 92, 96, and 100 were replaced by lysine, leucine, proline, proline, and proline, respectively, to prevent the possible formation of the C-terminal alpha-helix and another mutant in which the C-terminal segment from residue 90 to residue 120 was a noncytochrome c sequence had normal association. In contrast, replacing lysine-5, -7, and -8 by glutamine, glutamic acid, and asparagine, respectively, resulted in loss of the high-affinity phase. The same mutations in the apoprotein lacking the segment between residues 35 and 66 caused, in addition, a decrease of the low-affinity phase association. Thus, the N-terminal region is most critical for apocytochrome c association, but alternative segments of the central and/or C-terminal region can be utilized, where noncytochrome c sequences are ineffective. These results emphasize the wide disparity between the structural requirements for association with mitochondria and for the production of a functional holoprotein.',\n", - " 'author': ['Sprinkle, James R.',\n", - " 'Hakvoort, Theodorus B. M.',\n", - " 'Koshy, Thomas I.',\n", - " 'Miller, David D.',\n", - " 'Margoliash, E.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/87/15/5729\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/87/15/5729\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/87/15/5729\"}'],\n", - " 'title': ['Amino acid sequence requirements for the association of apocytochrome c with mitochondria.']},\n", - " {'bibcode': '2012ToxIH..28..614B',\n", - " 'abstract': 'Pollution by waste landfill leachate has prompted a number of studies on the toxic and potential health effects. This study assessed the genotoxicity of a municipal sludge leachate (MSL) in the somatic tissues (blood and bone marrow) and organs (liver, kidney, and spleen) of mice using the alkaline Comet assay. The possible cause of DNA damage via the study of antioxidant system (lipid peroxidation [LPO]; catalase [CAT]; reduced glutathione [GSH]; and superoxide dismutase [SOD]) responses in mouse liver was also investigated. Different concentrations (2.5%, 5%, 10%, and 15%) of the leachate were administered intraperitoneally for 5 consecutive days to male Swiss albino mice (4 mice/group). A significant ( p < 0.05) increase in DNA damage in organs and tissues of treated mice compared to the negative control was observed as evident from the Comet assay parameters: olive tail moment (OTM, arbitrary units) and tail DNA (%). Bone marrow showed maximum DNA damage followed by liver > spleen > kidney > blood as evident by the OTM. A significant increase ( p < 0.05) in the level of antioxidant enzymes (CAT and SOD) and LPO with a concurrent decrease in GSH in the liver of treated mice was also observed. Our finding demonstrates that the MSL induces DNA damage in the somatic tissues and organs of mouse as well as induces oxidative stress in the liver. These tissues and organs may be the potential targets in animal and human populations exposed to MSL. This is of relevance to public health; as such exposure could lead to adverse health effects via systemic genotoxicity.',\n", - " 'author': ['Bakare, Adekunle A.',\n", - " 'Patel, Sushila',\n", - " 'Pandey, Alok K.',\n", - " 'Bajpayee, Mahima',\n", - " 'Dhawan, Alok'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1177%2F0748233711420466\"}'],\n", - " 'title': ['DNA and oxidative damage induced in somatic organs and tissues of mouse by municipal sludge leachate']},\n", - " {'bibcode': '2010NRL.....5..108L',\n", - " 'abstract': 'Nano-TiO2 was shown to cause various toxic effects in both rats and mice; however, the molecular mechanism by which TiO2 exerts its toxicity is poorly understood. In this report, an interaction of nano-anatase TiO2 with liver DNA from ICR mice was systematically studied in vivo using ICP-MS, various spectral methods and gel electrophoresis. We found that the liver weights of the mice treated with higher amounts of nano-anatase TiO2 were significantly increased. Nano-anatase TiO2 could be accumulated in liver DNA by inserting itself into DNA base pairs or binding to DNA nucleotide that bound with three oxygen or nitrogen atoms and two phosphorous atoms of DNA with the Ti-O(N) and Ti-P bond lengths of 1.87 and 2.38 Å, respectively, and alter the conformation of DNA. And gel electrophoresis showed that higher dose of nano-anatase TiO2 could cause liver DNA cleavage in mice.',\n", - " 'author': ['Li, Na',\n", - " 'Ma, Linglan',\n", - " 'Wang, Jue',\n", - " 'Zheng, Lei',\n", - " 'Liu, Jie',\n", - " 'Duan, Yanmei',\n", - " 'Liu, Huiting',\n", - " 'Zhao, Xiaoyang',\n", - " 'Wang, Sisi',\n", - " 'Wang, Han',\n", - " 'Hong, Fashui',\n", - " 'Xie, Yaning'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1007%2Fs11671-009-9451-2\"}'],\n", - " 'title': ['Interaction Between Nano-Anatase TiO2 and Liver DNA from Mice In Vivo']},\n", - " {'bibcode': '2014PLoSO...9k4782L',\n", - " 'author': ['Lee, Jun Choul',\n", - " 'Park, Byung Kil',\n", - " 'Choung, Sorim',\n", - " 'Kim, Ji Min',\n", - " 'Joung, Kyong Hye',\n", - " 'Lee, Ju Hee',\n", - " 'Kim, Koon Soon',\n", - " 'Kim, Hyun Jin',\n", - " 'Jeong, Jae-Wook',\n", - " 'Rhee, Sang Dal',\n", - " 'Ku, Bon Jeong'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0114782\"}'],\n", - " 'title': ['Amelioration of Hypercholesterolemia by an EGFR Tyrosine Kinase Inhibitor in Mice with Liver-Specific Knockout of Mig-6']},\n", - " {'bibcode': '2020ESPR...27..264M',\n", - " 'author': ['Mohamed, Hanan R. H.',\n", - " 'Welson, Mary',\n", - " 'Yaseen, Ahmed Essa',\n", - " 'EL-Ghor, Akmal A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1007%2Fs11356-019-06930-0\"}'],\n", - " 'title': ['Estimation of genomic instability and mutation induction by graphene oxide nanoparticles in mice liver and brain tissues']},\n", - " {'bibcode': '1994PNAS...9112808H',\n", - " 'abstract': \"A transgenic mouse strain that expresses the hepatitis B virus (HBV) large envelope protein in the liver was used to determine the extent of oxidative DNA damage that occurs during chronic HBV infection. This mouse strain develops a chronic necroinflammatory liver disease that mimics the inflammation, cellular hyperplasia, and increased risk for cancer that is evident in human chronic active hepatitis. When perfused in situ with nitroblue tetrazolium, an indicator for superoxide formation, the liver of transgenic mice displayed intense formazan deposition in Kupffer cells, indicating oxygen radical production, and S-phase hepatocytes were commonly seen adjacent to the stained Kupffer cells. Similar changes were not observed in nontransgenic control livers. To determine whether these events were associated with oxidative DNA damage, genomic DNA from the livers of transgenic mice and nontransgenic controls was isolated and examined for 8-oxo-2'-deoxyguanosine, an oxidatively modified adduct of deoxyguanosine. Results showed a significant, sustained accumulation in steady-state 8-oxo-2'-deoxyguanosine that started early in life exclusively in the transgenic mice and increased progressively with advancing disease. The most pronounced increase occurred in livers exhibiting microscopic nodular hyperplasia, adenomas, and hepatocellular carcinoma. Thus, HBV transgenic mice with chronic active hepatitis display greatly increased hepatic oxidative DNA damage. Moreover, the DNA damage occurs in the presence of heightened hepatocellular proliferation, increasing the probability of fixation of the attendant genetic and chromosomal abnormalities and the development of hepatocellular carcinoma.\",\n", - " 'author': ['Hagen, Tory M.',\n", - " 'Huang, Shaonan',\n", - " 'Curnutte, John',\n", - " 'Fowler, Patricia',\n", - " 'Martinez, Violeta',\n", - " 'Wehr, Carol M.',\n", - " 'Ames, Bruce N.',\n", - " 'Chisari, Francis V.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/91/26/12808\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/91/26/12808\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/91/26/12808\"}'],\n", - " 'title': ['Extensive oxidative DNA damage in hepatocytes of transgenic mice with chronic active hepatitis destined to develop hepatocellular carcinoma.']},\n", - " {'bibcode': '1983Natur.306..332B',\n", - " 'abstract': 'Transgenic mice were produced by microinjection of a rearranged, functional immunoglobulin κ gene into fertilized mouse eggs and implantation of the microinjected embryos into foster mothers. Mice that integrated the injected gene were mated and the DNA, RNA and serum κ chains of their offspring were analysed. The data from offspring of three different transgenic mice indicate that the microinjected gene is expressed in the spleen, but not the liver of mice which inherited the injected gene.',\n", - " 'author': ['Brinster, Ralph L.',\n", - " 'Ritchie, Kindred A.',\n", - " 'Hammer, Robert E.',\n", - " \"O'Brien, Rebecca L.\",\n", - " 'Arp, Benjamin',\n", - " 'Storb, Ursula'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F306332a0\"}'],\n", - " 'title': ['Expression of a microinjected immunoglobulin gene in the spleen of transgenic mice']},\n", - " {'bibcode': '2005PNAS..10212501M',\n", - " 'abstract': 'There are four known stearoyl-CoA desaturase (SCD) enzyme isoforms in mouse and two in humans that are required for the biosynthesis of monounsaturated fatty acids, mainly oleate. SCD1 isoform plays a role in the regulation of energy metabolism and lipid synthesis, but the roles of the other SCD isoforms have not been investigated. Here we show that the SCD2 isoform is important in lipid synthesis in early development and is required for survival. SCD2-deficient (Scd2-/-) neonatal mice have a skin permeability barrier defect and a specific repartitioning of linoleic acid from epidermal acylceramide species into phospholipids. SCD2 expression is high in liver of wild-type mouse embryos and neonates between embryonic day 18.5 and 21 days of age and is decreased in adult mice. SCD1 expression, on the other hand, is induced after weaning. The liver, skin, and plasma triglyceride contents are decreased in the neonates but are not altered in the adult Scd2-/- mice. These results indicate that, although SCD1 expression is important in adult mice, SCD2 is crucial in the synthesis of monounsaturated fatty acids that are required for maintaining normal epidermal permeability barrier function and biosynthesis of lipids during early skin and liver development.',\n", - " 'author': ['Miyazaki, Makoto',\n", - " 'Dobrzyn, Agnieszka',\n", - " 'Elias, Peter M.',\n", - " 'Ntambi, James M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/102/35/12501\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/102/35/12501\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/102/35/12501\"}'],\n", - " 'title': ['Stearoyl-CoA desaturase-2 gene expression is required for lipid synthesis during early skin and liver development']},\n", - " {'bibcode': '1969PNAS...63..123A',\n", - " 'abstract': 'Rates of DNA synthesis in root tip cells of diploid and autotetraploid snapdragon (Antirrhinum majus) seedlings and in diploid and tetraploid (mononucleate and bidiploid-nucleate) regenerating mouse-liver cells have been studied. The increase in this rate in the tetraploid cells is closely correlated with the increase in nuclear surface area, but not with the nuclear volume; this suggests a possible control of the rate of DNA synthesis by the nuclear membrane.',\n", - " 'author': ['Alfert, Max', 'Das, Nirmal K.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/63/1/123\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/63/1/123\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/63/1/123\"}'],\n", - " 'title': ['Evidence for Control of the Rate of Nuclear DNA Synthesis by the Nuclear Membrane in Eukaryotic Cells']},\n", - " {'bibcode': '2012PLoSO...751007F',\n", - " 'author': ['Fan, Shengjie',\n", - " 'Zhang, Yu',\n", - " 'Hu, Na',\n", - " 'Sun, Qinhu',\n", - " 'Ding, Xiaobo',\n", - " 'Li, Guowen',\n", - " 'Zheng, Bin',\n", - " 'Gu, Ming',\n", - " 'Huang, Feisi',\n", - " 'Sun, Yin-Qiang',\n", - " 'Zhou, Zhiqin',\n", - " 'Lu, Xiong',\n", - " 'Huang, Cheng',\n", - " 'Ji, Guang'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0051007\"}'],\n", - " 'title': ['Extract of Kuding Tea Prevents High-Fat Diet-Induced Metabolic Disorders in C57BL/6 Mice via Liver X Receptor (LXR) β Antagonism']},\n", - " {'bibcode': '1978JRadR..19..197B',\n", - " 'author': ['Bhatia, A. L.', 'Gupta, M. L.', 'Singh, R. P.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1269%2Fjrr.19.197\"}'],\n", - " 'title': ['Response of Mice Liver to Continuous β-Irradiation from Tritiated Water']},\n", - " {'bibcode': '2014Natur.513..110S',\n", - " 'abstract': 'Mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 are among the most common genetic alterations in intrahepatic cholangiocarcinoma (IHCC), a deadly liver cancer1,2,3,4,5. Mutant IDH proteins in IHCC and other malignancies acquire an abnormal enzymatic activity allowing them to convert α-ketoglutarate (αKG) to 2-hydroxyglutarate (2HG), which inhibits the activity of multiple αKG-dependent dioxygenases, and results in alterations in cell differentiation, survival, and extracellular matrix maturation6,7,8,9,10. However, the molecular pathways by which IDH mutations lead to tumour formation remain unclear. Here we show that mutant IDH blocks liver progenitor cells from undergoing hepatocyte differentiation through the production of 2HG and suppression of HNF-4α, a master regulator of hepatocyte identity and quiescence. Correspondingly, genetically engineered mouse models expressing mutant IDH in the adult liver show an aberrant response to hepatic injury, characterized by HNF-4α silencing, impaired hepatocyte differentiation, and markedly elevated levels of cell proliferation. Moreover, IDH and Kras mutations, genetic alterations that co-exist in a subset of human IHCCs4,5, cooperate to drive the expansion of liver progenitor cells, development of premalignant biliary lesions, and progression to metastatic IHCC. These studies provide a functional link between IDH mutations, hepatic cell fate, and IHCC pathogenesis, and present a novel genetically engineered mouse model of IDH-driven malignancy.',\n", - " 'author': ['Saha, Supriya K.',\n", - " 'Parachoniak, Christine A.',\n", - " 'Ghanta, Krishna S.',\n", - " 'Fitamant, Julien',\n", - " 'Ross, Kenneth N.',\n", - " 'Najem, Mortada S.',\n", - " 'Gurumurthy, Sushma',\n", - " 'Akbay, Esra A.',\n", - " 'Sia, Daniela',\n", - " 'Cornella, Helena',\n", - " 'Miltiadous, Oriana',\n", - " 'Walesky, Chad',\n", - " 'Deshpande, Vikram',\n", - " 'Zhu, Andrew X.',\n", - " 'Hezel, Aram F.',\n", - " 'Yen, Katharine E.',\n", - " 'Straley, Kimberly S.',\n", - " 'Travins, Jeremy',\n", - " 'Popovici-Muller, Janeta',\n", - " 'Gliser, Camelia',\n", - " 'Ferrone, Cristina R.',\n", - " 'Apte, Udayan',\n", - " 'Llovet, Josep M.',\n", - " 'Wong, Kwok-Kin',\n", - " 'Ramaswamy, Sridhar',\n", - " 'Bardeesy, Nabeel'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"data\", \"url\": \"http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse57002\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature13441\"}'],\n", - " 'title': ['Mutant IDH inhibits HNF-4α to block hepatocyte differentiation and promote biliary cancer']},\n", - " {'bibcode': '1987PNAS...84.3457C',\n", - " 'abstract': 'Genetically hypotransferrinemic mice accumulate iron in the liver and pancreas. A similar pattern of tissue iron accumulation occurs in humans with hereditary hemochromatosis. In both disorders, there is a decreased plasma concentration of apotransferrin. To test the hypothesis that nontransferrin-bound iron exists and is cleared by the parenchymal tissues, the tissue distribution of 59Fe was studied in animals lacking apotransferrin. Two groups of animals were used: normal rats and mice whose transferrin had been saturated by an intravenous injection of nonradiolabeled iron, and mice with congenital hypotransferrinemia. In control animals, injected 59Fe was found primarily in the bone marrow and spleen. In the transferrin iron-saturated animals, injected 59Fe accumulated in the liver and pancreas. Gastrointestinally absorbed iron in hypotransferrinemic or transferrin iron-saturated mice was deposited in the liver. This indicates that newly absorbed iron is released from mucosal cells not bound to transferrin. Clearance studies demonstrated that transferrin-bound 59Fe was removed from the circulation of rats with a half-time of 50 min. In transferrin iron-saturated animals, injected 59Fe was removed with a half-time of less than 30 s. Analysis of the distribution of 59Fe in serum samples by polyacrylamide gel electrophoresis demonstrated the presence of 59Fe not bound to transferrin. These results demonstrate the existence of and an uptake system for non-transferrin-bound iron. These observations support the hypothesis that parenchymal iron overload is a consequence of reduced concentrations of apotransferrin.',\n", - " 'author': ['Craven, C. M.',\n", - " 'Alexander, J.',\n", - " 'Eldridge, M.',\n", - " 'Kushner, J. P.',\n", - " 'Bernstein, S.',\n", - " 'Kaplan, J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/84/10/3457\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/84/10/3457\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/84/10/3457\"}'],\n", - " 'title': ['Tissue distribution and clearance kinetics of non-transferrin-bound iron in the hypotransferrinemic mouse: a rodent model for hemochromatosis.']},\n", - " {'bibcode': '1998PNAS...95.8847C',\n", - " 'abstract': 'Hepatocellular carcinoma (HCC) is the major primary malignant tumor in the human liver, but the molecular changes leading to liver cell transformation remain largely unknown. The Wnt-β-catenin pathway is activated in colon cancers and some melanoma cell lines, but has not yet been investigated in HCC. We have examined the status of the β-catenin gene in different transgenic mouse lines of HCC obtained with the oncogenes c-myc or H-ras. Fifty percent of the hepatic tumors in these transgenic mice had activating somatic mutations within the β-catenin gene similar to those found in colon cancers and melanomas. These alterations in the β-catenin gene (point mutations or deletions) lead to a disregulation of the signaling function of β-catenin and thus to carcinogenesis. We then analyzed human HCCs and found similar mutations in eight of 31 (26%) human liver tumors tested and in HepG2 and HuH6 hepatoma cells. The mutations led to the accumulation of β-catenin in the nucleus. Thus alterations in the β-catenin gene frequently are selected for during liver tumorigenesis and suggest that disregulation of the Wnt-β-catenin pathway is a major event in the development of HCC in humans and mice.',\n", - " 'author': ['Coste, Alix de La',\n", - " 'Romagnolo, Béatrice',\n", - " 'Billuart, Pierre',\n", - " 'Renard, Claire-Angélique',\n", - " 'Buendia, Marie-Annick',\n", - " 'Soubrane, Olivier',\n", - " 'Fabre, Monique',\n", - " 'Chelly, Jamel',\n", - " 'Beldjord, Cherif',\n", - " 'Kahn, Axel',\n", - " 'Perret, Christine'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.95.15.8847\"}'],\n", - " 'title': ['Somatic mutations of the β-catenin gene are frequent in mouse and human hepatocellular carcinomas']},\n", - " {'bibcode': '1996PNAS...93.9126K',\n", - " 'abstract': 'The interaction of the hormone erythropoietin and its receptor (EpoR) is though to be required for normal hematopoiesis. To define the role of EpoR in this process, the murine EpoR was disrupted by homologous recombination. Mice lacking the EpoR died in utero at embryonic day 11-12.5 with severe anemia. Embryonic erythropoiesis was markedly diminished, while fetal liver hematopoiesis was blocked at the proerythroblast stage. Other cell types known to express EpoR, including megakaryocytes, mast, and neural cells were morphologically normal. Reverse transcription-coupled PCR analysis of RNA from embryonic yolk sac, peripheral blood, and fetal liver demonstrated near normal transcripts levels for EKLF, thrombopoietin (Tpo), c-MPL, GATA-1, GATA-2, and alpha- and embryonic beta H1-globin but non for adult beta maj-globin. While colony-forming unit-erythroid (CFU-E) and burst-forming unit-erythroid (BFU-E) colonies were not present in cultures derived from EpoR-/- liver or yolk sac cells, hemoglobin-containing BFU-E colonies were detected in cultures treated with recombinant Tpo and Kit ligand or with Tpo and interleukin 3 and 11. Rescued BFU-E colonies expressed adult beta-globin and c-MPL and appeared morphologically normal. Thus, erythroid progenitors are formed in vivo in mice lacking the EpoR, and our studies demonstrate that a signal transmitted through the Tpo receptor c-MPL stimulates proliferation and terminal differentiation of these progenitors in vitro.',\n", - " 'author': ['Kieran, Mark W.',\n", - " 'Perkins, Andrew C.',\n", - " 'Orkin, Stuart H.',\n", - " 'Zon, Leonard I.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/93/17/9126\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/93/17/9126\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/93/17/9126\"}'],\n", - " 'title': ['Thrombopoietin rescues in vitro erythroid colony formation from mouse embryos lacking the erythropoietin receptor.']},\n", - " {'bibcode': '2001PNAS...9810630C',\n", - " 'abstract': 'We present genome-wide microarray expression analysis of 11,000 genes in an aging potentially mitotic tissue, the liver. This organ has a major impact on health and homeostasis during aging. The effects of life- and health-span-extending caloric restriction (CR) on gene expression among young and old mice and between long-term CR (LT-CR) and short-term CR (ST-CR) were examined. This experimental design allowed us to accurately distinguish the effects of aging from those of CR on gene expression. Aging was accompanied by changes in gene expression associated with increased inflammation, cellular stress, and fibrosis, and reduced capacity for apoptosis, xenobiotic metabolism, normal cell-cycling, and DNA replication. LT-CR and just 4 weeks of ST-CR reversed the majority of these changes. LT-CR produced in young mice a pattern of gene expression that is a subset of the changes found in old LT-CR mice. It is possible that the early changes in gene expression, which extend into old age, are key to the life- and health-span-extending effects of CR. Further, ST-CR substantially shifted the \"normo-aging\" genomic profile of old control mice toward the \"slow-aging\" profile associated with LT-CR. Therefore, many of the genomic effects of CR are established rapidly. Thus, expression profiling should prove useful in quickly identifying CR- mimetic drugs and treatments.',\n", - " 'author': ['Cao, Shelley X.',\n", - " 'Dhahbi, Joseph M.',\n", - " 'Mote, Patricia L.',\n", - " 'Spindler, Stephen R.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/98/19/10630\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/98/19/10630\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/98/19/10630\"}'],\n", - " 'title': ['Genomic profiling of short- and long-term caloric restriction effects in the liver of aging mice']},\n", - " {'bibcode': '1998HETox..17..668M',\n", - " 'abstract': 'Metabolism of both carbamazepine (CBZ) and oxcarbaze-pine (OCBZ) were catalyzed by human liver microsomes and microsomes from livers of CBZ-induced or non-induced C57BL/6 mice. Human placental microsomes metabolized only OCBZ. Mouse liver microsomes metabolized CBZ to carbamazepine-10,11-epoxide (CBZ-E), 10- hydroxy-10,11-dihydro-carbamazepine (10-OH-CBZ), 3- hydroxy-carbamazepine (3-OH-CBZ), 10,11-trans-dihydroxy-10,11-dihydro-carbamazepine (10,11-D) and to an unidentified metabolite. CBZ-pretreatment of mice increased both ethoxyresorufin O-deethylase activity in the liver and the amount of CBZ-E in microsomal incubations regardless of the age of mice. Human liver microsomes catalyzed the formation of CBZ to 9-hydroxymethyl-10-carbamoyl acridan (9-AC) in addition to CBZ-E, 3-OH-CBZ and 10-OH-CBZ. OCBZ was metabolized to its active metabolite in all incubations. An unknown metabolite was also present in some of the incubations. Human liver microsomes catalyzed only minute covalent binding of CBZ and OCBZ to DNA. Binding of OCBZ was, however, one order of magnitude greater than binding of CBZ. Human placental micro-somes from the mothers on CBZ therapy did not catalyze CBZ metabolism. The same microsomes catalyzed OCBZ metabolism to 10-OH-CBZ and to an unknown metabolite. These results indicate autoinduction in CBZ metabolism in mouse liver. Due to the higher binding of OCBZ than CBZ to DNA in vitro, further studies on the potential mutagenicity of OCBZ may be warranted.',\n", - " 'author': ['Myllynen, P.',\n", - " 'Pienimäki, P.',\n", - " 'Raunio, H.',\n", - " 'Vähäkangas, K.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1177%2F096032719801701204\"}'],\n", - " 'title': ['Microsomal metabolism of carbamazepine and oxcarbazepine in liver and placenta']},\n", - " {'bibcode': '1990Sci...250.1273Y',\n", - " 'abstract': 'The current studies were designed to determine whether chronic overexpression of low density lipoprotein (LDL) receptors in the liver would protect mice from the increase in plasma LDL-cholesterol that is induced by high-fat diets. A line of transgenic mice was studied that express the human LDL receptor gene in the liver under control of the transferrin promoter. When fed a diet containing cholesterol, saturated fat, and bile acids for 3 weeks, the transgenic mice, in contrast to normal mice, did not develop a detectable increase in plasma LDL. The current data indicate that unregulated overexpression of LDL receptors can protect against diet-induced hypercholesterolemia in mice.',\n", - " 'author': ['Yokode, Masayuki',\n", - " 'Hammer, Robert E.',\n", - " 'Ishibashi, Shun',\n", - " 'Brown, Michael S.',\n", - " 'Goldstein, Joseph L.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.2244210\"}'],\n", - " 'title': ['Diet-Induced Hypercholesterolemia in Mice: Prevention by Overexpression of LDL Receptors']},\n", - " {'bibcode': '2013Nanot..24N5102N',\n", - " 'abstract': 'Although nanomaterials are being used in various fields, their safety is not yet sufficiently understood. We have been attempting to establish a nanomaterials safety-assessment system by using biomarkers to predict nanomaterial-induced adverse biological effects. Here, we focused on microRNAs (miRNAs) because of their tissue-specific expression and high degree of stability in the blood. We previously showed that high intravenous doses of silica nanoparticles of 70 nm diameter (nSP70) induced liver damage in mice. In this study, we compared the effectiveness of serum levels of liver-specific or -enriched miRNAs (miR-122, miR-192, and miR-194) with that of conventional hepatic biomarkers (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) as biomarkers for nSP70. After mice had been treated with nSP70, their serum miRNAs levels were measured by using quantitative RT-PCR. Serum levels of miR-122 in nSP70-treated mice were the highest among the three miRNAs. The sensitivity of miR-122 for liver damage was at least as good as those of ALT and AST. Like ALT and AST, miR-122 may be a useful biomarker of nSP70. We believe that these findings will help in the establishment of a nanomaterials safety-assessment system.',\n", - " 'author': ['Nagano, Takashi',\n", - " 'Higashisaka, Kazuma',\n", - " 'Kunieda, Akiyoshi',\n", - " 'Iwahara, Yuki',\n", - " 'Tanaka, Kota',\n", - " 'Nagano, Kazuya',\n", - " 'Abe, Yasuhiro',\n", - " 'Kamada, Haruhiko',\n", - " 'Tsunoda, Shin-ichi',\n", - " 'Nabeshi, Hiromi',\n", - " 'Yoshikawa, Tomoaki',\n", - " 'Yoshioka, Yasuo',\n", - " 'Tsutsumi, Yasuo'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1088%2F0957-4484%2F24%2F40%2F405102\"}'],\n", - " 'title': ['Liver-specific microRNAs as biomarkers of nanomaterial-induced liver damage']},\n", - " {'bibcode': '2023SPIE12627E..1HT',\n", - " 'abstract': \"This study presents an artificial intelligence algorithm to classify the heterogeneity and homogeneity of ex vivo mouse liver tumor phantom using dynamic thermal imaging. The algorithm suggests that the phantom's temperature response to a 1340 nm collimated narrow laser beam results in a thermal pattern that may help separate tumor tissue from healthy tissue. The algorithm can classify homogeneity and heterogeneity with an accuracy of 98.6%.\",\n", - " 'author': ['Tosun, Emirhan',\n", - " 'Dinc, Omer Faruk',\n", - " 'Arli, Berfin',\n", - " 'Tozburun, Serhat'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1117%2F12.2672244\"}'],\n", - " 'title': ['A classifier for dynamic thermal imaging']},\n", - " {'bibcode': '2006PNAS..103.5060H',\n", - " 'abstract': 'Central to fibrogenesis and the scarring of organs is the activation of fibroblasts into matrix-secreting myofibroblasts. We demonstrate that Galectin-3 expression is up-regulated in established human fibrotic liver disease and is temporally and spatially related to the induction and resolution of experimental hepatic fibrosis. Disruption of the Galectin-3 gene blocks myofibroblast activation and procollagen (I) expression in vitro and in vivo, markedly attenuating liver fibrosis. Addition of exogenous recombinant Galectin-3 in vitro reversed this abnormality. The reduction in hepatic fibrosis observed in the Galectin-3-/- mouse occurred despite equivalent liver injury and inflammation, and similar tissue expression of TGF-β. TGF-β failed to transactivate Galectin-3-/- hepatic stellate cells, in contrast with WT hepatic stellate cells; however, TGF-β-stimulated Smad-2 and -3 activation was equivalent. These data suggest that Galectin-3 is required for TGF-β mediated myofibroblast activation and matrix production. Finally, in vivo siRNA knockdown of Galectin-3 inhibited myofibroblast activation after hepatic injury and may therefore provide an alternative therapeutic approach to the prevention and treatment of liver fibrosis.',\n", - " 'author': ['Henderson, Neil C.',\n", - " 'Mackinnon, Alison C.',\n", - " 'Farnworth, Sarah L.',\n", - " 'Poirier, Francoise',\n", - " 'Russo, Francesco P.',\n", - " 'Iredale, John P.',\n", - " 'Haslett, Christopher',\n", - " 'Simpson, Kenneth J.',\n", - " 'Sethi, Tariq'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/103/13/5060\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/103/13/5060\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/full/103/13/5060\"}'],\n", - " 'title': ['Galectin-3 regulates myofibroblast activation and hepatic fibrosis']},\n", - " {'bibcode': '2006Natur.443..586K',\n", - " 'abstract': 'The movement of anionic porphyrins (for example, haem) across intracellular membranes is crucial to many biological processes, but their mitochondrial translocation and coordination with haem biosynthesis is not understood. Transport of porphyrins into isolated mitochondria is energy-dependent, as expected for the movement of anions into a negatively charged environment. ATP-binding cassette transporters actively facilitate the transmembrane movement of substances. We found that the mitochondrial ATP-binding cassette transporter ABCB6 is upregulated (messenger RNA and protein in human and mouse cells) by elevation of cellular porphyrins and postulated that ABCB6 has a function in porphyrin transport. We also predicted that ABCB6 is functionally linked to haem biosynthesis, because its mRNA is found in both human bone marrow and CD71+ early erythroid cells (by database searching), and because our results show that ABCB6 is highly expressed in human fetal liver, and Abcb6 in mouse embryonic liver. Here we demonstrate that ABCB6 is uniquely located in the outer mitochondrial membrane and is required for mitochondrial porphyrin uptake. After ABCB6 is upregulated in response to increased intracellular porphyrin, mitochondrial porphyrin uptake activates de novo porphyrin biosynthesis. This process is blocked when the Abcb6 gene is silenced. Our results challenge previous assumptions about the intracellular movement of porphyrins and the factors controlling haem biosynthesis.',\n", - " 'author': ['Krishnamurthy, Partha C.',\n", - " 'Du, Guoqing',\n", - " 'Fukuda, Yu',\n", - " 'Sun, Daxi',\n", - " 'Sampath, Janardhan',\n", - " 'Mercer, Kelly E.',\n", - " 'Wang, Junfeng',\n", - " 'Sosa-Pineda, Beatriz',\n", - " 'Murti, K. Gopal',\n", - " 'Schuetz, John D.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature05125\"}'],\n", - " 'title': ['Identification of a mammalian mitochondrial porphyrin transporter']},\n", - " {'bibcode': '2017NatSR...741854L',\n", - " 'abstract': 'Mequindox (MEQ) is a synthetic antimicrobial agent of quinoxaline-1,4-dioxide group (QdNOs). The liver is regarded as the toxicity target of QdNOs, and the role of N\\u2009→\\u2009O group-associated various toxicities mediated by QdNOs is well recognized. However, the mechanism underlying the in vivo effects of MEQ on the liver, and whether the metabolic pathway of MEQ is altered in response to the pathophysiological conditions still remain unclear. We now provide evidence that MEQ triggers oxidative damage in the liver. Moreover, using LC/MS-ITTOF analysis, two metabolites of MEQ were detected in the liver, which directly confirms the potential connection between N\\u2009→\\u2009O group reduction metabolism of MEQ and liver toxicity. The gender difference in MEQ-induced oxidative stress might be due to adrenal toxicity and the generation of M4 (2-isoethanol 1-desoxymequindox). Furthermore, up-regulation of the MAPK and Nrf2-Keap1 family and phase II detoxifying enzymes (HO-1, GCLC and NQO1) were also observed. The present study demonstrated for the first time the protein peroxidation and a proposal metabolic pathway after chronic exposure of MEQ, and illustrated that the MAPK, Nrf2-Keap1 and NF-кB signaling pathways, as well as the altered metabolism of MEQ, were involved in oxidative toxicity mediated by MEQ in vivo.',\n", - " 'author': ['Liu, Qianying',\n", - " 'Lei, Zhixin',\n", - " 'Huang, Anxiong',\n", - " 'Wu, Qinghua',\n", - " 'Xie, Shuyu',\n", - " 'Awais, Ihsan',\n", - " 'Dai, Menghong',\n", - " 'Wang, Xu',\n", - " 'Yuan, Zonghui'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep41854\"}'],\n", - " 'title': ['Toxic metabolites, MAPK and Nrf2/Keap1 signaling pathways involved in oxidative toxicity in mice liver after chronic exposure to Mequindox']},\n", - " {'bibcode': '2003PNAS..10015712H',\n", - " 'abstract': 'Syndrome X, typified by obesity, insulin resistance (IR), dyslipidemia, and other metabolic abnormalities, is responsive to antidiabetic thiazolidinediones (TZDs). Peroxisome proliferator-activated receptor (PPAR) γ, a target of TZDs, is expressed abundantly in adipocytes, suggesting an important role for this tissue in the etiology and treatment of IR. Targeted deletion of PPARγ in adipose tissue resulted in marked adipocyte hypocellularity and hypertrophy, elevated levels of plasma free fatty acids and triglyceride, and decreased levels of plasma leptin and ACRP30. In addition, increased hepatic glucogenesis and IR were observed. Despite these defects, blood glucose, glucose and insulin tolerance, and insulin-stimulated muscle glucose uptake were all comparable to those of control mice. However, targeted mice were significantly more susceptible to high-fat diet-induced steatosis, hyperinsulinemia, and IR. Surprisingly, TZD treatment effectively reversed liver IR, whereas it failed to lower plasma free fatty acids. These results suggest that syndrome X may be comprised of separable PPARγ-dependent components whose origins and therapeutic sites may reside in distinct tissues.',\n", - " 'author': ['He, Weimin',\n", - " 'Barak, Yaacov',\n", - " 'Hevener, Andrea',\n", - " 'Olson, Peter',\n", - " 'Liao, Debbie',\n", - " 'Le, Jamie',\n", - " 'Nelson, Michael',\n", - " 'Ong, Estelita',\n", - " 'Olefsky, Jerrold M.',\n", - " 'Evans, Ronald M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/100/26/15712\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.2536828100\"}'],\n", - " 'title': ['Adipose-specific peroxisome proliferator-activated receptor γ knockout causes insulin resistance in fat and liver but not in muscle']},\n", - " {'bibcode': '2000Sci...288..682Y',\n", - " 'abstract': 'In multicellular organisms, circadian oscillators are organized into multitissue systems which function as biological clocks that regulate the activities of the organism in relation to environmental cycles and provide an internal temporal framework. To investigate the organization of a mammalian circadian system, we constructed a transgenic rat line in which luciferase is rhythmically expressed under the control of the mouse Per1 promoter. Light emission from cultured suprachiasmatic nuclei (SCN) of these rats was invariably and robustly rhythmic and persisted for up to 32 days in vitro. Liver, lung, and skeletal muscle also expressed circadian rhythms, which damped after two to seven cycles in vitro. In response to advances and delays of the environmental light cycle, the circadian rhythm of light emission from the SCN shifted more rapidly than did the rhythm of locomotor behavior or the rhythms in peripheral tissues. We hypothesize that a self-sustained circadian pacemaker in the SCN entrains circadian oscillators in the periphery to maintain adaptive phase control, which is temporarily lost following large, abrupt shifts in the environmental light cycle.',\n", - " 'author': ['Yamazaki, Shin',\n", - " 'Numano, Rika',\n", - " 'Abe, Michikazu',\n", - " 'Hida, Akiko',\n", - " 'Takahashi, Ri-ichi',\n", - " 'Ueda, Masatsugu',\n", - " 'Block, Gene D.',\n", - " 'Sakaki, Yoshiyuki',\n", - " 'Menaker, Michael',\n", - " 'Tei, Hajime'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.288.5466.682\"}'],\n", - " 'title': ['Resetting Central and Peripheral Circadian Oscillators in Transgenic Rats']},\n", - " {'bibcode': '1996HETox..15..105B',\n", - " 'abstract': '1 A modified mouse liver slice culture technique was established and the viability of the system was assessed on the basis of leakage of cytosolic enzymes viz. lactate dehydrogenase (LDH), alkaline phosphatase (ALP), ala nine aminotransferase (ALT), aspartic aminotransferase (AST) and slice histology. 2 This system was employed for toxicity screening of five algal species of Indian origin on the basis of the EC50 for LDH leakage (dose of cyanobacteria resulting in leakage of 50% of enzyme) of a known toxic cyano bacterial strain Microcystis aeruginosa (PCC 7820). On the basis of both in vitro and in vivo toxicity none of the five species screened exhibited toxicity. 3 The toxicity of PCC 7820 was compared with a purified cyanobacterial hepatotoxin, Microcystin-LR. Various biochemical indices and histological changes confirm the hepatotoxic nature of the toxins. 4 The toxins did not induce glutathione-mediated lipid peroxidation but they did cause significant mitochondrial damage based on an MTT assay. 5 The study illustrates the utility of this in vitro system in identifying naturally occurring toxic cyanobacteria, particularly hepatotoxic species.',\n", - " 'author': ['Bhattacharya, R.',\n", - " 'Lakshmana Rao, PV',\n", - " 'Bhaskar, Asb',\n", - " 'Pant, SC',\n", - " 'Dube, SN'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1177%2F096032719601500202\"}'],\n", - " 'title': ['Liver slice culture for assessing hepatotoxicity of freshwater cyanobacteria']},\n", - " {'bibcode': '2021APS..MARC05003M',\n", - " 'abstract': 'Tissue function requires specific spatial organization of different cell types, yet should be flexible to allow for cell division and growth. Liquid-crystal order can serve this purpose. We computationally reconstructed 3D tissue geometry from microscopy images of mouse liver tissue and analyzed it using concepts from biaxial liquid crystal theory. We show that nematic apical and basal cell polarity axes of hepatocytes (the main cell type in the liver) follow long-range liquid-crystal order. These tissue-level patterns of hepatocyte cell polarity are co-aligned with a structural anisotropy of two transport networks, blood-transporting sinusoids and bile-transporting canaliculi that intertwine the tissue. Silencing communication from hepatocytes to sinusoids via Integrin-β1 knockdown disrupted both liquid-crystal order of hepatocytes and organization of the sinusoidal network, suggesting that bi-directional communication between hepatocytes and sinusoids orchestrates liver tissue architecture. Using a network generation algorithm, we computationally explore the resilience of anisotropic sinusoidal networks to local damage, thus addressing the link between form and function in a complex tissue with liquid-crystal order.',\n", - " 'author': ['Morales-Navarette, Hernan',\n", - " 'Nonaka, Hidenori',\n", - " 'Scholich, Andre',\n", - " 'Segovia-Miranda, Fabian',\n", - " 'de Back, Walter',\n", - " 'Meyer, Kirstin',\n", - " 'Bogorad, Roman',\n", - " 'Kotelianski, Victor',\n", - " 'Brusch, Lutz',\n", - " 'Kalaidizidis, Yannis',\n", - " 'Julicher, Frank',\n", - " 'Friedrich, Benjamin',\n", - " 'Zerial, Marino'],\n", - " 'title': ['Liquid-crystal organization of liver tissue']},\n", - " {'bibcode': '2017NatSR...7.5274D',\n", - " 'abstract': 'Vertical sleeve gastrectomy (VSG) produces sustainable weight loss, remission of type 2 diabetes (T2D), and improvement of nonalcoholic fatty liver disease (NAFLD). However, the molecular mechanisms underlying the metabolic benefits of VSG have remained elusive. According to our previous results, diet-induced obesity induces epigenetic modifications to chromatin in mouse liver. We demonstrate here that VSG in C57BL/6J wild-type male mice can reverse these chromatin modifications and thereby impact the expression of key metabolic genes. Genes involved in lipid metabolism, especially omega-6 fatty acid metabolism, are up-regulated in livers of mice after VSG while genes in inflammatory pathways are down-regulated after VSG. Consistent with gene expression changes, regulatory regions near genes involved in inflammatory response displayed decreased chromatin accessibility after VSG. Our results indicate that VSG induces global regulatory changes that impact hepatic inflammatory and lipid metabolic pathways, providing new insight into the mechanisms underlying the beneficial metabolic effects induced by VSG.',\n", - " 'author': ['Du, Juan',\n", - " 'Tian, Jingyan',\n", - " 'Ding, Lili',\n", - " 'Trac, Candi',\n", - " 'Xia, Brian',\n", - " 'Sun, Siming',\n", - " 'Schones, Dustin E.',\n", - " 'Huang, Wendong'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-017-05349-2\"}'],\n", - " 'title': ['Vertical sleeve gastrectomy reverses diet-induced gene-regulatory changes impacting lipid metabolism']},\n", - " {'bibcode': '2022NatSR..12.6666N',\n", - " 'abstract': 'Body weight loss of ≥ 10% improves the metabolic derangements and liver disease in the majority of non-alcoholic steatohepatitis (NASH) patients, suggesting metabolic modulators may be effective in controlling disease. The pharmacodynamics of ALT-801, a GLP-1/glucagon receptor dual agonist optimized for NASH and weight loss, were compared to semaglutide (GLP-1 receptor agonist) and elafibranor (peroxisome proliferator-activated receptor, PPAR-α/δ, agonist) in a biopsy-confirmed, diet-induced obese (DIO) mouse model of NASH (DIO-NASH). Male C57BL/6J mice were fed Amylin Liver NASH (AMLN) diet for 32 weeks. Animals with biopsy-confirmed steatosis and fibrosis received ALT-801, semaglutide, elafibranor, or vehicle daily for 12 weeks while maintained on the AMLN diet. Study endpoints included body and liver weight, liver and plasma total cholesterol and triglycerides, plasma aminotransferases, histological analysis of liver steatosis, inflammation (galectin-3) and fibrosis (collagen type 1 alpha 1), and evaluation of individual animal changes in composite Non-alcoholic Fatty Liver Disease Activity Score (NAS), and fibrosis stage. ALT-801 demonstrated significant reductions in body weight (approx. 25%), plasma aminotransferases, plasma total cholesterol and liver triglycerides/total cholesterol in conjunction with improved liver steatosis, with greater reductions (p < 0.05) compared to semaglutide and elafibranor. ALT-801 significantly reduced the inflammation marker galectin-3 and the fibrosis marker collagen type 1 alpha 1 vs. vehicle (p < 0.05), with ALT-801 producing greater reductions in galectin-3 vs. elafibranor (p < 0.05). Importantly, all animals treated with ALT-801 significantly improved composite NAS compared to the active controls. This study provides evidence for a potential role for ALT-801 in the therapeutic treatment of NASH.',\n", - " 'author': ['Nestor, John J.',\n", - " 'Parkes, David',\n", - " 'Feigh, Michael',\n", - " 'Suschak, John J.',\n", - " 'Harris, M. Scott'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-022-10577-2\"}'],\n", - " 'title': ['Effects of ALT-801, a GLP-1 and glucagon receptor dual agonist, in a translational mouse model of non-alcoholic steatohepatitis']},\n", - " {'bibcode': '2010PNAS..107.1821C',\n", - " 'abstract': 'Chemical reactions that enable selective biomolecule labeling in living organisms offer a means to probe biological processes in vivo. Very few reactions possess the requisite bioorthogonality, and, among these, only the Staudinger ligation between azides and triarylphosphines has been employed for direct covalent modification of biomolecules with probes in the mouse, an important model organism for studies of human disease. Here we explore an alternative bioorthogonal reaction, the 1,3-dipolar cycloaddition of azides and cyclooctynes, also known as \"Cu-free click chemistry,\" for labeling biomolecules in live mice. Mice were administered peracetylated N-azidoacetylmannosamine (Ac4ManNAz) to metabolically label cell-surface sialic acids with azides. After subsequent injection with cyclooctyne reagents, glycoconjugate labeling was observed on isolated splenocytes and in a variety of tissues including the intestines, heart, and liver, with no apparent toxicity. The cyclooctynes tested displayed various labeling efficiencies that likely reflect the combined influence of intrinsic reactivity and bioavailability. These studies establish Cu-free click chemistry as a bioorthogonal reaction that can be executed in the physiologically relevant context of a mouse.',\n", - " 'author': ['Chang, Pamela V.',\n", - " 'Prescher, Jennifer A.',\n", - " 'Sletten, Ellen M.',\n", - " 'Baskin, Jeremy M.',\n", - " 'Miller, Isaac A.',\n", - " 'Agard, Nicholas J.',\n", - " 'Lo, Anderson',\n", - " 'Bertozzi, Carolyn R.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/107/5/1821\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0911116107\"}'],\n", - " 'title': ['Copper-free click chemistry in living animals']},\n", - " {'bibcode': '2014Nanos...7..625Y',\n", - " 'abstract': 'In spite of the immense benefits from iron oxide magnetic nanoparticles (IOMNs), there is scanty information regarding their metabolic activities and toxicity in vivo. In this study, we investigated the size dependent in vivo biodistribution, toxicokinetics, and toxicity and gene expression changes of various sizes of carboxyl coated IOMNs (diameters of 10, 20, 30, and 40 nm). Our findings demonstrated that the various sizes of IOMNs accumulated primarily in the liver and spleen on the first day post-injection. Interestingly, size dependent biodistribution and transport were observed: the smallest IOMNs (10 nm) showed the highest uptake by the liver, whereas the largest IOMNs (40 nm) showed the highest uptake by the spleen. Moreover, the IOMNs with the smallest size (10 nm) were cleared faster from the liver and kidneys, but more readily entered the brain and the uterus. IOMNs with the largest size (40 nm) accumulated more readily but were easily eliminated in the spleen. However, the level of iron in the heart decreased in all IOMN exposed groups. In addition, blood biochemistry, hematological analyses and histological examination demonstrated that there was no apparent acute toxicity caused by IOMNs in mice. However, smaller IOMNs (10 nm and 20 nm) more effectively changed the expression level of sensitive genes related to oxidant stress, iron transport, metabolic process, apoptosis, and others.In spite of the immense benefits from iron oxide magnetic nanoparticles (IOMNs), there is scanty information regarding their metabolic activities and toxicity in vivo. In this study, we investigated the size dependent in vivo biodistribution, toxicokinetics, and toxicity and gene expression changes of various sizes of carboxyl coated IOMNs (diameters of 10, 20, 30, and 40 nm). Our findings demonstrated that the various sizes of IOMNs accumulated primarily in the liver and spleen on the first day post-injection. Interestingly, size dependent biodistribution and transport were observed: the smallest IOMNs (10 nm) showed the highest uptake by the liver, whereas the largest IOMNs (40 nm) showed the highest uptake by the spleen. Moreover, the IOMNs with the smallest size (10 nm) were cleared faster from the liver and kidneys, but more readily entered the brain and the uterus. IOMNs with the largest size (40 nm) accumulated more readily but were easily eliminated in the spleen. However, the level of iron in the heart decreased in all IOMN exposed groups. In addition, blood biochemistry, hematological analyses and histological examination demonstrated that there was no apparent acute toxicity caused by IOMNs in mice. However, smaller IOMNs (10 nm and 20 nm) more effectively changed the expression level of sensitive genes related to oxidant stress, iron transport, metabolic process, apoptosis, and others.

Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr05061d',\n", - " 'author': ['Yang, Lin',\n", - " 'Kuang, Huijuan',\n", - " 'Zhang, Wanyi',\n", - " 'Aguilar, Zoraida P.',\n", - " 'Xiong, Yonghua',\n", - " 'Lai, Weihua',\n", - " 'Xu, Hengyi',\n", - " 'Wei, Hua'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1039%2Fc4nr05061d\"}'],\n", - " 'title': ['Size dependent biodistribution and toxicokinetics of iron oxide magnetic nanoparticles in mice']},\n", - " {'bibcode': '1993Natur.365..179H',\n", - " 'abstract': 'THE proto-oncogene c-jun is the cellular homologue of v-jun, the transforming oncogene of the avian sarcoma virus 17 (ref. 1). c-jun encodes one major component of the AP-1 transcription fac-tor complex and is expressed in many organs during mouse development and in the adult2-4. Because of its rapid induction in cells following growth stimulation and the presence of AP-1 binding sites in the promoter regions of many genes, the c-Jun protein is thought to have important functions in cell proliferation and differentiation2,5-10. But embryonic stem (ES) cells lacking c-Jun are viable and have a normal in vitro differentiation capacity, although c-Jun appears to be important for growth of teratocarcinomas in vivo11. To define the function of c-jun better, targeted ES cells were used to generate mice lacking c-Jun. Here we report that heterozygous mutant mice appear normal, but embryos lacking c-Jun die at mid- to late-gestation and exhibit impaired hepatogenesis, altered fetal liver erythropoiesis and generalized oedema. Interestingly, c-jun-/- ES cells can',\n", - " 'author': ['Hilberg, Frank',\n", - " 'Aguzzi, Adriano',\n", - " 'Howells, Norma',\n", - " 'Wagner, Erwin F.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F365179a0\"}'],\n", - " 'title': ['c-Jun is essential for normal mouse development and hepatogenesis']},\n", - " {'bibcode': '1998Natur.391..900W',\n", - " 'abstract': 'Human type 2 diabetes is characterized by defects in both insulin action and insulin secretion. It has been difficult to identify a single molecular abnormality underlying these features. Insulin-receptor substrates (IRS proteins) may be involved in type 2 diabetes: they mediate pleiotropic signals initiated by receptors for insulin and other cytokines. Disruption of IRS-1 in mice retards growth, but diabetes does not develop because insulin secretion increases to compensate for the mild resistance to insulin,. Here we show that disruption of IRS-2 impairs both peripheral insulin signalling and pancreatic β-cell function. IRS-2-deficient mice show progressive deterioration of glucose homeostasis because of insulin resistance in the liver and skeletal muscle and a lack of β-cell compensation for this insulin resistance. Our results indicate that dysfunction of IRS-2 may contribute to the pathophysiology of human type 2 diabetes.',\n", - " 'author': ['Withers, Dominic J.',\n", - " 'Gutierrez, Julio Sanchez',\n", - " 'Towery, Heather',\n", - " 'Burks, Deborah J.',\n", - " 'Ren, Jian-Ming',\n", - " 'Previs, Stephen',\n", - " 'Zhang, Yitao',\n", - " 'Bernal, Dolores',\n", - " 'Pons, Sebastian',\n", - " 'Shulman, Gerald I.',\n", - " 'Bonner-Weir, Susan',\n", - " 'White, Morris F.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F36116\"}'],\n", - " 'title': ['Disruption of IRS-2 causes type 2 diabetes in mice']},\n", - " {'bibcode': '2020Chmsp.238l4581T',\n", - " 'author': ['Togao, Masao',\n", - " 'Nakayama, Shouta M. M.',\n", - " 'Ikenaka, Yoshinori',\n", - " 'Mizukawa, Hazuki',\n", - " 'Makino, Yoshiki',\n", - " 'Kubota, Ayano',\n", - " 'Matsukawa, Takehisa',\n", - " 'Yokoyama, Kazuhito',\n", - " 'Hirata, Takafumi',\n", - " 'Ishizuka, Mayumi'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.chemosphere.2019.124581\"}'],\n", - " 'title': ['Bioimaging of Pb and STIM1 in mice liver, kidney and brain using Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) and immunohistochemistry']},\n", - " {'bibcode': '1967Natur.214.1366B',\n", - " 'abstract': \"ONE of the best ways to investigate the specific properties of the cell surface is by immunohistochemistry. For this antibodies are required which react selectively with the cell surface antigens. Rabbit serum against normal mouse liver cell ``ghosts'' (NLCG) has been shown to stain specifically the membranes of parenchyma cells1. It was not clear whether this staining was caused (at least partly) by the presence of organospecific antigen(s) on the cell surface. If this is so, then we wonder whether this antigen(s) is present at the surface of hepatoma cells.\",\n", - " 'author': ['Beloshapkina, T.', 'Khramkova, N.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F2141366a0\"}'],\n", - " 'title': ['Organospecificity of Liver Cell Surface Antigens and its Loss by Ascitic Hepatoma']},\n", - " {'bibcode': '2012EnvMM..53..334A',\n", - " 'abstract': 'Animal studies have linked perinatal bisphenol A (BPA) exposure to altered DNA methylation, but little attention is given to analyzing multiple physiologically relevant doses. Utilizing the viable yellow agouti (Avy) mouse, we examine the effects of developmental exposure through maternal diet to 50 ng BPA/kg (n = 14 litters), 50 μg BPA/kg (n = 9 litters), or 50 mg BPA/kg (n = 13 litters) on global and candidate gene methylation at postnatal day 22. Global methylation analysis reveals hypermethylation in tail tissue of a/a and Avy/a offspring across all dose groups compared with controls (n = 11 litters; P < 0.02). Analysis of coat color phenotype replicates previous work showing that the distribution of 50 mg BPA/kg Avy/a offspring shifts toward yellow (P = 0.006) by decreasing DNA methylation in the retrotransposon upstream of the Agouti gene (P = 0.03). Maternal exposure to 50 μg or 50 ng BPA/kg, however, results in altered coat color distributions in comparison with control (P = 0.04 and 0.02), but no DNA methylation effects at the Agouti gene are noted. DNA methylation at the CDK5 activator‑binding protein (CabpIAP) metastable epiallele shows hypermethylation in the 50 μg BPA/kg offspring, compared with controls (P = 0.02). Comparison of exposed mouse liver BPA levels to human fetal liver BPA levels indicates that the three experimental exposures are physiologically relevant. Thus, perinatal BPA exposure affects offspring phenotype and epigenetic regulation across multiple doses, indicating the need to evaluate dose effects in human clinical and population studies. Environ. Mol. Mutagen. 2012.',\n", - " 'author': ['Anderson, Olivia S.',\n", - " 'Nahar, Muna S.',\n", - " 'Faulk, Christopher',\n", - " 'Jones, Tamara R.',\n", - " 'Liao, Chunyang',\n", - " 'Kannan, Kurunthachalam',\n", - " 'Weinhouse, Caren',\n", - " 'Rozek, Laura S.',\n", - " 'Dolinoy, Dana C.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Fem.21692\"}'],\n", - " 'title': ['Epigenetic responses following maternal dietary exposure to physiologically relevant levels of bisphenol A']},\n", - " {'bibcode': '1997PNAS...9411573C',\n", - " 'abstract': \"Metastasis is the ultimate life-threatening stage of cancer. The lack of accurate model systems thwarted studies of the metastatic cell's basic biology. To follow continuously the succeeding stages of metastatic colony growth, we heritably labeled cells from the human lung adenocarcinoma cell line ANIP 973 with green fluorescent protein (GFP) by transfection with GFP cDNA. Labeled cells were then injected intravenously into nude mice, where, by 7 days, they formed brilliantly fluorescing metastatic colonies on mouse lung [Chishima, T., Miyagi, Y., Wang, X., Yang, M., Tan, Y., Shimada, H., Moossa, A. R. & Hoffman, R. M. (1997) Clin. Exp. Metastasis 15, 547-552]. The seeded lung tissue was then excised and incubated in the three-dimensional sponge-gel-matrix-supported histoculture that maintained the critical features of progressive in vivo tumor colonization while allowing continuous access for measurement and manipulation. Tumor progression was continuously visualized by GFP fluorescence in the same individual cultures over a 52-day period, during which the tumors spread throughout the lung. Histoculture tumor colonization was selective for lung cancer cells to grow on lung tissue, because no growth occurred on histocultured mouse liver tissue, which was also observed in vivo. The ability to support selective organ colonization in histoculture and visualize tumor progression by GFP fluorescence allows the in vitro study of the governing processes of metastasis [Kuo, T.-H., Kubota, T., Watanbe, M., Furukawa, T., Teramoto, T., Ishibiki, K., Kitajima, M., Moossa, A. R., Penman, S. & Hoffman, R. M. (1995) Proc. Natl. Acad. Sci. USA 92, 12085-12089]. The results presented here provide significant, new opportunities to understand and to develop treatments that prevent and possibly reverse metastasis.\",\n", - " 'author': ['Chishima, Takashi',\n", - " 'Yang, Meng',\n", - " 'Miyagi, Yohei',\n", - " 'Li, Lingna',\n", - " 'Tan, Yuying',\n", - " 'Baranov, Eugene',\n", - " 'Shimada, Hiroshi',\n", - " 'Moossa, A. Rahim',\n", - " 'Penman, Sheldon',\n", - " 'Hoffman, Robert M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/94/21/11573\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/94/21/11573\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/94/21/11573\"}'],\n", - " 'title': ['Governing Step of Metastasis Visualized in vitro']},\n", - " {'bibcode': '1999PNAS...96.4820E',\n", - " 'abstract': 'It has been hypothesized that a major factor in the progression of mitochondrial disease resulting from defects in oxidative phosphorylation (OXPHOS) is the stimulation of the mitochondrial production of reactive oxygen species (ROS) and the resulting damage to the mtDNA. To test this hypothesis, we examined the mitochondria from mice lacking the heart/muscle isoform of the adenine nucleotide translocator (Ant1), designated Ant1tm2Mgr (-/-) mice. The absence of Ant1 blocks the exchange of ADP and ATP across the mitochondrial inner membrane, thus inhibiting OXPHOS. Consistent with Ant1 expression, mitochondria isolated from skeletal muscle, heart, and brain of the Ant1-deficient mice produced markedly increased amounts of the ROS hydrogen peroxide, whereas liver mitochondria, which express a different Ant isoform, produced normally low levels of hydrogen peroxide. The increased production of ROS by the skeletal muscle and heart was associated with a dramatic increase in the ROS detoxification enzyme manganese superoxide dismutase (Sod2, also known as MnSod) in muscle tissue and muscle mitochondria, a modest increase in Sod2 in heart tissue, and no increase in heart mitochondria. The level of glutathione peroxidase-1 (Gpx1), a second ROS detoxifying enzyme, was increased moderately in the mitochondria of both tissues. Consistent with the lower antioxidant defenses in heart, the heart mtDNAs of the Ant1-deficient mice showed a striking increase in the accumulation of mtDNA rearrangements, whereas skeletal muscle, with higher antioxidant defenses, had fewer mtDNA rearrangements. Hence, inhibition of OXPHOS does increase mitochondrial ROS production, eliciting antioxidant defenses. If the antioxidant defenses are insufficient to detoxify the ROS, then an increased mtDNA mutation rate can result.',\n", - " 'author': ['Esposito, Luke A.',\n", - " 'Melov, Simon',\n", - " 'Panov, Alexander',\n", - " 'Cottrell, Barbara A.',\n", - " 'Wallace, Douglas C.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/96/9/4820\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/96/9/4820\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/96/9/4820\"}'],\n", - " 'title': ['Mitochondrial Disease in Mouse Results in Increased Oxidative Stress']},\n", - " {'bibcode': '2012PNAS..109.5523S',\n", - " 'abstract': 'Mitochondria are dynamic organelles that play a key role in energy conversion. Optimal mitochondrial function is ensured by a quality-control system tightly coupled to fusion and fission. In this connection, mitofusin 2 (Mfn2) participates in mitochondrial fusion and undergoes repression in muscle from obese or type 2 diabetic patients. Here, we provide in vivo evidence that Mfn2 plays an essential role in metabolic homeostasis. Liver-specific ablation of Mfn2 in mice led to numerous metabolic abnormalities, characterized by glucose intolerance and enhanced hepatic gluconeogenesis. Mfn2 deficiency impaired insulin signaling in liver and muscle. Furthermore, Mfn2 deficiency was associated with endoplasmic reticulum stress, enhanced hydrogen peroxide concentration, altered reactive oxygen species handling, and active JNK. Chemical chaperones or the antioxidant N-acetylcysteine ameliorated glucose tolerance and insulin signaling in liver-specific Mfn2 KO mice. This study provides an important description of a unique unexpected role of Mfn2 coordinating mitochondria and endoplasmic reticulum function, leading to modulation of insulin signaling and glucose homeostasis in vivo.',\n", - " 'author': ['Sebastián, David',\n", - " 'Hernández-Alvarez, María Isabel',\n", - " 'Segalés, Jessica',\n", - " 'Sorianello, Eleonora',\n", - " 'Muñoz, Juan Pablo',\n", - " 'Sala, David',\n", - " 'Waget, Aurélie',\n", - " 'Liesa, Marc',\n", - " 'Paz, José C.',\n", - " 'Gopalacharyulu, Peddinti',\n", - " 'Orešič, Matej',\n", - " 'Pich, Sara',\n", - " 'Burcelin, Rémy',\n", - " 'Palacín, Manuel',\n", - " 'Zorzano, Antonio'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/109/14/5523\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1108220109\"}'],\n", - " 'title': ['Mitofusin 2 (Mfn2) links mitochondrial and endoplasmic reticulum function with insulin signaling and is essential for normal glucose homeostasis']},\n", - " {'bibcode': '2013PNAS..110E1857B',\n", - " 'abstract': 'Toll-like receptor 5 (TLR5) is an innate immunity receptor that specifically recognizes and triggers immune response to bacterial flagellins. In addition to resistance to Salmonella infection, TLR5 agonists protect mammals from radiation and have anticancer effects, including suppression of tumor metastases. Using mouse models, we defined the liver as a major target for TLR5 agonists. Administration of pharmacologically optimized flagellin derivative CBLB502 leads to rapid activation of prosurvival nuclear factor kappa B (NF-κB) and STAT3 pathways in the liver and rescues mice from lethal doses of hepatotoxic Fas-agonistic antibodies. Thus, TLR5 agonists can be considered for treatment and prevention of liver metastasis and hepatoprotective applications.',\n", - " 'author': ['Burdelya, Lyudmila G.',\n", - " 'Brackett, Craig M.',\n", - " 'Kojouharov, Bojidar',\n", - " 'Gitlin, Ilya I.',\n", - " 'Leonova, Katerina I.',\n", - " 'Gleiberman, Anatoli S.',\n", - " 'Aygun-Sunar, Semra',\n", - " 'Veith, Jean',\n", - " 'Johnson, Christopher',\n", - " 'Haderski, Gary J.',\n", - " 'Stanhope-Baker, Patricia',\n", - " 'Allamaneni, Shyam',\n", - " 'Skitzki, Joseph',\n", - " 'Zeng, Ming',\n", - " 'Martsen, Elena',\n", - " 'Medvedev, Alexander',\n", - " 'Scheblyakov, Dmitry',\n", - " 'Artemicheva, Nataliya M.',\n", - " 'Logunov, Denis Y.',\n", - " 'Gintsburg, Alexander L.',\n", - " 'Naroditsky, Boris S.',\n", - " 'Makarov, Sergei S.',\n", - " 'Gudkov, Andrei V.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/110/20/E1857\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1222805110\"}'],\n", - " 'title': ['Central role of liver in anticancer and radioprotective activities of Toll-like receptor 5 agonist']},\n", - " {'bibcode': '1971Sci...172..165C',\n", - " 'abstract': 'The 11-hydroxy metabolites of Δ 8- and Δ 9-tetrahydrocannabinol are more active than the parent compounds when administered to mice by either the intravenous or intracerebral route. Both Δ 8- and Δ 9-tetrahydrocannabinol are rapidly and extensively metabolized by the liver and not by the brain. The hypothesis that the 11-hydroxy metabolites may be the active form of tetrahydrocannabinol is discussed.',\n", - " 'author': ['Christensen, H. D.',\n", - " 'Freudenthal, R. I.',\n", - " 'Gidley, J. T.',\n", - " 'Rosenfeld, R.',\n", - " 'Boegli, G.',\n", - " 'Testino, L.',\n", - " 'Brine, D. R.',\n", - " 'Pitt, C. G.',\n", - " 'Wall, M. E.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.jstor.org/stable/1730919?origin=ads\"}'],\n", - " 'title': ['Activity of Δ 8- and Δ 9-Tetrahydrocannabinol and Related Compounds in the Mouse']},\n", - " {'bibcode': '1990PNAS...87..841M',\n", - " 'abstract': 'Livers of a natural population of winter flounder from a contaminated site in Boston Harbor were examined for the presence of oncogenes by transfection of DNA into NIH 3T3 mouse fibroblasts. Tissues analyzed contained histopathologic lesions including abnormal vacuolation, biliary proliferation, and, in many cases, hepatocellular and cholangiocellular carcinomas. Fibroblasts transfected with liver DNA samples from 7 of 13 diseased animals were effective in the induction of subcutaneous sarcomas in nude mice. Further analysis revealed the presence of flounder c-Ki-ras oncogenes in all 10 nude mouse subcutaneous tumors analyzed. Direct DNA sequencing and allele-specific oligonucleotide hybridization following amplification of the tumor DNA by the polymerase chain reaction showed mutations in the 12th codon in this gene. Analysis of DNA from all nude mouse tumors as well as the livers from which they were derived showed mutations at this codon. The mutations comprised G.C----A.T or G.C----T.A base changes resulting in substitution of serine, valine, or cysteine for glycine. Liver DNA samples from five histologically normal livers of animals from a less polluted site were ineffective in the transfection assay and showed only wild-type DNA sequences (GGT) at the 12th codon of c-Ki-ras. The prevalence of mutations in this gene region was associated with the presence of liver lesions and could signify DNA damage resulting from environmental chemical exposure.',\n", - " 'author': ['McMahon, Gerald',\n", - " 'Huber, L. Julie',\n", - " 'Moore, Michael J.',\n", - " 'Stegeman, John J.',\n", - " 'Wogan, Gerald N.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/87/2/841\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/87/2/841\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/87/2/841\"}'],\n", - " 'title': ['Mutations in c-Ki-ras oncogenes in diseased livers of winter flounder from Boston Harbor.']},\n", - " {'bibcode': '2020NatSR..1019814T',\n", - " 'abstract': 'In order to foster animal welfare as well as high quality of research, many countries regulate by law that the severity of animal experiments must be evaluated and considered when performing biomedical research. It is well accepted that multiple parameters rather than a single readout parameter should be applied to describe animal distress or suffering. However, since the performance of readout parameters for animal distress is rarely defined and methods for multivariate analysis have only in rare cases been used, it is not known which methodology is most appropriate to define animal distress. This study used receiver operating characteristic curve analysis to quantify the performance of burrowing activity, body weight change and a distress score of mice after induction of liver damage by bile duct ligation or carbon tetrachloride. In addition, Support Vector Machine classification was used to compare the distress of these mouse models. This approach demonstrated that bile duct ligation causes much more distress than carbon tetrachloride-induced liver damage. This study, therefore, provides a prototype how to compare two animal models by considering several readout parameters. In the future these or similar methods for multivariate analysis will be necessary, when assessing and comparing the severity of animal models.',\n", - " 'author': ['Tang, Guanglin',\n", - " 'Seume, Nico',\n", - " 'Häger, Christine',\n", - " 'Kumstel, Simone',\n", - " 'Abshagen, Kerstin',\n", - " 'Bleich, André',\n", - " 'Vollmar, Brigitte',\n", - " 'Talbot, Steven R.',\n", - " 'Zhang, Xianbin',\n", - " 'Zechner, Dietmar'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-020-76391-w\"}'],\n", - " 'title': ['Comparing distress of mouse models for liver damage']},\n", - " {'bibcode': '2002Sci...297..240C',\n", - " 'abstract': \"Leptin elicits a metabolic response that cannot be explained by its anorectic effects alone. To examine the mechanism underlying leptin's metabolic actions, we used transcription profiling to identify leptin-regulated genes in ob/ob liver. Leptin was found to specifically repress RNA levels and enzymatic activity of hepatic stearoyl-CoA desaturase-1 (SCD-1), which catalyzes the biosynthesis of monounsaturated fatty acids. Mice lacking SCD-1 were lean and hypermetabolic. ob/ob mice with mutations in SCD-1 were significantly less obese than ob/ob controls and had markedly increased energy expenditure. ob/ob mice with mutations in SCD-1 had histologically normal livers with significantly reduced triglyceride storage and VLDL (very low density lipoprotein) production. These findings suggest that down-regulation of SCD-1 is an important component of leptin's metabolic actions.\",\n", - " 'author': ['Cohen, Paul',\n", - " 'Miyazaki, Makoto',\n", - " 'Socci, Nicholas D.',\n", - " 'Hagge-Greenberg, Aaron',\n", - " 'Liedtke, Wolfgang',\n", - " 'Soukas, Alexander A.',\n", - " 'Sharma, Ratnendra',\n", - " 'Hudgins, Lisa C.',\n", - " 'Ntambi, James M.',\n", - " 'Friedman, Jeffrey M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.1071527\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.1071527\"}'],\n", - " 'title': ['Role for Stearoyl-CoA Desaturase-1 in Leptin-Mediated Weight Loss']},\n", - " {'bibcode': '2014EnTox..29...64C',\n", - " 'author': ['Cheng, Jie',\n", - " 'Cheng, Zhe',\n", - " 'Hu, Renping',\n", - " 'Cui, Yaling',\n", - " 'Cai, Jingwei',\n", - " 'Li, Na',\n", - " 'Gui, Suxing',\n", - " 'Sang, Xuezi',\n", - " 'Sun, Qingqing',\n", - " 'Wang, Ling',\n", - " 'Hong, Fashui'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Ftox.20773\"}'],\n", - " 'title': ['Immune dysfunction and liver damage of mice following exposure to lanthanoids']},\n", - " {'bibcode': '2014Natur.510...84P',\n", - " 'abstract': 'Non-alcoholic fatty liver disease and its downstream sequelae, hepatic insulin resistance and type 2 diabetes, are rapidly growing epidemics, which lead to increased morbidity and mortality rates, and soaring health-care costs. Developing interventions requires a comprehensive understanding of the mechanisms by which excess hepatic lipid develops and causes hepatic insulin resistance and type 2 diabetes. Proposed mechanisms implicate various lipid species, inflammatory signalling and other cellular modifications. Studies in mice and humans have elucidated a key role for hepatic diacylglycerol activation of protein kinase Cɛ in triggering hepatic insulin resistance. Therapeutic approaches based on this mechanism could alleviate the related epidemics of non-alcoholic fatty liver disease and type 2 diabetes.',\n", - " 'author': ['Perry, Rachel J.',\n", - " 'Samuel, Varman T.',\n", - " 'Petersen, Kitt F.',\n", - " 'Shulman, Gerald I.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature13478\"}'],\n", - " 'title': ['The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes']},\n", - " {'bibcode': '2006PNAS..10310741T',\n", - " 'abstract': 'The c-Jun N-terminal kinases (JNKs) are key regulators of inflammation and interfere with insulin action in cultured cells and whole animals. Obesity increases total JNK activity, and JNK1, but not JNK2, deficiency results in reduced adiposity and improved insulin sensitivity. Interestingly, a higher-than-normal level of JNK activation is observed in Jnk2-/- mice, particularly in the liver, indicating an interaction between the isoforms that might have masked the metabolic activity of JNK2 in isolated mutant mice. To address the role of the JNK2 isoform in metabolic homeostasis, we intercrossed Jnk1-/- and Jnk2-/- mice and examined body weight and glucose metabolism in the resulting mutant allele combinations. Among all of the viable genotypes examined, we observed only reduced body weight and increased insulin sensitivity in Jnk1-/- and Jnk1+/-Jnk2-/- mice. These two groups of mice also exhibited reduced total JNK activity and cytokine expression in liver tissue compared with all other genotypes examined. These data indicate that the JNK2 isoform is also involved in metabolic regulation, but its function is not obvious when JNK1 is fully expressed because of regulatory crosstalk between the two isoforms.',\n", - " 'author': ['Tuncman, Gürol',\n", - " 'Hirosumi, Jiro',\n", - " 'Solinas, Giovanni',\n", - " 'Chang, Lufen',\n", - " 'Karin, Michael',\n", - " 'Hotamisligil, Gökhan S.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/103/28/10741\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/103/28/10741\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/full/103/28/10741\"}'],\n", - " 'title': ['Functional in vivo interactions between JNK1 and JNK2 isoforms in obesity and insulin resistance']},\n", - " {'bibcode': '1970Sci...168..864C',\n", - " 'abstract': 'The herbicide 2,4,5-trichlorophenoxyacetic acid is teratogenic and fetocidal in two strains of mice when administered either subcutaneously or orally and in one strain of rats when administered orally. The incidences of both cystic kidney and cleft palate were increased in the C57BL/6 mice as well as the incidence of cleft palate in the AKR mice. The incidence of cystic kidney was also increased in the rats. In addition, an increase in the ratio of liver weight to body weight in the mouse fetus and the occurrence of hemorrhagic gastrointestinal tract in the rat fetus suggest that this compound also has fetotoxic properties.',\n", - " 'author': ['Courtney, K. Diane',\n", - " 'Gaylor, D. W.',\n", - " 'Hogan, M. D.',\n", - " 'Falk, H. L.',\n", - " 'Bates, R. R.',\n", - " 'Mitchell, I.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.jstor.org/stable/1729698?origin=ads\"}'],\n", - " 'title': ['Teratogenic Evaluation of 2,4,5-T']},\n", - " {'bibcode': '2011PNAS..108.6323M',\n", - " 'abstract': 'The mammalian liver regenerates upon tissue loss, which induces quiescent hepatocytes to enter the cell cycle and undergo limited replication under the control of multiple hormones, growth factors, and cytokines. Endocannabinoids acting via cannabinoid type 1 receptors (CB1R) promote neural progenitor cell proliferation, and in the liver they promote lipogenesis. These findings suggest the involvement of CB1R in the control of liver regeneration. Here we report that mice lacking CB1R globally or in hepatocytes only and wild-type mice treated with a CB1R antagonist have a delayed proliferative response to two-thirds partial hepatectomy (PHX). In wild-type mice, PHX leads to increased hepatic expression of CB1R and hyperactivation of the biosynthesis of the endocannabinoid anandamide in the liver via an in vivo pathway involving conjugation of arachidonic acid and ethanolamine by fatty-acid amide hydrolase. In wild-type but not CB1R-/- mice, PHX induces robust up-regulation of key cell-cycle proteins involved in mitotic progression, including cyclin-dependent kinase 1 (Cdk1), cyclin B2, and their transcriptional regulator forkhead box protein M1 (FoxM1), as revealed by ultrahigh-throughput RNA sequencing and pathway analysis and confirmed by real-time PCR and Western blot analyses. Treatment of wild-type mice with anandamide induces similar changes mediated via activation of the PI3K/Akt pathway. We conclude that activation of hepatic CB1R by newly synthesized anandamide promotes liver regeneration by controlling the expression of cell-cycle regulators that drive M phase progression.',\n", - " 'author': ['Mukhopadhyay, Bani',\n", - " 'Cinar, Resat',\n", - " 'Yin, Shi',\n", - " 'Liu, Jie',\n", - " 'Tam, Joseph',\n", - " 'Godlewski, Grzegorz',\n", - " 'Harvey-White, Judith',\n", - " 'Mordi, Isioma',\n", - " 'Cravatt, Benjamin F.',\n", - " 'Lotersztajn, Sophie',\n", - " 'Gao, Bin',\n", - " 'Yuan, Qiaoping',\n", - " 'Schuebel, Kornel',\n", - " 'Goldman, David',\n", - " 'Kunos, George'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/108/15/6323\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1017689108\"}'],\n", - " 'title': ['From the Cover: Hyperactivation of anandamide synthesis and regulation of cell-cycle progression via cannabinoid type 1 (CB1) receptors in the regenerating liver']},\n", - " {'bibcode': '2023NatSR..13.6729B',\n", - " 'abstract': 'Hematopoiesis is the process by which blood cells are generated. During embryonic development, these cells migrate through different organs until they reach the bone marrow, their definitive place in adulthood. Around E10.5, the fetal liver starts budding from the gut, where first hematopoietic cells arrive and expand. Hematopoietic cell migration occurs through cytokine stimulation, receptor expression, and glycosylation patterns on the cell surface. In addition, carbohydrates can modulate different cell activation states. For this reason, we aimed to characterize and quantify fetal megakaryocytic cells in mouse fetal liver according to their glycan residues at different gestational ages through lectins. Mouse fetuses between E11.5 and E18.5 were formalin-fixed and, paraffin-embedded, for immunofluorescence analysis using confocal microscopy. The results showed that the following sugar residues were expressed in proliferating and differentiating megakaryocytes in the fetal liver at different gestational ages: α-mannose, α-glucose, galactose, GlcNAc, and two types of complex oligosaccharides. Megakaryocytes also showed three proliferation waves during liver development at E12.5, E14.5, and E18.5. Additionally, the lectins that exhibited high and specific pattern intensities at liver capsules and vessels were shown to be a less time-consuming and robust alternative alternative to conventional antibodies for displaying liver structures such as capsules and vessels, as well as for megakaryocyte differentiation in the fetal liver.',\n", - " 'author': ['Bomfim, Barbara Cristina Marcollino',\n", - " 'Azevedo-Silva, Jessyca',\n", - " 'Caminha, Giulia',\n", - " 'Santos, João Paulo Rodrigues',\n", - " 'Pelajo-Machado, Marcelo',\n", - " 'de Paula Ayres-Silva, Jackline'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-023-32863-3\"}'],\n", - " 'title': ['Lectin-based carbohydrate profile of megakaryocytes in murine fetal liver during development']},\n", - " {'bibcode': '2001PNAS...98.1583H',\n", - " 'abstract': 'von Hippel-Lindau (VHL) disease is a pleomorphic familial tumor syndrome that is characterized by the development of highly vascularized tumors. Homozygous disruption of the VHL gene in mice results in embryonic lethality. To investigate VHL function in the adult we have generated a conditional VHL null allele (2-lox allele) and null allele (1-lox allele) by Cre-mediated recombination in embryonic stem cells. We show here that mice heterozygous for the 1-lox allele develop cavernous hemangiomas of the liver, a rare manifestation of the human disease. Histologically these tumors were associated with hepatocellular steatosis and focal proliferations of small vessels. To study the cellular origin of these lesions we inactivated VHL tissue-specifically in hepatocytes. Deletion of VHL in the liver resulted in severe steatosis, many blood-filled vascular cavities, and foci of increased vascularization within the hepatic parenchyma. These histopathological changes were similar to those seen in livers from mice heterozygous for the 1-lox allele. Hypoxia-inducible mRNAs encoding vascular endothelial growth factor, glucose transporter 1, and erythropoietin were up-regulated. We thus provide evidence that targeted inactivation of mouse VHL can model clinical features of the human disease and underline the importance of the VHL gene product in the regulation of hypoxia-responsive genes in vivo.',\n", - " 'author': ['Haase, Volker H.',\n", - " 'Glickman, Jonathan N.',\n", - " 'Socolovsky, Merav',\n", - " 'Jaenisch, Rudolf'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/98/4/1583\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/98/4/1583\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/98/4/1583\"}'],\n", - " 'title': ['Vascular tumors in livers with targeted inactivation of the von Hippel-Lindau tumor suppressor']},\n", - " {'bibcode': '2005Natur.433..760C',\n", - " 'abstract': 'The decline of tissue regenerative potential is a hallmark of ageing and may be due to age-related changes in tissue-specific stem cells. A decline in skeletal muscle stem cell (satellite cell) activity due to a loss of Notch signalling results in impaired regeneration of aged muscle. The decline in hepatic progenitor cell proliferation owing to the formation of a complex involving cEBP-α and the chromatin remodelling factor brahma (Brm) inhibits the regenerative capacity of aged liver. To examine the influence of systemic factors on aged progenitor cells from these tissues, we established parabiotic pairings (that is, a shared circulatory system) between young and old mice (heterochronic parabioses), exposing old mice to factors present in young serum. Notably, heterochronic parabiosis restored the activation of Notch signalling as well as the proliferation and regenerative capacity of aged satellite cells. The exposure of satellite cells from old mice to young serum enhanced the expression of the Notch ligand (Delta), increased Notch activation, and enhanced proliferation in vitro. Furthermore, heterochronic parabiosis increased aged hepatocyte proliferation and restored the cEBP-α complex to levels seen in young animals. These results suggest that the age-related decline of progenitor cell activity can be modulated by systemic factors that change with age.',\n", - " 'author': ['Conboy, Irina M.',\n", - " 'Conboy, Michael J.',\n", - " 'Wagers, Amy J.',\n", - " 'Girma, Eric R.',\n", - " 'Weissman, Irving L.',\n", - " 'Rando, Thomas A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature03260\"}'],\n", - " 'title': ['Rejuvenation of aged progenitor cells by exposure to a young systemic environment']},\n", - " {'bibcode': '1996PNAS...93..728C',\n", - " 'abstract': 'The rodent liver displays marked age- and sex-dependent changes in androgen sensitivity due to the sexually dimorphic and temporally programmed expression of the androgen receptor (AR) gene. We have altered this normal phenotype by constitutive overexpression of the rat AR transgene in the mouse liver by targeting it via the human phenylalanine hydroxylase (hPAH) gene promoter. These transgenic animals in their heterozygous state produce an approximately 30-fold higher level of the AR in the liver as compared with the nontransgenic control. Androgen inactivation via sulfonation of the hormone by dehydroepiandrosterone sulfotransferase (DST), an androgen-repressible enzyme, also contributes to the age- and sex-dependent regulation of hepatic androgen sensitivity. DST has a broad range of substrate specificity and is responsible for the age- and sex-specific activation of certain polycyclic aromatic hepatocarcinogens as well, by converting them to electrophilic sulfonated derivatives. In the transgenic female, the hepatic expression of DST was approximately 4-fold lower than in normal females, a level comparable to that in normal males. The hPAH-AR mice will serve as a valuable model for studying the sex- and age-invariant expression of liver-specific genes, particularly those involved in the activation of environmental hepatocarcinogens such as the aromatic hydrocarbons.',\n", - " 'author': ['Chatterjee, Bandana',\n", - " 'Song, Chung S.',\n", - " 'Jung, Myeong H.',\n", - " 'Chen, Shuo',\n", - " 'Walter, Christi A.',\n", - " 'Herbert, Damon C.',\n", - " 'Weaker, Frank J.',\n", - " 'Mancini, Michael A.',\n", - " 'Roy, Arun K.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/93/2/728\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/93/2/728\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/93/2/728\"}'],\n", - " 'title': ['Targeted overexpression of androgen receptor with a liver-specific promoter in transgenic mice.']},\n", - " {'bibcode': '2018NatSR...816523Q',\n", - " 'abstract': 'Many anticancer drugs are genotoxic agents inducing DNA breaks in actively proliferating cancer cells. However, these same drugs also induce mutations, mostly genome structural variations (GSVs). The detection of GSVs in normal cells and tissues is a major challenge due to the very low abundance of these mutations, which are essentially only detectable in clonal outgrowths, such as tumors. Previously we developed Structural Variant Search (SVS) - an NGS-based assay for the quantitative detection of somatic GSVs in normal cells. Using an improved version of SVS we now demonstrate that the same dose of the anti-cancer drug bleomycin induces about 5 times more somatic GSVs in quiescent primary human fibroblasts than in proliferating cells. GVS induction in non-dividing, normal cells was subsequently confirmed in vivo by demonstrating that a single dose of bleomycin leads to a significant increase of GSV frequency in mouse liver and heart, two postmitotic tissues. Our findings suggest that normal non-cycling differentiated cells may serve as a reservoir of iatrogenically induced mutations. These results provide more insight into the possible molecular mechanisms that underlie late-life morbidities in cancer survivors exposed to chemotherapy.',\n", - " 'author': ['Quispe-Tintaya, Wilber',\n", - " 'Lee, Moonsook',\n", - " 'Dong, Xiao',\n", - " 'Weiser, Daniel A.',\n", - " 'Vijg, Jan',\n", - " 'Maslov, Alexander Y.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-018-34580-8\"}'],\n", - " 'title': ['Bleomycin-induced genome structural variations in normal, non-tumor cells']},\n", - " {'bibcode': '2021Photo...8...25Y',\n", - " 'abstract': 'Optoacoustic tomography (OAT) is a hybrid biomedical imaging modality that usually employs a transducer array to detect laser-generated ultrasonic signals. The reconstructed image suffers low contrast and degraded resolution due to the limited bandwidth and the spatial directivity of the transducer element. Here, we introduce a modified image deconvolution method with a hybrid reweighted adaptive total variation tailored to improve the image quality of OAT. The effectiveness and the parameter dependency of the proposed method are verified on standard test images. The performance of the proposed method in OAT is then characterized on both simulated phantoms and in vivo mice experiments, which demonstrates that the modified deconvolution algorithm is able to restore the sharp edges and fine details in OAT simultaneously. The signal-to-noise ratios (SNRs) of the target structures in mouse liver and brain were improved by 4.90 and 12.69 dB, respectively. We also investigated the feasibility of using Fourier ring correlation (FRC) as an indicator of the image quality to monitor the deconvolution progress in OAT. Based on the experimental results, a practical guide for image deconvolution in OAT was summarized. We anticipate that the proposed method will be a promising post-processing tool to enhance the visualization of micro-structures in OAT.',\n", - " 'author': ['Yang, Chen', 'Jiao, Yang', 'Jian, Xiaohua', 'Cui, Yaoyao'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.3390%2Fphotonics8020025\"}'],\n", - " 'title': ['Image Deconvolution with Hybrid Reweighted Adaptive Total Variation (HRATV) for Optoacoustic Tomography']},\n", - " {'bibcode': '2021NatCo..12.4446F',\n", - " 'abstract': 'The type 2 deiodinase (D2) in the neonatal liver accelerates local thyroid hormone triiodothyronine (T3) production and expression of T3-responsive genes. Here we show that this surge in T3 permanently modifies hepatic gene expression. Liver-specific Dio2 inactivation (Alb-D2KO) transiently increases H3K9me3 levels during post-natal days 1-5 (P1-P5), and results in methylation of 1,508 DNA sites (H-sites) in the adult mouse liver. These sites are associated with 1,551 areas of reduced chromatin accessibility (RCA) within core promoters and 2,426 within intergenic regions, with reduction in the expression of 1,363 genes. There is strong spatial correlation between density of H-sites and RCA sites. Chromosome conformation capture (Hi-C) data reveals a set of 81 repressed genes with a promoter RCA in contact with an intergenic RCA ~300 Kbp apart, within the same topologically associating domain (χ2 = 777; p < 0.00001). These data explain how the systemic hormone T3 acts locally during development to define future expression of hepatic genes.',\n", - " 'author': ['Fonseca, Tatiana L.',\n", - " 'Garcia, Tzintzuni',\n", - " 'Fernandes, Gustavo W.',\n", - " 'Nair, T. Murlidharan',\n", - " 'Bianco, Antonio C.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41467-021-24748-8\"}'],\n", - " 'title': ['Neonatal thyroxine activation modifies epigenetic programming of the liver']},\n", - " {'bibcode': '1986IJBm...30..283L',\n", - " 'abstract': 'Mice exposed to intermittent hypobaric hypoxia for 20 hours a day, 6 days a week, develop extracellular adaptive responses similar to those found in humans exposed to oxygen tension equivalent to that found at an altitude of 4500 m. Isolated liver mitochondria from these animals show no significant differences in rates of substrate-stimulated respiration, ADP-stimulated respiration and the respiratory control ratio (RCR), when compared with sea level controls. Undetectable or negligible differences in these parameters are also noted when sea level animals are exposed for one hour to severe hypoxia (7% O2). We therefore conclude that the oxidative phosphorylation capacity of the isolated mouse liver mitochondria remains unaltered in both acute and chronic hypoxia. However the in vivo oxygen consumption by mice at this degree of hypoxia was markedly reduced. Lack of observable changes in oxidative phosphorylation could be accounted for by extracellular adaptations in mitochondria isolated from acclimatized animals. This explanation, however, is not consistent with the lack of changes on oxidative phosphorylation in mitochondria isolated from mice undergoing acute hypoxia at sea level. It is then suggested that isolated mitochondrial preparations are of limited value for investigating biochemical mechanisms underlying the variation of cellular respiration occurring in vivo.',\n", - " 'author': ['Leon-Velarde, F.', 'Whittembury, J.', 'Monge, C.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1007%2FBF02189472\"}'],\n", - " 'title': ['Oxidative phosphorylation of liver mitochondria from mice acclimatized to hypobaric hypoxia']},\n", - " {'bibcode': '2003PNAS..100.3065S',\n", - " 'abstract': 'Recent work shows that S-adenosylmethionine (AdoMet) helps maintain normal liver function as chronic hepatic deficiency results in spontaneous development of steatohepatitis and hepatocellular carcinoma. The mechanisms by which these nontraditional functions of AdoMet occur are unknown. Here, we use knockout mice deficient in hepatic AdoMet synthesis (MAT1A-/-) to study the proteome of the liver during the development of steatohepatitis. One hundred and seventeen protein spots, differentially expressed during the development of steatohepatitis, were selected and identified by peptide mass fingerprinting. Among them, 12 proteins were found to be affected from birth, when MAT1A-/- expression is switched on in WT mouse liver, to the rise of histological lesions, which occurs at ≈8 months. Of the 12 proteins, 4 [prohibitin 1 (PHB1), cytochrome c oxidase I and II, and ATPase β-subunit] have known roles in mitochondrial function. We show that the alteration in expression of PHB1 correlates with a loss of mitochondrial function. Experiments in isolated rat hepatocytes indicate that AdoMet regulates PHB1 content, thus suggesting ways by which steatohepatitis may be induced. Importantly, we found the expression of these mitochondrial proteins was abnormal in ob/ob mice and obese patients who are at risk for nonalcoholic steatohepatitis.',\n", - " 'author': ['Santamaría, Enrique',\n", - " 'Avila, Matías A.',\n", - " 'Latasa, M. Ujue',\n", - " 'Rubio, Angel',\n", - " 'Martín-Duce, Antonio',\n", - " 'Lu, Shelly C.',\n", - " 'Mato, José M.',\n", - " 'Corrales, Fernando J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/100/6/3065\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0536625100\"}'],\n", - " 'title': ['From the Cover: Functional proteomics of nonalcoholic steatohepatitis: Mitochondrial proteins as targets of S-adenosylmethionine']},\n", - " {'bibcode': '2016EnTox..31.1796B',\n", - " 'author': ['Ben Saad, Hajer',\n", - " 'Driss, Dorra',\n", - " 'Ben Amara, Ibtissem',\n", - " 'Boudawara, Ons',\n", - " 'Boudawara, Tahia',\n", - " 'Ellouz Chaabouni, Samia',\n", - " 'Mounir Zeghal, Khaled',\n", - " 'Hakim, Ahmed'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Ftox.22181\"}'],\n", - " 'title': ['Altered hepatic mRNA expression of immune response-associated DNA damage in mice liver induced by potassium bromate: Protective role of vanillin']},\n", - " {'bibcode': '1994HETox..13..764L',\n", - " 'abstract': 'The rodent liver carcinogen and hepatic peroxisome proliferator methylclofenapate (MCP) has been evaluated for genetic toxicity in a range of in vitro and rodent genotoxicity assays. It gave a negative response in each of the following assays: mutagenicity to S.typhimurium and E.coli (± S9 mix, plate and pre-incubation assays), clastogenicity to cultured human lymphocytes and CHO cells (± S9 mix), a mouse bone marrow micronucleus assay (24h and 48h sampling), a rat liver assay for UDS in vivo (12h sampling), assays for lac I (Big Blue™) and lac Z (Muta™ Mouse) mutations in the liver of transgenic mice, and an assay of the ability of MCP to modify the mutagenicity to the liver of dimethylnitrosamine in both transgenic mutation assays. The micronucleus and UDS assays were conducted using a single administration of MCP at its maximum tolerated dose, while the transgenic assays were conducted using nine daily administrations of MCP at its cancer bioassay dose level. These nine daily administrations were shown to double the weight of the liver of non-transgenic, Big Blue™ and Muta™ Mice, as well as leading to a dramatic proliferation of peroxisomes (electron microscopy) in the livers of each strain. These changed parameters had returned to control levels when the mutation analyses were conducted (10 days after the final dose of MCP). Despite the liver enlargement observed following MCP administration, no evidence of mitotic activity was observed in treated livers, although an increased number of cells were undergoing replicative DNA synthesis during the final 3 days of the 9 days of administration (BUdR assessment of S-phase). Liver biochemistry parameters (ALT, AST, AP, CK, GGT and albumin) were unaffected by the chronic (9 day) administration of MCP indicating an absence of hepatic toxicity, These combined observations favour a non-genotoxic mechanism of action for the hepatic carcinogenicity of MCP. The clastogenicity in vitro of the peroxisome proliferator Wyeth 14,643 has been confirmed in CHO cells, but it is noted that this chemical is more soluble than is MCP. In particular, at the highest dose level at which MCP could be tested, Wy 14,643 was also nonclastogenic.',\n", - " 'author': ['Lefevre, P. A.',\n", - " 'Tinwell, H.',\n", - " 'Galloway, S. M.',\n", - " 'Hill, R.',\n", - " 'Mackay, J. M.',\n", - " 'Elcombe, C. R.',\n", - " 'Foster, J.',\n", - " 'Randall, V.',\n", - " 'Callander, R. D.',\n", - " 'Ashby, J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1177%2F096032719401301105\"}'],\n", - " 'title': ['Evaluation of the Genetic Toxicity of the Peroxisome Proliferator and Carcinogen Methyl Clofenapate, Including Assays Usin Muta TM Mouse and Big Blue™ Transgenic Mice']},\n", - " {'bibcode': '2007IJMSp.260..137W',\n", - " 'abstract': 'Time-of-flight secondary ion mass spectrometry (ToF-SIMS) equipped with a gold ion gun was used to image mouse embryo sections and differentiate tissue types (brain, spinal cord, skull, rib, heart and liver). Embryos were paraffin-embedded and then deparaffinized. The robustness and repeatability of the method was determined by analyzing ten tissue slices from three different embryos over a period of several weeks. Using principal component analysis (PCA) to reduce the spectral data generated by ToF-SIMS, histopathologically identified tissue types of the mouse embryos can be differentiated based on the characteristic differences in their mass spectra. These results demonstrate the ability of ToF-SIMS to determine subtle chemical differences even in fixed histological specimens.',\n", - " 'author': ['Wu, Ligang',\n", - " 'Lu, Xiaochen',\n", - " 'Kulp, Kristen S.',\n", - " 'Knize, Mark G.',\n", - " 'Berman, Elena S. F.',\n", - " 'Nelson, Erik J.',\n", - " 'Felton, James S.',\n", - " 'Wu, Kuang Jen J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.sciencedirect.com/science/article/B6VND-4MHPHYX-1/2/6596084282137a9ca19a50efae6f538f\"}'],\n", - " 'title': ['Imaging and differentiation of mouse embryo tissues by ToF-SIMS']},\n", - " {'bibcode': '2019Natur.575..505D',\n", - " 'abstract': 'Chronic liver disease due to alcohol-use disorder contributes markedly to the global burden of disease and mortality1-3. Alcoholic hepatitis is a severe and life-threatening form of alcohol-associated liver disease. The gut microbiota promotes ethanol-induced liver disease in mice4, but little is known about the microbial factors that are responsible for this process. Here we identify cytolysin—a two-subunit exotoxin that is secreted by Enterococcus faecalis5,6—as a cause of hepatocyte death and liver injury. Compared with non-alcoholic individuals or patients with alcohol-use disorder, patients with alcoholic hepatitis have increased faecal numbers of E. faecalis. The presence of cytolysin-positive (cytolytic) E. faecalis correlated with the severity of liver disease and with mortality in patients with alcoholic hepatitis. Using humanized mice that were colonized with bacteria from the faeces of patients with alcoholic hepatitis, we investigated the therapeutic effects of bacteriophages that target cytolytic E. faecalis. We found that these bacteriophages decrease cytolysin in the liver and abolish ethanol-induced liver disease in humanized mice. Our findings link cytolytic E. faecalis with more severe clinical outcomes and increased mortality in patients with alcoholic hepatitis. We show that bacteriophages can specifically target cytolytic E. faecalis, which provides a method for precisely editing the intestinal microbiota. A clinical trial with a larger cohort is required to validate the relevance of our findings in humans, and to test whether this therapeutic approach is effective for patients with alcoholic hepatitis.',\n", - " 'author': ['Duan, Yi',\n", - " 'Llorente, Cristina',\n", - " 'Lang, Sonja',\n", - " 'Brandl, Katharina',\n", - " 'Chu, Huikuan',\n", - " 'Jiang, Lu',\n", - " 'White, Richard C.',\n", - " 'Clarke, Thomas H.',\n", - " 'Nguyen, Kevin',\n", - " 'Torralba, Manolito',\n", - " 'Shao, Yan',\n", - " 'Liu, Jinyuan',\n", - " 'Hernandez-Morales, Adriana',\n", - " 'Lessor, Lauren',\n", - " 'Rahman, Imran R.',\n", - " 'Miyamoto, Yukiko',\n", - " 'Ly, Melissa',\n", - " 'Gao, Bei',\n", - " 'Sun, Weizhong',\n", - " 'Kiesel, Roman',\n", - " 'Hutmacher, Felix',\n", - " 'Lee, Suhan',\n", - " 'Ventura-Cots, Meritxell',\n", - " 'Bosques-Padilla, Francisco',\n", - " 'Verna, Elizabeth C.',\n", - " 'Abraldes, Juan G.',\n", - " 'Brown, Robert S.',\n", - " 'Vargas, Victor',\n", - " 'Altamirano, Jose',\n", - " 'Caballería, Juan',\n", - " 'Shawcross, Debbie L.',\n", - " 'Ho, Samuel B.',\n", - " 'Louvet, Alexandre',\n", - " 'Lucey, Michael R.',\n", - " 'Mathurin, Philippe',\n", - " 'Garcia-Tsao, Guadalupe',\n", - " 'Bataller, Ramon',\n", - " 'Tu, Xin M.',\n", - " 'Eckmann, Lars',\n", - " 'van der Donk, Wilfred A.',\n", - " 'Young, Ry',\n", - " 'Lawley, Trevor D.',\n", - " 'Stärkel, Peter',\n", - " 'Pride, David',\n", - " 'Fouts, Derrick E.',\n", - " 'Schnabl, Bernd'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41586-019-1742-x\"}'],\n", - " 'title': ['Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease']},\n", - " {'bibcode': '2019NRL....14..180I',\n", - " 'abstract': 'The prevalent use of engineered nanoparticles (ENPs) has increased our exposure to these particles. The current available analytical techniques fail to simultaneously quantify and analyze the physical properties of ENPs in biological tissues. Therefore, new methods are required to evaluate the exposure conditions to ENPs. Single particle inductively coupled plasma-mass spectrometry (sp-ICP-MS) is an attractive approach that can perform quantitative and qualitative analyses of ENPs. However, the application of this approach for biological samples is limited because of the lack of pretreatment methods for effectively recovering ENPs from biological tissues. In this study, we evaluated various pretreatment methods and identified the optimal pretreatment conditions for sp-ICP-MS analyses of ENPs in biological tissues using silver nanoparticles (nAg) as a model. We screened five reagents as pretreatment solvents (sodium hydroxide, tetramethylammonium hydroxide, nitric acid, hydrochloric acid, and proteinase K). Our results showed that treatment with sodium hydroxide was optimal for detecting nAg in the mouse liver. Moreover, this pretreatment method can be applied to other organs, such as the heart, lung, spleen, and kidney. Finally, we evaluated the applicability of this method by analyzing the quantity and physical properties of silver in the mouse blood and liver, after intravenous administration of nAg or silver ion. Our sp-ICP-MS method revealed that nAg administered into the blood was partially ionized and tended to be distributed in the particle form (approximately 80%) in the liver and in ionic form (approximately 95%) in the blood. In conclusion, we optimized pretreatment strategies for sp-ICP-MS evaluation of ENPs in biological tissues and demonstrated its applicability by evaluating the changes in the physical properties of nAg in the liver and blood. We also showed that partial changes from the particle form to the ionic form of nAg influences their kinetics and distribution when administered to mice.',\n", - " 'author': ['Ishizaka, Takuya',\n", - " 'Nagano, Kazuya',\n", - " 'Tasaki, Ikkei',\n", - " 'Tao, Hong',\n", - " 'Gao, Jian-Qing',\n", - " 'Harada, Kazuo',\n", - " 'Hirata, Kazumasa',\n", - " 'Saito, Shigeru',\n", - " 'Tsujino, Hirofumi',\n", - " 'Higashisaka, Kazuma',\n", - " 'Tsutsumi, Yasuo'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1186%2Fs11671-019-3016-9\"}'],\n", - " 'title': ['Optimization and Evaluation of Pretreatment Method for sp-ICP-MS to Reveal the Distribution of Silver Nanoparticles in the Body']},\n", - " {'bibcode': '1966Sci...151.1228K',\n", - " 'abstract': 'A drug-induced stimulation of heme biosynthesis in mouse liver was accompanied by altered fumarate metabolism. In liver homogenate, fumarate-1,4-C14 was incorporated, via succinate and succinyl coenzyme A, into heme at an accelerated rate. This pathway of fumarate utilization was inhibited by acetoacetate but not by β -hydroxybutyrate. Fumarate reduction to succinate required reduced nicotinamide adenine dinucleotide. The enzyme fumarate reductase is suggested as a link between terminal oxidation and cellular control of the heme biosynthetic pathway.',\n", - " 'author': ['Kurumada, Takao', 'Labbe, Robert F.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.jstor.org/stable/1718458?origin=ads\"}'],\n", - " 'title': ['Fumarate Reductase in the Control of Heme Biosynthesis']},\n", - " {'bibcode': '1998PNAS...9514395S',\n", - " 'abstract': 'SOCS-1, a member of the suppressor of cytokine signaling (SOCS) family, was identified in a genetic screen for inhibitors of interleukin 6 signal transduction. SOCS-1 transcription is induced by cytokines, and the protein binds and inhibits Janus kinases and reduces cytokine-stimulated tyrosine phosphorylation of signal transducers and activators of transcription 3 and the gp130 component of the interleukin 6 receptor. Thus, SOCS-1 forms part of a feedback loop that modulates signal transduction from cytokine receptors. To examine the role of SOCS-1 in vivo, we have used gene targeting to generate mice lacking this protein. SOCS-1-/- mice exhibited stunted growth and died before weaning with fatty degeneration of the liver and monocytic infiltration of several organs. In addition, the thymus of SOCS-1-/- mice was reduced markedly in size, and there was a progressive loss of maturing B lymphocytes in the bone marrow, spleen, and peripheral blood. Thus, SOCS-1 is required for in vivo regulation of multiple cell types and is indispensable for normal postnatal growth and survival.',\n", - " 'author': ['Starr, Robyn',\n", - " 'Metcalf, Donald',\n", - " 'Elefanty, Andrew G.',\n", - " 'Brysha, Marta',\n", - " 'Willson, Tracy A.',\n", - " 'Nicola, Nicos A.',\n", - " 'Hilton, Douglas J.',\n", - " 'Alexander, Warren S.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/95/24/14395\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/95/24/14395\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/95/24/14395\"}'],\n", - " 'title': ['Liver Degeneration and Lymphoid Deficiencies in Mice Lacking Suppressor of Cytokine Signaling-1']},\n", - " {'bibcode': '1997PNAS...94..961S',\n", - " 'abstract': \"Food-ingested foreign DNA is not completely degraded in the gastrointestinal tract of mice. Phage M13mp18 DNA as a test molecule devoid of homology to mouse DNA was pipette-fed to or added to the food supply of mice. The fate of this foreign DNA in the animals was followed by several methods. In 84 animals, fragments of M13mp18 DNA were detected in the contents of the small intestine, the cecum (until 18 h), the large intestine, or the feces. In 254 animals, M13mp18 DNA fragments of up to 976 bp were found in blood 2-8 h after feeding. In buffer-fed control animals, M13mp18 DNA could not be detected. M13mp18 DNA fragments were traced by PCR in peripheral leukocytes and located by fluorescent in situ hybridization in about 1 of 1000 white cells between 2 and 8 h, and in spleen or liver cells up to 24 h after feeding, but not later. M13mp18 DNA could be traced by fluorescent in situ hybridization in the columnar epithelial cells, in the leukocytes in Peyer's patches of the cecum wall, in liver cells, and in B cells, T cells, and macrophages from spleen. These findings suggest transport of foreign DNA through the intestinal wall and Peyer's patches to peripheral blood leukocytes and into several organs. Upon extended feeding, M13mp18 DNA could be recloned from total spleen DNA into a λ vector. Among about 2.5 × 107 λ plaques, one plaque was isolated that contained a 1299 nucleotide pair fragment (nt 4736-6034) of sequence-identified M13mp18 DNA. This fragment was covalently linked to an 80 nt DNA segment with 70% homology to the mouse IgE receptor gene. The DNA from another λ plaque also contained mouse DNA, bacterial DNA, and rearranged λ DNA. Two additional plaques contained M13mp18 DNA fragments of at least 641 (nt 2660-3300) or 794 (nt 4640-5433) nucleotide pairs. The medical and evolutionary implications of these observations may be considerable.\",\n", - " 'author': ['Schubbert, Rainer',\n", - " 'Renz, Doris',\n", - " 'Schmitz, Birgit',\n", - " 'Doerfler, Walter'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/94/3/961\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/94/3/961\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/94/3/961\"}'],\n", - " 'title': ['Foreign (M13) DNA Ingested by Mice Reaches Peripheral Leukocytes, Spleen, and Liver Via the Intestinal Wall Mucosa and can be Covalently Linked to Mouse DNA']},\n", - " {'bibcode': '2011Natur.479..547K',\n", - " 'abstract': \"Upon the aberrant activation of oncogenes, normal cells can enter the cellular senescence program, a state of stable cell-cycle arrest, which represents an important barrier against tumour development in vivo. Senescent cells communicate with their environment by secreting various cytokines and growth factors, and it was reported that this `secretory phenotype' can have pro- as well as anti-tumorigenic effects. Here we show that oncogene-induced senescence occurs in otherwise normal murine hepatocytes in vivo. Pre-malignant senescent hepatocytes secrete chemo- and cytokines and are subject to immune-mediated clearance (designated as `senescence surveillance'), which depends on an intact CD4+ T-cell-mediated adaptive immune response. Impaired immune surveillance of pre-malignant senescent hepatocytes results in the development of murine hepatocellular carcinomas (HCCs), thus showing that senescence surveillance is important for tumour suppression in vivo. In accordance with these observations, ras-specific Th1 lymphocytes could be detected in mice, in which oncogene-induced senescence had been triggered by hepatic expression of NrasG12V. We also found that CD4+ T cells require monocytes/macrophages to execute the clearance of senescent hepatocytes. Our study indicates that senescence surveillance represents an important extrinsic component of the senescence anti-tumour barrier, and illustrates how the cellular senescence program is involved in tumour immune surveillance by mounting specific immune responses against antigens expressed in pre-malignant senescent cells.\",\n", - " 'author': ['Kang, Tae-Won',\n", - " 'Yevsa, Tetyana',\n", - " 'Woller, Norman',\n", - " 'Hoenicke, Lisa',\n", - " 'Wuestefeld, Torsten',\n", - " 'Dauch, Daniel',\n", - " 'Hohmeyer, Anja',\n", - " 'Gereke, Marcus',\n", - " 'Rudalska, Ramona',\n", - " 'Potapova, Anna',\n", - " 'Iken, Marcus',\n", - " 'Vucur, Mihael',\n", - " 'Weiss, Siegfried',\n", - " 'Heikenwalder, Mathias',\n", - " 'Khan, Sadaf',\n", - " 'Gil, Jesus',\n", - " 'Bruder, Dunja',\n", - " 'Manns, Michael',\n", - " 'Schirmacher, Peter',\n", - " 'Tacke, Frank',\n", - " 'Ott, Michael',\n", - " 'Luedde, Tom',\n", - " 'Longerich, Thomas',\n", - " 'Kubicka, Stefan',\n", - " 'Zender, Lars'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature10599\"}'],\n", - " 'title': ['Senescence surveillance of pre-malignant hepatocytes limits liver cancer development']},\n", - " {'bibcode': '2007PNAS..10416480C',\n", - " 'abstract': 'Acetyl-CoA carboxylase 2 (ACC)2 is a key regulator of mitochondrial fat oxidation. To examine the impact of ACC2 deletion on whole-body energy metabolism, we measured changes in substrate oxidation and total energy expenditure in Acc2-/- and WT control mice fed either regular or high-fat diets. To determine insulin action in vivo, we also measured whole-body insulin-stimulated liver and muscle glucose metabolism during a hyperinsulinemic-euglycemic clamp in Acc2-/- and WT control mice fed a high-fat diet. Contrary to previous studies that have suggested that increased fat oxidation might result in lower glucose oxidation, both fat and carbohydrate oxidation were simultaneously increased in Acc2-/- mice. This increase in both fat and carbohydrate oxidation resulted in an increase in total energy expenditure, reductions in fat and lean body mass and prevention from diet-induced obesity. Furthermore, Acc2-/- mice were protected from fat-induced peripheral and hepatic insulin resistance. These improvements in insulin-stimulated glucose metabolism were associated with reduced diacylglycerol content in muscle and liver, decreased PKCθ activity in muscle and PKCε activity in liver, and increased insulin-stimulated Akt2 activity in these tissues. Taken together with previous work demonstrating that Acc2-/- mice have a normal lifespan, these data suggest that Acc2 inhibition is a viable therapeutic option for the treatment of obesity and type 2 diabetes.',\n", - " 'author': ['Choi, Cheol Soo',\n", - " 'Savage, David B.',\n", - " 'Abu-Elheiga, Lutfi',\n", - " 'Liu, Zhen-Xiang',\n", - " 'Kim, Sheene',\n", - " 'Kulkarni, Ameya',\n", - " 'Distefano, Alberto',\n", - " 'Hwang, Yu-Jin',\n", - " 'Reznick, Richard M.',\n", - " 'Codella, Roberto',\n", - " 'Zhang, Dongyan',\n", - " 'Cline, Gary W.',\n", - " 'Wakil, Salih J.',\n", - " 'Shulman, Gerald I.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/104/42/16480\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0706794104\"}'],\n", - " 'title': ['Continuous fat oxidation in acetyl CoA carboxylase 2 knockout mice increases total energy expenditure, reduces fat mass, and improves insulin sensitivity']},\n", - " {'bibcode': '1991PNAS...88.2726W',\n", - " 'abstract': 'Foreign genes were expressed in liver and skin cells of live mice by using a new apparatus to accelerate DNA-coated microprojectiles into tissues. After introduction of a plasmid in which the firefly luciferase gene was controlled by the human beta-actin promoter, luciferase activity was detectable for up to 14 days in mouse tissues (skin and liver). In situ hybridization histochemistry revealed that microprojectiles penetrated through multiple cell layers without evidence of tissue injury and that 10-20% of the cells in the bombarded area expressed the foreign gene. An advantage of the new design is that internal organs, such as liver, can be transfected without subjecting the tissue to a vacuum. This procedure potentially is applicable to a wide variety of tissues and cell types for studies of transcriptional control elements and for expression of foreign proteins in intact animals.',\n", - " 'author': ['Williams, R. S.',\n", - " 'Johnston, S. A.',\n", - " 'Riedy, M.',\n", - " 'DeVit, M. J.',\n", - " 'McElligott, S. G.',\n", - " 'Sanford, J. C.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/88/7/2726\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.88.7.2726\"}'],\n", - " 'title': ['Introduction of foreign genes into tissues of living mice by DNA-coated microprojectiles.']},\n", - " {'bibcode': '2015Sci...350..830S',\n", - " 'abstract': 'In healthy individuals, the intestinal microbiota cannot access the liver, spleen, or other peripheral tissues. Some pathogenic bacteria can reach these sites, however, and can induce a systemic immune response. How such compartmentalization is achieved is unknown. We identify a gut-vascular barrier (GVB) in mice and humans that controls the translocation of antigens into the blood stream and prohibits entry of the microbiota. Salmonella typhimurium can penetrate the GVB in a manner dependent on its pathogenicity island (Spi) 2-encoded type III secretion system and on decreased β-catenin-dependent signaling in gut endothelial cells. The GVB is modified in celiac disease patients with elevated serum transaminases, which indicates that GVB dismantling may be responsible for liver damage in these patients. Understanding the GVB may provide new insights into the regulation of the gut-liver axis.',\n", - " 'author': ['Spadoni, Ilaria',\n", - " 'Zagato, Elena',\n", - " 'Bertocchi, Alice',\n", - " 'Paolinelli, Roberta',\n", - " 'Hot, Edina',\n", - " 'Di Sabatino, Antonio',\n", - " 'Caprioli, Flavio',\n", - " 'Bottiglieri, Luca',\n", - " 'Oldani, Amanda',\n", - " 'Viale, Giuseppe',\n", - " 'Penna, Giuseppe',\n", - " 'Dejana, Elisabetta',\n", - " 'Rescigno, Maria'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.aad0135\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.aad0135\"}'],\n", - " 'title': ['A gut-vascular barrier controls the systemic dissemination of bacteria']},\n", - " {'bibcode': '2018E3SWC..3106001A',\n", - " 'abstract': 'When people are exposed to mercury chloride, it can produce a variety of health effects in the blood and liver. Coconut water contains Zn, Fe, Vit. C, Vit B11, Vit. B6, and Se to reduce mercury chloride level in the blood and improve blood profile and liver cells. Aim of this study was to analysis the effect of green coconut water supplementation in overcoming the toxic effect of Hg chlorid in the blood and liver of Sprague dawley rats exposed to Hg chloride. Samples were randomly about 36 animals rats exposed to HgCl2 through forced feeding by 20 mg/kgBW sondage per day for 14 days, which divided into control group, and intervention groups were given fresh green coconut water in each by 6, 8, and 10 mL/kgBW for intervention 7 and 17 days. The result of this study showed that there is a significant effect and the decrease in mercury levels in the blood. There is no significant affect on the hemoglobin level, hematocrit level and platelet count with the treatment of green coconut water in the mice with exposure Hg. There is no significant effect between treatments using green coconut water with SGPT levels; there is a decrease in SGPT levels at the increasing number of doses of green coconut water and the length of treatment.',\n", - " 'author': ['Abdulrzag, Ehmeeda M.',\n", - " 'Nur Kristina, Tri',\n", - " 'Suwondo, Ari',\n", - " 'Sunoko, Henna Rya'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1051%2Fe3sconf%2F20183106001\"}'],\n", - " 'title': ['The Effectivity of Green Coconut Water To Reduce Mercury Level In The Blood And To Improve Blood Profiles And Liver Cells Appearance (Study In Sprague Dawley Rats)']},\n", - " {'bibcode': '2017NatMa..16.1252L',\n", - " 'abstract': 'The role of pathological angiogenesis on liver fibrogenesis is still unknown. Here, we developed fibrotic microniches (FμNs) that recapitulate the interaction of liver sinusoid endothelial cells (LSECs) and hepatic stellate cells (HSCs). We investigated how the mechanical properties of their substrates affect the formation of capillary-like structures and how they relate to the progression of angiogenesis during liver fibrosis. Differences in cell response in the FμNs were synonymous of the early and late stages of liver fibrosis. The stiffness of the early-stage FμNs was significantly elevated due to condensation of collagen fibrils induced by angiogenesis, and led to activation of HSCs by LSECs. We utilized these FμNs to understand the response to anti-angiogenic drugs, and it was evident that these drugs were effective only for early-stage liver fibrosis in vitro and in an in vivo mouse model of liver fibrosis. Late-stage liver fibrosis was not reversed following treatment with anti-angiogenic drugs but rather with inhibitors of collagen condensation. Our work reveals stage-specific angiogenesis-induced liver fibrogenesis via a previously unrevealed mechanotransduction mechanism which may offer precise intervention strategies targeting stage-specific disease progression.',\n", - " 'author': ['Liu, Longwei',\n", - " 'You, Zhifeng',\n", - " 'Yu, Hongsheng',\n", - " 'Zhou, Lyu',\n", - " 'Zhao, Hui',\n", - " 'Yan, Xiaojun',\n", - " 'Li, Dulei',\n", - " 'Wang, Bingjie',\n", - " 'Zhu, Lu',\n", - " 'Xu, Yuzhou',\n", - " 'Xia, Tie',\n", - " 'Shi, Yan',\n", - " 'Huang, Chenyu',\n", - " 'Hou, Wei',\n", - " 'Du, Yanan'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnmat5024\"}'],\n", - " 'title': ['Mechanotransduction-modulated fibrotic microniches reveal the contribution of angiogenesis in liver fibrosis']},\n", - " {'bibcode': '1989EnvMM..14..155M',\n", - " 'abstract': \"The in vivo‑in vitro hepatocyte DNA repair assay has been shown to be useful for studying genotoxic hepatocarcinogens. In addition, measurement of S‑phase synthesis (SPS) provides an indirect indicator of hepatocellular proliferation, which may be an important mechanism in rodent carcinogenesis. This assay was used to examine 24 chemicals for their ability to induce unscheduled DNA synthesis (UDS) or SPS in Fischer‑344 rats or B6C3F1 mice following in vivo treatment. Hepatocytes were isolated by liver perfusion and incubated with 3H‑thymidine following in vivo treatment by gavage. UDS was measured by quantitative autoradiography as net grains/ nucleus (NG). Controls from both sexes of both species yielded <0.0 NG. Chemicals chosen for testing were from the National Toxicology Program (NTP) genetic toxicology testing program and most were also evaluated in long‑term animal studies conducted by the NTP. 11‑Aminoun‑decanoic acid, benzyl acetate, bis(2‑chloro‑1‑methylethyl)ether (BCMEE), C.I. Solvent Yellow 14, cinnamaldehyde, cinnamyl anthranilate, dichloromethane, dichlorvos, glutaraldehyde, 4,4′‑methylenedianiline (MDA), 4‑nitrotoluene, 4,4′‑oxydianiline, a polybrominated biphenyl mixture (PBB), reserpine, 1,1,2,2‑tetrachloroethane, 1,1,2‑trichloroethane, trichloroethylene, and 2,6‑xylidine all failed to induce UDS in rats and/or mice. Dinitrotoluene and Michler's Ketone induced positive UDS response in rat, while N‑nitrosodiethanolamine and selenium sulfide induced equivocal UDS results in mouse and rat, respectively. BCMEE, bromoform, chloroform, PBB, 1,1,2‑trichloroethane, and trichloroethylene were all potent inducers of SPS in mouse liver, while C.I. Solvent Yellow 14, and 1,1,2,2‑tetrachloroethane yielded equivocal SPS results in rat and mouse, respectively. These results indicate that most of the test compounds do not induce UDS in the liver; however, the significant S‑phase response induced by many of these compounds, especially the halogenated solvents, may be an important mechanism in their hepatocarcinogenicity.\",\n", - " 'author': ['Mirsalis, Jon C.',\n", - " 'Tyson, C. Kim',\n", - " 'Steinmetz, Karen L.',\n", - " 'Loh, Erica K.',\n", - " 'Hamilton, Carol M.',\n", - " 'Bakke, James P.',\n", - " 'Spalding, Judson W.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Fem.2850140305\"}'],\n", - " 'title': ['Measurement of unscheduled DNA synthesis and S‑phase synthesis in rodent hepatocytes following in vivo treatment: Testing of 24 compounds']},\n", - " {'bibcode': '1996PNAS...93.6731S',\n", - " 'abstract': 'The Ah receptor (AHR) is a ligand-activated transcription factor that mediates a pleiotropic response to environmental contaminants such as benzo[a]pyrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin. In an effort to gain insight into the physiological role of the AHR and to develop models useful in risk assessment, gene targeting was used to inactivate the murine Ahr gene by homologous recombination. Ahr-/- mice are viable and fertile but show a spectrum of hepatic defects that indicate a role for the AHR in normal liver growth and development. The Ahr-/- phenotype is most severe between 0-3 weeks of age and involves slowed early growth and hepatic defects, including reduced liver weight, transient microvesicular fatty metamorphosis, prolonged extramedullary hematopoiesis, and portal hypercellularity with thickening and fibrosis.',\n", - " 'author': ['Schmidt, Jennifer V.',\n", - " 'Huei-Ting Su, Gloria',\n", - " 'Reddy, Janardan K.',\n", - " 'Celeste Simon, M.',\n", - " 'Bradfield, Christopher A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/93/13/6731\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/93/13/6731\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/93/13/6731\"}'],\n", - " 'title': ['Characterization of a murine Ahr null allele: involvement of the Ah receptor in hepatic growth and development.']},\n", - " {'bibcode': '2011NatSR...1E.134H',\n", - " 'abstract': 'Aging is characterized by a general decline in cellular function, which ultimately will affect whole body homeostasis. Although DNA damage and oxidative stress all contribute to aging, metabolic dysfunction is a common hallmark of aging at least in invertebrates. Since a comprehensive overview of metabolic changes in otherwise healthy aging mammals is lacking, we here compared metabolic parameters of young and 2 year old mice. We systemically integrated in vivo phenotyping with gene expression, biochemical analysis, and metabolomics, thereby identifying a distinguishing metabolic footprint of aging. Among the affected pathways in both liver and muscle we found glucose and fatty acid metabolism, and redox homeostasis. These alterations translated in decreased long chain acylcarnitines and increased free fatty acid levels and a marked reduction in various amino acids in the plasma of aged mice. As such, these metabolites serve as biomarkers for aging and healthspan.',\n", - " 'author': ['Houtkooper, Riekelt H.',\n", - " 'Argmann, Carmen',\n", - " 'Houten, Sander M.',\n", - " 'Cantó, Carles',\n", - " 'Jeninga, Ellen H.',\n", - " 'Andreux, Pénélope A.',\n", - " 'Thomas, Charles',\n", - " 'Doenlen, Raphaël',\n", - " 'Schoonjans, Kristina',\n", - " 'Auwerx, Johan'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep00134\"}'],\n", - " 'title': ['The metabolic footprint of aging in mice']},\n", - " {'bibcode': '2019SPIE10859E..0BH',\n", - " 'abstract': 'We used intravital multiphoton microscopy to study the recovery of hepatobiliary metabolism following carbon tetrachloride (CCl4) induced hepatotoxicity in mouse. Our images were processed by a first order kinetic model to generate rate constant resolved images of the mouse liver. At Day 14 following induction, a restoration of the mouse hepatobiliary function was found. Our approach allows the study of the response of hepatic functions to chemical agents in real time and is useful for studying pharmacokinetics of drug molecules through optical microscopic imaging.',\n", - " 'author': ['Huang, Hsu-Cheng',\n", - " 'Lin, Chih-Ju',\n", - " 'Lee, Sheng-Lin',\n", - " 'Lee, Hsuan-Shu',\n", - " 'Dong, Chen-Yuan'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1117%2F12.2507347\"}'],\n", - " 'title': ['Multiphoton imaging of the toxic effect of carbon tetrachloride on hepatobiliary metabolism in vivo']},\n", - " {'bibcode': '1965Natur.208..499A',\n", - " 'abstract': \"Blyumenfel'd and Kalmanson1 as well as Gordy2 and Miyagawa3 have already reported that radicals are formed in lyophilized rat liver by ionizing radiation using electron spin resonance techniques. Moreover, Gordy and Miyagawa have shown that oxygen and cysteine, which was allowed to diffuse into the liver before freeze-drying, alter the electron spin resonance spectra. This report describes investigations on X-irradiated mouse liver. The study also includes preparations of liver in which solutions of cysteine were injected before freeze-dry ing. To some extent we obtained results different from those described by the foregoing authors.\",\n", - " 'author': ['Abe, Mitsuyuki', 'Mönig, Hans', 'Koch, Ruprecht'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F208499a0\"}'],\n", - " 'title': ['Influence of Oxygen and Cysteine on the Radical State of X-irradiated Lyophilized Liver']},\n", - " {'bibcode': '1980PNAS...77.5216B',\n", - " 'abstract': '2(3)-tert-Butyl-4-hydroxyanisole (BHA) is one of several widely used antioxidant food additives that protect against chemical carcinogenesis and toxicity. The present report concerns the enhancement of dicoumarol-inhibited NAD(P)H:quinone reductase [NAD(P)H dehydrogenase (quinone); NAD(P)H:(quinone acceptor) oxidoreductase, EC 1.6.99.2] activity in mouse tissues in response to dietary administration of BHA. Cytosolic quinone reductase specific activity was increased significantly in 10 of 15 tissues examined from BHA-fed mice. The greatest proportionate increase, to 10 times control levels, was observed in liver. BHA also increased the quinone reductase activities of kidney, lung, and the mucosa of the upper small intestine severalfold. The increases of quinone reductase activities in liver and digestive tissues in response to BHA were comparable to the increases previously observed in glutathione S-transferase (EC 2.5.1.18) and epoxide hydratase (EC 3.3.2.3) activities. Quinones are among the toxic products of oxidative metabolism of aromatic hydrocarbons. NAD(P)H:quinone reductase exhibits broad specificity for structurally diverse hydrophobic quinones and may facilitate the microsomal metabolism of quinones to readily excreted conjugates. The protective effects of BHA appear to be due, at least in part, to the ability of this antioxidant to increase the activities in rodent tissues of several enzymes involved in the nonoxidative metabolism of a wide variety of xenobiotics.',\n", - " 'author': ['Benson, Ann M.', 'Hunkeler, Markus J.', 'Talalay, Paul'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/77/9/5216\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/77/9/5216\"}'],\n", - " 'title': ['Increase of NAD(P)H:quinone reductase by dietary antioxidants: possible role in protection against carcinogenesis and toxicity.']},\n", - " {'bibcode': '2023Heliy...922464Q',\n", - " 'abstract': 'Purpose. Non-alcoholic fatty liver disease (NAFLD) represents an increasingly prevalent set of liver diseases. Tryptophan 2,3-dioxygenase 2 (TDO2) is the major enzyme of tryptophan catabolism and is abnormally expressed in liver cancer, but the function of TDO2 in NAFLD remains unclear. The current study was designed to probe into the effect and mechanism of TDO2 on NAFLD.

Methods. C57BL/6 mice and TDO2-knockout (KO) mice were fed with a high-fat diet for 16 weeks to construct the NAFLD model in vivo; primary hepatocytes isolated from TDO2-KO mice were exposed to palmitate (PA) to establish the NAFLD model in vitro. The expression of TDO2 was determined using Western blot. The function and mechanism of TDO2 were evaluated by enzyme-linked immunosorbent assay, hematoxylin-eosin staining, Oil Red O staining, immunohistochemical assay, and Western blot.

Results. The expression of TDO2 in the liver tissue of NAFLD mice was more than three times that in the control group. Functionally, TDO2 knockout reduced hepatic lipid deposition and liver fibrosis in NAFLD mice in vivo and primary hepatocytes induced by 200 μM PA in vitro. Mechanistically, the loss of TDO2 restrained hepatic lipid deposition and expression levels of fibrosis-related markers in PA-treated primary hepatocytes, and these trends were partially reversed by 10 ng/ml receptor activator of the nuclear factor kappa-B ligand (RANKL, an activator of the NF-κB pathway).

Conclusion. Knocking out TDO2 repressed hepatic lipid deposition and liver fibrosis in mice with NAFLD, and reduced hepatic lipid deposition and expressions of fibrosis-related markers in PA-treated primary hepatocytes by inactivating the NF-κB pathway.',\n", - " 'author': ['Qin, Zhi', 'Zhou, Min'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.heliyon.2023.e22464\"}'],\n", - " 'title': ['TDO2 deficiency attenuates the hepatic lipid deposition and liver fibrosis in mice with diet-induced non-alcoholic fatty liver disease']},\n", - " {'bibcode': '1988PNAS...85.7293S',\n", - " 'abstract': 'Glutathione transferase (GT; EC 2.5.1.18) mRNA levels were measured in human liver samples by using mouse and human cDNA clones that encode class-mu and class-alpha GT. Although all the RNA samples examined contained class-alpha GT mRNA, class-mu GT mRNA was found only in individuals whose peripheral leukocytes expressed GT activity on the substrate trans-stilbene oxide. The mouse class-mu cDNA clone was used to identify a human class-mu GT cDNA clone, lambda GTH411. The amino acid sequence of the GT encoded by lambda GTH411 is identical with the 23 residues determined for the human liver GT-mu isoenzyme and shares 76-81% identity with mouse and rat class-mu GT isoenzymes. The mouse and human class-mu GT cDNA inserts hybridize with multiple BamHI and EcoRI restriction fragments in the human genome. One of these hybridizing fragments is missing in the DNA of individuals who lack GT activity on trans-stilbene oxide. Hybridizations with nonoverlapping subfragments of lambda GTH411 suggest that there are at least three class-mu genes in the human genome. One of these genes appears to be deleted in individuals lacking GT activity on trans-stilbene oxide.',\n", - " 'author': ['Seidegard, Janeric',\n", - " 'Vorachek, William R.',\n", - " 'Pero, Ronald W.',\n", - " 'Pearson, William R.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/85/19/7293\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/85/19/7293\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/85/19/7293\"}'],\n", - " 'title': ['Hereditary differences in the expression of the human glutathione transferase active on trans-stilbene oxide are due to a gene deletion.']},\n", - " {'bibcode': '2001PNAS...98.4611C',\n", - " 'abstract': 'Nrf2, a member of the \"cap `n collar\" group of transcription factors, is important for protecting cells against oxidative damage. We investigated its role in the detoxification of acetaminophen [N-acetyl-p-aminophenol (APAP)]-induced hepatotoxicity. When Nrf2 knockout (Nrf2-/-) and wild-type mice were given APAP by i.p. injection, the Nrf2-/- mice were highly susceptible to APAP treatment. With doses of APAP that were tolerated by wild-type mice, the Nrf2-/- mice died of liver failure. When hepatic glutathione was depleted after a dose of 400 mg/kg of APAP, the wild-type mice were able to compensate and regain the normal glutathione level. In contrast, the glutathione level in the Nrf2-/- mice was not compensated and remained low. This was because of the decrease in the gene expression of gcsH and gcsL as well as gss in the livers of the Nrf2-/- mice. In addition, the expression of ugt1a6 and gstpi that detoxify APAP by conjugation was also decreased. This increased susceptibility of the Nrf2-/- mice to APAP, because of an impaired capacity to replenish their glutathione stores, compounded with a decreased detoxification capability, highlights the importance of Nrf2 in the regulation of glutathione synthesis and cellular detoxification processes.',\n", - " 'author': ['Chan, Kaimin', 'Han, Xiao-Dong', 'Kan, Yuet Wai'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/98/8/4611\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/98/8/4611\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/98/8/4611\"}'],\n", - " 'title': ['An important function of Nrf2 in combating oxidative stress: Detoxification of acetaminophen']},\n", - " {'bibcode': '2019AcSpA.206..529Z',\n", - " 'abstract': 'Hydrogen peroxide (H2O2), a member of small-molecule reactive oxygen species (ROS), plays an important role in physiological and/or pathological process within live systems. Herein, to quantitatively investigate the biological role of H2O2 in subcellular level, we constructed of a novel two-photon (TP) in near-infrared (NIR) out fluorescent probe (TP-NIR-H2O2) for visualization of mitochondria H2O2 in living cells and tissues. Specifically, TP-NIR-H2O2 utilized the oxonium ion as the mitochondrial targeting unit and phenylboric acid as the H2O2 reaction moiety. After the phenylboric acid moiety reaction with H2O2, TP-NIR-H2O2 displayed a ~105-fold fluorescence intensity enhancement in 665 nm. Selectivity experiment demonstrated that the probe can detect H2O2 with high selectivity over other ROS. Moreover, TP-NIR-H2O2 could be employed for imaging H2O2 in mice liver tissues with large tissue-image depth (50-170 μm) under two-photon excitation (800 nm).',\n", - " 'author': ['Zhou, Liyi', 'Ding, Haiyuan', 'Zhao, Wen', 'Hu, Shunqin'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.saa.2018.08.042\"}'],\n", - " 'title': ['A mitochondria targetable two-photon excited near-infrared fluorescent probe for imaging of H2O2 in live cells and tissues']},\n", - " {'bibcode': '1967Sci...157.1327F',\n", - " 'abstract': 'Fetal mouse erythropoiesis proceeds initially in yolk-sac blood islands (8 to 12 days) and, subsequently, in liver (12 to at least 16 days). Yolk-sac cells synthesize three hemoglobins, Hb EI, Hb EII and Hb EIII. Hb EI has x- and y-globin chains; Hb EII has α and y; HB EIII, α and z. No detectable β -globin is formed in these cells. Liver erythroid cells form only adult hemoglobin, composed of α - and β -chains.',\n", - " 'author': ['Fantoni, Antonio', 'Bank, Arthur', 'Marks, Paul A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.jstor.org/stable/1722181?origin=ads\"}'],\n", - " 'title': ['Globin Composition and Synthesis of Hemoglobins in Developing Fetal Mice Erythroid Cells']},\n", - " {'bibcode': '1958Natur.182.1088B',\n", - " 'abstract': 'INVESTIGATION of rat and mouse liver prepared by solvent substitution1,2 with 1 per cent mercuric chloride in absolute methanol has shown that a considerable portion of the cytoplasmic ribonucleic acid compounds combine with mercury. The nucleic acid compounds of the nucleus do not appear to combine with mercury under the experimental conditions used, that is, cooling to -190° C. and exposing to solvent at -65° C. for 48 hr. and then warming to room temperature. It is considered likely, though not conclusively proved, that the mercury has access to the nuclei during the solvent substitution.',\n", - " 'author': ['Bell, L. G. E.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F1821088a0\"}'],\n", - " 'title': ['Sulphydryl Groups and Ribonucleic Acid']},\n", - " {'bibcode': '2007PNAS..104.1570S',\n", - " 'abstract': 'In contrast to the deregulated hepatocellular division that is a feature of many hepatic diseases and malignancies, physiologic liver growth during embryonic development and after partial hepatectomy (PH) in adults is characterized by tightly controlled cell proliferation. We used forward genetic screening in zebrafish to test the hypothesis that a similar genetic program governs physiologic liver growth during hepatogenesis and regeneration after PH. We identified the uhrf1 gene, a cell cycle regulator and transcriptional activator of top2a expression, as required for hepatic outgrowth and embryonic survival. By developing a methodology to perform PH on adult zebrafish, we found that liver regeneration inuhrf1+/- adult animals is impaired.uhrf1 transcript levels dramatically increase after PH in both mice, and zebrafish and top2a is not up-regulated in uhrf1+/- livers after PH. This indicates that uhrf1 is required for physiologic liver growth in both embryos and adults and illustrates that zebrafish livers regenerate.',\n", - " 'author': ['Sadler, Kirsten C.',\n", - " 'Krahn, Katherine N.',\n", - " 'Gaur, Naseem A.',\n", - " 'Ukomadu, Chinweike'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/104/5/1570\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0610774104\"}'],\n", - " 'title': ['Liver growth in the embryo and during liver regeneration in zebrafish requires the cell cycle regulator, uhrf1']},\n", - " {'bibcode': '1995Natur.373..699S',\n", - " 'abstract': 'POLYPEPTIDE growth factors are important effectors of cell growth and differentiation in vitro and are thought to be critical for processes such as specification of cell fate, tissue growth and organogenesis in vivo. Scatter factor1-3/hepatocyte growth factor4,5 (SF/HGF) is the prototype of an emerging family of growth factors that resemble in their domain structure and mechanism of activation the blood proteinase plasminogen6,7. The cellular responses of SF/HGF are mediated by the c-Met tyrosine kinase receptor8-10. Here we report that mice lacking SF/HGF fail to complete development and die in utero. The mutation affects the embryonic liver, which is reduced in size and shows extensive loss of parenchymal cells. In addition, development of the placenta, particularly of trophoblast cells, is impaired. Thus, SF/HGF is essential for the development of several epithelial organs.',\n", - " 'author': ['Schmidt, Claudia',\n", - " 'Bladt, Friedhelm',\n", - " 'Goedecke, Stefanie',\n", - " 'Brinkmann, Volker',\n", - " 'Zschiesche, Wolfgang',\n", - " 'Sharpe, Melanie',\n", - " 'Gherardi, Ermanno',\n", - " 'Birchmeler, Carmen'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F373699a0\"}'],\n", - " 'title': ['Scatter factor/hepatocyte growth factor is essential for liver development']},\n", - " {'bibcode': '1986Sci...232..881F',\n", - " 'abstract': \"A specific DNA probe was used to study the effect of recombinant rat, mouse, and human γ -interferon (γ IFN) on the course of sporozoite-induced malaria infections. In mice and rats infected with sporozoites of Plasmodium berghei, mouse and rat γ -IFN's strongly inhibited the development of the exoerythrocytic forms in the liver cells of the hosts, but not the development of the erythrocytic stages. The degree of inhibition of the exoerythrocytic forms was proportional to the dose of γ -IFN administered, but was independent of the number of sporozoites used for challenge. A 30 percent reduction in the development of exoerythrocytic forms in rat liver was achieved when 150 units (about 15 nanograms of protein) of rat γ -IFN were injected a few hours before sporozoite challenge; the reduction was 90 percent or more with higher doses of γ -IFN. The effect was less pronounced if the γ -IFN was administered 18 hours before or a few hours after challenge. Human γ -IFN also diminished the parasitemia in chimpanzees infected with sporozoites of the human malaria parasite Plasmodium vivax. The target of γ -IFN activity may be the infected hepatocytes themselves, as shown by in vitro experiments in which small doses of the human lymphokine inhibited the development of exoerythrocytic forms of Plasmodium berghei in a human hepatoma cell line. These results suggest that immunologically induced interferon may be involved in controlling malaria infection under natural conditions.\",\n", - " 'author': ['Ferreira, Arturo',\n", - " 'Schofield, Louis',\n", - " 'Enea, Vincenzo',\n", - " 'Schellekens, Huub',\n", - " 'van der Meide, Peter',\n", - " 'Collins, William E.',\n", - " 'Nussenzweig, Ruth S.',\n", - " 'Nussenzweig, Victor'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.3085218\"}'],\n", - " 'title': ['Inhibition of Development of Exoerythrocytic Forms of Malaria Parasites by γ -Interferon']},\n", - " {'bibcode': '2018NatSR...8.1310R',\n", - " 'abstract': 'This study deals with the isolation and purification of an important variant of microcystins namely microcystin-RR (MCYST-RR) from Microcystis aeruginosa and reports its effects on mice liver protein profile and cellular functions. Protein profiling by 2-dimensional gel electrophoresis revealed changes in the number and accumulation of protein spots in liver of mice treated with different concentrations of MCYST-RR. Untreated (control) mice liver showed 368 protein spots while the number was 355, 348 and 332 in liver of mice treated with 200, 300 and 400 µg kg body wt-1 of MCYST-RR respectively. Altogether 102, 97, and 92 spots were differentially up-accumulated and 93, 91, and 87 spots were down- accumulated respectively with the treatment of 200, 300, 400 µg kg body wt-1. Eighteen differentially accumulated proteins present in all the four conditions were identified by MALDI-TOF MS. Of these eighteen proteins, 12 appeared to be involved in apoptosis/toxicological manifestations. Pathway analysis by Reactome and PANTHER database also mapped the identified proteins to programmed cell death/apoptosis clade. That MCYST-RR induces apoptosis in liver tissues was also confirmed by DNA fragmentation assay. Results of this study elucidate the proteomic basis for the hepatotoxicity of MCYST-RR which is otherwise poorly understood till date.',\n", - " 'author': ['Rai, Ashutosh Kumar', 'Chaturvedi, Rupesh', 'Kumar, Ashok'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-018-19299-w\"}'],\n", - " 'title': ['Proteomic evidences for microcystin-RR-induced toxicological alterations in mice liver']},\n", - " {'bibcode': '2021ScTEn.784n7221W',\n", - " 'author': ['Wang, Hua-Jie',\n", - " 'Yang, Gang-Gang',\n", - " 'Wu, Sha-Sha',\n", - " 'Meng, Zhi-Fen',\n", - " 'Zhang, Jia-Min',\n", - " 'Cao, Ying',\n", - " 'Zhang, Yu-Ping'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.scitotenv.2021.147221\"}'],\n", - " 'title': ['Toxicity of CuS/CdS semiconductor nanocomposites to liver cells and mice liver']},\n", - " {'bibcode': '2010EnTox..25...77W',\n", - " 'abstract': 'Although it has been reported that hexavalent chromium (Cr(VI)) could induce apoptosis in a variety of cell types, the molecular mechanisms underlying this process is still largely unknown. This study was undertaken to determine effects of single oral 0, 25, 50, and 100 mg/kg body weight doses of potassium dichromate on the expression level of p53, Bcl‑2, Bax, cytochrome c, and caspase‑3, which are vital regulators of apoptosis, in mice liver. The results showed that Cr(VI) could upregulate the protein expression of p53, Bax, cytochrome c, and caspase‑3 and downregulate the expression of Bcl‑2 in mice liver. All these results suggested that p53, Bcl‑2, Bax, cytochrome c, and caspase‑3 may be involved in the regulation of Cr(VI) induced apoptosis in vivo.',\n", - " 'author': ['Wang, Xiao-Feng',\n", - " 'Lou, Xiao-Ming',\n", - " 'Shen, Ying',\n", - " 'Xing, Ming-Luan',\n", - " 'Xu, Li-Hong'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Ftox.20478\"}'],\n", - " 'title': ['Apoptotic‑related protein changes induced by hexavalent chromium in mice liver']},\n", - " {'bibcode': '2002PNAS...9913878W',\n", - " 'abstract': 'Liver X receptors (LXRα and -β) are nuclear receptors abundant in the liver where they are regulators of lipid homeostasis. Both LXRs are also expressed in the brain, but their roles in this tissue remain to be clarified. We examined the brains of mice in which the genes of both LXRα and -β have been disrupted and found several severe abnormalities. One of the most striking features is that the lateral ventricles are closed and lined with lipid-laden cells. In addition, there are enlarged brain blood vessels, especially in the pars reticularis of the substantia nigra and in the globus pallidus. Other features of the brains are excessive lipid deposits, proliferation of astrocytes, loss of neurons, and disorganized myelin sheaths. Electron micrographs revealed that, as mice aged, lipid vacuoles accumulated in astrocytes surrounding blood vessels. Comparison of mRNA profiles in LXR knockout mice and wild-type littermates showed that expression of several LXR target genes involved in cholesterol efflux from astrocytes was reduced. These findings show that LXRs have an important function in lipid homeostasis in the brain, and that loss of these receptors results in neurodegenerative diseases. Further characterization of the role of LXRs in the brain could lead to new insights into the etiology and treatment of some neurodegenerative disorders.',\n", - " 'author': ['Wang, Ling',\n", - " 'Schuster, Gertrud U.',\n", - " 'Hultenby, Kjell',\n", - " 'Zhang, Qinghong',\n", - " 'Andersson, Sandra',\n", - " 'Gustafsson, Jan-Åke'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/99/21/13878\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/99/21/13878\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/99/21/13878\"}'],\n", - " 'title': ['Liver X receptors in the central nervous system: From lipid homeostasis to neuronal degeneration']},\n", - " {'bibcode': '2023Heliy...920591M',\n", - " 'abstract': 'Objective. Autoimmune hepatitis (AIH) is a chronic immune-mediated inflammatory liver disease. Intestinal flora disturbance in AIH is closely related to TFH/TFR cell imbalances. As a new method of microbial therapy, the role of fecal microbiota transplantation (FMT) in AIH remains elusive. Here, we attempted to verify the functional role and molecular mechanism of FMT in AIH.

Methods. An experimental autoimmune hepatitis (EAH) mouse model was established to mimic the characteristics of AIH. H&E staining was used to detect histological features in mouse liver tissues. Serological tests were employed to identify several liver function biomarkers. Flow cytometry was utilized to examine the status of TFH/TFR cell subsets. Western blotting was used to evaluate TLR pathway-associated protein abundance. RT−qPCR was applied to evaluate Treg cell markers and inflammation marker levels in mouse liver tissues.

Results. There was significant liver inflammation and dysregulated TFR/TFH cells with elevated levels of liver inflammation-associated biomarkers in EAH mice. Interestingly, transferring therapeutic FMT into EAH mice dramatically reduced liver injury and improved the imbalance between splenic TFR and TFH cells. FMT treatment also reduced elevated contents of serum alanine transaminase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) in EAH mice. Furthermore, therapeutic FMT reversed the increased levels of IL-21 while promoting IL-10 and TGF-β cytokines. Mechanistically, FMT regulated TFH cell response in EAH mice in a TLR4/11/MyD88 pathway-dependent manner.

Conclusion. Our findings demonstrated that liver injury and dysregulation between TFR and TFH cells in EAH might be reversed by therapeutic FMT via the TLR4/11-MyD88 signaling pathway.',\n", - " 'author': ['Ma, Liang',\n", - " 'Song, Jianguo',\n", - " 'Chen, Xueping',\n", - " 'Dai, Duan',\n", - " 'Chen, Jianping',\n", - " 'Zhang, Liwen'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.heliyon.2023.e20591\"}'],\n", - " 'title': ['Fecal microbiota transplantation regulates TFH/TFR cell imbalance via TLR/MyD88 pathway in experimental autoimmune hepatitis']},\n", - " {'bibcode': '2016EnTox..31.1009F',\n", - " 'author': ['Faustino-Rocha, Ana I.',\n", - " 'Rodrigues, D.',\n", - " 'da Costa, R. Gil',\n", - " 'Diniz, C.',\n", - " 'Aragão, S.',\n", - " 'Talhada, D.',\n", - " 'Botelho, M.',\n", - " 'Colaço, A.',\n", - " 'Pires, M. J.',\n", - " 'Peixoto, F.',\n", - " 'Oliveira, P. A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Ftox.22110\"}'],\n", - " 'title': ['Trihalomethanes in liver pathology: Mitochondrial dysfunction and oxidative stress in the mouse']},\n", - " {'bibcode': '2020GeneE..42....7S',\n", - " 'abstract': 'Backgound A variety of in vivo and in vitro studies to assess the genotoxicity of titanium dioxide nanoparticles (TiO2 NPs) have been reported, but the results are inconsistent. Recently, we reported that TiO2 NPs exhibit no genotoxic effects in the liver and erythrocytes during a relatively brief period following intravenous injection into mice. However, there is no information about long-term genotoxicity due to TiO2 NP accumulation in tissues. In this study, we investigated the long-term mutagenic effects of TiO2 NPs and the localization of residual TiO2 NPs in mouse liver after multiple intravenous injections. Results Male gpt delta C57BL/6 J mice were administered with various doses of TiO2 NPs weekly for 4 consecutive weeks. The long-term mutagenic effects on the liver were analyzed using gpt and Spi− mutation assays 90 days after the final injection. We also quantified the amount of titanium in the liver using inductively coupled plasma mass spectrometry and observed the localization of TiO2 NPs in the liver using transmission electron microscopy. Although TiO2 NPs were found in the liver cells, the gpt and Spi− mutation frequencies in the liver were not significantly increased by the TiO2 NP administration. Conclusions These results clearly show that TiO2 NPs have no mutagenic effects on the liver, even though the particles remain in the liver long-term.',\n", - " 'author': ['Suzuki, Tetsuya',\n", - " 'Miura, Nobuhiko',\n", - " 'Hojo, Rieko',\n", - " 'Yanagiba, Yukie',\n", - " 'Suda, Megumi',\n", - " 'Hasegawa, Tatsuya',\n", - " 'Miyagawa, Muneyuki',\n", - " 'Wang, Rui-Sheng'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1186%2Fs41021-020-0146-3\"}'],\n", - " 'title': ['Genotoxicity assessment of titanium dioxide nanoparticle accumulation of 90 days in the liver of gpt delta transgenic mice']},\n", - " {'bibcode': '2020NatSR..10.7596B',\n", - " 'abstract': 'Enzymatic and non-enzymatic posttranslational protein modifications by oxidation, glycation and acylation are key regulatory mechanisms in hallmarks of aging like inflammation, altered epigenetics and decline in proteostasis. In this study a mouse cohort was used to monitor changes of posttranslational modifications in the aging process. A protocol for the extraction of histones, cytosolic and mitochondrial proteins from mouse liver was developed and validated. In total, 6 lysine acylation structures, 7 advanced glycation endproducts, 6 oxidative stress markers, and citrullination were quantitated in proteins of subcellular compartments using HPLC-MS/MS. Methionine sulfoxide, acetylation, formylation, and citrullination were the most abundant modifications. Histone proteins were extraordinary high modified and non-enzymatic modifications accumulated in all subcellular compartments during the aging process. Compared to acetylation of histone proteins which gave between 350 and 305 µmol/mol leucine equivalents in young and old animals, modifications like acylation, glycation, and citrullination raised to 43%, 20%, and 18% of acetylation, respectively. On the other hand there was an age related increase of selected oxidative stress markers by up to 150%. The data and patterns measured in this study are mandatory for further studies and will strongly facilitate understanding of the molecular mechanisms in aging.',\n", - " 'author': ['Baldensperger, Tim',\n", - " 'Eggen, Michael',\n", - " 'Kappen, Jonas',\n", - " 'Winterhalter, Patrick R.',\n", - " 'Pfirrmann, Thorsten',\n", - " 'Glomb, Marcus A.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-020-64265-0\"}'],\n", - " 'title': ['Comprehensive analysis of posttranslational protein modifications in aging of subcellular compartments']},\n", - " {'bibcode': '2014BioMa...9b5002Y',\n", - " 'abstract': 'Many types of hemostatic agents have been studied for the effective control of bleeding. In this study, a powdery medical adhesive composed of aldehyded dextran and ɛ-poly (L-lysine) was used with the recombinant batroxobin. Batroxobin is a venomous component from the snake Bothrops atrox moojeni and catalyzes fibrinogen conversion to form soluble fibrin clots. This research aims to examine the performance of the batroxobin-containing adhesive for hemostasis, and evaluate its potential as a novel hemostatic adhesive. The fibrinogen conversion ability of batroxobin was evaluated by a fibrinogen clotting assay and a whole blood clotting assay. Both experiments demonstrated the effectiveness of the batroxobin-containing adhesive for blood clot formation. Animal experiments were also conducted. After a pricking wound was made in an ICR (imprinting control region) mouse liver, the adhesive and various concentrations of batroxobin were applied. The total amount of blood loss was reduced with increasing concentrations of batroxobin. For excessive bleeding conditions, the femoral artery wound model of SD (Sprague-Dawley) rats was adopted. With higher concentrations of batroxobin, hemostasis was more rapidly achieved. Histological analysis of the liver model also supports the hemostatic effects through fibrin clot formation. In conclusion, batroxobin and medical adhesive effectively facilitate blood coagulation, and could be developed for clinical use.',\n", - " 'author': ['You, Kyung Eun',\n", - " 'Koo, Min-Ah',\n", - " 'Lee, Dae-Hyung',\n", - " 'Kwon, Byeong-Ju',\n", - " 'Lee, Mi Hee',\n", - " 'Hyon, Suong-Hyu',\n", - " 'Seomun, Young',\n", - " 'Kim, Jong-Tak',\n", - " 'Park, Jong-Chul'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1088%2F1748-6041%2F9%2F2%2F025002\"}'],\n", - " 'title': ['The effective control of a bleeding injury using a medical adhesive containing batroxobin']},\n", - " {'bibcode': '2016NatSR...635633A',\n", - " 'abstract': 'Vildagliptin is a potent, orally active inhibitor of dipeptidyl peptidase-4 (DPP-4) for the treatment of type 2 diabetes mellitus. It has been reported that vildagliptin can cause hepatic dysfunction in patients. However, the molecular-mechanism of vildagliptin-induced liver dysfunction has not been elucidated. In this study, we employed an expression microarray to determine hepatic genes that were highly regulated by vildagliptin in mice. We found that pro-inflammatory S100 calcium-binding protein (S100) a8 and S100a9 were induced more than 5-fold by vildagliptin in the mouse liver. We further examined the effects of vildagliptin and its major metabolite M20.7 on the mRNA expression levels of S100A8 and S100A9 in human hepatoma HepG2 and leukemia HL-60 cells. In HepG2 cells, vildagliptin, M20.7, and sitagliptin - another DPP-4 inhibitor - induced S100A9 mRNA. In HL-60 cells, in contrast, S100A8 and S100A9 mRNAs were significantly induced by vildagliptin and M20.7, but not by sitagliptin. The release of S100A8/A9 complex in the cell culturing medium was observed in the HL-60 cells treated with vildagliptin and M20.7. Therefore, the parental vildagliptin- and M20.7-induced release of S100A8/A9 complex from immune cells, such as neutrophils, might be a contributing factor of vildagliptin-associated liver dysfunction in humans.',\n", - " 'author': ['Asakura, Mitsutoshi',\n", - " 'Karaki, Fumika',\n", - " 'Fujii, Hideaki',\n", - " 'Atsuda, Koichiro',\n", - " 'Itoh, Tomoo',\n", - " 'Fujiwara, Ryoichi'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep35633\"}'],\n", - " 'title': ['Vildagliptin and its metabolite M20.7 induce the expression of S100A8 and S100A9 in human hepatoma HepG2 and leukemia HL-60 cells']},\n", - " {'bibcode': '2010Natur.464..121H',\n", - " 'abstract': 'Sirtuins are NAD+-dependent protein deacetylases. They mediate adaptive responses to a variety of stresses, including calorie restriction and metabolic stress. Sirtuin 3 (SIRT3) is localized in the mitochondrial matrix, where it regulates the acetylation levels of metabolic enzymes, including acetyl coenzyme A synthetase 2 (refs 1, 2). Mice lacking both Sirt3 alleles appear phenotypically normal under basal conditions, but show marked hyperacetylation of several mitochondrial proteins. Here we report that SIRT3 expression is upregulated during fasting in liver and brown adipose tissues. During fasting, livers from mice lacking SIRT3 had higher levels of fatty-acid oxidation intermediate products and triglycerides, associated with decreased levels of fatty-acid oxidation, compared to livers from wild-type mice. Mass spectrometry of mitochondrial proteins shows that long-chain acyl coenzyme A dehydrogenase (LCAD) is hyperacetylated at lysine 42 in the absence of SIRT3. LCAD is deacetylated in wild-type mice under fasted conditions and by SIRT3 in vitro and in vivo; and hyperacetylation of LCAD reduces its enzymatic activity. Mice lacking SIRT3 exhibit hallmarks of fatty-acid oxidation disorders during fasting, including reduced ATP levels and intolerance to cold exposure. These findings identify acetylation as a novel regulatory mechanism for mitochondrial fatty-acid oxidation and demonstrate that SIRT3 modulates mitochondrial intermediary metabolism and fatty-acid use during fasting.',\n", - " 'author': ['Hirschey, Matthew D.',\n", - " 'Shimazu, Tadahiro',\n", - " 'Goetzman, Eric',\n", - " 'Jing, Enxuan',\n", - " 'Schwer, Bjoern',\n", - " 'Lombard, David B.',\n", - " 'Grueter, Carrie A.',\n", - " 'Harris, Charles',\n", - " 'Biddinger, Sudha',\n", - " 'Ilkayeva, Olga R.',\n", - " 'Stevens, Robert D.',\n", - " 'Li, Yu',\n", - " 'Saha, Asish K.',\n", - " 'Ruderman, Neil B.',\n", - " 'Bain, James R.',\n", - " 'Newgard, Christopher B.',\n", - " 'Farese, Robert V., Jr.',\n", - " 'Alt, Frederick W.',\n", - " 'Kahn, C. Ronald',\n", - " 'Verdin, Eric'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature08778\"}'],\n", - " 'title': ['SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation']},\n", - " {'bibcode': '2013NatCo...4.2434L',\n", - " 'abstract': 'Carbohydrates with high glycaemic index are proposed to promote the development of obesity, insulin resistance and fatty liver, but the mechanism by which this occurs remains unknown. High serum glucose concentrations are known to induce the polyol pathway and increase fructose generation in the liver. Here we show that this hepatic, endogenously produced fructose causes systemic metabolic changes. We demonstrate that mice unable to metabolize fructose are protected from an increase in energy intake and body weight, visceral obesity, fatty liver, elevated insulin levels and hyperleptinaemia after exposure to 10% glucose for 14 weeks. In normal mice, glucose consumption is accompanied by aldose reductase and polyol pathway activation in steatotic areas. In this regard, we show that aldose reductase-deficient mice are protected against glucose-induced fatty liver. We conclude that endogenous fructose generation and metabolism in the liver represents an important mechanism by which glucose promotes the development of metabolic syndrome.',\n", - " 'author': ['Lanaspa, Miguel A.',\n", - " 'Ishimoto, Takuji',\n", - " 'Li, Nanxing',\n", - " 'Cicerchi, Christina',\n", - " 'Orlicky, David J.',\n", - " 'Ruzicky, Philip',\n", - " 'Rivard, Christopher',\n", - " 'Inaba, Shinichiro',\n", - " 'Roncal-Jimenez, Carlos A.',\n", - " 'Bales, Elise S.',\n", - " 'Diggle, Christine P.',\n", - " 'Asipu, Aruna',\n", - " 'Petrash, J. Mark',\n", - " 'Kosugi, Tomoki',\n", - " 'Maruyama, Shoichi',\n", - " 'Sanchez-Lozada, Laura G.',\n", - " 'McManaman, James L.',\n", - " 'Bonthron, David T.',\n", - " 'Sautin, Yuri Y.',\n", - " 'Johnson, Richard J.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fncomms3434\"}'],\n", - " 'title': ['Endogenous fructose production and metabolism in the liver contributes to the development of metabolic syndrome']},\n", - " {'bibcode': '2016Sci...352..459M',\n", - " 'abstract': 'Tissue-resident memory T (Trm) cells permanently localize to portals of pathogen entry, where they provide immediate protection against reinfection. To enforce tissue retention, Trm cells up-regulate CD69 and down-regulate molecules associated with tissue egress; however, a Trm-specific transcriptional regulator has not been identified. Here, we show that the transcription factor Hobit is specifically up-regulated in Trm cells and, together with related Blimp1, mediates the development of Trm cells in skin, gut, liver, and kidney in mice. The Hobit-Blimp1 transcriptional module is also required for other populations of tissue-resident lymphocytes, including natural killer T (NKT) cells and liver-resident NK cells, all of which share a common transcriptional program. Our results identify Hobit and Blimp1 as central regulators of this universal program that instructs tissue retention in diverse tissue-resident lymphocyte populations.',\n", - " 'author': ['Mackay, Laura K.',\n", - " 'Minnich, Martina',\n", - " 'Kragten, Natasja A. M.',\n", - " 'Liao, Yang',\n", - " 'Nota, Benjamin',\n", - " 'Seillet, Cyril',\n", - " 'Zaid, Ali',\n", - " 'Man, Kevin',\n", - " 'Preston, Simon',\n", - " 'Freestone, David',\n", - " 'Braun, Asolina',\n", - " 'Wynne-Jones, Erica',\n", - " 'Behr, Felix M.',\n", - " 'Stark, Regina',\n", - " 'Pellicci, Daniel G.',\n", - " 'Godfrey, Dale I.',\n", - " 'Belz, Gabrielle T.',\n", - " 'Pellegrini, Marc',\n", - " 'Gebhardt, Thomas',\n", - " 'Busslinger, Meinrad',\n", - " 'Shi, Wei',\n", - " 'Carbone, Francis R.',\n", - " 'van Lier, René A. W.',\n", - " 'Kallies, Axel',\n", - " 'van Gisbergen, Klaas P. J. M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.aad2035\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.aad2035\"}'],\n", - " 'title': ['Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes']},\n", - " {'bibcode': '1998PNAS...95.9448M',\n", - " 'abstract': 'The chemokine stromal cell-derived factor 1, SDF-1, is an important regulator of leukocyte and hematopoietic precursor migration and pre-B cell proliferation. The receptor for SDF-1, CXCR4, also functions as a coreceptor for T-tropic HIV-1 entry. We find that mice deficient for CXCR4 die perinatally and display profound defects in the hematopoietic and nervous systems. CXCR4-deficient mice have severely reduced B-lymphopoiesis, reduced myelopoiesis in fetal liver, and a virtual absence of myelopoiesis in bone marrow. However, T-lymphopoiesis is unaffected. Furthermore, the cerebellum develops abnormally with an irregular external granule cell layer, ectopically located Purkinje cells, and numerous chromophilic cell clumps of abnormally migrated granule cells within the cerebellar anlage. Identical defects are observed in mice lacking SDF-1, suggesting a monogamous relationship between CXCR4 and SDF-1. This receptor-ligand selectivity is unusual among chemokines and their receptors, as is the function in migration of nonhematopoietic cells.',\n", - " 'author': ['Ma, Qing',\n", - " 'Jones, Dan',\n", - " 'Borghesani, Paul R.',\n", - " 'Segal, Rosalind A.',\n", - " 'Nagasawa, Takashi',\n", - " 'Kishimoto, Tadamitsu',\n", - " 'Bronson, Roderick T.',\n", - " 'Springer, Timothy A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/95/16/9448\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/95/16/9448\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/95/16/9448\"}'],\n", - " 'title': ['Impaired B-Lymphopoiesis, Myelopoiesis, and Derailed Cerebellar Neuron Migration in CXCR4- and SDF-1-Deficient Mice']},\n", - " {'bibcode': '2006PNAS..103.4598T',\n", - " 'abstract': 'Implantation of small liver grafts causes liver injury and defective regeneration leading to graft failure. We investigated whether Kupffer cell-dependent TNF-α signaling contributes to this poor outcome. Partial 30% liver transplantation was performed in C57BL/6 wild-type mice (control group), and in three groups with down-regulation of the TNF-α pathway: (i) TNF receptor 1 knockout [TNFR-1(-/-)] mice, and mice pretreated with (ii) gadolinium chloride or (iii) pentoxifylline (PTX). Fifty-percent partial liver transplantation, a model associated with full recovery, and transplantation in IL-6 knockout [IL-6(-/-)] mice were performed in some experiments. Graft injury, regeneration, portal flow, liver microcirculation, leukocyte adhesion, and animal survival were assessed. Animal survival rates were 14% in the control group vs. 43% in the gadolinium chloride group, 57% for the TNFR-1(-/-) group, and 86% in the PTX group (P < 0.001). Markers of liver injury were reduced in all treated groups when compared with controls. Each treated group disclosed better portal flow and sinusoid perfusion, decreased leukocyte adherence, particularly in the PTX group. Liver regeneration occurred only in the treated groups. IL-6 and IL-10 levels were dramatically up-regulated (50×) in the PTX group, and at lower levels in other experimental groups. The protective effect of PTX was lost in IL-6(-/-) mice and protection was restored by a single dose of r-IL-6. In conclusion, interruption of TNF-α signaling or depletion of Kupffer cells improves survival after 30% liver transplantation, reduces liver injury, and enhances regeneration. The superior effects of PTX are mediated by IL-6.',\n", - " 'author': ['Tian, Yinghua',\n", - " 'Jochum, Wolfram',\n", - " 'Georgiev, Panco',\n", - " 'Moritz, Wolfgang',\n", - " 'Graf, Rolf',\n", - " 'Clavien, Pierre-Alain'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/103/12/4598\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/103/12/4598\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/full/103/12/4598\"}'],\n", - " 'title': ['Kupffer cell-dependent TNF-α signaling mediates injury in the arterialized small-for-size liver transplantation in the mouse']},\n", - " {'bibcode': '2005Natur.436..356Y',\n", - " 'abstract': \"In obesity and type 2 diabetes, expression of the GLUT4 glucose transporter is decreased selectively in adipocytes. Adipose-specific Glut4 (also known as Slc2a4) knockout (adipose-Glut4-/-) mice show insulin resistance secondarily in muscle and liver. Here we show, using DNA arrays, that expression of retinol binding protein-4 (RBP4) is elevated in adipose tissue of adipose-Glut4-/- mice. We show that serum RBP4 levels are elevated in insulin-resistant mice and humans with obesity and type 2 diabetes. RBP4 levels are normalized by rosiglitazone, an insulin-sensitizing drug. Transgenic overexpression of human RBP4 or injection of recombinant RBP4 in normal mice causes insulin resistance. Conversely, genetic deletion of Rbp4 enhances insulin sensitivity. Fenretinide, a synthetic retinoid that increases urinary excretion of RBP4, normalizes serum RBP4 levels and improves insulin resistance and glucose intolerance in mice with obesity induced by a high-fat diet. Increasing serum RBP4 induces hepatic expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) and impairs insulin signalling in muscle. Thus, RBP4 is an adipocyte-derived `signal' that may contribute to the pathogenesis of type 2 diabetes. Lowering RBP4 could be a new strategy for treating type 2 diabetes.\",\n", - " 'author': ['Yang, Qin',\n", - " 'Graham, Timothy E.',\n", - " 'Mody, Nimesh',\n", - " 'Preitner, Frederic',\n", - " 'Peroni, Odile D.',\n", - " 'Zabolotny, Janice M.',\n", - " 'Kotani, Ko',\n", - " 'Quadro, Loredana',\n", - " 'Kahn, Barbara B.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature03711\"}'],\n", - " 'title': ['Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes']},\n", - " {'bibcode': '2019ApNan..10..879A',\n", - " 'abstract': 'Oxidative stress has significant contribution in on-set and progression of diabetes. The disease onset leads to elevated levels of free radicals rendering the oxidant-inducing mechanisms incapable of protecting cellular organelles from inflicted damage. Herein, β-galactosidase-mediated bio-enzymatic synthesis of zinc oxide nanoparticles (ZnO NPs) was pioneered and characterized. These obtained ZnO NPs were assessed for their antidiabetic activity against streptozotocin (STZ)-induced diabetic mice. For this objective, 36 male albino mice were separated into 6 groups. The diabetes was induced in mice with STZ (120 mg kg-1 body weight), and further treated with three different doses of ZnO NPs (0.5 mg kg-1, 1 mg kg-1, and 2 mg kg-1) for 28 days. The results unveiled protective effects in diabetic mice treated with ZnO NPs through restoration of changes in body weight and normal glucose levels. The effects of ZnO NPs on lipid peroxidation and carbonyl contents were protective in liver, kidney and pancreas of diseased groups. Levels of serum biomarkers such as cholesterol, triglycerides and HDL-C indicated ZnO NPs treatment caused these levels to plummet towards control parameters. Normal liver function markers and urea levels in serum indicated successful treatment of diabetic mice with ZnO NPs. Histopathological studies revealed protective and non-toxic effects of ZnO NPs over vital tissues of kidney, liver, and pancreas. The results divulge efficacious pharmaceutical potential of ZnO NPs against formation of reactive oxygen species by scavenging free radicals enhancing the functioning of antioxidant fortifying enzymes generating sustenance over hyperglycemic conditions.',\n", - " 'author': ['Ahmed, Faizan',\n", - " 'Husain, Qayyum',\n", - " 'Ansari, Mohd Owais',\n", - " 'Shadab, G. G. H. A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://dx.doi.org/10.1007/s13204-019-01169-0\"}'],\n", - " 'title': ['Antidiabetic and oxidative stress assessment of bio-enzymatically synthesized zinc oxide nanoformulation on streptozotocin-induced hyperglycemic mice']},\n", - " {'bibcode': '2011PNAS..10817444H',\n", - " 'abstract': 'Macrophage migration inhibitory factor (MIF) is a pleiotropic inflammatory cytokine that has been implicated in various inflammatory diseases. Chronic inflammation is a mainstay of liver fibrosis, a leading cause of morbidity worldwide, but the role of MIF in liver scarring has not yet been elucidated. Here we have uncovered an unexpected antifibrotic role for MIF. Mice genetically deleted in Mif (Mif-/-) showed strongly increased fibrosis in two models of chronic liver injury. Pronounced liver fibrosis in Mif-/- mice was associated with alterations in fibrosis-relevant genes, but not by a changed intrahepatic immune cell infiltration. Next, a direct impact of MIF on hepatic stellate cells (HSC) was assessed in vitro. Although MIF alone had only marginal effects on HSCs, it markedly inhibited PDGF-induced migration and proliferation of these cells. The inhibitory effects of MIF were mediated by CD74, which we detected as the most abundant known MIF receptor on HSCs. MIF promoted the phosphorylation of AMP-activated protein kinase (AMPK) in a CD74-dependent manner and, in turn, inhibition of AMPK reversed the inhibition of PDGF-induced HSC activation by MIF. The pivotal role of CD74 in MIF-mediated antifibrotic properties was further supported by augmented liver scarring of Cd74-/- mice. Moreover, mice treated with recombinant MIF displayed a reduced fibrogenic response in vivo. In conclusion, we describe a previously unexplored antifibrotic function of MIF that is mediated by the CD74/AMPK signaling pathway in HSCs. The results imply MIF and CD74 as targets for treatment of liver diseases.',\n", - " 'author': ['Heinrichs, Daniel',\n", - " 'Knauel, Meike',\n", - " 'Offermanns, Christian',\n", - " 'Berres, Marie-Luise',\n", - " 'Nellen, Andreas',\n", - " 'Leng, Lin',\n", - " 'Schmitz, Petra',\n", - " 'Bucala, Richard',\n", - " 'Trautwein, Christian',\n", - " 'Weber, Christian',\n", - " 'Bernhagen, Jürgen',\n", - " 'Wasmuth, Hermann E.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/108/42/17444\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1107023108\"}'],\n", - " 'title': ['Macrophage migration inhibitory factor (MIF) exerts antifibrotic effects in experimental liver fibrosis via CD74']},\n", - " {'bibcode': '2003Natur.422..901V',\n", - " 'abstract': 'Results from several experimental systems suggest that cells from one tissue type can form other tissue types after transplantation. This could be due to the presence of multipotential or several types of adult stem cells in donor tissues, or alternatively, to fusion of donor and recipient cells. In a model of tyrosinaemia type I, mice with mutations in the fumarylacetoacetate hydrolase gene (Fah-/-) regain normal liver function after transplantation of Fah+/+ bone marrow cells, and form regenerating liver nodules with normal histology that express Fah. Here we show that these hepatic nodules contain more mutant than wild-type Fah alleles, and that their hepatocytes express both donor and host genes, consistent with polyploid genome formation by fusion of host and donor cells. Using bone marrow cells marked with integrated foamy virus vectors that express green fluorescent protein, we identify common proviral junctions in hepatic nodules and haematopoietic cells. We also show that the haematopoietic donor genome adopts a more hepatocyte-specific expression profile after cell fusion, as the wild-type Fah gene was activated and the pan-haematopoietic CD45 marker was no longer expressed.',\n", - " 'author': ['Vassilopoulos, George', 'Wang, Pei-Rong', 'Russell, David W.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature01539\"}'],\n", - " 'title': ['Transplanted bone marrow regenerates liver by cell fusion']},\n", - " {'bibcode': '2006Sci...312.1656U',\n", - " 'abstract': 'Coordinated control of energy metabolism and glucose homeostasis requires communication between organs and tissues. We identified a neuronal pathway that participates in the cross talk between the liver and adipose tissue. By studying a mouse model, we showed that adenovirus-mediated expression of peroxisome proliferator-activated receptor (PPAR)-γ2 in the liver induces acute hepatic steatosis while markedly decreasing peripheral adiposity. These changes were accompanied by increased energy expenditure and improved systemic insulin sensitivity. Hepatic vagotomy and selective afferent blockage of the hepatic vagus revealed that the effects on peripheral tissues involve the afferent vagal nerve. Furthermore, an antidiabetic thiazolidinedione, a PPARγ agonist, enhanced this pathway. This neuronal pathway from the liver may function to protect against metabolic perturbation induced by excessive energy storage.',\n", - " 'author': ['Uno, Kenji',\n", - " 'Katagiri, Hideki',\n", - " 'Yamada, Tetsuya',\n", - " 'Ishigaki, Yasushi',\n", - " 'Ogihara, Takehide',\n", - " 'Imai, Junta',\n", - " 'Hasegawa, Yutaka',\n", - " 'Gao, Junhong',\n", - " 'Kaneko, Keizo',\n", - " 'Iwasaki, Hiroko',\n", - " 'Ishihara, Hisamitsu',\n", - " 'Sasano, Hironobu',\n", - " 'Inukai, Kouichi',\n", - " 'Mizuguchi, Hiroyuki',\n", - " 'Asano, Tomoichiro',\n", - " 'Shiota, Masakazu',\n", - " 'Nakazato, Masamitsu',\n", - " 'Oka, Yoshitomo'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.1126010\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.1126010\"}'],\n", - " 'title': ['Neuronal Pathway from the Liver Modulates Energy Expenditure and Systemic Insulin Sensitivity']},\n", - " {'bibcode': '2010PNAS..10710371H',\n", - " 'abstract': 'Only little is known about how cells coordinately behave to establish functional tissue structure and restore microarchitecture during regeneration. Research in this field is hampered by a lack of techniques that allow quantification of tissue architecture and its development. To bridge this gap, we have established a procedure based on confocal laser scans, image processing, and three-dimensional tissue reconstruction, as well as quantitative mathematical modeling. As a proof of principle, we reconstructed and modeled liver regeneration in mice after damage by CCl4, a prototypical inducer of pericentral liver damage. We have chosen the regenerating liver as an example because of the tight link between liver architecture and function: the complex microarchitecture formed by hepatocytes and microvessels, i.e. sinusoids, ensures optimal exchange of metabolites between blood and hepatocytes. Our model captures all hepatocytes and sinusoids of a liver lobule during a 16 days regeneration process. The model unambiguously predicted a so-far unrecognized mechanism as essential for liver regeneration, whereby daughter hepatocytes align along the orientation of the closest sinusoid, a process which we named \"hepatocyte-sinusoid alignment\" (HSA). The simulated tissue architecture was only in agreement with the experimentally obtained data when HSA was included into the model and, moreover, no other likely mechanism could replace it. In order to experimentally validate the model of prediction of HSA, we analyzed the three-dimensional orientation of daughter hepatocytes in relation to the sinusoids. The results of this analysis clearly confirmed the model prediction. We believe our procedure is widely applicable in the systems biology of tissues.',\n", - " 'author': ['Hoehme, Stefan',\n", - " 'Brulport, Marc',\n", - " 'Bauer, Alexander',\n", - " 'Bedawy, Essam',\n", - " 'Schormann, Wiebke',\n", - " 'Hermes, Matthias',\n", - " 'Puppe, Verena',\n", - " 'Gebhardt, Rolf',\n", - " 'Zellmer, Sebastian',\n", - " 'Schwarz, Michael',\n", - " 'Bockamp, Ernesto',\n", - " 'Timmel, Tobias',\n", - " 'Hengstler, Jan G.',\n", - " 'Drasdo, Dirk'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/107/23/10371\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0909374107\"}'],\n", - " 'title': ['Prediction and validation of cell alignment along microvessels as order principle to restore tissue architecture in liver regeneration']},\n", - " {'bibcode': '2002PNAS...9911848L',\n", - " 'abstract': 'Adenovirus-induced hyperleptinemia causes rapid disappearance of body fat in normal rats, presumably by up-regulating fatty acid oxidation within white adipocytes. To determine the role of peroxisomal proliferation-activated receptor (PPAR)α expression, which was increased during the rapid loss of fat, we infused adenovirus-leptin into PPARα-/- and PPARα+/+ mice. Despite similar degrees of hyperleptinemia and reduction in food intake, epididymal fat pad weight declined 55% in wild-type but only 6% in PPARα-/- mice; liver triacylglycerol fell 39% in the wild-type group but was unchanged in PPAR-/- mice. Carnitine palmitoyl transferase-1 mRNA rose 52% in the wild-type mice but did not increase in PPARα-/- mice. PPARγ coactivator-1α rose 3-fold in the fat and 46% in the liver of wild-type mice but was unchanged in PPARα-/- mice. Although AMP-activated protein kinase could not be implicated in the lipopenic actions of hyperleptinemia, acetyl CoA carboxylase protein was reduced in the liver of wild-type but not in PPARα-/- mice. Thus, in PPARα-/- mice, up-regulation of carnitine palmitoyl transferase-1 mRNA in fat, down-regulation of acetyl CoA carboxylase in liver, and up-regulation of PPARγ coactivator-1α mRNA in both tissues are abolished, as is the reduction in their triacylglycerol content.',\n", - " 'author': ['Lee, Y.',\n", - " 'Yu, X.',\n", - " 'Gonzales, F.',\n", - " 'Mangelsdorf, D. J.',\n", - " 'Wang, May-Yun',\n", - " 'Richardson, C.',\n", - " 'Witters, L. A.',\n", - " 'Unger, R. H.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/99/18/11848\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/99/18/11848\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/99/18/11848\"}'],\n", - " 'title': ['PPARα is necessary for the lipopenic action of hyperleptinemia on white adipose and liver tissue']},\n", - " {'bibcode': '2003PNAS..100.7797Z',\n", - " 'abstract': 'A major concern in therapy of acute liver failure is protection of hepatocytes to prevent apoptosis and maintain liver function. Small interfering RNA (siRNA) is a powerful tool to silence gene expression in mammalian cells. To evaluate the therapeutic efficacy of siRNA in vivo we used different mouse models of acute liver failure. We directed 21-nt siRNAs against caspase 8, which is a key enzyme in death receptor-mediated apoptosis. Systemic application of caspase 8 siRNA results in inhibition of caspase 8 gene expression in the liver, thereby preventing Fas (CD95)-mediated apoptosis. Protection of hepatocytes by caspase 8 siRNA significantly attenuated acute liver damage induced by agonistic Fas (CD95) antibody (Jo2) or by adenovirus expressing Fas ligand (AdFasL). However, in a clinical situation the siRNAs most likely would be applied after the onset of acute liver failure. Therefore we injected caspase 8 siRNA at a time point during AdFasL- and adenovirus wild type (Adwt)-mediated liver failure with already elevated liver transaminases. Improvement of survival due to RNA interference was significant even when caspase 8 siRNA was applied during ongoing acute liver failure. In addition, it is of particular interest that caspase 8 siRNA treatment was successful not only in acute liver failure mediated by specific Fas agonistic agents (Jo2 and AdFasL) but also in acute liver failure mediated by Adwt, which is an animal model reflecting multiple molecular mechanisms involved in human acute viral hepatitis. Consequently, our data raise hope for future successful application of siRNA in patients with acute liver failure.',\n", - " 'author': ['Zender, Lars',\n", - " 'Hütker, Sebastian',\n", - " 'Liedtke, Christian',\n", - " 'Tillmann, Hans Ludger',\n", - " 'Zender, Steffen',\n", - " 'Mundt, Bettina',\n", - " 'Waltemathe, Morlen',\n", - " 'Gösling, Thomas',\n", - " 'Flemming, Peer',\n", - " 'Malek, Nisar Peter',\n", - " 'Trautwein, Christian',\n", - " 'Manns, Michael Peter',\n", - " 'Kühnel, Florian',\n", - " 'Kubicka, Stefan'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/100/13/7797\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1330920100\"}'],\n", - " 'title': ['Caspase 8 small interfering RNA prevents acute liver failure in mice']},\n", - " {'bibcode': '2012PNAS..10913656L',\n", - " 'abstract': 'Recently, hepatic peroxisome proliferator-activated receptor (PPAR)γ has been implicated in hepatic lipid accumulation. We found that the C3H mouse strain does not express PPARγ in the liver and, when subject to a high-fat diet, is resistant to hepatic steatosis, compared with C57BL/6 (B6) mice. Adenoviral PPARγ2 injection into B6 and C3H mice caused hepatic steatosis, and microarray analysis demonstrated that hepatic PPARγ2 expression is associated with genes involved in fatty acid transport and the triglyceride synthesis pathway. In particular, hepatic PPARγ2 expression significantly increased the expression of monoacylglycerol O-acyltransferase 1 (MGAT1). Promoter analysis by luciferase assay and electrophoretic mobility shift assay as well as chromatin immunoprecipitation assay revealed that PPARγ2 directly regulates the MGAT1 promoter activity. The MGAT1 overexpression in cultured hepatocytes enhanced triglyceride synthesis without an increase of PPARγ expression. Importantly, knockdown of MGAT1 in the liver significantly reduced hepatic steatosis in 12-wk-old high-fat-fed mice as well as ob/ob mice, accompanied by weight loss and improved glucose tolerance. These results suggest that the MGAT1 pathway induced by hepatic PPARγ is critically important in the development of hepatic steatosis during diet-induced obesity.',\n", - " 'author': ['Lee, Yoo Jeong',\n", - " 'Ko, Eun Hee',\n", - " 'Kim, Ji Eun',\n", - " 'Kim, Eunha',\n", - " 'Lee, Hyemin',\n", - " 'Choi, Hyeonjin',\n", - " 'Yu, Jung Hwan',\n", - " 'Kim, Hyo Jung',\n", - " 'Seong, Je-Kyung',\n", - " 'Kim, Kyung-Sup',\n", - " 'Kim, Jae-woo'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/109/34/13656\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1203218109\"}'],\n", - " 'title': ['Nuclear receptor PPARγ-regulated monoacylglycerol O-acyltransferase 1 (MGAT1) expression is responsible for the lipid accumulation in diet-induced hepatic steatosis']},\n", - " {'bibcode': '1991PNAS...88..911B',\n", - " 'abstract': 'The frequency and pattern of mutations at codon 61 of the c-Ha-ras gene have been analyzed in 195 liver tumors and 132 precancerous liver lesions from various rodent strains with differing susceptibility to hepatocarcinogenesis. By using the polymerase chain reaction and allele-specific oligonucleotide hybridization, C----A transversions at the first base and A----T transversions or A----G transitions at the second base of c-Ha-ras codon 61 were detected in 20-60% of spontaneous or carcinogen-induced liver tumors of the C3H/He, CBA, CF1, and B6C3F1 mouse strains, which are highly susceptible to hepatocarcinogenesis. No such mutations, however, could be found in any of the 31 liver tumors of the insensitive C57BL/6J and BALB/c mouse strains or in any of the 35 liver tumors of the comparatively resistant Wistar rat. Further analyses of c-Ha-ras codon 12 mutations in liver tumors from the three insensitive rodent strains also failed to give any positive results. In early precancerous liver lesions, c-Ha-ras codon 61 mutations were found in 13-14% of lesions of the sensitive C3H/He and B6C3F1 mouse strains but not in any of the 34 lesions of the insensitive C57BL/6J mouse. Taken together, our results indicate a close correlation between the mutational activation of the c-Ha-ras gene in liver tumors of the different rodent strains and their susceptibility to hepatocarcinogenesis, whereby the mutations appear to provide a selective growth advantage, leading to a clonal expansion of the mutated liver cell population, only in livers of sensitive but not of insensitive strains.',\n", - " 'author': ['Buchmann, Albrecht',\n", - " 'Bauer-Hofmann, Richard',\n", - " 'Mahr, Johanna',\n", - " 'Drinkwater, Norman R.',\n", - " 'Luz, Arne',\n", - " 'Schwarz, Michael'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/88/3/911\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/88/3/911\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/88/3/911\"}'],\n", - " 'title': ['Mutational activation of the c-Ha-ras gene in liver tumors of different rodent strains: correlation with susceptibility to hepatocarcinogenesis.']},\n", - " {'bibcode': '2023PNAS..12003703Y',\n", - " 'abstract': 'In our study, we describe an initial in vivo map of the O-glycoproteome and a practical approach to quantitatively map O-glycosites in complex samples such as tissue extracts and biological fluids. This represents an essential initial step toward revealing structure-function relationships of O-glycosylation in both normal physiology and in a disease context. We illustrate the value of this approach by mapping a set of proteins in mouse liver that contain GalNAc-T2-specific O-glycosites. The identification of these proteins provides a mechanistic framework to explain the clinical presentation of the congenital glycosylation disorder of GALNT2 (which encodes GalNAc-T2).',\n", - " 'author': ['Yang, Weiming',\n", - " 'Tian, E.',\n", - " 'Chernish, Aliona',\n", - " 'McCluggage, Peggy',\n", - " 'Dalal, Kruti',\n", - " 'Lara, Alexander',\n", - " 'Ten Hagen, Kelly G.',\n", - " 'Tabak, Lawrence A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.2303703120\"}'],\n", - " 'title': ['Quantitative mapping of the in vivo O-GalNAc glycoproteome in mouse tissues identifies GalNAc-T2 O-glycosites in metabolic disorder']},\n", - " {'bibcode': '2017PNAS..114.3654T',\n", - " 'abstract': 'After partial hepatectomy, the adult mammalian liver regenerates through the mobilization of all hepatocytes characterized by a few cycles of cell division and subsequent hypertrophy with loss of global architecture. We have discovered a form of regeneration in the neonatal mouse liver, specific to the first week of life, where we observe numerous rounds of cell division and reconstitution of lobe architecture much like in amphibian limbs. This regenerative process is characterized by clonal expansion of select hepatocyte-specific stem or progenitors that localize to the central vein and is one of the first characterized instances of true mammalian regeneration.',\n", - " 'author': ['Tsai, Jonathan M.',\n", - " 'Koh, Pang Wei',\n", - " 'Stefanska, Ania',\n", - " 'Xing, Liujing',\n", - " 'Walmsley, Graham G.',\n", - " 'Poux, Nicolas',\n", - " 'Weissman, Irving L.',\n", - " 'Rinkevich, Yuval'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1621361114\"}'],\n", - " 'title': ['Localized hepatic lobular regeneration by central-vein-associated lineage-restricted progenitors']},\n", - " {'bibcode': '2018PNAS..115.3138L',\n", - " 'abstract': 'High salt intake is common in Western diets and likely contributes to hypertension and cardiovascular disease. Recently high salt intake has also been found to both be associated and predict the development of obesity, insulin resistance, and metabolic syndrome. Here we show that high-salt diet activates the aldose reductase (polyol) pathway in the liver, resulting in endogenous fructose production that then induces leptin resistance and the development of metabolic syndrome and fatty liver. Blocking fructose metabolism blocks the effects of high-salt diet. High salt intake also predicts diabetes and nonalcoholic fatty liver disease in Japanese adults. Thus, high-salt diet, an essential micronutrient with no intrinsic caloric value, may have a contributory role in driving obesity and diabetes.',\n", - " 'author': ['Lanaspa, Miguel A.',\n", - " 'Kuwabara, Masanari',\n", - " 'Andres-Hernando, Ana',\n", - " 'Li, Nanxing',\n", - " 'Cicerchi, Christina',\n", - " 'Jensen, Thomas',\n", - " 'Orlicky, David J.',\n", - " 'Roncal-Jimenez, Carlos A.',\n", - " 'Ishimoto, Takuji',\n", - " 'Nakagawa, Takahiko',\n", - " 'Rodriguez-Iturbe, Bernardo',\n", - " 'MacLean, Paul S.',\n", - " 'Johnson, Richard J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1713837115\"}'],\n", - " 'title': ['High salt intake causes leptin resistance and obesity in mice by stimulating endogenous fructose production and metabolism']},\n", - " {'bibcode': '2012PNAS..109.4320I',\n", - " 'abstract': 'Fructose intake from added sugars correlates with the epidemic rise in obesity, metabolic syndrome, and nonalcoholic fatty liver disease. Fructose intake also causes features of metabolic syndrome in laboratory animals and humans. The first enzyme in fructose metabolism is fructokinase, which exists as two isoforms, A and C. Here we show that fructose-induced metabolic syndrome is prevented in mice lacking both isoforms but is exacerbated in mice lacking fructokinase A. Fructokinase C is expressed primarily in liver, intestine, and kidney and has high affinity for fructose, resulting in rapid metabolism and marked ATP depletion. In contrast, fructokinase A is widely distributed, has low affinity for fructose, and has less dramatic effects on ATP levels. By reducing the amount of fructose for metabolism in the liver, fructokinase A protects against fructokinase C-mediated metabolic syndrome. These studies provide insights into the mechanisms by which fructose causes obesity and metabolic syndrome.',\n", - " 'author': ['Ishimoto, Takuji',\n", - " 'Lanaspa, Miguel A.',\n", - " 'Le, MyPhuong T.',\n", - " 'Garcia, Gabriela E.',\n", - " 'Diggle, Christine P.',\n", - " 'MacLean, Paul S.',\n", - " 'Jackman, Matthew R.',\n", - " 'Asipu, Aruna',\n", - " 'Roncal-Jimenez, Carlos A.',\n", - " 'Kosugi, Tomoki',\n", - " 'Rivard, Christopher J.',\n", - " 'Maruyama, Shoichi',\n", - " 'Rodriguez-Iturbe, Bernardo',\n", - " 'Sánchez-Lozada, Laura G.',\n", - " 'Bonthron, David T.',\n", - " 'Sautin, Yuri Y.',\n", - " 'Johnson, Richard J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/109/11/4320\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1119908109\"}'],\n", - " 'title': ['Opposing effects of fructokinase C and A isoforms on fructose-induced metabolic syndrome in mice']},\n", - " {'bibcode': '2010PNAS..107.1864L',\n", - " 'abstract': 'Significant effort has been applied to discover and develop vehicles which can guide small interfering RNAs (siRNA) through the many barriers guarding the interior of target cells. While studies have demonstrated the potential of gene silencing in vivo, improvements in delivery efficacy are required to fulfill the broadest potential of RNA interference therapeutics. Through the combinatorial synthesis and screening of a different class of materials, a formulation has been identified that enables siRNA-directed liver gene silencing in mice at doses below 0.01 mg/kg. This formulation was also shown to specifically inhibit expression of five hepatic genes simultaneously, after a single injection. The potential of this formulation was further validated in nonhuman primates, where high levels of knockdown of the clinically relevant gene transthyretin was observed at doses as low as 0.03 mg/kg. To our knowledge, this formulation facilitates gene silencing at orders-of-magnitude lower doses than required by any previously described siRNA liver delivery system.',\n", - " 'author': ['Love, Kevin T.',\n", - " 'Mahon, Kerry P.',\n", - " 'Levins, Christopher G.',\n", - " 'Whitehead, Kathryn A.',\n", - " 'Querbes, William',\n", - " 'Dorkin, J. Robert',\n", - " 'Qin, June',\n", - " 'Cantley, William',\n", - " 'Qin, Liu Liang',\n", - " 'Racie, Timothy',\n", - " 'Frank-Kamenetsky, Maria',\n", - " 'Yip, Ka Ning',\n", - " 'Alvarez, Rene',\n", - " 'Sah, Dinah W. Y.',\n", - " 'de Fougerolles, Antonin',\n", - " 'Fitzgerald, Kevin',\n", - " 'Koteliansky, Victor',\n", - " 'Akinc, Akin',\n", - " 'Langer, Robert',\n", - " 'Anderson, Daniel G.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/107/5/1864\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0910603106\"}'],\n", - " 'title': ['Lipid-like materials for low-dose, in vivo gene silencing']},\n", - " {'bibcode': '1995PNAS...9211608Y',\n", - " 'abstract': 'We have used a \"plug and socket\" targeting technique to generate a mouse model of beta 0-thalassemia in which both the b1 and b2 adult globin genes have been deleted. Mice homozygous for this deletion (Hbbth-3/Hbbth-3) die perinatally, similar to the most severe form of Cooley anemia in humans. Mice heterozygous for the deletion appear normal, but their hematologic indices show characteristics typical of severe thalassemia, including dramatically decreased hematocrit, hemoglobin, red blood cell counts, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration, as well as dramatically increased reticulocyte counts, serum bilirubin concentrations, and red cell distribution widths. Tissue and organ damage typical of beta-thalassemia, such as bone deformities and splenic enlargement due to increased hematopoiesis, are also seen in the heterozygous animals, as is spontaneous iron overload in the spleen, liver, and kidneys. The mice homozygous for the b1 and b2 deletions should be of great value in developing therapies for the treatment of thalassemias in utero. The heterozygous animals will be useful for studying the pathophysiology of thalassemias and have the potential of generating a model of sickle cell anemia when mated with appropriate transgenic animals.',\n", - " 'author': ['Yang, Baoli',\n", - " 'Kirby, Suzanne',\n", - " 'Lewis, Jada',\n", - " 'Detloff, Peter J.',\n", - " 'Maeda, Nobuyo',\n", - " 'Smithies, Oliver'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/92/25/11608\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/92/25/11608\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/92/25/11608\"}'],\n", - " 'title': ['A Mouse Model for β^0-Thalassemia']},\n", - " {'bibcode': '1986Sci...233.1318R',\n", - " 'abstract': 'The adoptive transfer of tumor-infiltrating lymphocytes (TIL) expanded in interleukin-2 (IL-2) to mice bearing micrometastases from various types of tumors showed that TIL are 50 to 100 times more effective in their therapeutic potency than are lymphokine-activated killer (LAK) cells. Therefore the use of TIL was explored for the treatment of mice with large pulmonary and hepatic metastatic tumors that do not respond to LAK cell therapy. Although treatment of animals with TIL alone or cyclophosphamide alone had little impact, these two modalities together mediated the elimination of large metastatic cancer deposits in the liver and lung. The combination of TIL and cyclophosphamide was further potentiated by the simultaneous administration of IL-2. With the combination of cyclophosphamide, TIL, and IL-2, 100% of mice (n = 12) bearing the MC-38 colon adenocarcinoma were cured of advanced hepatic metastases, and up to 50% of mice were cured of advanced pulmonary metastases. Techniques have been developed to isolate TIL from human tumors. These experiments provide a rationale for the use of TIL in the treatment of humans with advanced cancer.',\n", - " 'author': ['Rosenberg, Steven A.', 'Spiess, Paul', 'Lafreniere, Rene'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.3489291\"}'],\n", - " 'title': ['A New Approach to the Adoptive Immunotherapy of Cancer with Tumor-Infiltrating Lymphocytes']},\n", - " {'bibcode': '2004PNAS..101.8852M',\n", - " 'abstract': 'Insulin resistance, a hallmark of type 2 diabetes, is associated with oxidative stress. However, the role of reactive oxygen species or specific antioxidant enzymes in its development has not been tested under physiological conditions. The objective of our study was to investigate the impact of overexpression of glutathione peroxidase 1 (GPX1), an intracellular selenoprotein that reduces hydrogen peroxide (H2O2) in vivo, on glucose metabolism and insulin function. The GPX1-overexpressing (OE) and WT male mice (n = 80) were fed a selenium-adequate diet (0.4 mg/kg) from 8 to 24 weeks of age. Compared with the WT, the OE mice developed (P < 0.05) hyperglycemia (117 vs. 149 mg/dl), hyperinsulinemia (419 vs. 1,350 pg/ml), and elevated plasma leptin (5 vs. 16 ng/ml) at 24 weeks of age. Meanwhile, these mice were heavier (37 vs. 27 g, P < 0.001) and fatter (37% vs. 17% fat, P < 0.01) than the WT mice. At 30-60 min after an insulin challenge, the OE mice had 25% less (P < 0.05) of a decrease in blood glucose than the WT mice. Their insulin resistance was associated with a 30-70% reduction (P < 0.05) in the insulin-stimulated phosphorylations of insulin receptor (β-subunit) in liver and Akt (Ser473 and Thr308) in liver and soleus muscle. Here we report the development of insulin resistance in mammals with elevated expression of an antioxidant enzyme and suggest that increased GPX1 activity may interfere with insulin function by overquenching intracellular reactive oxygen species required for insulin sensitizing.',\n", - " 'author': ['McClung, James P.',\n", - " 'Roneker, Carol A.',\n", - " 'Mu, Weipeng',\n", - " 'Lisk, Donald J.',\n", - " 'Langlais, Paul',\n", - " 'Liu, Feng',\n", - " 'Lei, Xin Gen'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/101/24/8852\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0308096101\"}'],\n", - " 'title': ['Development of insulin resistance and obesity in mice overexpressing cellular glutathione peroxidase']},\n", - " {'bibcode': '1993PNAS...90.7533Q',\n", - " 'abstract': 'Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, induces endothelial proliferation in vitro and vascular permeability in vivo. The human transmembrane c-fms-like tyrosine kinase Flt-1 has recently been identified as a VEGF receptor. Flt-1 kinase has seven immunoglobulin-like extracellular domains and a kinase insert sequence, features shared by two other human gene-encoded proteins, kinase insert domain-containing receptor (KDR) and FLT-4. In this study we show that the mouse homologue of KDR, Flk-1, is a second functional VEGF receptor. Flk-1 binds VEGF with high affinity, undergoes autophosphorylation, and mediates VEGF-dependent Ca2+ efflux in Xenopus oocytes injected with Flk-1 mRNA. We also demonstrate by in situ hybridization that Flk-1 protein expression in the mouse embryo is restricted to the vascular endothelium and the umbilical cord stroma. VEGF and its receptors Flk-1/KDR and Flt-1 may play a role in vascular development and regulation of vascular permeability.',\n", - " 'author': ['Quinn, Timothy P.',\n", - " 'Peters, Kevin G.',\n", - " 'de Vries, Carlie',\n", - " 'Ferrara, Napoleone',\n", - " 'Williams, Lewis T.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/90/16/7533\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/90/16/7533\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/90/16/7533\"}'],\n", - " 'title': ['Fetal liver kinase 1 is a receptor for vascular endothelial growth factor and is selectively expressed in vascular endothelium.']},\n", - " {'bibcode': '2010PNAS..10719320P',\n", - " 'abstract': 'Increased endoplasmic reticulum (ER) stress is one of the central mechanisms that lead to dysregulated metabolic homeostasis in obesity. It is thus crucial to understand the underpinnings of the mechanisms that lead to the development of ER stress. A high level of ER Ca2+ is imperative for maintenance of normal ER function and this high Ca2+ concentration of ER is maintained by sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA). Here, we show that SERCA2b protein and mRNA levels are dramatically reduced in the liver of obese mice and restoration of SERCA2b in the liver of obese and diabetic mice alleviates ER stress, increases glucose tolerance, and significantly reduces the blood glucose levels. Furthermore, overexpression of SERCA2b in the liver of obese mice significantly reduces the lipogenic gene expression and the triglyceride content in the liver. Our results document the importance of SERCA2b in dysregulated glucose and lipid homeostasis in the liver of obese mice and suggest development of drugs to increase SERCA2b activity for treatment of type 2 diabetes and nonalcoholic steatohepatitis.',\n", - " 'author': ['Park, Sang Won',\n", - " 'Zhou, Yingjiang',\n", - " 'Lee, Jaemin',\n", - " 'Lee, Justin',\n", - " 'Ozcan, Umut'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/107/45/19320\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1012044107\"}'],\n", - " 'title': ['Sarco(endo)plasmic reticulum Ca2+-ATPase 2b is a major regulator of endoplasmic reticulum stress and glucose homeostasis in obesity']},\n", - " {'bibcode': '2002PNAS...99.5622T',\n", - " 'abstract': 'Hereditary hemochromatosis (HH) is a disorder of iron metabolism in which enhanced iron absorption of dietary iron causes increased iron accumulation in the liver, heart, and pancreas. Most individuals with HH are homozygous for a C282Y mutation in the HFE gene. The function of HFE protein is unknown, but it is hypothesized that it acts in association with β2-microglobulin and transferrin receptor 1 to regulate iron uptake from plasma transferrin by the duodenum, the proposed mechanism by which body iron levels are sensed. The aim of this study was to test this hypothesis by comparing clearance of transferrin-bound iron in Hfe knockout (KO) mice with that observed in C57BL/6 control mice. The mice were fed either an iron-deficient, control, or iron-loaded diet for 6 weeks to alter body iron status. The mice then were injected i.v. with 59Fe-transferrin, and blood samples were taken over 2 h to determine the plasma 59Fe turnover. After 2 h, the mice were killed and the amount of radioactivity in the duodenum, liver, and kidney was measured. In both Hfe KO and C57BL/6 mice, plasma iron turnover and iron uptake from plasma transferrin by the duodenum, liver, and kidney correlated positively with plasma iron concentration. However, duodenal iron uptake from plasma transferrin was decreased in the Hfe KO mice compared with the control mice. Despite this difference in duodenal uptake, the Hfe KO mice showed no decrease in iron uptake by the liver and kidney or alteration in the plasma iron turnover when compared with C57BL/6 mice. These data support the hypothesis that HFE regulates duodenal uptake of transferrin-bound iron from plasma, and that this mechanism of sensing body iron status, as reflected in plasma iron levels, is impaired in HH.',\n", - " 'author': ['Trinder, Debbie',\n", - " 'Olynyk, John K.',\n", - " 'Sly, William S.',\n", - " 'Morgan, Evan H.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/99/8/5622\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/99/8/5622\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/99/8/5622\"}'],\n", - " 'title': ['Iron uptake from plasma transferrin by the duodenum is impaired in the Hfe knockout mouse']},\n", - " {'bibcode': '2005PNAS..102.2058S',\n", - " 'abstract': 'Liver receptor homolog 1 (LRH-1) is an orphan nuclear receptor that synergizes with β-catenin/T cell factor 4 signaling to stimulate intestinal crypt cell renewal. We evaluated here the impact of haploinsufficiency of LRH-1 on intestinal tumorigenesis by using two independent mouse models of human colon tumorigenesis. Haploinsufficiency of LRH-1 blunts intestinal tumorigenesis in the ApcMin/+ mice, a genetic model of intestinal cancer. Likewise, Lrh-1+/- mice are protected against the formation of aberrant crypt foci in the colon of mice exposed to the carcinogen azoxymethane. LRH-1 gene expression is reduced in tumors that express elevated levels of the proinflammatory cytokine TNF-α. Reciprocally, decreased LRH-1 expression in Lrh-1+/- mice attenuates TNF-α expression. Compared with normal human colon, expression and subcellular localization of LRH-1 is significantly altered in neoplastic colon. In combination, these data suggest a role of LRH-1 in the initiation of intestinal tumorigenesis both by affecting cell cycle control as well as through its impact on inflammatory pathways.',\n", - " 'author': ['Schoonjans, Kristina',\n", - " 'Dubuquoy, Laurent',\n", - " 'Mebis, Joseph',\n", - " 'Fayard, Elisabeth',\n", - " 'Wendling, Olivia',\n", - " 'Haby, Céline',\n", - " 'Geboes, Karel',\n", - " 'Auwerx, Johan'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/102/6/2058\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0409756102\"}'],\n", - " 'title': ['Liver receptor homolog 1 contributes to intestinal tumor formation through effects on cell cycle and inflammation']},\n", - " {'bibcode': '2011PNAS..108..308O',\n", - " 'abstract': 'Cirrhosis is the end result of chronic liver disease. Hepatic stellate cells (HSC) are believed to be the major source of collagen-producing myofibroblasts in cirrhotic livers. Portal fibroblasts, bone marrow-derived cells, and epithelial to mesenchymal transition (EMT) might also contribute to the myofibroblast population in damaged livers. Fibroblast-specific protein 1 (FSP1, also called S100A4) is considered a marker of fibroblasts in different organs undergoing tissue remodeling and is used to identify fibroblasts derived from EMT in several organs including the liver. The aim of this study was to characterize FSP1-positive cells in human and experimental liver disease. FSP1-positive cells were increased in human and mouse experimental liver injury including liver cancer. However, FSP1 was not expressed by HSC or type I collagen-producing fibroblasts. Likewise, FSP1-positive cells did not express classical myofibroblast markers, including αSMA and desmin, and were not myofibroblast precursors in injured livers as evaluated by genetic lineage tracing experiments. Surprisingly, FSP1-positive cells expressed F4/80 and other markers of the myeloid-monocytic lineage as evaluated by double immunofluorescence staining, cell fate tracking, flow cytometry, and transcriptional profiling. Similar results were obtained for bone marrow-derived and peritoneal macrophages. FSP1-positive cells were characterized by increased expression of COX2, osteopontin, inflammatory cytokines, and chemokines but reduced expression of MMP3 and TIMP3 compared with Kupffer cells/macrophages. These findings suggest that FSP1 is a marker of a specific subset of inflammatory macrophages in liver injury, fibrosis, and cancer.',\n", - " 'author': ['Österreicher, Christoph H.',\n", - " 'Penz-Österreicher, Melitta',\n", - " 'Grivennikov, Sergei I.',\n", - " 'Guma, Monica',\n", - " 'Koltsova, Ekaterina K.',\n", - " 'Datz, Christian',\n", - " 'Sasik, Roman',\n", - " 'Hardiman, Gary',\n", - " 'Karin, Michael',\n", - " 'Brenner, David A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/108/1/308\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1017547108\"}'],\n", - " 'title': ['Fibroblast-specific protein 1 identifies an inflammatory subpopulation of macrophages in the liver']},\n", - " {'bibcode': '1999PNAS...9614505L',\n", - " 'abstract': 'The Sanfilippo syndrome type B is an autosomal recessive disorder caused by mutation in the gene (NAGLU) encoding α-N-acetylglucosaminidase, a lysosomal enzyme required for the stepwise degradation of heparan sulfate. The most serious manifestations are profound mental retardation, intractable behavior problems, and death in the second decade. To generate a model for studies of pathophysiology and of potential therapy, we disrupted exon 6 of Naglu, the homologous mouse gene. Naglu-/- mice were healthy and fertile while young and could survive for 8-12 mo. They were totally deficient in α-N-acetylglucosaminidase and had massive accumulation of heparan sulfate in liver and kidney as well as secondary changes in activity of several other lysosomal enzymes in liver and brain and elevation of gangliosides GM2 and GM3 in brain. Vacuolation was seen in many cells, including macrophages, epithelial cells, and neurons, and became more prominent with age. Although most vacuoles contained finely granular material characteristic of glycosaminoglycan accumulation, large pleiomorphic inclusions were seen in some neurons and pericytes in the brain. Abnormal hypoactive behavior was manifested by 4.5-mo-old Naglu-/- mice in an open field test; the hyperactivity that is characteristic of affected children was not observed even in younger mice. In a Pavlovian fear conditioning test, the 4.5-mo-old mutant mice showed normal response to context, indicating intact hippocampal-dependent learning, but reduced response to a conditioning tone, perhaps attributable to hearing impairment. The phenotype of the α-N-acetylglucosaminidase-deficient mice is sufficiently similar to that of patients with the Sanfilippo syndrome type B to make these mice a good model for study of pathophysiology and for development of therapy.',\n", - " 'author': ['Li, Hong Hua',\n", - " 'Yu, Wei-Hong',\n", - " 'Rozengurt, Nora',\n", - " 'Zhao, Hui-Zhi',\n", - " 'Lyons, Karen M.',\n", - " 'Anagnostaras, Stephan',\n", - " 'Fanselow, Michael S.',\n", - " 'Suzuki, Kunihiko',\n", - " 'Vanier, Marie T.',\n", - " 'Neufeld, Elizabeth F.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/96/25/14505\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/96/25/14505\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/96/25/14505\"}'],\n", - " 'title': ['Mouse Model of Sanfilippo Syndrome Type B Produced by Targeted Disruption of the Gene Encoding α -N-acetylglucosaminidase']},\n", - " {'bibcode': '2022ScTEn.806o0703C',\n", - " 'author': ['Chen, Ying',\n", - " 'Wang, Yewei',\n", - " 'Charkoftaki, Georgia',\n", - " 'Orlicky, David J.',\n", - " 'Davidson, Emily',\n", - " 'Wan, Fengjie',\n", - " 'Ginsberg, Gary',\n", - " 'Thompson, David C.',\n", - " 'Vasiliou, Vasilis'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.scitotenv.2021.150703\"}'],\n", - " 'title': ['Oxidative stress and genotoxicity in 1,4-dioxane liver toxicity as evidenced in a mouse model of glutathione deficiency']},\n", - " {'bibcode': '1987Sci...235...53H',\n", - " 'abstract': \"The 5' flanking region of the mouse alpha-fetoprotein (AFP) gene contains a tissue-specific promoter and three upstream regulatory elements that behave as classical enhancers. At least one of these enhancers is now shown to be required for the tissue-specific expression of the AFP gene when it is introduced into the mouse genome by microinjection of cloned DNA fragments into fertilized eggs. Each enhancer can direct expression in the appropriate tissues, the visceral endoderm of the yolk sac, the fetal liver, and the gastrointestinal tract, but each exerts different influence in these three tissues. These differences may explain the tissue-specific diversity in the levels of expression characteristic of the AFP gene. The postnatal repression of transcription of the AFP gene in both liver and gut, as well as the reinitiation of its transcription during liver regeneration, is mimicked by the introduced gene when it is linked to the enhancer domains together or singly. Thus, the DNA sequence elements responsible for directing the activation of AFP transcription, its repression, and reinduction are contained in a limited segment of DNA within or 5 ' to the gene (or both) and are operative in the absence of the closely linked albumin gene.\",\n", - " 'author': ['Hammer, Robert E.',\n", - " 'Krumlauf, Robb',\n", - " 'Camper, Sally A.',\n", - " 'Brinster, Ralph L.',\n", - " 'Tilghman, Shirley M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.2432657\"}'],\n", - " 'title': ['Diversity of Alpha-Fetoprotein Gene Expression in Mice is Generated by a Combination of Separate Enhancer Elements']},\n", - " {'bibcode': '2014NatCo...5.4699G',\n", - " 'abstract': 'Endolysosomal organelles play a key role in trafficking, breakdown and receptor-mediated recycling of different macromolecules such as low-density lipoprotein (LDL)-cholesterol, epithelial growth factor (EGF) or transferrin. Here we examine the role of two-pore channel (TPC) 2, an endolysosomal cation channel, in these processes. Embryonic mouse fibroblasts and hepatocytes lacking TPC2 display a profound impairment of LDL-cholesterol and EGF/EGF-receptor trafficking. Mechanistically, both defects can be attributed to a dysfunction of the endolysosomal degradation pathway most likely on the level of late endosome to lysosome fusion. Importantly, endolysosomal acidification or lysosomal enzyme function are normal in TPC2-deficient cells. TPC2-deficient mice are highly susceptible to hepatic cholesterol overload and liver damage consistent with non-alcoholic fatty liver hepatitis. These findings indicate reduced metabolic reserve of hepatic cholesterol handling. Our results suggest that TPC2 plays a crucial role in trafficking in the endolysosomal degradation pathway and, thus, is potentially involved in the homoeostatic control of many macromolecules and cell metabolites.',\n", - " 'author': ['Grimm, Christian',\n", - " 'Holdt, Lesca M.',\n", - " 'Chen, Cheng-Chang',\n", - " 'Hassan, Sami',\n", - " 'Müller, Christoph',\n", - " 'Jörs, Simone',\n", - " 'Cuny, Hartmut',\n", - " 'Kissing, Sandra',\n", - " 'Schröder, Bernd',\n", - " 'Butz, Elisabeth',\n", - " 'Northoff, Bernd',\n", - " 'Castonguay, Jan',\n", - " 'Luber, Christian A.',\n", - " 'Moser, Markus',\n", - " 'Spahn, Saskia',\n", - " 'Lüllmann-Rauch, Renate',\n", - " 'Fendel, Christina',\n", - " 'Klugbauer, Norbert',\n", - " 'Griesbeck, Oliver',\n", - " 'Haas, Albert',\n", - " 'Mann, Matthias',\n", - " 'Bracher, Franz',\n", - " 'Teupser, Daniel',\n", - " 'Saftig, Paul',\n", - " 'Biel, Martin',\n", - " 'Wahl-Schott, Christian'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fncomms5699\"}'],\n", - " 'title': ['High susceptibility to fatty liver disease in two-pore channel 2-deficient mice']},\n", - " {'bibcode': '2018NatSR...8.8637K',\n", - " 'abstract': 'Nicotinamide N-methyltransferase (NNMT) catalyses the reaction between nicotinamide (NAM) and S-adenosylmethionine to produce 1-methylnicotinamide and S-adenosylhomocysteine. Recently, this enzyme has also been reported to modulate hepatic nutrient metabolism, but its role in the liver has not been fully elucidated. We developed transgenic mice overexpressing NNMT to elucidate its role in hepatic nutrient metabolism. When fed a high fat diet containing NAM, a precursor for nicotinamide adenine dinucleotide (NAD)+, these NNMT-overexpressing mice exhibit fatty liver deterioration following increased expression of the genes mediating fatty acid uptake and decreased very low-density lipoprotein secretion. NNMT overactivation decreased the NAD+ content in the liver and also decreased gene activity related to fatty acid oxidation by inhibiting NAD+-dependent deacetylase Sirt3 function. Moreover, the transgenic mice showed liver fibrosis, with the induction of inflammatory and fibrosis genes. Induced NNMT expression decreased the tissue methylation capacity, thereby reducing methylation of the connective tissue growth factor (CTGF) gene promoter, resulting in increased CTGF expression. These data indicate that NNMT links the NAD+ and methionine metabolic pathways and promotes liver steatosis and fibrosis. Therefore, targeting NNMT may serve as a therapeutic strategy for treating fatty liver and fibrosis.',\n", - " 'author': ['Komatsu, Motoaki',\n", - " 'Kanda, Takeshi',\n", - " 'Urai, Hidenori',\n", - " 'Kurokochi, Arata',\n", - " 'Kitahama, Rina',\n", - " 'Shigaki, Shuhei',\n", - " 'Ono, Takashi',\n", - " 'Yukioka, Hideo',\n", - " 'Hasegawa, Kazuhiro',\n", - " 'Tokuyama, Hirobumi',\n", - " 'Kawabe, Hiroshi',\n", - " 'Wakino, Shu',\n", - " 'Itoh, Hiroshi'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-018-26882-8\"}'],\n", - " 'title': ['NNMT activation can contribute to the development of fatty liver disease by modulating the NAD+ metabolism']},\n", - " {'bibcode': '2010PNAS..107.3441L',\n", - " 'abstract': 'The livers of insulin-resistant, diabetic mice manifest selective insulin resistance, suggesting a bifurcation in the insulin signaling pathway: Insulin loses its ability to block glucose production (i.e., it fails to suppress PEPCK and other genes of gluconeogenesis), yet it retains its ability to stimulate fatty acid synthesis (i.e., continued enhancement of genes of lipogenesis). Enhanced lipogenesis is accompanied by an insulin-stimulated increase in the mRNA encoding SREBP-1c, a transcription factor that activates the entire lipogenic program. Here, we report a branch point in the insulin signaling pathway that may account for selective insulin resistance. Exposure of rat hepatocytes to insulin produced a 25-fold increase in SREBP-1c mRNA and a 95% decrease in PEPCK mRNA. Insulin-mediated changes in both mRNAs were blocked by inhibitors of PI3K and Akt, indicating that these kinases are required for both pathways. In contrast, subnanomolar concentrations of rapamycin, an inhibitor of the mTORC1 kinase, blocked insulin induction of SREBP-1c, but had no effect on insulin suppression of PEPCK. We observed a similar selective effect of rapamycin in livers of rats and mice that experienced an insulin surge in response to a fasting-refeeding protocol. A specific inhibitor of S6 kinase, a downstream target of mTORC1, did not block insulin induction of SREBP-1c, suggesting a downstream pathway distinct from S6 kinase. These results establish mTORC1 as an essential component in the insulin-regulated pathway for hepatic lipogenesis but not gluconeogenesis, and may help to resolve the paradox of selective insulin resistance in livers of diabetic rodents.',\n", - " 'author': ['Li, Shijie', 'Brown, Michael S.', 'Goldstein, Joseph L.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/107/8/3441\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0914798107\"}'],\n", - " 'title': ['Bifurcation of insulin signaling pathway in rat liver: mTORC1 required for stimulation of lipogenesis, but not inhibition of gluconeogenesis']},\n", - " {'bibcode': '2007PNAS..104.3003G',\n", - " 'abstract': 'Heterotrimeric G proteins of the Gi class have been implicated in signaling pathways regulating growth and metabolism under physiological and pathophysiological conditions. Knockout mice carrying inactivating mutations in both of the widely expressed Gαi class genes, Gαi2 and Gαi3, demonstrate shared as well as gene-specific functions. The presence of a single active allele of Gαi3 is sufficient for embryonic development, whereas at least one allele of Gαi2 is required for extrauterine life. Mice lacking both Gαi2 and Gαi3 are massively growth-retarded and die in utero. We have used biochemical and cell biological methods together with in situ liver perfusion experiments to study Gαi isoform-specific functions in Gαi2- and Gαi3-deficient mice. The subcellular localization of Gαi3 in isolated mouse hepatocytes depends on the cellular metabolic status. Gαi3 localizes to autophagosomes upon starvation-induced autophagy and distributes to the plasma membrane upon insulin stimulation. Analysis of autophagic proteolysis in perfused mouse livers showed that mice lacking Gαi3 are deficient in the inhibitory action of insulin. These data indicate that Gαi3 is crucial for the antiautophagic action of insulin and suggest an as-yet-unrecognized function for Gαi3 on autophagosomal membranes.',\n", - " 'author': ['Gohla, Antje',\n", - " 'Klement, Karinna',\n", - " 'Piekorz, Roland P.',\n", - " 'Pexa, Katja',\n", - " 'vom Dahl, Stephan',\n", - " 'Spicher, Karsten',\n", - " 'Dreval, Vladyslav',\n", - " 'Häussinger, Dieter',\n", - " 'Birnbaumer, Lutz',\n", - " 'Nürnberg, Bernd'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/104/8/3003\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0611434104\"}'],\n", - " 'title': ['From the Cover: An obligatory requirement for the heterotrimeric G protein Gi3 in the antiautophagic action of insulin in the liver']},\n", - " {'bibcode': '1964Natur.201..618S',\n", - " 'abstract': 'THE rapid rate of cell division in early embryogenesis is accompanied by rapid synthesis of DNA1. The function of deoxyribonuclease II (DNase) is essentially catabolic and is probably concerned with the breakdown of DNA from dead cells. DNase would then be expected to be required by the body shortly after embryogenesis and its time of appearance in the star-fish, frog and chicken is essentially similar2. During early embryogenesis of the chick DNase II is difficult to detect but increases rapidly after four daysof incubation2. The onset of DNase activity in the whole mouse embryo and the developing mouse liver has been investigated and been shown to follow a similar ontogenetic pattern as in the other species named here.',\n", - " 'author': ['Solomon, J. B.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F201618a0\"}'],\n", - " 'title': ['Deoxyribonuclease II in the Developing Mouse Embryo']},\n", - " {'bibcode': '1973Natur.246...35W',\n", - " 'abstract': 'THE ability of mouse liver to convert mouse or bovine albumin to a faster migrating band under acid conditions of electrophoresis has recently been found to be controlled by a dominant gene, as observed in the SWR/J and several other strains of mice1. Other strains, such as C3H/HeJ, had the recessive allele and were unable to convert albumin. The conditions used included a pH at which conformational changes in albumin are known to occur, suggesting that the strains of mice differ in a factor in the liver capable of converting albumin to a different conformational state. I report here evidence that the conversion of albumin can be reversed by lowering the pH markedly. This provides further evidence that a conformational change has taken place.',\n", - " 'author': ['Wilcox, F. H.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F246035a0\"}'],\n", - " 'title': ['Genetic Differences in Conformational Changes of Albumin in the House Mouse']},\n", - " {'bibcode': '1961Natur.190..720B',\n", - " 'abstract': 'DURING recent years reports from various laboratories have indicated that phenolic steroids substituted at C6 may have biological significance. Thus, Mueller and Rumney1 provided evidence for the conversion of radioactive œstradiol-17β to 6-hydroxyœstradiol-17β by mouse liver microsomes in vitro. Furthermore, 6-hydroxyœstradiol-17β has been isolated as a metabolite after incubation of œstradiol-17β with slices of rat liver2 and human fœtal liver3. Bush et al.4 detected 6-hydroxyœstradiol-17β in the follicular fluid of the mare, and Marrian5 reported on the isolation of a new Kober chromogen (KC-6B) which appears to be identical with a 6-hydroxyœstrone.',\n", - " 'author': ['Breuer, H.', 'Knuppen, R.', 'Pangels, Gerta'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F190720a0\"}'],\n", - " 'title': ['Configuration of the 6-Hydroxyl Group in Phenolic Steroids']},\n", - " {'bibcode': '1992PNAS...89.1502I',\n", - " 'abstract': 'The interaction of the mouse c-kit receptor, designated Kit receptor, and steel factor promotes the proliferation and differentiation of hematopoietic progenitor cells. Monoclonal antibodies against the extracellular portion of the mouse Kit receptor were established. Five percent to 10% of total bone marrow cells expressed the Kit receptor, and half of them lack the expression of lineage markers. The Kit receptor was expressed on 70-80% of Thy-1.1lo Lin-Sca-1+ cells, which express Thy-1.1 antigen at a low level and constitute approximately 0.05% of adult bone marrow and fetal liver; by previous studies, these cells have been shown to be highly enriched for multipotent hematopoietic stem cells (HSCs) and are the only hematopoietic cell subset with this activity. Spleen colony formation and long-term multilineage reconstitution activities were contained in the Kit+ but not in the Kit- subpopulations of Thy-1lo Lin-Sca-1+ cells from adult bone marrow, suggesting that the Kit receptor is expressed on HSCs from the earliest stage-i.e., pluripotent HSCs. The role of steel factor in the development and self-renewal of HSCs was tested with Sl/Sl homozygote fetuses, which lack genes to encode functional steel factor. They were shown to have 30-40% of the number of HSCs on days 13-15 when compared with normal litermates. However, the absolute number of HSCs increased during fetal development in the Sl/Sl mice. The results suggest that the Kit receptor-steel factor interaction may not be essential for the initiation of hematopoiesis and the self-renewal of (at least) fetal HSCs.',\n", - " 'author': ['Ikuta, Koichi', 'Weissman, Irving L.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/89/4/1502\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/89/4/1502\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/89/4/1502\"}'],\n", - " 'title': ['Evidence that hematopoietic stem cells express mouse c-kit but do not depend on steel factor for their generation.']},\n", - " {'bibcode': '2013NatCo...4.1336S',\n", - " 'abstract': 'SR family RNA binding proteins regulate splicing of nascent RNAs in vitro but their physiological role in vivo is largely unexplored, as genetic deletion of many SR protein genes results in embryonic lethality. Here we show that SRSF3HKO mice carrying a hepatocyte-specific deletion of Srsf3 (homologous to human SRSF3/SRp20) have a disrupted hepatic architecture and show pre- and postnatal growth retardation. SRSF3HKO mice exhibit impaired hepatocyte maturation with alterations in glucose and lipid homeostasis characterized by reduced glycogen storage, fasting hypoglycemia, increased insulin sensitivity and reduced cholesterol synthesis. We identify various splicing alterations in the SRSF3HKO liver that explain the in vivo phenotype. In particular, loss of SRSF3 causes aberrant splicing of Hnf1α, Ern1, Hmgcs1, Dhcr7 and Scap genes, which are critical regulators of glucose and lipid metabolism. Our study provides the first evidence for a SRSF3-driven genetic programme required for morphological and functional differentiation of hepatocytes that may have relevance for human liver disease and metabolic dysregulation.',\n", - " 'author': ['Sen, Supriya', 'Jumaa, Hassan', 'Webster, Nicholas J. G.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fncomms2342\"}'],\n", - " 'title': ['Splicing factor SRSF3 is crucial for hepatocyte differentiation and metabolic function']},\n", - " {'bibcode': '1988PNAS...85.6949G',\n", - " 'abstract': 'The rapid clearance of circulating liposomes from the bloodstream, coupled with their high uptake by liver and spleen, has thus far been an obstacle to any attempts at targeting to tumors. We have assessed the impact of liposome composition on their clearance from the circulation in normal and tumor-bearing mice and on their uptake by tumors and various normal tissues. By selective changes in lipid composition, while maintaining a mean particle diameter of approximately equal to 100 nm, we have achieved up to a 60-fold increase in the fraction of recovered dose present in blood 24 hr after i.v. injection. Concomitantly, there was a decrease by a factor of 4 of the recovered dose localizing in the liver and spleen, the major organs of the reticuloendothelial system. Parallel experiments in tumor-bearing mice demonstrated a 25-fold increase of the liposome concentration in the tumor when formulations with long and short blood residence time were compared. The most favorable results were obtained with liposomes containing a small molar fraction of a negatively charged glycolipid, such as monosialoganglioside or phosphatidylinositol, and a solid-phase neutral phospholipid as the bulk component. The bio-distribution of such formulations is of considerable therapeutic potential in cancer for increasing the concentration of cytotoxic agents in tumors while minimizing the likelihood of toxicity to the reticuloendothelial system.',\n", - " 'author': ['Gabizon, Alberto', 'Papahadjopoulos, Demetrios'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/85/18/6949\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/85/18/6949\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/85/18/6949\"}'],\n", - " 'title': ['Liposome formulations with prolonged circulation time in blood and enhanced uptake by tumors.']},\n", - " {'bibcode': '1987PNAS...84.4989S',\n", - " 'abstract': 'The pre-B-cell cloning assay is an in vitro differentiation system in which B-lymphocyte precursors expand and generate colonies containing immunoglobulin-secreting cells. Analysis of surface characteristics, growth requirements, and kinetics suggested that these cells represent early stages of the B-cell differentiation pathway. Here we describe a modification of the assay, which allowed us to determine the differentiative potential of these clonable pre-B cells. Using a nitrocellulose protein-transfer technique, we studied immunoglobulin light chain expression in colonies derived from fetal mouse liver B-cell precursors; in particular, we explored whether the B-cell precursors are already committed to the expression of a particular light chain gene at the initiation of culture. Our results show that fetal liver-derived B-cell progenitors generate colonies in vitro that secrete kappa and lambda light chains at a ratio similar to that found in colonies derived from adult splenic B cells. Further, we document the existence of colonies that are derived from single cells and that simultaneously secrete both types of light chains. This indicates that the progenitors of (kappa + lambda)-producing colonies are light chain-uncommitted at the initiation of culture. These cells are able to rearrange their light chain genes in vitro and differentiate along the B-cell pathway to form colonies secreting both kappa and lambda chains.',\n", - " 'author': ['Sauter, Helmut', 'Paige, Christopher J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/84/14/4989\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/84/14/4989\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/84/14/4989\"}'],\n", - " 'title': ['Detection of Normal B-Cell Precursors that Give Rise to Colonies Producing Both kappa and λ Light Immunoglobulin Chains']},\n", - " {'bibcode': '1990PNAS...87.4996H',\n", - " 'abstract': '35S-labeled Drosophila melanogaster apocytochrome c was made by in vitro transcription/translation of the gene and purified to the monomeric, fully reduced form. It was found that in the presence of a wheat germ extract factor there was a high-affinity phase of the uptake into mouse liver mitochondria at 10-300 pM apocytochrome c, and a lower-affinity phase through 4000 pM. Without the factor, the high-affinity phase was absent. The stimulatory effect of the factor could not be elicited with various reductants, such as NADH, FMN, and ferrous protoheme IX. Conversely, when mitochondria loaded with apocytochrome c were resuspended in fresh medium, the protein readily reequilibrated. Successive washings depleted greater than 95% of the associated apoprotein but removed no holoprotein. Proteases (proteinase K or trypsin) added to a suspension of mitochondria loaded with apoprotein digested an amount of apoprotein similar to that which would have been dissociated during the same time, as measured by successive washings in the absence of protease. Mitochondria loaded with apoprotein and similarly treated with protease continued exporting the apoprotein, even after the protease was inhibited and removed, suggesting that most of the apoprotein associated with the organelle was in a protease-resistant compartment. Apocytochrome c mutants in which serines or alanines replaced cysteines 14 and 17, which bind the prosthetic group, behaved like the cysteine-containing protein, indicating that the covalent attachment of the heme is unrelated to the translocation of the apoprotein.',\n", - " 'author': ['Hakvoort, Theodorus B. M.',\n", - " 'Sprinkle, James R.',\n", - " 'Margoliash, E.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/87/13/4996\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/87/13/4996\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/87/13/4996\"}'],\n", - " 'title': ['Reversible import of apocytochrome c into mitochondria.']},\n", - " {'bibcode': '2018NatSR...814848T',\n", - " 'abstract': 'In mammals, the central circadian clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus and it orchestrates peripheral clocks in the whole body to organize physiological and behavioral rhythms. Light-induced phase-shift of the SCN clock enables synchronization of the circadian clock system with 24-h environmental light/dark cycle. We previously found that adenosine deaminase acting on RNA 2 (Adar2), an A-to-I RNA editing enzyme catalyzing rhythmic A-to-I RNA editing, governs a wide range of mRNA rhythms in the mouse liver and regulates the circadian behavior. In brain, ADAR2-mediated A-to-I RNA editing was reported to occur in various transcripts encoding ion channels and neurotransmitter receptors, which could influence neuronal function of the SCN. Here we show that ADAR2 plays a crucial role for light-induced phase-shift of the circadian clock. Intriguingly, exposure of Adar2-knockout mice to a light pulse at late night caused an aberrant phase-advance of the locomotor rhythms. By monitoring the bioluminescence rhythms of the mutant SCN slices, we found that a phase-advance induced by treatment with pituitary adenylyl cyclase-activating polypeptide (PACAP) was markedly attenuated. The present study suggests that A-to-I RNA editing in the SCN regulates a proper phase response to light in the mouse circadian system.',\n", - " 'author': ['Terajima, Hideki',\n", - " 'Yoshitane, Hikari',\n", - " 'Yoshikawa, Tomoko',\n", - " 'Shigeyoshi, Yasufumi',\n", - " 'Fukada, Yoshitaka'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-018-33114-6\"}'],\n", - " 'title': ['A-to-I RNA editing enzyme ADAR2 regulates light-induced circadian phase-shift']},\n", - " {'bibcode': '2020NatSR..1019412W',\n", - " 'abstract': 'Prominin 1 (PROM1) is one of a few clinically relevant progenitor markers in human alcoholic hepatitis (AH) and hepatocellular carcinoma (HCC), and mouse liver tumor initiating stem cell-like cells (TICs). However, the origin, fate and functions of PROM1+ cells in AH and HCC are unknown. Here we show by genetic lineage tracing that PROM1+ cells are derived in part from hepatocytes in AH and become tumor cells in mice with diethyl nitrosamine (DEN)-initiated, Western alcohol diet-promoted liver tumorigenesis. Our RNA sequencing analysis of mouse PROM1+ cells, reveals transcriptomic landscapes indicative of their identities as ductular reaction progenitors (DRPs) and TICs. Indeed, single-cell RNA sequencing reveals two subpopulations of Prom1+ Afp- DRPs and Prom1+ Afp+ TICs in the DEN-WAD model. Integrated bioinformatic analysis identifies Discodin Domain Receptor 1 (DDR1) as a uniquely upregulated and patient-relevant gene in PROM1+ cells in AH and HCC. Translational relevance of DDR1 is supported by its marked elevation in HCC which is inversely associated with patient survival. Further, knockdown of Ddr1 suppresses the growth of TICs and TIC-derived tumor growth in mice. These results suggest the importance of PROM1+ cells in the evolution of liver cancer and DDR1 as a potential driver of this process.',\n", - " 'author': ['Wu, Raymond',\n", - " 'Pan, Stephanie',\n", - " 'Chen, Yibu',\n", - " 'Nakano, Yasuhiro',\n", - " 'Li, Meng',\n", - " 'Balog, Steven',\n", - " 'Tsukamoto, Hidekazu'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-020-76458-8\"}'],\n", - " 'title': ['Fate and functional roles of Prominin 1+ cells in liver injury and cancer']},\n", - " {'bibcode': '2016NatSR...620559Z',\n", - " 'abstract': 'Bile acid (BA) metabolism is tightly controlled by nuclear receptor signaling to coordinate regulation of BA synthetic enzymes and transporters. Here we reveal a molecular cascade consisting of the antiapoptotic protein BCL2, nuclear receptor Shp, and long non-coding RNA (lncRNA) H19 to maintain BA homeostasis. Bcl2 was overexpressed in liver of C57BL/6J mice using adenovirus mediated gene delivery for two weeks. Hepatic overexpression of Bcl2 caused drastic accumulation of serum BA and bilirubin levels and dysregulated BA synthetic enzymes and transporters. Bcl2 reactivation triggered severe liver injury, fibrosis and inflammation, which were accompanied by a significant induction of H19. Bcl2 induced rapid SHP protein degradation via the activation of caspase-8 pathway. The induction of H19 in Bcl2 overexpressed mice was contributed by a direct loss of Shp transcriptional repression. H19 knockdown or Shp re-expression largely rescued Bcl2-induced liver injury. Strikingly different than Shp, the expression of Bcl2 and H19 was hardly detectable in adult liver but was markedly increased in fibrotic/cirrhotic human and mouse liver. We demonstrated for the first time a detrimental effect of Bcl2 and H19 associated with cholestatic liver fibrosis and an indispensable role of Shp to maintain normal liver function.',\n", - " 'author': ['Zhang, Yuxia',\n", - " 'Liu, Chune',\n", - " 'Barbier, Olivier',\n", - " 'Smalling, Rana',\n", - " 'Tsuchiya, Hiroyuki',\n", - " 'Lee, Sangmin',\n", - " 'Delker, Don',\n", - " 'Zou, An',\n", - " 'Hagedorn, Curt H.',\n", - " 'Wang, Li'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep20559\"}'],\n", - " 'title': ['Bcl2 is a critical regulator of bile acid homeostasis by dictating Shp and lncRNA H19 function']},\n", - " {'bibcode': '1981Sci...213..559P',\n", - " 'abstract': 'Mice fed a purified diet low in copper display anemia, hypoceruloplasminemia, depressed concentrations of liver copper, and elevated concentrations of liver iron. An impaired humoral-mediated immune response (decreased numbers of antibody-producing cells) is observed in mice with severe as well as marginal copper deficiency. The magnitude of this impairment is highly correlated with the degree of functional copper deficiency (hypoceruloplasminemia).',\n", - " 'author': ['Prohaska, Joseph R.', 'Lukasewycz, Omelan A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.7244654\"}'],\n", - " 'title': ['Copper Deficiency Suppresses the Immune Response of Mice']},\n", - " {'bibcode': '1993Natur.364...67G',\n", - " 'abstract': 'DEFINITIVE erythropoiesis in birds originates from stem cells that emerge in the splanchnopleural mesoderm near the embryonic aorta1-4. The yolk sac is still generally held to be the unique provider of haematopoietic stem cells during mammalian ontogeny5, although there may be an alternative intraembryonic source of stem cells in the mouse fetus6,7. Here we search for a possible non-yolk-sac source of stem cells by grafting intraembryonic splanchnopleura from 10- to 18-somite mouse embryos into adult immunodeficient SCID mice. We find significant amounts of donor-derived serum IgM, normal numbers of IgM-secreting plasma cells, and the Bla (IgMa brightB220dullCD5+) cell subset to be fully reconstituted by donor progenitors 3 to 6 months after engraftment. The haematogenic capacity revealed in our experiments is present in a previously unrecognized site, the earliest described in the embryo, 12 hours before fetal liver colonization.',\n", - " 'author': ['Godin, Isabelle E.',\n", - " 'Garcia-Porrero, Juan A.',\n", - " 'Coutinho, Antonio',\n", - " 'Dieterlen-Lièvre, Françoise',\n", - " 'Marcos, Miguel A. R.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F364067a0\"}'],\n", - " 'title': ['Para-aortic splanchnopleura from early mouse embryos contains B1a cell progenitors']},\n", - " {'bibcode': '2008NYASA1140..368L',\n", - " 'abstract': 'Exposure of maternal mice to inorganic arsenic through the drinking water induces liver tumors and aberrant gene expression in offspring when they reach adulthood. To help define if these are direct fetal effects of arsenic, fetal liver cells were isolated from untreated mice at gestation day 13.5 by mechanical dissection and centrifugation. Two hours after seeding the cells on collagen1‑coated plates in William E media containing 10% fetal bovine serum, 1x ITS (insulin, transferrin, and selenium) and antibiotics, inorganic arsenite (0, 0.1, 0.3, and 1.0 μM) was added to the fresh media for 72 h. Cell morphology and viability were not significantly altered by these arsenic concentrations. At the end of arsenic exposure, cells were harvested into Trizol, and total RNA was extracted, purified, and subjected to real‑time reverse transcriptase polymerase chain reaction (RT‑PCR) analysis. Arsenite exposure produced a concentration‑dependent induction of heme oxygenase‑1 (up to eight‑fold) and metallothionein‑1 (up to five‑fold), indicative of stress response to adapt to arsenic insult. Expression of genes related to steroid metabolism, such as 17β‑hydroxysteroid dehydrogenase‑7 (HSD17β7) and Cyp2a4, were increased approximately two‑fold, together with increases in estrogen receptor‑α (ER‑α) and ER‑α‑linked genes, such as anterior gradient‑2, keratin 1–19, and trefoil factor‑3. Arsenic in vitro induced a three‑fold increase in the expression of α‑fetoprotein (AFP), a biomarker associated with transplacental arsenic‑induced mouse liver tumors. Thus, exposure of mouse fetal liver cells to arsenic induces adaptive responses and aberrant gene expression, which could alter genetic programming at a very early life stage, potentially contributing to tumor formation much later in life.',\n", - " 'author': ['Liu, Jie',\n", - " 'Yu, Limei',\n", - " 'Tokar, Erik J.',\n", - " 'Bortner, Carl',\n", - " 'Sifre, Maria I.',\n", - " 'Sun, Yang',\n", - " 'Waalkes, Michael P.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1196%2Fannals.1454.028\"}'],\n", - " 'title': ['Arsenic‑induced Aberrant Gene Expression in Fetal Mouse Primary Liver‑Cell Cultures']},\n", - " {'bibcode': '1995Sci...267.1506M',\n", - " 'abstract': 'bcl-x is a member of the bcl-2 gene family, which may regulate programmed cell death. Mice were generated that lacked Bcl-x. The Bcl-x-deficient mice died around embryonic day 13. Extensive apoptotic cell death was evident in postmitotic immature neurons of the developing brain, spinal cord, and dorsal root ganglia. Hematopoietic cells in the liver were also apoptotic. Analyses of bcl-x double-knockout chimeric mice showed that the maturation of Bcl-x-deficient lymphocytes was diminished. The life-span of immature lymphocytes, but not mature lymphocytes, was shortened. Thus, Bcl-x functions to support the viability of immature cells during the development of the nervous and hematopoietic systems.',\n", - " 'author': ['Motoyama, Noboru',\n", - " 'Wang, Fanping',\n", - " 'Roth, Kevin A.',\n", - " 'Sawa, Hirofumi',\n", - " 'Nakayama, Kei-Ichi',\n", - " 'Nakayama, Keiko',\n", - " 'Negishi, Izumi',\n", - " 'Senju, Satoru',\n", - " 'Zhang, Qing',\n", - " 'Fujii, Satoshi',\n", - " 'Loh, Dennis Y.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.7878471\"}'],\n", - " 'title': ['Massive Cell Death of Immature Hematopoietic Cells and Neurons in Bcl-x- Deficient Mice']},\n", - " {'bibcode': '1999Natur.401...73S',\n", - " 'abstract': 'Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by a paucity of adipose (fat) tissue which is evident at birth and is accompanied by a severe resistance to insulin, leading to hyperinsulinaemia, hyperglycaemia and enlarged fatty liver. We have developed a mouse model that mimics these features of CGL: the syndrome occurs in transgenic mice expressing a truncated version of a nuclear protein known as nSREBP-1c (for sterol-regulatory-element-binding protein-1c) under the control of the adipose-specific aP2 enhancer. Adipose tissue from these mice was markedly deficient in messenger RNAs encoding several fat-specific proteins, including leptin, a fat-derived hormone that regulates food intake and energy metabolism. Here we show that insulin resistance in our lipodystrophic mice can be overcome by a continuous systemic infusion of low doses of recombinant leptin, an effect that is not mimicked by chronic food restriction. Our results support the idea that leptin modulates insulin sensitivity and glucose disposal independently of its effect on food intake, and that leptin deficiency accounts for the insulin resistance found in CGL.',\n", - " 'author': ['Shimomura, Iichiro',\n", - " 'Hammer, Robert E.',\n", - " 'Ikemoto, Shinji',\n", - " 'Brown, Michael S.',\n", - " 'Goldstein, Joseph L.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F43448\"}'],\n", - " 'title': ['Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy']},\n", - " {'bibcode': '2022FrCh...10.4893C',\n", - " 'abstract': 'Hand-to-mouth activity is considered to be the main way for children to come into contact with contaminated soil, and bioavailability is an important factor affecting their health risk. To reduce soil As risk to humans by oral exposure, nanoscale zero-valent iron (nZVI) has been extensively studied for immobilizing As-contaminated soil, but its efficiency has not been investigated using in vitro assay and its influence on As-RBA. In this study, two contaminated soil samples (A and B) were amended with 1% and 2% (w/w) nZVI for 56 days to study its effect on As fraction by sequence extraction, As bioaccessibility by SBRC assay, and As relative bioavailability (RBA) by the mouse liver and kidney model. Based on the sequence extraction, the As associated with the E1 (exchangeable fraction) and C2 (carbonate fraction) fractions were decreased from 3.00% to 1.68% for soil A and from 21.6% to 7.86% for soil B after being treated with 2% nZVI for 56 days. When assessing As bioaccessibility in all soils treated with nZVI by SBRC assay, it was found that As bioaccessibility was significantly higher in the gastric phase (GP) and lower in the intestinal phase (IP) (p < 0.05), and the bioaccessible Fe concentration decreased significantly from the gastric to intestinal phase at the same time. Based on the mouse liver-kidney model, the As-RBA in soil A increased from 21.6% to 22.3% and 39.9%, but in soil B decreased from 73.0% to 55.3% and 68.9%, respectively. In addition, there was a significant difference between As bioaccessibility based on GP or IP of SBRC assay and As-RBA in two soils after being treated with nZVI for 56 days. To more accurately assess the effects of nZVI human arsenic exposure, As-RBA should be considered in concert with secondary evidence provided through fraction and bioaccessibility assessments. In addition, it is necessary to develop a suitable in vitro assay to predict As-RBA in nZVI-amended soils.',\n", - " 'author': ['Chen, Shuo',\n", - " 'Han, Lei',\n", - " 'Wang, Qiu',\n", - " 'Liu, Chenglang',\n", - " 'Liu, Yuzhen',\n", - " 'Li, Jie'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.3389%2Ffchem.2022.964893\"}'],\n", - " 'title': ['Effect of Nanoscale Zero-Valent Iron on Arsenic Bioaccessibility and Bioavailability in Soil']},\n", - " {'bibcode': '2016NatSR...624399Y',\n", - " 'abstract': 'The activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is closely associated with the development and progression of non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet. Therefore, we investigated whether oral administration of sulforaphane (SFN) prevented high-fat diet-induced NAFLD in mice by regulation of the NLRP3 inflammasome in the liver. Daily oral administrations of SFN reduced hepatic steatosis scores, serum ALT and AST levels, and hepatic levels of cholesterol, triglycerides, and free fatty acids in mice fed a high-fat diet. These were correlated with the suppression of NLRP3 inflammasome activation in the liver by SFN as evidenced by decrease in mRNA levels of ASC and caspase-1, caspase-1 enzyme activity, and IL-1β levels. SFN inhibited saturated fatty acid-induced activation of the NLRP3 inflammasome in primary mouse hepatocytes, accompanied by the restoration of mitochondrial dysfunction. The suppression of NLRP3 inflammasome by SFN was mediated by the regulation of AMP-activated protein kinase-autophagy axis. Our findings demonstrated that the suppression of NLRP3 inflammasome activation by an orally available small molecule inhibitor leads to the alleviation of the hepatic steatosis symptoms associated with NAFLD induced by a high-fat diet.',\n", - " 'author': ['Yang, Gabsik', 'Lee, Hye Eun', 'Lee, Joo Young'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep24399\"}'],\n", - " 'title': ['A pharmacological inhibitor of NLRP3 inflammasome prevents non-alcoholic fatty liver disease in a mouse model induced by high fat diet']},\n", - " {'bibcode': '2015NatCo...6.7079O',\n", - " 'abstract': 'FoxO proteins are major targets of insulin action. To better define the role of FoxO1 in mediating insulin effects in the liver, we generated liver-specific insulin receptor knockout (LIRKO) and IR/FoxO1 double knockout (LIRFKO) mice. Here we show that LIRKO mice are severely insulin resistant based on glucose, insulin and C-peptide levels, and glucose and insulin tolerance tests, and genetic deletion of hepatic FoxO1 reverses these effects. 13C-glucose and insulin clamp studies indicate that regulation of both hepatic glucose production (HGP) and glucose utilization is impaired in LIRKO mice, and these defects are also restored in LIRFKO mice corresponding to changes in gene expression. We conclude that (1) inhibition of FoxO1 is critical for both direct (hepatic) and indirect effects of insulin on HGP and utilization, and (2) extrahepatic effects of insulin are sufficient to maintain normal whole-body and hepatic glucose metabolism when liver FoxO1 activity is disrupted.',\n", - " 'author': ['O-Sullivan, Insug',\n", - " 'Zhang, Wenwei',\n", - " 'Wasserman, David H.',\n", - " 'Liew, Chong Wee',\n", - " 'Liu, Jonathan',\n", - " 'Paik, Jihye',\n", - " 'Depinho, Ronald A.',\n", - " 'Stolz, Donna Beer',\n", - " 'Kahn, C. Ronald',\n", - " 'Schwartz, Michael W.',\n", - " 'Unterman, Terry G.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fncomms8079\"}'],\n", - " 'title': ['FoxO1 integrates direct and indirect effects of insulin on hepatic glucose production and glucose utilization']},\n", - " {'bibcode': '2016NatSR...630111K',\n", - " 'abstract': 'Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent causes of liver disease and its prevalence is a serious and growing clinical problem. Caloric restriction (CR) is commonly recommended for improvement of obesity-related diseases such as NAFLD. However, the effects of CR on hepatic metabolism remain unknown. We investigated the effects of CR on metabolic dysfunction in the liver of obese diabetic db/db mice. We found that CR of db/db mice reverted insulin resistance, hepatic steatosis, body weight and adiposity to those of db/m mice. 1H-NMR- and UPLC-QTOF-MS-based metabolite profiling data showed significant metabolic alterations related to lipogenesis, ketogenesis, and inflammation in db/db mice. Moreover, western blot analysis showed that lipogenesis pathway enzymes in the liver of db/db mice were reduced by CR. In addition, CR reversed ketogenesis pathway enzymes and the enhanced autophagy, mitochondrial biogenesis, collagen deposition and endoplasmic reticulum stress in db/db mice. In particular, hepatic inflammation-related proteins including lipocalin-2 in db/db mice were attenuated by CR. Hepatic metabolomic studies yielded multiple pathological mechanisms of NAFLD. Also, these findings showed that CR has a therapeutic effect by attenuating the deleterious effects of obesity and diabetes-induced multiple complications.',\n", - " 'author': ['Kim, Kyung Eun',\n", - " 'Jung, Youngae',\n", - " 'Min, Soonki',\n", - " 'Nam, Miso',\n", - " 'Heo, Rok Won',\n", - " 'Jeon, Byeong Tak',\n", - " 'Song, Dae Hyun',\n", - " 'Yi, Chin-Ok',\n", - " 'Jeong, Eun Ae',\n", - " 'Kim, Hwajin',\n", - " 'Kim, Jeonghyun',\n", - " 'Jeong, Seon-Yong',\n", - " 'Kwak, Woori',\n", - " 'Ryu, Do Hyun',\n", - " 'Horvath, Tamas L.',\n", - " 'Roh, Gu Seob',\n", - " 'Hwang, Geum-Sook'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep30111\"}'],\n", - " 'title': ['Caloric restriction of db/db mice reverts hepatic steatosis and body weight with divergent hepatic metabolism']},\n", - " {'bibcode': '2019Natur.574..268W',\n", - " 'abstract': 'Liver cancer remains difficult to treat, owing to a paucity of drugs that target critical dependencies1,2; broad-spectrum kinase inhibitors such as sorafenib provide only a modest benefit to patients with hepatocellular carcinoma3. The induction of senescence may represent a strategy for the treatment of cancer, especially when combined with a second drug that selectively eliminates senescent cancer cells (senolysis)4,5. Here, using a kinome-focused genetic screen, we show that pharmacological inhibition of the DNA-replication kinase CDC7 induces senescence selectively in liver cancer cells with mutations in TP53. A follow-up chemical screen identified the antidepressant sertraline as an agent that kills hepatocellular carcinoma cells that have been rendered senescent by inhibition of CDC7. Sertraline suppressed mTOR signalling, and selective drugs that target this pathway were highly effective in causing the apoptotic cell death of hepatocellular carcinoma cells treated with a CDC7 inhibitor. The feedback reactivation of mTOR signalling after its inhibition6 is blocked in cells that have been treated with a CDC7 inhibitor, which leads to the sustained inhibition of mTOR and cell death. Using multiple in vivo mouse models of liver cancer, we show that treatment with combined inhibition of of CDC7 and mTOR results in a marked reduction of tumour growth. Our data indicate that exploiting an induced vulnerability could be an effective treatment for liver cancer.',\n", - " 'author': ['Wang, Cun',\n", - " 'Vegna, Serena',\n", - " 'Jin, Haojie',\n", - " 'Benedict, Bente',\n", - " 'Lieftink, Cor',\n", - " 'Ramirez, Christel',\n", - " 'de Oliveira, Rodrigo Leite',\n", - " 'Morris, Ben',\n", - " 'Gadiot, Jules',\n", - " 'Wang, Wei',\n", - " 'du Chatinier, Aimée',\n", - " 'Wang, Liqin',\n", - " 'Gao, Dongmei',\n", - " 'Evers, Bastiaan',\n", - " 'Jin, Guangzhi',\n", - " 'Xue, Zheng',\n", - " 'Schepers, Arnout',\n", - " 'Jochems, Fleur',\n", - " 'Sanchez, Antonio Mulero',\n", - " 'Mainardi, Sara',\n", - " 'te Riele, Hein',\n", - " 'Beijersbergen, Roderick L.',\n", - " 'Qin, Wenxin',\n", - " 'Akkari, Leila',\n", - " 'Bernards, René'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41586-019-1607-3\"}'],\n", - " 'title': ['Inducing and exploiting vulnerabilities for the treatment of liver cancer']},\n", - " {'bibcode': '2005PNAS..10217059C',\n", - " 'abstract': 'The Sleeping Beauty (SB) transposon system can integrate foreign sequences of DNA in the genome of mouse somatic cells eliciting long-term expression in vivo. This technology holds great promise for human gene therapy as a nonviral technology to deliver therapeutic genes. SB also provides a means to study the effects of defined genetic elements, such as oncogenes, on somatic cells in mice. Here, we test the ability of the SB transposon system to facilitate somatic integration of a transposon containing an activated NRAS oncogene in mouse hepatocytes to elicit tumor formation. NRAS oncogene-driven tumors developed when such vectors were delivered to the livers of p19Arf-null or heterozygous mice. Delivery of the NRAS transposon cooperates with Arf loss to cause carcinomas of hepatocellular or biliary origin. These tumors allowed characterization of transposon integration and expression at the single-cell level, revealing robust NRAS expression and both transposase-mediated and random insertion of delivered vectors. Random integration and expression of the SB transposase plasmid was also observed in one instance. In addition, studies using effector loop mutants of activated NRAS provide evidence that mitogen-activated protein kinase activation alone cannot efficiently induce liver carcinomas. This system can be used to rapidly model tumors caused by defined genetic changes.',\n", - " 'author': ['Carlson, Corey M.',\n", - " 'Frandsen, Joel L.',\n", - " 'Kirchhof, Nicole',\n", - " 'McIvor, R. Scott',\n", - " 'Largaespada, David A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/102/47/17059\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/102/47/17059\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/full/102/47/17059\"}'],\n", - " 'title': ['Somatic integration of an oncogene-harboring Sleeping Beauty transposon models liver tumor development in the mouse']},\n", - " {'bibcode': '2015PLoSO..1032672D',\n", - " 'author': ['Deol, Poonamjot',\n", - " 'Evans, Jane R.',\n", - " 'Dhahbi, Joseph',\n", - " 'Chellappa, Karthikeyani',\n", - " 'Han, Diana S.',\n", - " 'Spindler, Stephen',\n", - " 'Sladek, Frances M.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0132672\"}'],\n", - " 'title': ['Soybean Oil Is More Obesogenic and Diabetogenic than Coconut Oil and Fructose in Mouse: Potential Role for the Liver']},\n", - " {'bibcode': '1992Natur.356..612C',\n", - " 'abstract': 'LYMPHOCYTES(B and T cells) derive continuously from the same multipotential stem cells that produce myeloid cells, including erythrocytes, granulocytes and macrophages1,2. Tri- and bipotential myeloid intermediates between the multipotential stem cells and later unipotential cells have been identified using clonal methods in culture. Although similar methods have detected committed pre-B cells in mouse fetal liver3, earlier progenitors with additional non-B lineage options have not been demonstrated in normal tissues. We report the characterization and purification of fetal liver cells that generate clones containing both macrophages and B cells, identified biochemically and morphologically. The common origin of the two cell types was shown by culture of single precursor cells. Their dual potential and unreal-ranged i mm u no-globulin loci place the precursors before exclusive B-lineage commitment in the haematopoietic hierarchy. The availability of such cells in purified form will allow direct study of lineage choice in cells having both lymphoid and non-lymphoid options.',\n", - " 'author': ['Cumano, Ana',\n", - " 'Paige, Christopher J.',\n", - " 'Iscove, Norman N.',\n", - " 'Brady, Gerard'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F356612a0\"}'],\n", - " 'title': ['Bipotential precursors of B cells and macrophages in murine fetal liver']},\n", - " {'bibcode': '2021AcSpA.24618960W',\n", - " 'abstract': 'Drug-induced liver injury (DILI) is a prevalent liver disease and the leading cause for acute liver failure (ALF) worldwide. Screening of DILI in patients is central to ensure drug safety and improve therapy efficiency. Mounting evidences revealed that peroxynitrite (ONOO-) is involved in the DILI process and can be a potential biomarker for DILI. Thus far, there are few two-photon fluorescence probes for ONOO- that can accomplish this challenging task in DILI liver tissues. Hereby, a peroxynitrite activatable two-photon fluorescence probe BN-PN for the imaging of ONOO- in mice liver was elaborately constructed. The probe specifically reacted with peroxynitrite to furnish 140-fold fluorescence increase in vitro, which elucidated a high sensitivity for ONOO-. Thus, subtle changes of ONOO- levels in live cells can be sensitively imaged with this probe by two-photon microscopy. The probe also denoted the overproduction of ONOO- in APAP-induced liver injury, and proved that administration with NAC can effectively alleviate DILI and reduce ONOO- production in mouse liver. Further, the probe demonstrated the rapid rise of ONOO- level in the liver of DILI mice administrated with alcohol. This work disclosed the rational construction of a two-photon fluorescence probe-based DILI screening method, which would help the estimation of drug safety and new drug development.',\n", - " 'author': ['Wang, Zhao',\n", - " 'Zhang, Fan',\n", - " 'Xiong, Jianhua',\n", - " 'Mao, Zhiqiang',\n", - " 'Liu, Zhihong'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.saa.2020.118960\"}'],\n", - " 'title': ['Investigations of drug-induced liver injury by a peroxynitrite activatable two-photon fluorescence probe']},\n", - " {'bibcode': '1999PNAS...96.3906W',\n", - " 'abstract': 'Mice generated by disrupting the clotting factor IX gene exhibit severe bleeding disorder and closely resemble the phenotype seen in hemophilia B patients. Here we demonstrate that a single intraportal injection of a recombinant adeno-associated virus (AAV) vector encoding canine factor IX cDNA under the control of a liver-specific enhancer/promoter leads to a long-term and complete correction of the bleeding disorder. High level expression of up to 15-20 μg/ml of canine factor IX was detected in the plasma of mice injected with 5.6 × 1011 particles of an AAV vector for >5 months. The activated partial thromboplastin time of the treated mice was fully corrected to higher than normal levels. Liver-specific expression of canine factor IX was confirmed by immunofluorescence staining, and secreted factor IX protein was identified in the mouse plasma by Western blotting. All treated mice survived the tail clip test without difficulty. Thus, a single intraportal injection of a recombinant adeno-associated virus vector expressing factor IX successfully cured the bleeding disorder of hemophilia B mice, proving the feasibility of using AAV-based vectors for liver-targeted gene therapy of genetic diseases.',\n", - " 'author': ['Wang, Lili',\n", - " 'Takabe, Kazuaki',\n", - " 'Bidlingmaier, Scott M.',\n", - " 'Ill, Charles R.',\n", - " 'Verma, Inder M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/96/7/3906\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/96/7/3906\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/96/7/3906\"}'],\n", - " 'title': ['Sustained Correction of Bleeding Disorder in Hemophilia B Mice by Gene Therapy']},\n", - " {'bibcode': '2013PLoSO...869114C',\n", - " 'author': ['Chiang, Dian J.',\n", - " 'Roychowdhury, Sanjoy',\n", - " 'Bush, Katelyn',\n", - " 'McMullen, Megan R.',\n", - " 'Pisano, Sorana',\n", - " 'Niese, Kathryn',\n", - " 'Olman, Mitchell A.',\n", - " 'Pritchard, Michele T.',\n", - " 'Nagy, Laura E.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1371%2Fjournal.pone.0069114\"}'],\n", - " 'title': ['Adenosine 2A Receptor Antagonist Prevented and Reversed Liver Fibrosis in a Mouse Model of Ethanol-Exacerbated Liver Fibrosis']},\n", - " {'bibcode': '2020PNAS..117.9630G',\n", - " 'abstract': 'Protein synthesis is a fundamental and tightly controlled process which allows organisms to respond rapidly to external signals such as nutrient availability or stress conditions. While the initiation step is well studied, the determinants of translation elongation rate on mRNAs are poorly understood, particularly in mammals. Here we combined computational and molecular biology approaches to shed light on the determinants of translation elongation rates and their relationships with aminoacyl-tRNAs in livers of normally fed and fasted mice. We found that the ribosome dwell times in mouse liver depend on codon pairs, were robust to prolonged fasting, and can be explained to some extent by a combination of aminoacyl-tRNA level and codon usage/tRNA balance.',\n", - " 'author': ['Gobet, Cédric',\n", - " 'Weger, Benjamin Dieter',\n", - " 'Marquis, Julien',\n", - " 'Martin, Eva',\n", - " 'Neelagandan, Nagammal',\n", - " 'Gachon, Frédéric',\n", - " 'Naef, Felix'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1918145117\"}'],\n", - " 'title': ['Robust landscapes of ribosome dwell times and aminoacyl-tRNAs in response to nutrient stress in liver']},\n", - " {'bibcode': '2009PNAS..10615956C',\n", - " 'abstract': 'Expressed in liver, aquaglyceroporin-9 (AQP9) is permeated by glycerol, arsenite, and other small, neutral solutes. To evaluate a possible protective role, AQP9-null mice were evaluated for in vivo arsenic toxicity. After injection with NaAsO2, AQP9-null mice suffer reduced survival rates (LD50, 12 mg/kg) compared with WT mice (LD50, 15 mg/kg). The highest tissue level of arsenic is in heart, with AQP9-null mice accumulating 10-20 times more arsenic than WT mice. Within hours after NaAsO2 injection, AQP9-null mice sustain profound bradycardia, despite normal serum electrolytes. Increased arsenic levels are also present in liver, lung, spleen, and testis of AQP9-null mice. Arsenic levels in the feces and urine of AQP9-null mice are only ≈10% of the WT levels, and reduced clearance of multiple arsenic species by the AQP9-null mice suggests that AQP9 is involved in the export of multiple forms of arsenic. Immunohistochemical staining of liver sections revealed that AQP9 is most abundant in basolateral membrane of hepatocytes adjacent to the sinusoids. AQP9 is not detected in heart or kidney by PCR or immunohistochemistry. We propose that AQP9 provides a route for excretion of arsenic by the liver, thereby providing partial protection of the whole animal from arsenic toxicity.',\n", - " 'author': ['Carbrey, Jennifer M.',\n", - " 'Song, Linhua',\n", - " 'Zhou, Yao',\n", - " 'Yoshinaga, Masafumi',\n", - " 'Rojek, Aleksandra',\n", - " 'Wang, Yiding',\n", - " 'Liu, Yangjian',\n", - " 'Lujan, Heidi L.',\n", - " 'DiCarlo, Stephen E.',\n", - " 'Nielsen, Søren',\n", - " 'Rosen, Barry P.',\n", - " 'Agre, Peter',\n", - " 'Mukhopadhyay, Rita'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/106/37/15956\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0908108106\"}'],\n", - " 'title': ['Reduced arsenic clearance and increased toxicity in aquaglyceroporin-9-null mice']},\n", - " {'bibcode': '2013BioBu..40..519Z',\n", - " 'author': ['Zinevich, L. S.',\n", - " 'Goncharova, N. O.',\n", - " 'Uryvaeva, I. V.',\n", - " 'Delone, G. V.',\n", - " 'Mikaelyan, A. S.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1134%2FS1062359013060150\"}'],\n", - " 'title': ['Igf-1 and its isoform expression in hepatic cell tumors and the surrounding tissue in mice liver carcinogenesis induced by diethylnitrozamine']},\n", - " {'bibcode': '2023Chmsp.315m7751Q',\n", - " 'author': ['Qi, Lei',\n", - " 'Dong, Yan-Mei',\n", - " 'Chao, Hong',\n", - " 'Zhao, Peng',\n", - " 'Ma, Shu-Li',\n", - " 'Li, Gang'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.chemosphere.2023.137751\"}'],\n", - " 'title': ['Glyphosate based-herbicide disrupts energy metabolism and activates inflammatory response through oxidative stress in mice liver']},\n", - " {'bibcode': '2007Natur.450..435M',\n", - " 'abstract': \"In programmed cell death, a large number of cells undergo apoptosis, and are engulfed by macrophages to avoid the release of noxious materials from the dying cells. In definitive erythropoiesis, nuclei are expelled from erythroid precursor cells and are engulfed by macrophages. Phosphatidylserine is exposed on the surface of apoptotic cells and on the nuclei expelled from erythroid precursor cells; it works as an `eat me' signal for phagocytes. Phosphatidylserine is also expressed on the surface of exosomes involved in intercellular signalling. Here we established a library of hamster monoclonal antibodies against mouse peritoneal macrophages, and found an antibody that strongly inhibited the phosphatidylserine-dependent engulfment of apoptotic cells. The antigen recognized by the antibody was identified by expression cloning as a type I transmembrane protein called Tim4 (T-cell immunoglobulin- and mucin-domain-containing molecule; also known as Timd4). Tim4 was expressed in Mac1+ cells in various mouse tissues, including spleen, lymph nodes and fetal liver. Tim4 bound apoptotic cells by recognizing phosphatidylserine via its immunoglobulin domain. The expression of Tim4 in fibroblasts enhanced their ability to engulf apoptotic cells. When the anti-Tim4 monoclonal antibody was administered into mice, the engulfment of apoptotic cells by thymic macrophages was significantly blocked, and the mice developed autoantibodies. Among the other Tim family members, Tim1, but neither Tim2 nor Tim3, specifically bound phosphatidylserine. Tim1- or Tim4-expressing Ba/F3 B cells were bound by exosomes via phosphatidylserine, and exosomes stimulated the interaction between Tim1 and Tim4. These results indicate that Tim4 and Tim1 are phosphatidylserine receptors for the engulfment of apoptotic cells, and may also be involved in intercellular signalling in which exosomes are involved.\",\n", - " 'author': ['Miyanishi, Masanori',\n", - " 'Tada, Kazutoshi',\n", - " 'Koike, Masato',\n", - " 'Uchiyama, Yasuo',\n", - " 'Kitamura, Toshio',\n", - " 'Nagata, Shigekazu'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature06307\"}'],\n", - " 'title': ['Identification of Tim4 as a phosphatidylserine receptor']},\n", - " {'bibcode': '1994PNAS...91.9151V',\n", - " 'abstract': 'An increase in hepatic gluconeogenesis is believed to be an important factor responsible for the fasting hyperglycemia detected in patients with non-insulin-dependent diabetes mellitus (NIDDM). Phosphoenolpyruvate carboxykinase (GTP) (PEPCK; EC 4.1.1.32) is a regulatory enzyme of gluconeogenesis. To study the role of the expression of PEPCK gene in the development of NIDDM, we have produced lines of transgenic mice expressing a PEPCK minigene under control of its own promoter. Transgenic mice were hyperglycemic and had higher serum insulin concentrations. In addition, alterations in liver glycogen content and muscle glucose transporter GLUT-4 gene expression were detected. The overexpression of the PEPCK gene led to an increase in glucose production from pyruvate in hepatocytes in primary culture. When intraperitoneal glucose tolerance tests were performed, blood glucose levels were higher than those detected in normal mice. This animal model shows that primary alterations in the rate of liver glucose production may induce insulin resistance and NIDDM.',\n", - " 'author': ['Valera, Alfons',\n", - " 'Pujol, Anna',\n", - " 'Pelegrin, Mireia',\n", - " 'Bosch, Fatima'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/91/19/9151\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/91/19/9151\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/91/19/9151\"}'],\n", - " 'title': ['Transgenic mice overexpressing phosphoenolpyruvate carboxykinase develop non-insulin-dependent diabetes mellitus.']},\n", - " {'bibcode': '2014NatNa...9..648D',\n", - " 'abstract': 'Dysfunctional endothelium contributes to more diseases than any other tissue in the body. Small interfering RNAs (siRNAs) can help in the study and treatment of endothelial cells in vivo by durably silencing multiple genes simultaneously, but efficient siRNA delivery has so far remained challenging. Here, we show that polymeric nanoparticles made of low-molecular-weight polyamines and lipids can deliver siRNA to endothelial cells with high efficiency, thereby facilitating the simultaneous silencing of multiple endothelial genes in vivo. Unlike lipid or lipid-like nanoparticles, this formulation does not significantly reduce gene expression in hepatocytes or immune cells even at the dosage necessary for endothelial gene silencing. These nanoparticles mediate the most durable non-liver silencing reported so far and facilitate the delivery of siRNAs that modify endothelial function in mouse models of vascular permeability, emphysema, primary tumour growth and metastasis.',\n", - " 'author': ['Dahlman, James E.',\n", - " 'Barnes, Carmen',\n", - " 'Khan, Omar F.',\n", - " 'Thiriot, Aude',\n", - " 'Jhunjunwala, Siddharth',\n", - " 'Shaw, Taylor E.',\n", - " 'Xing, Yiping',\n", - " 'Sager, Hendrik B.',\n", - " 'Sahay, Gaurav',\n", - " 'Speciner, Lauren',\n", - " 'Bader, Andrew',\n", - " 'Bogorad, Roman L.',\n", - " 'Yin, Hao',\n", - " 'Racie, Tim',\n", - " 'Dong, Yizhou',\n", - " 'Jiang, Shan',\n", - " 'Seedorf, Danielle',\n", - " 'Dave, Apeksha',\n", - " 'Singh Sandhu, Kamaljeet',\n", - " 'Webber, Matthew J.',\n", - " 'Novobrantseva, Tatiana',\n", - " 'Ruda, Vera M.',\n", - " 'Lytton-Jean, Abigail K. R.',\n", - " 'Levins, Christopher G.',\n", - " 'Kalish, Brian',\n", - " 'Mudge, Dayna K.',\n", - " 'Perez, Mario',\n", - " 'Abezgauz, Ludmila',\n", - " 'Dutta, Partha',\n", - " 'Smith, Lynelle',\n", - " 'Charisse, Klaus',\n", - " 'Kieran, Mark W.',\n", - " 'Fitzgerald, Kevin',\n", - " 'Nahrendorf, Matthias',\n", - " 'Danino, Dganit',\n", - " 'Tuder, Rubin M.',\n", - " 'von Andrian, Ulrich H.',\n", - " 'Akinc, Akin',\n", - " 'Panigrahy, Dipak',\n", - " 'Schroeder, Avi',\n", - " 'Koteliansky, Victor',\n", - " 'Langer, Robert',\n", - " 'Anderson, Daniel G.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnnano.2014.84\"}'],\n", - " 'title': ['In vivo endothelial siRNA delivery using polymeric nanoparticles with low molecular weight']},\n", - " {'bibcode': '2021NatCo..12..613R',\n", - " 'abstract': 'Induction of intrinsic liver regeneration is an unmet need that can be achieved by temporally activating key hepatocyte regenerative pathways. Here, we establish an efficient, safe, non-integrative method to transiently express hepatocyte-growth-factor (HGF) and epidermal-growth-factor (EGF) in hepatocytes via nucleoside-modified, lipid-nanoparticle-encapsulated mRNA (mRNA-LNP) delivery in mice. We confirm specific hepatotropism of mRNA-LNP via intravenous injection of firefly luciferase encoding mRNA-LNP, with protein expression lasting about 3 days. In the liver, virtually all hepatocytes are transfected along with a subpopulation of endothelial and Kupffer cells. In homeostasis, HGF mRNA-LNP efficiently induce hepatocyte proliferation. In a chronic liver injury mouse model recapitulating non-alcoholic fatty liver disease, injections of both HGF and EGF mRNA-LNP sharply reverse steatosis and accelerate restoration of liver function. Likewise, HGF and EGF mRNA-LNP accelerate liver regeneration after acetaminophen-induced acute liver injury with rapid return to baseline ALT levels. This study introduces mRNA-LNP as a potentially translatable safe therapeutic intervention to harness liver regeneration via controlled expression of endogenous mitogens in vivo.',\n", - " 'author': ['Rizvi, Fatima',\n", - " 'Everton, Elissa',\n", - " 'Smith, Anna R.',\n", - " 'Liu, Hua',\n", - " 'Osota, Elizabeth',\n", - " 'Beattie, Mitchell',\n", - " 'Tam, Ying',\n", - " 'Pardi, Norbert',\n", - " 'Weissman, Drew',\n", - " 'Gouon-Evans, Valerie'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41467-021-20903-3\"}'],\n", - " 'title': ['Murine liver repair via transient activation of regenerative pathways in hepatocytes using lipid nanoparticle-complexed nucleoside-modified mRNA']},\n", - " {'bibcode': '2010PNAS..107..798Y',\n", - " 'abstract': 'To better define the mechanism(s) likely responsible for viral clearance during hepatitis B virus (HBV) infection, viral clearance was studied in a panel of immunodeficient mouse strains that were hydrodynamically transfected with a plasmid containing a replication-competent copy of the HBV genome. Neither B cells nor perforin were required to clear the viral DNA transcriptional template from the liver. In contrast, the template persisted for at least 60 days at high levels in NOD/Scid mice and at lower levels in the absence of CD4+ and CD8+ T cells, NK cells, Fas, IFN-gamma (IFN-γ), IFN-alpha/beta receptor (IFN-α/βR1), and TNF receptor 1 (TNFR1), indicating that each of these effectors was required to eliminate the transcriptional template from the liver. Interestingly, viral replication was ultimately terminated in all lineages except the NOD/Scid mice, suggesting the existence of redundant pathways that inhibit HBV replication. Finally, induction of a CD8+ T cell response in these animals depended on the presence of CD4+ T cells. These results are consistent with a model in which CD4+ T cells serve as master regulators of the adaptive immune response to HBV; CD8+ T cells are the key cellular effectors mediating HBV clearance from the liver, apparently by a Fas-dependent, perforin-independent process in which NK cells, IFN-γ, TNFR1, and IFN-α/βR play supporting roles. These results provide insight into the complexity of the systems involved in HBV clearance, and they suggest unique directions for analysis of the mechanism(s) responsible for HBV persistence.',\n", - " 'author': ['Yang, Priscilla L.',\n", - " 'Althage, Alana',\n", - " 'Chung, Josan',\n", - " 'Maier, Holly',\n", - " 'Wieland, Stefan',\n", - " 'Isogawa, Masanori',\n", - " 'Chisari, Francis V.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/107/2/798\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0913498107\"}'],\n", - " 'title': ['Immune effectors required for hepatitis B virus clearance']},\n", - " {'bibcode': '2017NatSR...714493Z',\n", - " 'abstract': \"MicroRNAs are implicated as crucial mediators in metabolic diseases including obesity, diabetes, and non-alcoholic fatty liver diseases (NAFLD). Here, we show miR-27a attenuated hepatic de novo lipogenesis and alleviated obesity-initiated NAFLD through inhibiting Fasn and Scd1 in liver. Hepatic levels of miR-27a were significantly augmented in HFD-fed and ob/ob mice. Further studies demonstrated that miR-27a directly interacted with 3' untranslated region (3'-UTR) of hepatic Fasn and Scd1 mRNAs and reduced their expression levels in mice. Adenovirus-mediated overexpression of miR-27a robustly blocked sodium oleate-induced triglyceride (TG) accumulation in mouse primary hepatocytes and reduced liver TG contents in mice via repressing hepatic lipogenesis. Furthermore, ectopic expression of hepatic miR-27a impaired lipid contents of livers and attenuated NAFLD development through suppressing lipogenesis in HCD-fed and ob/ob mice. Together, our results reveal a critical role of miR-27a in lipid homeostasis of liver and pathogenesis of NAFLD.\",\n", - " 'author': ['Zhang, Meiyuan', 'Sun, Weilan', 'Zhou, Minghao', 'Tang, Yan'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-017-15141-x\"}'],\n", - " 'title': ['MicroRNA-27a regulates hepatic lipid metabolism and alleviates NAFLD via repressing FAS and SCD1']},\n", - " {'bibcode': '2009PNAS..10613511Z',\n", - " 'abstract': 'Raman spectroscopy is a newly developed, noninvasive preclinical imaging technique that offers picomolar sensitivity and multiplexing capabilities to the field of molecular imaging. In this study, we demonstrate the ability of Raman spectroscopy to separate the spectral fingerprints of up to 10 different types of surface enhanced Raman scattering (SERS) nanoparticles in a living mouse after s.c. injection. Based on these spectral results, we simultaneously injected the five most intense and spectrally unique SERS nanoparticles i.v. to image their natural accumulation in the liver. All five types of SERS nanoparticles were successfully identified and spectrally separated using our optimized noninvasive Raman imaging system. In addition, we were able to linearly correlate Raman signal with SERS concentration after injecting four spectrally unique SERS nanoparticles either s.c. (R2 = 0.998) or i.v. (R2 = 0.992). These results show great potential for multiplexed imaging in living subjects in cases in which several targeted SERS probes could offer better detection of multiple biomarkers associated with a specific disease.',\n", - " 'author': ['Zavaleta, Cristina L.',\n", - " 'Smith, Bryan R.',\n", - " 'Walton, Ian',\n", - " 'Doering, William',\n", - " 'Davis, Glenn',\n", - " 'Shojaei, Borzoyeh',\n", - " 'Natan, Michael J.',\n", - " 'Gambhir, Sanjiv S.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/106/32/13511\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0813327106\"}'],\n", - " 'title': ['Multiplexed imaging of surface enhanced Raman scattering nanotags in living mice using noninvasive Raman spectroscopy']},\n", - " {'bibcode': '2003Sci...302..255M',\n", - " 'abstract': 'Cell division in many mammalian tissues is associated with specific times of day, but just how the circadian clock controls this timing has not been clear. Here, we show in the regenerating liver (of mice) that the circadian clock controls the expression of cell cycle-related genes that in turn modulate the expression of active Cyclin B1-Cdc2 kinase, a key regulator of mitosis. Among these genes, expression of wee1 was directly regulated by the molecular components of the circadian clockwork. In contrast, the circadian clockwork oscillated independently of the cell cycle in single cells. Thus, the intracellular circadian clockwork can control the cell-division cycle directly and unidirectionally in proliferating cells.',\n", - " 'author': ['Matsuo, Takuya',\n", - " 'Yamaguchi, Shun',\n", - " 'Mitsui, Shigeru',\n", - " 'Emi, Aki',\n", - " 'Shimoda, Fukuko',\n", - " 'Okamura, Hitoshi'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.1086271\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.1086271\"}'],\n", - " 'title': ['Control Mechanism of the Circadian Clock for Timing of Cell Division in Vivo']},\n", - " {'bibcode': '2015NatSR...5E8616P',\n", - " 'abstract': 'Liver transplantation is the treatment of choice for chronic liver failure, although it is complicated by donor shortage, surgery-related complications, and immunological rejection. Cell transplantation is an alternative, minimally invasive treatment option with potentially fewer complications. We used human palatine tonsil as a novel source of mesenchymal stem cells (T-MSCs) and examined their ability to differentiate into hepatocyte-like cells in vivo and in vitro. Carbon tetrachloride (CCl4) mouse model was used to investigate the ability of T-MSCs to home to the site of liver injury. T-MSCs were only detected in the damaged liver, suggesting that they are disease-responsive. Differentiation of T-MSCs into hepatocyte-like cells was confirmed in vitro as determined by expression of hepatocyte markers. Next, we showed resolution of liver fibrosis by T-MSCs via reduction of TGF-β expression and collagen deposition in the liver. We hypothesized that autophagy activation was a possible mechanism for T-MSC-mediated liver recovery. In this report, we demonstrate for the first time that T-MSCs can differentiate into hepatocyte-like cells and ameliorate liver fibrosis via autophagy activation and down-regulation of TGF-β. These findings suggest that T-MSCs could be used as a novel source for stem cell therapy targeting liver diseases.',\n", - " 'author': ['Park, Minhwa',\n", - " 'Kim, Yu-Hee',\n", - " 'Woo, So-Youn',\n", - " 'Lee, Hye Jin',\n", - " 'Yu, Yeonsil',\n", - " 'Kim, Han Su',\n", - " 'Park, Yoon Shin',\n", - " 'Jo, Inho',\n", - " 'Park, Joo-Won',\n", - " 'Jung, Sung-Chul',\n", - " 'Lee, Hyukjin',\n", - " 'Jeong, Byeongmoon',\n", - " 'Ryu, Kyung-Ha'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep08616\"}'],\n", - " 'title': ['Tonsil-derived Mesenchymal Stem Cells Ameliorate CCl4-induced Liver Fibrosis in Mice via Autophagy Activation']},\n", - " {'bibcode': '1994Natur.368..339K',\n", - " 'abstract': 'lNTERLEUKIN-6 (IL-6) is a multifunctional cytokine that regulates various aspects of the immune response, acute-phase reaction and haematopoiesis (for reviews see refs 1, 2). In vitro, leukaemia inhibitory factor, oncostatin M, ciliary neurotrophic factor and interleukin-11 display overlapping activities with IL-6. This functional redundancy may be explained by the interactions of specific binding receptors with a common signal-transducing receptor (gp130) (for reviews see refs 3, 4). To elucidate the unique function of IL-6 in vivo, we have disrupted the IL-6 gene by homologous recombination. IL-6-deficient mice develop normally. They fail to control efficiently vaccinia virus and infection with Listeria monocytogenes, a facultative intracellular bacterium. The T-cell-dependent antibody response against vesicular stomatitis virus is impaired. Further, the inflammatory acute-phase response after tissue damage or infection is severely compromised, whereas it is only moderately affected after challenge with lipopolysaccharide. We conclude that IL-6 production induced by injury or infection is an important in vivo SOS signal which coordinates activities of liver cells, macrophages and lymphocytes.',\n", - " 'author': ['Kopf, Manfred',\n", - " 'Baumann, Heinz',\n", - " 'Freer, Giulia',\n", - " 'Freudenberg, Marina',\n", - " 'Lamers, Marinus',\n", - " 'Kishimoto, Tadamitsu',\n", - " 'Zinkernagel, Rolf',\n", - " 'Bluethmann, Horst',\n", - " 'Köhler, Georges'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F368339a0\"}'],\n", - " 'title': ['Impaired immune and acute-phase responses in interleukin-6-deficient mice']},\n", - " {'bibcode': '2007PNAS..10410601Z',\n", - " 'abstract': \"Alzheimer's disease (AD) is an age-dependent neurodegenerative disease that causes progressive cognitive impairment. The initiation and progression of AD has been linked to cholesterol metabolism and inflammation, processes that can be modulated by liver x receptors (LXRs). We show here that endogenous LXR signaling impacts the development of AD-related pathology. Genetic loss of either Lxrα or Lxrβ in APP/PS1 transgenic mice results in increased amyloid plaque load. LXRs regulate basal and inducible expression of key cholesterol homeostatic genes in the brain and act as potent inhibitors of inflammatory gene expression. Ligand activation of LXRs attenuates the inflammatory response of primary mixed glial cultures to fibrillar amyloid β peptide (fAβ) in a receptor-dependent manner. Furthermore, LXRs promote the capacity of microglia to maintain fAβ-stimulated phagocytosis in the setting of inflammation. These results identify endogenous LXR signaling as an important determinant of AD pathogenesis in mice. We propose that LXRs may be tractable targets for the treatment of AD due to their ability to modulate both lipid metabolic and inflammatory gene expression in the brain.\",\n", - " 'author': ['Zelcer, Noam',\n", - " 'Khanlou, Negar',\n", - " 'Clare, Ryan',\n", - " 'Jiang, Qingguang',\n", - " 'Reed-Geaghan, Erin G.',\n", - " 'Landreth, Gary E.',\n", - " 'Vinters, Harry V.',\n", - " 'Tontonoz, Peter'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/104/25/10601\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0701096104\"}'],\n", - " 'title': [\"Attenuation of neuroinflammation and Alzheimer's disease pathology by liver x receptors\"]},\n", - " {'bibcode': '1993PNAS...90.8088M',\n", - " 'abstract': 'We report the generation of transgenic mice deficient in the metallothionein MT-I and MT-II genes. The mutations were introduced into embryonic stem cells by homologous recombination. Chimeric mice resulting from the targeted embryonic stem cells transmitted the disrupted alleles through their germ line. Homozygous animals were born alive and appeared phenotypically normal and fertile. Absence of MT proteins was confirmed by direct measurement in liver extracts. Challenging the mutant animals with moderate levels of CdSO4 indicated their greater susceptibility to cadmium toxicity than wild-type animals. These mice should provide a useful model to allow detailed study of the physiological roles of MT-I and MT-II.',\n", - " 'author': ['Michalska, Anna E.', 'Choo, K. H. Andy'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/90/17/8088\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/90/17/8088\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/90/17/8088\"}'],\n", - " 'title': ['Targeting and germ-line transmission of a null mutation at the metallothionein I and II loci in mouse.']},\n", - " {'bibcode': '2011Natur.478..123H',\n", - " 'abstract': 'Spinal muscular atrophy (SMA) is a motor neuron disease and the leading genetic cause of infant mortality; it results from loss-of-function mutations in the survival motor neuron 1 (SMN1) gene. Humans have a paralogue, SMN2, whose exon 7 is predominantly skipped, but the limited amount of functional, full-length SMN protein expressed from SMN2 cannot fully compensate for a lack of SMN1. SMN is important for the biogenesis of spliceosomal small nuclear ribonucleoprotein particles, but downstream splicing targets involved in pathogenesis remain elusive. There is no effective SMA treatment, but SMN restoration in spinal cord motor neurons is thought to be necessary and sufficient. Non-central nervous system (CNS) pathologies, including cardiovascular defects, were recently reported in severe SMA mouse models and patients, reflecting autonomic dysfunction or direct effects in cardiac tissues. Here we compared systemic versus CNS restoration of SMN in a severe mouse model. We used an antisense oligonucleotide (ASO), ASO-10-27, that effectively corrects SMN2 splicing and restores SMN expression in motor neurons after intracerebroventricular injection. Systemic administration of ASO-10-27 to neonates robustly rescued severe SMA mice, much more effectively than intracerebroventricular administration; subcutaneous injections extended the median lifespan by 25 fold. Furthermore, neonatal SMA mice had decreased hepatic Igfals expression, leading to a pronounced reduction in circulating insulin-like growth factor 1 (IGF1), and ASO-10-27 treatment restored IGF1 to normal levels. These results suggest that the liver is important in SMA pathogenesis, underscoring the importance of SMN in peripheral tissues, and demonstrate the efficacy of a promising drug candidate.',\n", - " 'author': ['Hua, Yimin',\n", - " 'Sahashi, Kentaro',\n", - " 'Rigo, Frank',\n", - " 'Hung, Gene',\n", - " 'Horev, Guy',\n", - " 'Bennett, C. Frank',\n", - " 'Krainer, Adrian R.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature10485\"}'],\n", - " 'title': ['Peripheral SMN restoration is essential for long-term rescue of a severe spinal muscular atrophy mouse model']},\n", - " {'bibcode': '2011Sci...332..963X',\n", - " 'abstract': 'Transcriptionally silent genes can be marked by histone modifications and regulatory proteins that indicate the genes’ potential to be activated. Such marks have been identified in pluripotent cells, but it is unknown how such marks occur in descendant, multipotent embryonic cells that have restricted cell fate choices. We isolated mouse embryonic endoderm cells and assessed histone modifications at regulatory elements of silent genes that are activated upon liver or pancreas fate choices. We found that the liver and pancreas elements have distinct chromatin patterns. Furthermore, the histone acetyltransferase P300, recruited via bone morphogenetic protein signaling, and the histone methyltransferase Ezh2 have modulatory roles in the fate choice. These studies reveal a functional “prepattern” of chromatin states within multipotent progenitors and potential targets to modulate cell fate induction.',\n", - " 'author': ['Xu, Cheng-Ran',\n", - " 'Cole, Philip A.',\n", - " 'Meyers, David J.',\n", - " 'Kormish, Jay',\n", - " 'Dent, Sharon',\n", - " 'Zaret, Kenneth S.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.1202845\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.1202845\"}'],\n", - " 'title': ['Chromatin “Prepattern” and Histone Modifiers in a Fate Choice for Liver and Pancreas']},\n", - " {'bibcode': '2017RSCAd...732198Q',\n", - " 'author': ['Qi, Guoyuan',\n", - " 'Mi, Yashi',\n", - " 'Fan, Rong',\n", - " 'Li, Runnan',\n", - " 'Wang, Yiwen',\n", - " 'Li, Xingyu',\n", - " 'Huang, Shuxian',\n", - " 'Liu, Xuebo'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1039%2FC7RA05000C\"}'],\n", - " 'title': ['Tea polyphenols ameliorate hydrogen peroxide- and constant darkness-triggered oxidative stress via modulating the Keap1/Nrf2 transcriptional signaling pathway in HepG2 cells and mice liver']},\n", - " {'bibcode': '2017NatSR...7..325T',\n", - " 'abstract': 'Chronic hepatitis C virus (HCV) infection is one of the major causes of serious liver diseases, including liver cirrhosis. There are no anti-fibrotic drugs with efficacy against liver cirrhosis. Wnt/β-catenin signaling has been implicated in the pathogenesis of a variety of tissue fibrosis. In the present study, we investigated the effects of a β-catenin/CBP (cyclic AMP response element binding protein) inhibitor on liver fibrosis. The anti-fibrotic activity of PRI-724, a selective inhibitor of β-catenin/CBP, was assessed in HCV GT1b transgenic mice at 18 months after HCV genome expression. PRI-724 was injected intraperitoneally or subcutaneously in these mice for 6 weeks. PRI-724 reduced liver fibrosis, which was indicated by silver stain, Sirius Red staining, and hepatic hydroxyproline levels, in HCV mice while attenuating αSMA induction. PRI-724 led to increased levels of matrix metalloproteinase (MMP)-8 mRNA in the liver, along with elevated levels of intrahepatic neutrophils and macrophages/monocytes. The induced intrahepatic neutrophils and macrophages/monocytes were identified as the source of MMP-8. In conclusion, PRI-724 ameliorated HCV-induced liver fibrosis in mice. We hypothesize that inhibition of hepatic stellate cells activation and induction of fibrolytic cells expressing MMP-8 contribute to the anti-fibrotic effects of PRI-724. PRI-724 is a drug candidate which possesses anti-fibrotic effect.',\n", - " 'author': ['Tokunaga, Yuko',\n", - " 'Osawa, Yosuke',\n", - " 'Ohtsuki, Takahiro',\n", - " 'Hayashi, Yukiko',\n", - " 'Yamaji, Kenzaburo',\n", - " 'Yamane, Daisuke',\n", - " 'Hara, Mitsuko',\n", - " 'Munekata, Keisuke',\n", - " 'Tsukiyama-Kohara, Kyoko',\n", - " 'Hishima, Tsunekazu',\n", - " 'Kojima, Soichi',\n", - " 'Kimura, Kiminori',\n", - " 'Kohara, Michinori'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-017-00282-w\"}'],\n", - " 'title': ['Selective inhibitor of Wnt/β-catenin/CBP signaling ameliorates hepatitis C virus-induced liver fibrosis in mouse model']},\n", - " {'bibcode': '1975PNAS...72.3893D',\n", - " 'abstract': 'Previous studies have shown that in mammalian cells proteins of large molecular weight are degraded more rapidly than small ones. Evidence is presented here that half-lives of proteins are also related to their isoelectric points. A double-isotope method was used to compare degradative rates of soluble proteins separated by isoelectric focusing. In rat liver, skeletal muscle, kidney, and brain, more rapid rates of catabolism were found for acidic protein fractions than for neutral or basic ones. Acidic proteins also tended to be degraded faster in several mouse tissues. A literature survey confirmed this trend. For 22 proteins from rat liver, a highly significant correlation was found between rates of degradation and isoelectric points (r = 0.824; P less than 0.01). This relationship between isoelectric point and half-life appears to be distinct from that between protein size and half-life.',\n", - " 'author': ['Dice, J. Fred', 'Goldberg, Alfred L.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/72/10/3893\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/72/10/3893\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/72/10/3893\"}'],\n", - " 'title': ['Relationship between in vivo degradative rates and isoelectric points of proteins.']},\n", - " {'bibcode': '2005Natur.434..520K',\n", - " 'abstract': 'Natural killer T (NKT) cells constitute a highly conserved T lymphocyte subpopulation that has the potential to regulate many types of immune responses through the rapid secretion of cytokines. NKT cells recognize glycolipids presented by CD1d, a class I-like antigen-presenting molecule. They have an invariant T-cell antigen receptor (TCR) α-chain, but whether this invariant TCR recognizes microbial antigens is still controversial. Here we show that most mouse and human NKT cells recognize glycosphingolipids from Sphingomonas, Gram-negative bacteria that do not contain lipopolysaccharide. NKT cells are activated in vivo after exposure to these bacterial antigens or bacteria, and mice that lack NKT cells have a marked defect in the clearance of Sphingomonas from the liver. These data suggest that NKT cells are T lymphocytes that provide an innate-type immune response to certain microorganisms through recognition by their antigen receptor, and that they might be useful in providing protection from bacteria that cannot be detected by pattern recognition receptors such as Toll-like receptor 4.',\n", - " 'author': ['Kinjo, Yuki',\n", - " 'Wu, Douglass',\n", - " 'Kim, Gisen',\n", - " 'Xing, Guo-Wen',\n", - " 'Poles, Michael A.',\n", - " 'Ho, David D.',\n", - " 'Tsuji, Moriya',\n", - " 'Kawahara, Kazuyoshi',\n", - " 'Wong, Chi-Huey',\n", - " 'Kronenberg, Mitchell'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature03407\"}'],\n", - " 'title': ['Recognition of bacterial glycosphingolipids by natural killer T cells']},\n", - " {'bibcode': '2022AGUFMIN15C0290C',\n", - " 'abstract': 'High-throughput nucleic acid sequencing (DNA-seq, RNA-seq) has become widespread in biomedical research due to the growing availability and affordability of these assays. Data analysis has been accelerated in recent years by the adoption of artificial intelligence (AI) and machine learning (ML) techniques by biomedical researchers. In space biology research, RNA-seq datasets from space-flown experimental samples are critical for characterizing the gene expression aberrations associated with exposure to spaceflight stressors. However, space biological experiments tend to have a very low sample size, so identifying proper AI/ML algorithms for sequencing data analysis is an ongoing challenge since these algorithms typically require large sample sizes.

The NASA Science Mission Directorate (SMD) has started the \"Benchmark Initiative for AI/ML\", focused on creating datasets meant for three main applications: 1) scientific benchmarking, which finds the best algorithm for a specific problem; 2) application benchmarking, which measures algorithm performance against a set of parameters; and 3) system benchmarking, which evaluates performance of hardware and software architecture. These scientific benchmarks consist of an AI-ready dataset and a reference implementation on a specific scientific question. In this work, we focused on generating standardized datasets to allow the scientific community to benchmark AI/ML algorithms in the domain of space biology.

We present here a standardized, AI-ready, publicly available benchmark dataset for space biology RNA-seq data as a collaboration between the NASA AI4LS (Artificial Intelligence for Life Sciences) working group and NASA\\'s SMD. This dataset consists of space-flown and ground control mouse liver found in the NASA GeneLab omics database. However, to amplify the small sample number (n=112) for ML purposes, we employ Gaussian noise and a generative adversarial network to extend this dataset to 6,000 synthetic samples, matching the original gene expression characteristics.

We believe that this dataset will be a valuable, publicly available resource for researchers in space biology who wish to test and develop new AI/ML algorithms for gene expression data analysis.',\n", - " 'author': ['Casaletto, James',\n", - " 'Gurung, Iksha',\n", - " 'Ramasubramanian, Muthukumaran',\n", - " 'Sanders, Lauren',\n", - " 'Maskey, Manil',\n", - " 'Costes, Sylvain'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://agu.confex.com/agu/fm22/meetingapp.cgi/Paper/1180341\"}'],\n", - " 'title': ['Space Flown Rodent Liver RNA Sequencing Data for Machine Learning in Space Biology Research']},\n", - " {'bibcode': '2014SPIE.9041E..0HT',\n", - " 'abstract': 'Stimulated Raman scattering (SRS) spectral microscopy is a promising imaging method, based on vibrational spectroscopy, which can visualize biological tissues with chemical specificity. SRS spectral microscopy has been used to obtain two-dimensional spectral images of rat liver tissue, three-dimensional images of a vessel in rat liver, and in vivo spectral images of mouse ear skin. Various multivariate analysis techniques, such as principal component analysis and independent component analysis, have been used to obtain spectral images. In this study, we propose a digital staining method. This method uses SRS spectra and statistical machine learning that makes use of prior knowledge of spectral peaks and their two-dimensional distributional patterns corresponding to the composition of tissue samples. The method selects spectral peaks on the basis of Mahalanobis distance, which is defined as the ratio of inter-group variation to intragroup variation. We also make use of higher-order local autocorrelations as feature values for two-dimensional distributional patterns. This combination of techniques allows groups corresponding to different intracellular structures to be clearly discriminated in the multidimensional feature space. We investigate the performance of our method on mouse liver tissue samples and show that the proposed method can digitally stain each intracellular structure such as cell nuclei, cytoplasm, and erythrocytes separately and clearly without time-consuming chemical staining processes. We anticipate that our method could be applied to computer-aided pathological diagnosis.',\n", - " 'author': ['Tanji, K.',\n", - " 'Otsuka, Y.',\n", - " 'Satoh, S.',\n", - " 'Hashimoto, H.',\n", - " 'Ozeki, Y.',\n", - " 'Itoh, Kazuyoshi'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1117%2F12.2042820\"}'],\n", - " 'title': ['Toward digital staining using stimulated Raman scattering and statistical machine learning']},\n", - " {'bibcode': '2018NatSR...812284H',\n", - " 'abstract': 'Glycine N-methyltransferase (GNMT) is a tumor suppressor for HCC. It is down-regulated in HCC, but the mechanism is not fully understood. MicroRNA-224 (miR-224) acts as an onco-miR in HCC. This study is the first to investigate miR-224 targeting the coding region of GNMT transcript. The GNMT-MT plasmid containing a miR-224 binding site silent mutation of the GNMT coding sequence can escape the suppression of miR-224 in HEK293T cells. Expression of both exogenous and endogenous GNMT was suppressed by miR-224, while miR-224 inhibitor enhanced GNMT expression. miR-224 counteracts the effects of GNMT on the reduction of cell proliferation and tumor growth. The levels of miR-224 and GNMT mRNA showed a significant inverse relationship in tumor specimens from HCC patients. Utilizing CCl4-treated hepatoma cells and mice as a cell damage of inflammatory or liver injury model, we observed that the decreased expression levels of GNMT were accompanied with the elevated expression levels of miR-224 in hepatoma cells and mouse liver. Finally, hepatic AAV-mediated GNMT also reduced CCl4-induced miR-224 expression and liver fibrosis. These results indicated that AAV-mediated GNMT has potential liver protection activity. miR-224 can target the GNMT mRNA coding sequence and plays an important role in GNMT suppression during liver tumorigenesis.',\n", - " 'author': ['Hung, Jung-Hsien',\n", - " 'Li, Chung-Hsien',\n", - " 'Yeh, Ching-Hua',\n", - " 'Huang, Pin-Cheng',\n", - " 'Fang, Cheng-Chieh',\n", - " 'Chen, Yen-Fu',\n", - " 'Lee, Kuo-Jui',\n", - " 'Chou, Chih-Hung',\n", - " 'Cheng, Hsin-Yun',\n", - " 'Huang, Hsien-Da',\n", - " 'Chen, Marcelo',\n", - " 'Tsai, Ting-Fen',\n", - " 'Lin, Anya Maan-Yuh',\n", - " 'Yen, Chia-Hung',\n", - " 'Tsou, Ann-Ping',\n", - " 'Tyan, Yu-Chang',\n", - " 'Chen, Yi-Ming Arthur'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-018-30682-5\"}'],\n", - " 'title': ['MicroRNA-224 down-regulates Glycine N-methyltransferase gene expression in Hepatocellular Carcinoma']},\n", - " {'bibcode': '2018SPIE10573E..4IL',\n", - " 'abstract': 'Theranostics is an innovative research field that aims to develop high target specificity cancer treatments by administering small metal-based nanoparticles (NPs). This new generation of compounds exhibits diagnostic and therapeutic properties due to the high atomic number of their metal component. In the framework of a combined research program on low dose X-ray imaging and theranostic NPs, X-ray Phase Contrast Tomography (XPCT) was performed at ESRF using a 3 μm pixel optical system on two samples: a mouse brain bearing melanoma metastases injected with gadolinium NPs and, a mouse liver injected with gold NPs. XPCT is a non-destructive technique suitable to achieve the 3D reconstruction of a specimen and, widely used at micro-scale to detect abnormalities of the vessels, which are associated to the tumor growth or to the development of neurodegenerative diseases. Moreover, XPCT represents a promising and complementary tool to study the biodistribution of theranostic NPs in biological materials, thanks to the strong contrast with respect to soft tissues that metal-based NPs provide in radiological images. This work is relied on an original imaging approach based on the evaluation of the contrast differences between the images acquired below and above K-edge energies, as a proof of the certain localization of NPs. We will present different methods aiming to enhance the localization of NPs and a 3D map of their distribution in large volume of tissues.',\n", - " 'author': ['Longo, E.',\n", - " 'Bravin, A.',\n", - " 'Brun, F.',\n", - " 'Bukreeva, I.',\n", - " 'Cedola, A.',\n", - " 'De La Rochefoucauld, O.',\n", - " 'Fratini, M.',\n", - " 'Le Guevel, X.',\n", - " 'Massimi, L.',\n", - " 'Sancey, L.',\n", - " 'Tillement, O.',\n", - " 'Zeitoun, P.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1117%2F12.2293090\"}'],\n", - " 'title': ['3D imaging of theranostic nanoparticles in mice organs by means of x-ray phase contrast tomography']},\n", - " {'bibcode': '2015NatSR...513106A',\n", - " 'abstract': 'Iron imbalance is a feature of liver damage. However, the biological correlation of serum hepcidin, a key regulator of iron homeostasis, with liver malfunction is undefined. To this end, we piloted the Chinese population studies to address whether hepcidin is linked to liver functionality. The serum hepcidin, ferritin, alanine transaminase, aspartate transaminase, gamma-glutamyltransferase and bilirubin were examined in two independent Chinese cohorts consisted of 3455 individuals. After adjustment for sex, age, body mass index, smoking habits, drinking categories and diabetic status, a positive association between hepcidin and alanine transaminase (ALT) (beta\\u2009=\\u20090.18\\u2009±\\u20090.01, P\\u2009<\\u20090.0001) was discovered using linear regression in a cohort consisting of 1813 individuals. This association was then validated in the second independent cohort of 1642 individuals (beta\\u2009=\\u20090.08\\u2009±\\u20090.02, P\\u2009<\\u20090.0001). Furthermore, consistent with cohort study, by applying both CCl4 and lipopolysaccharide induced mouse liver injury models, at least 2-fold elevations in hepcidin expression, serum ALT and inflammatory cytokine IL-6 were discovered during the initiation stage of liver injury. Our findings suggest that increased serum hepcidin may reflect a protective response to the iron status and elevated serum cytokines during liver injury. Additional studies are warranted to validate these findings and test their potential clinical relevance in patients.',\n", - " 'author': ['An, Peng',\n", - " 'Wang, Hao',\n", - " 'Wu, Qian',\n", - " 'Guo, Xin',\n", - " 'Wu, Aimin',\n", - " 'Zhang, Zhou',\n", - " 'Zhang, Di',\n", - " 'Xu, Xiaochen',\n", - " 'Mao, Qianyun',\n", - " 'Shen, Xiaoyun',\n", - " 'Zhang, Lihong',\n", - " 'Xiong, Zhiqi',\n", - " 'He, Lin',\n", - " 'Liu, Yun',\n", - " 'Min, Junxia',\n", - " 'Zhou, Daizhan',\n", - " 'Wang, Fudi'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep13106\"}'],\n", - " 'title': ['Elevated serum transaminase activities were associated with increased serum levels of iron regulatory hormone hepcidin and hyperferritinemia risk']},\n", - " {'bibcode': '2015NatSR...517762L',\n", - " 'abstract': 'Hepatic fibrosis is associated with bone marrow derived mesenchymal stem cells (BM-MSCs). In this study, we aimed to determine what role MSCs play in the process and how they mobilize from bone marrow (BM). We employed a mouse model of carbon tetrachloride(CCl4)-induced liver fibrosis. Frozen section was used to detect MSCs recruited to mice and human fibrotic liver. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was detected to assess liver function. It was found that MSCs of both exogenous and endogenous origin could aggravate liver fibrosis and attenuate liver damage as indicated by lower serum ALT and AST levels. Stromal cell-derived factor-1 (SDF-1α)/ CXCR4 was the most important chemotactic axis regulating MSCs migration from BM to fibrotic liver. Frozen section results showed that the migration did not start from the beginning of liver injury but occured when the expression balance of SDF-1α between liver and BM was disrupted, where SDF-1α expression in liver was higher than that in BM. Our findings provide further evidence to show the role of BM-MSCs in liver fibrosis and to elucidate the mechanism underlying MSCs mobilization in our early liver fibrosis mice model induced by CCl4.',\n", - " 'author': ['Liu, Yan',\n", - " 'Yang, Xue',\n", - " 'Jing, Yingying',\n", - " 'Zhang, Shanshan',\n", - " 'Zong, Chen',\n", - " 'Jiang, Jinghua',\n", - " 'Sun, Kai',\n", - " 'Li, Rong',\n", - " 'Gao, Lu',\n", - " 'Zhao, Xue',\n", - " 'Wu, Dong',\n", - " 'Shi, Yufang',\n", - " 'Han, Zhipeng',\n", - " 'Wei, Lixin'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep17762\"}'],\n", - " 'title': ['Contribution and Mobilization of Mesenchymal Stem Cells in a mouse model of carbon tetrachloride-induced liver fibrosis']},\n", - " {'bibcode': '2018NatCo...9.4824C',\n", - " 'abstract': 'Nonalcoholic fatty liver disease (NAFLD) is increasing in worldwide prevalence, closely tracking the obesity epidemic, but specific pharmaceutical treatments for NAFLD are lacking. Defining the key molecular pathways underlying the pathogenesis of NAFLD is essential for developing new drugs. Here we demonstrate that inhibition of gut-derived serotonin synthesis ameliorates hepatic steatosis through a reduction in liver serotonin receptor 2A (HTR2A) signaling. Local serotonin concentrations in the portal blood, which can directly travel to and affect the liver, are selectively increased by high-fat diet (HFD) feeding in mice. Both gut-specific Tph1 knockout mice and liver-specific Htr2a knockout mice are resistant to HFD-induced hepatic steatosis, without affecting systemic energy homeostasis. Moreover, selective HTR2A antagonist treatment prevents HFD-induced hepatic steatosis. Thus, the gut TPH1-liver HTR2A axis shows promise as a drug target to ameliorate NAFLD with minimal systemic metabolic effects.',\n", - " 'author': ['Choi, Wonsuk',\n", - " 'Namkung, Jun',\n", - " 'Hwang, Inseon',\n", - " 'Kim, Hyeongseok',\n", - " 'Lim, Ajin',\n", - " 'Park, Hye Jung',\n", - " 'Lee, Hye Won',\n", - " 'Han, Kwang-Hyub',\n", - " 'Park, Seongyeol',\n", - " 'Jeong, Ji-Seon',\n", - " 'Bang, Geul',\n", - " 'Kim, Young Hwan',\n", - " 'Yadav, Vijay K.',\n", - " 'Karsenty, Gerard',\n", - " 'Ju, Young Seok',\n", - " 'Choi, Chan',\n", - " 'Suh, Jae Myoung',\n", - " 'Park, Jun Yong',\n", - " 'Park, Sangkyu',\n", - " 'Kim, Hail'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41467-018-07287-7\"}'],\n", - " 'title': ['Serotonin signals through a gut-liver axis to regulate hepatic steatosis']},\n", - " {'bibcode': '2020NatCo..11.3232W',\n", - " 'abstract': 'CRISPR-Cas9 has emerged as a powerful technology that relies on Cas9/sgRNA ribonucleoprotein complexes (RNPs) to target and edit DNA. However, many therapeutic targets cannot currently be accessed due to the lack of carriers that can deliver RNPs systemically. Here, we report a generalizable methodology that allows engineering of modified lipid nanoparticles to efficiently deliver RNPs into cells and edit tissues including muscle, brain, liver, and lungs. Intravenous injection facilitated tissue-specific, multiplexed editing of six genes in mouse lungs. High carrier potency was leveraged to create organ-specific cancer models in livers and lungs of mice though facile knockout of multiple genes. The developed carriers were also able to deliver RNPs to restore dystrophin expression in DMD mice and significantly decrease serum PCSK9 level in C57BL/6 mice. Application of this generalizable strategy will facilitate broad nanoparticle development for a variety of disease targets amenable to protein delivery and precise gene correction approaches.',\n", - " 'author': ['Wei, Tuo',\n", - " 'Cheng, Qiang',\n", - " 'Min, Yi-Li',\n", - " 'Olson, Eric N.',\n", - " 'Siegwart, Daniel J.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41467-020-17029-3\"}'],\n", - " 'title': ['Systemic nanoparticle delivery of CRISPR-Cas9 ribonucleoproteins for effective tissue specific genome editing']},\n", - " {'bibcode': '1987PNAS...84.7056B',\n", - " 'abstract': \"Previous experiments have demonstrated that the human beta-globin gene is correctly regulated in transgenic mice. The beta-globin gene is not expressed in yolk sac-derived erythroid cells in early embryonic development but is expressed concomitantly with the adult mouse beta-globin genes in 14- to 16-day fetal liver and adult reticulocytes. In an attempt to localize sequences that direct erythroid-specific expression, fragments of the human beta-globin gene were inserted in the opposite orientation 200 base pairs (bp) upstream of an intact human A gamma marker gene, which is not expressed on its own in mouse fetal liver. In the experiments reported here, two beta-globin 3' sequences activated the marker gene specifically in fetal liver. One sequence is located in a 250-bp Pst I fragment 550-800 bp downstream from the poly(A) site; the other is located near an EcoRI site in the third exon. These two sequences are active individually, and their combined effect is greater than their effects alone. beta-Globin 5' sequences from -815 to -50 were also analyzed for activity in this assay. The 5' sequences did not activate the marker gene when tested alone but did stimulate expression that was already directed to adult erythroid tissue by the two 3' sequences. These results suggest that three separate sequences are involved in human beta-globin gene regulation. The two 3' sequences act as adult erythroid enhancers and the 5' sequence stimulates expression that is already determined to be erythroid specific.\",\n", - " 'author': ['Behringer, Richard R.',\n", - " 'Hammer, Robert E.',\n", - " 'Brinster, Ralph L.',\n", - " 'Palmiter, Richard D.',\n", - " 'Townes, Tim M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/84/20/7056\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/84/20/7056\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/84/20/7056\"}'],\n", - " 'title': [\"Two 3' Sequences Direct Adult Erythroid-Specific Expression of Human β -globin Genes in Transgenic Mice\"]},\n", - " {'bibcode': '1964Sci...145.1059N',\n", - " 'abstract': 'Within a given species (rat, mouse, guinea pig, rabbit) the histones of brain, liver, and kidney are indistinguishable on disc electrophoresis in polyacrylamide gels. However, characteristic species differences were observed. In the immature rat, the histones of brain and liver, while very similar to each other, differ from those of the adult. The histones of the thymus of the immature and adult rat exhibited a pattern corresponding to that of the immature brain and liver.',\n", - " 'author': ['Neidle, Amos', 'Waelsch, Heinrich'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.jstor.org/stable/1714098?origin=ads\"}'],\n", - " 'title': ['Histones: Species and Tissue Specificity']},\n", - " {'bibcode': '2020NatSR..10.5186C',\n", - " 'abstract': 'The Wnt/β-catenin pathway plays a pivotal role in liver structural and metabolic homeostasis. Wnt activity is tightly regulated by the acyltransferase Porcupine through the addition of palmitoleate. Interestingly palmitoleate can be endogenously produced by the stearoyl-CoA desaturase 1 (SCD1), a lipogenic enzyme transcriptionally regulated by insulin. This study aimed to determine whether nutritional conditions, and insulin, regulate Wnt pathway activity in liver. An adenoviral TRE-Luciferase reporter was used as a readout of Wnt/β-catenin pathway activity, in vivo in mouse liver and in vitro in primary hepatocytes. Refeeding enhanced TRE-Luciferase activity and expression of Wnt target genes in mice liver, revealing a nutritional regulation of the Wnt/β-catenin pathway. This effect was inhibited in liver specific insulin receptor KO (iLIRKO) mice and upon wortmannin or rapamycin treatment. Overexpression or inhibition of SCD1 expression regulated Wnt/β-catenin activity in primary hepatocytes. Similarly, palmitoleate added exogenously or produced by SCD1-mediated desaturation of palmitate, induced Wnt signaling activity. Interestingly, this effect was abolished in the absence of Porcupine, suggesting that both SCD1 and Porcupine are key mediators of insulin-induced Wnt/β-catenin activity in hepatocytes. Altogether, our findings suggest that insulin and lipogenesis act as potential novel physiological inducers of hepatic Wnt/β-catenin pathway.',\n", - " 'author': ['Cabrae, Régine',\n", - " 'Dubuquoy, Céline',\n", - " 'Caüzac, Michèle',\n", - " 'Morzyglod, Lucille',\n", - " 'Guilmeau, Sandra',\n", - " 'Noblet, Bénédicte',\n", - " 'Fève, Bruno',\n", - " 'Postic, Catherine',\n", - " 'Burnol, Anne-Françoise',\n", - " 'Moldes, Marthe'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-020-61869-4\"}'],\n", - " 'title': ['Insulin activates hepatic Wnt/β-catenin signaling through stearoyl-CoA desaturase 1 and Porcupine']},\n", - " {'bibcode': '2023BioBu..50.1273G',\n", - " 'author': ['Guo, Fan',\n", - " 'Lei, Ningfei',\n", - " 'Huang, Rongshuang',\n", - " 'Huang, Zhuo',\n", - " 'Zhao, Ping',\n", - " 'Xu, Xiangning',\n", - " 'Zhang, Weizhen'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1134%2FS1062359023600794\"}'],\n", - " 'title': ['Study on the Role and Mechanism of HDAC6 in Cd-Induced Inflammation and Fibrosis in Mice Liver']},\n", - " {'bibcode': '2006PNAS..103.1864V',\n", - " 'abstract': 'Endogenously formed reactive oxygen species continuously damage cellular constituents including DNA. These challenges, coupled with exogenous exposure to agents that generate reactive oxygen species, are both associated with normal aging processes and linked to cardiovascular disease, cancer, cataract formation, and fatty liver disease. Although not all of these diseases have been definitively shown to originate from mutations in nuclear DNA or mitochondrial DNA, repair of oxidized, saturated, and ring-fragmented bases via the base excision repair pathway is known to be critical for maintaining genomic stability. One enzyme that initiates base excision repair of ring-fragmented purines and some saturated pyrimidines is NEIL1, a mammalian homolog to Escherichia coli endonuclease VIII. To investigate the organismal consequences of a deficiency in NEIL1, a knockout mouse model was created. In the absence of exogenous oxidative stress, neil1 knockout (neil1-/-) and heterozygotic (neil1+/-) mice develop severe obesity, dyslipidemia, and fatty liver disease and also have a tendency to develop hyperinsulinemia. In humans, this combination of clinical manifestations, including hypertension, is known as the metabolic syndrome and is estimated to affect >40 million people in the United States. Additionally, mitochondrial DNA from neil1-/- mice show increased levels of steady-state DNA damage and deletions relative to wild-type controls. These data suggest an important role for NEIL1 in the prevention of the diseases associated with the metabolic syndrome.',\n", - " 'author': ['Vartanian, Vladimir',\n", - " 'Lowell, Brian',\n", - " 'Minko, Irina G.',\n", - " 'Wood, Thomas G.',\n", - " 'Ceci, Jeffrey D.',\n", - " 'George, Shakeeta',\n", - " 'Ballinger, Scott W.',\n", - " 'Corless, Christopher L.',\n", - " 'McCullough, Amanda K.',\n", - " 'Lloyd, R. Stephen'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/103/6/1864\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/103/6/1864\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/full/103/6/1864\"}'],\n", - " 'title': ['The metabolic syndrome resulting from a knockout of the NEIL1 DNA glycosylase']},\n", - " {'bibcode': '2019Sci...365..386C',\n", - " 'abstract': 'Ceramides contribute to the lipotoxicity that underlies diabetes, hepatic steatosis, and heart disease. By genetically engineering mice, we deleted the enzyme dihydroceramide desaturase 1 (DES1), which normally inserts a conserved double bond into the backbone of ceramides and other predominant sphingolipids. Ablation of DES1 from whole animals or tissue-specific deletion in the liver and/or adipose tissue resolved hepatic steatosis and insulin resistance in mice caused by leptin deficiency or obesogenic diets. Mechanistic studies revealed ceramide actions that promoted lipid uptake and storage and impaired glucose utilization, none of which could be recapitulated by (dihydro)ceramides that lacked the critical double bond. These studies suggest that inhibition of DES1 may provide a means of treating hepatic steatosis and metabolic disorders.',\n", - " 'author': ['Chaurasia, Bhagirath',\n", - " 'Tippetts, Trevor S.',\n", - " 'Mayoral Monibas, Rafael',\n", - " 'Liu, Jinqi',\n", - " 'Li, Ying',\n", - " 'Wang, Liping',\n", - " 'Wilkerson, Joseph L.',\n", - " 'Sweeney, C. Rufus',\n", - " 'Pereira, Renato Felipe',\n", - " 'Sumida, Doris Hissako',\n", - " 'Maschek, J. Alan',\n", - " 'Cox, James E.',\n", - " 'Kaddai, Vincent',\n", - " 'Lancaster, Graeme Iain',\n", - " 'Siddique, Monowarul Mobin',\n", - " 'Poss, Annelise',\n", - " 'Pearson, Mackenzie',\n", - " 'Satapati, Santhosh',\n", - " 'Zhou, Heather',\n", - " 'McLaren, David G.',\n", - " 'Previs, Stephen F.',\n", - " 'Chen, Ying',\n", - " 'Qian, Ying',\n", - " 'Petrov, Aleksandr',\n", - " 'Wu, Margaret',\n", - " 'Shen, Xiaolan',\n", - " 'Yao, Jun',\n", - " 'Nunes, Christian N.',\n", - " 'Howard, Andrew D.',\n", - " 'Wang, Liangsu',\n", - " 'Erion, Mark D.',\n", - " 'Rutter, Jared',\n", - " 'Holland, William L.',\n", - " 'Kelley, David E.',\n", - " 'Summers, Scott A.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.aav3722\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.aav3722\"}'],\n", - " 'title': ['Targeting a ceramide double bond improves insulin resistance and hepatic steatosis']},\n", - " {'bibcode': '1989PNAS...86.7505K',\n", - " 'abstract': 'Tfm (testicular feminization) mutant mice lack functional androgen receptors. By studying liver tumor development in Tfm mice, we have shown that the greater susceptibility of male mice relative to female mice for liver tumor induction by N,N-diethylnitrosamine is androgen receptor-dependent. C57BL/6J normal and Tfm mutant mice were injected at 12 days of age with N,N-diethylnitrosamine (0.2 mumol/g, i.p.), and liver tumors were enumerated in 50-week-old animals. Normal males averaged 20 liver tumors per animal; Tfm males, 0.7; normal females, 0.6; and Tfm/+ heterozygous females, 1.5. The androgen receptor gene and the Tfm mutation are X chromosome linked. Because of random X chromosome inactivation, hepatocytes from Tfm/+ heterozygous female mice are mosaic with respect to the expression of mutant or wild-type receptors. To determine if testosterone acts directly as a liver tumor promoter, through the androgen receptor in preneoplastic hepatocytes, or by an indirect mechanism, we chronically treated these mosaic female mice with testosterone and measured the androgen receptor content of the resulting tumors. B6C3F1 Tfm/+ mosaic and +/+ wild-type female mice were injected i.p. at 12 days of age with N,N-diethylnitrosamine (0.1 mumol/g) and ovariectomized at 8 weeks of age. Half of the mice of each group subsequently received biweekly s.c. injections of testosterone (0.15 mg per mouse) for 30 weeks. Tumor multiplicity was the same for wild-type and Tfm/+ mosaic females treated with testosterone (31-32 tumors per animal at 38 weeks of age) and was increased relative to females not treated with testosterone (13-17 tumors per animal at 50 weeks of age). Testosterone treatment did not significantly increase the percentage of androgen receptor-positive tumors in Tfm/+ mosaic females: 58% of the tumors from Tfm/+ mosaic females treated with testosterone were receptor positive compared to 48% in Tfm/+ females not treated with testosterone and 92% in wild-type females treated with testosterone. Finally, the number of androgen receptors in the majority of liver tumors examined was greatly decreased relative to the surrounding normal liver tissue. We conclude that liver tumor promotion by testosterone requires a functional androgen receptor in the intact animal. However, this promotion is not cell autonomous; that is, the response of the preneoplastic hepatocyte is not dependent on the expression of functional receptor in the target cell.',\n", - " 'author': ['Kemp, Christopher J.',\n", - " 'Leary, Cynthia N.',\n", - " 'Drinkwater, Norman R.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/86/19/7505\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/86/19/7505\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/86/19/7505\"}'],\n", - " 'title': ['Promotion of murine hepatocarcinogenesis by testosterone is androgen receptor-dependent but not cell autonomous.']},\n", - " {'bibcode': '2004PNAS..10115597I',\n", - " 'abstract': 'Carbohydrate response element (ChRE)-binding protein (ChREBP) is a recently discovered transcription factor that is activated in response to high glucose concentrations in liver independently of insulin. ChREBP was first identified by its ability to bind the ChRE of the liver pyruvate kinase (LPK) gene. We recently reported that the increase in expression of multiple liver lipogenic enzyme mRNAs elicited by feeding a high-carbohydrate diet as well as that of LPK mRNA is markedly reduced in mice lacking ChREBP gene expression (ChREBP-/-) in comparison to WT mice. The present study provides evidence for a direct and dominant role of ChREBP in the glucose regulation of two key liver lipogenic enzymes, acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). ACC, FAS, and LPK mRNA levels were higher in WT hepatocytes cultured with high (25 mM) rather than low (5.5 mM) glucose medium, but there was no effect of glucose concentration on these mRNA levels in ChREBP-/- hepatocytes. Similarly, reporter constructs containing ACC, FAS, or LPK gene ChREs were responsive to glucose when transfected into WT but not ChREBP-/- hepatocytes, and glucose transactivation of the constructs in ChREBP-/- hepatocytes was restored by cotransfection with a ChREBP expression plasmid. ChREBP binding to ACC, FAS, and LPK ChRE sequences in vitro was demonstrated by electrophoretic mobility super shift assays. In vivo binding of ChREBP to ACC, FAS, and LPK gene promoters in intact liver nuclei from rats fed a high-carbohydrate diet was demonstrated by using a formaldehyde crosslinking and chromatin immunoprecipitation procedure.',\n", - " 'author': ['Ishii, Seiji',\n", - " 'IIzuka, Katsumi',\n", - " 'Miller, Bonnie C.',\n", - " 'Uyeda, Kosaku'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/101/44/15597\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0405238101\"}'],\n", - " 'title': ['Carbohydrate response element binding protein directly promotes lipogenic enzyme gene transcription']},\n", - " {'bibcode': '2011PNAS..108.5378W',\n", - " 'abstract': 'Platensimycin (PTM) is a recently discovered broad-spectrum antibiotic produced by Streptomyces platensis. It acts by selectively inhibiting the elongation-condensing enzyme FabF of the fatty acid biosynthesis pathway in bacteria. We report here that PTM is also a potent and highly selective inhibitor of mammalian fatty acid synthase. In contrast to two agents, C75 and cerulenin, that are widely used as inhibitors of mammalian fatty acid synthase, platensimycin specifically inhibits fatty acid synthesis but not sterol synthesis in rat primary hepatocytes. PTM preferentially concentrates in liver when administered orally to mice and potently inhibits hepatic de novo lipogenesis, reduces fatty acid oxidation, and increases glucose oxidation. Chronic administration of platensimycin led to a net reduction in liver triglyceride levels and improved insulin sensitivity in db/+ mice fed a high-fructose diet. PTM also reduced ambient glucose levels in db/db mice. These results provide pharmacological proof of concept of inhibiting fatty acid synthase for the treatment of diabetes and related metabolic disorders in animal models.',\n", - " 'author': ['Wu, Margaret',\n", - " 'Singh, Sheo B.',\n", - " 'Wang, Jun',\n", - " 'Chung, Christine C.',\n", - " 'Salituro, Gino',\n", - " 'Karanam, Bindhu V.',\n", - " 'Lee, Sang Ho',\n", - " 'Powles, Maryann',\n", - " 'Ellsworth, Kenneth P.',\n", - " 'Lassman, Michael E.',\n", - " 'Miller, Corey',\n", - " 'Myers, Robert W.',\n", - " 'Tota, Michael R.',\n", - " 'Zhang, Bei B.',\n", - " 'Li, Cai'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/108/13/5378\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1002588108\"}'],\n", - " 'title': ['Antidiabetic and antisteatotic effects of the selective fatty acid synthase (FAS) inhibitor platensimycin in mouse models of diabetes']},\n", - " {'bibcode': '2011PNAS..108.8943W',\n", - " 'abstract': 'Fluorescent imaging in the second near-infrared window (NIR II, 1-1.4 μm) holds much promise due to minimal autofluorescence and tissue scattering. Here, using well-functionalized biocompatible single-walled carbon nanotubes (SWNTs) as NIR II fluorescent imaging agents, we performed high-frame-rate video imaging of mice during intravenous injection of SWNTs and investigated the path of SWNTs through the mouse anatomy. We observed in real-time SWNT circulation through the lungs and kidneys several seconds postinjection, and spleen and liver at slightly later time points. Dynamic contrast-enhanced imaging through principal component analysis (PCA) was performed and found to greatly increase the anatomical resolution of organs as a function of time postinjection. Importantly, PCA was able to discriminate organs such as the pancreas, which could not be resolved from real-time raw images. Tissue phantom studies were performed to compare imaging in the NIR II region to the traditional NIR I biological transparency window (700-900 nm). Examination of the feature sizes of a common NIR I dye (indocyanine green) showed a more rapid loss of feature contrast and integrity with increasing feature depth as compared to SWNTs in the NIR II region. The effects of increased scattering in the NIR I versus NIR II region were confirmed by Monte Carlo simulation. In vivo fluorescence imaging in the NIR II region combined with PCA analysis may represent a powerful approach to high-resolution optical imaging through deep tissues, useful for a wide range of applications from biomedical research to disease diagnostics.',\n", - " 'author': ['Welsher, Kevin', 'Sherlock, Sarah P.', 'Dai, Hongjie'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/108/22/8943\"}',\n", - " '{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"preprint\", \"url\": \"http://arxiv.org/abs/1105.3536\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1014501108\"}'],\n", - " 'title': ['Deep-tissue anatomical imaging of mice using carbon nanotube fluorophores in the second near-infrared window']},\n", - " {'bibcode': '2008PNAS..105.2094K',\n", - " 'abstract': 'Administration of β-sitosterol (42 mg/kg per day) for 3 weeks to 8-month-old male LXRβ-/- mice resulted in the death of motor neurons in the lumbar region of the spinal cord and loss of tyrosine hydroxylase-positive dopaminergic neurons in the substantia nigra. In mice at 5 months of age, β-sitosterol had no observed toxicity but at 16 months of age, it caused severe paralysis and symptoms typical of dopaminergic dysfunction in LXRβ-/- mice. WT mice were not affected by these doses of β-sitosterol. In 5-month-old mice, levels of the intestinal transporters, ABCG5/8 and Niemann-Pick C1 Like 1, were not affected by loss of liver X receptor (LXR) β and/or treatment with β-sitosterol nor were there changes in plasma levels of cholesterol or β-sitosterol. In 8-month-old LXRβ-/- mice there was activation of microglia in the substantia nigra pars reticulata and aggregates of ubiquitin and TDP-43 in the cytoplasm of large motor neurons in the lumbar spinal cord. Brain cholesterol concentrations were higher in LXRβ-/- than in their WT counterparts, and treatment with β-sitosterol reduced brain cholesterol in both WT and LXRβ-/- mice. In LXRβ-/- mice but not in WT mice levels of 24-hydrocholesterol were increased upon β-sitosterol treatment. These data indicate that multiple mechanisms are involved in the sensitivity of LXRβ-/- mice to β-sitosterol. These include activation of microglia, accumulation of protein aggregates in the cytoplasm of large motor neurons, and depletion of brain cholesterol.',\n", - " 'author': ['Kim, Hyun-Jin',\n", - " 'Fan, Xiaotang',\n", - " 'Gabbi, Chiara',\n", - " 'Yakimchuk, Konstantin',\n", - " 'Parini, Paolo',\n", - " 'Warner, Margaret',\n", - " 'Gustafsson, Jan-Åke'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/105/6/2094\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/105/6/2094.full.pdf\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0711599105\"}'],\n", - " 'title': [\"Liver X receptor β (LXRβ): A link between β-sitosterol and amyotrophic lateral sclerosis-Parkinson's dementia\"]},\n", - " {'bibcode': '2008Sci...321.1837R',\n", - " 'abstract': 'Almost two decades after CFTR was identified as the gene responsible for cystic fibrosis (CF), we still lack answers to many questions about the pathogenesis of the disease, and it remains incurable. Mice with a disrupted CFTR gene have greatly facilitated CF studies, but the mutant mice do not develop the characteristic manifestations of human CF, including abnormalities of the pancreas, lung, intestine, liver, and other organs. Because pigs share many anatomical and physiological features with humans, we generated pigs with a targeted disruption of both CFTR alleles. Newborn pigs lacking CFTR exhibited defective chloride transport and developed meconium ileus, exocrine pancreatic destruction, and focal biliary cirrhosis, replicating abnormalities seen in newborn humans with CF. The pig model may provide opportunities to address persistent questions about CF pathogenesis and accelerate discovery of strategies for prevention and treatment.',\n", - " 'author': ['Rogers, Christopher S.',\n", - " 'Stoltz, David A.',\n", - " 'Meyerholz, David K.',\n", - " 'Ostedgaard, Lynda S.',\n", - " 'Rokhlina, Tatiana',\n", - " 'Taft, Peter J.',\n", - " 'Rogan, Mark P.',\n", - " 'Pezzulo, Alejandro A.',\n", - " 'Karp, Philip H.',\n", - " 'Itani, Omar A.',\n", - " 'Kabel, Amanda C.',\n", - " 'Wohlford-Lenane, Christine L.',\n", - " 'Davis, Greg J.',\n", - " 'Hanfland, Robert A.',\n", - " 'Smith, Tony L.',\n", - " 'Samuel, Melissa',\n", - " 'Wax, David',\n", - " 'Murphy, Clifton N.',\n", - " 'Rieke, August',\n", - " 'Whitworth, Kristin',\n", - " 'Uc, Aliye',\n", - " 'Starner, Timothy D.',\n", - " 'Brogden, Kim A.',\n", - " 'Shilyansky, Joel',\n", - " 'McCray, Paul B.',\n", - " 'Zabner, Joseph',\n", - " 'Prather, Randall S.',\n", - " 'Welsh, Michael J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.1163600\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.1163600\"}'],\n", - " 'title': ['Disruption of the CFTR Gene Produces a Model of Cystic Fibrosis in Newborn Pigs']},\n", - " {'bibcode': '2012MedPh..39.6847R',\n", - " 'abstract': 'Purpose:To determine the potential of spectral computed tomography (CT) with Medipix3 for quantifying fat, calcium, and iron in soft tissues within small animal models and surgical specimens of diseases such as fatty liver (metabolic syndrome) and unstable atherosclerosis.Methods:The spectroscopic method was applied to tomographic data acquired using a micro‑CT system incorporating a Medipix3 detector array with silicon sensor layer and microfocus x‑ray tube operating at 50 kVp. A 10 mm diameter perspex phantom containing a fat surrogate (sunflower oil) and aqueous solutions of ferric nitrate, calcium chloride, and iodine was imaged with multiple energy bins. The authors used the spectroscopic characteristics of the CT number to establish a basis for the decomposition of soft tissue components. The potential of the method of constrained least squares for quantifying different sets of materials was evaluated in terms of information entropy and degrees of freedom, with and without the use of a volume conservation constraint. The measurement performance was evaluated quantitatively using atheroma and mouse equivalent phantoms. Finally the decomposition method was assessed qualitatively using a euthanized mouse and an excised human atherosclerotic plaque.Results:Spectral CT measurements of a phantom containing tissue surrogates confirmed the ability to distinguish these materials by the spectroscopic characteristics of their CT number. The assessment of performance potential in terms of information entropy and degrees of freedom indicated that certain sets of up to three materials could be decomposed by the method of constrained least squares. However, there was insufficient information within the data set to distinguish calcium from iron within soft tissues. The quantification of calcium concentration and fat mass fraction within atheroma and mouse equivalent phantoms by spectral CT correlated well with the nominal values (R2 = 0.990 and R2 = 0.985, respectively). In the euthanized mouse and excised human atherosclerotic plaque, regions of calcium and fat were appropriately decomposed according to their spectroscopic characteristics.Conclusions:Spectral CT, using the Medipix3 detector and silicon sensor layer, can quantify certain sets of up to three materials using the proposed method of constrained least squares. The system has some ability to independently distinguish calcium, fat, and water, and these have been quantified within phantom equivalents of fatty liver and atheroma. In this configuration, spectral CT cannot distinguish iron from calcium within soft tissues.',\n", - " 'author': ['Ronaldson, J. Paul',\n", - " 'Zainon, Rafidah',\n", - " 'Scott, Nicola Jean Agnes',\n", - " 'Gieseg, Steven Paul',\n", - " 'Butler, Anthony P.',\n", - " 'Butler, Philip H.',\n", - " 'Anderson, Nigel G.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1118%2F1.4760773\"}'],\n", - " 'title': ['Toward quantifying the composition of soft tissues by spectral CT with Medipix3']},\n", - " {'bibcode': '2020NatSR..1011785S',\n", - " 'abstract': 'The widely used mood stabilizer valproate (VPA) causes perturbation of energy metabolism, which is implicated in both the therapeutic mechanism of action of the drug as well as drug toxicity. To gain insight into these mechanisms, we determined the effects of VPA on energy metabolism in yeast. VPA treatment increased levels of glycolytic intermediates, increased expression of glycolysis genes, and increased ethanol production. Increased glycolysis was likely a response to perturbation of mitochondrial function, as reflected in decreased membrane potential and oxygen consumption. Interestingly, yeast, mouse liver, and isolated bovine cytochrome c oxidase were directly inhibited by the drug, while activities of other oxidative phosphorylation complexes (III and V) were not affected. These findings have implications for mechanisms of therapeutic action and toxicity.',\n", - " 'author': ['Salsaa, Michael',\n", - " 'Pereira, Bianca',\n", - " 'Liu, Jenney',\n", - " 'Yu, Wenxi',\n", - " 'Jadhav, Shyamalagauri',\n", - " 'Hüttemann, Maik',\n", - " 'Greenberg, Miriam L.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41598-020-68725-5\"}'],\n", - " 'title': ['Valproate inhibits mitochondrial bioenergetics and increases glycolysis in Saccharomyces cerevisiae']},\n", - " {'bibcode': '1970RSPSB.176..277P',\n", - " 'abstract': 'Chromatin (chromosomal nucleoprotein) from mammalian cells is used as a template for the synthesis of RNA which is characterized and compared with other RNA by RNA-DNA hybridization. It is found to be transcribed from a restricted set of sequences and cannot be distinguished from natural RNA from the same organ as the chromatin. In contrast, it is different from RNA from other organs. Hence, DNA is masked in an organ-specific way in vivo and the masking is preserved on isolation. When cell division is induced in mouse liver and kidney a very early event is a change in masking in chromatin. This precedes changes in RNA populations; both precede DNA synthesis. Chromatin can be accurately reconstructed from DNA, histones and non-histone proteins. Experiments using this system indicate that histones non-specifically mask DNA; non-histone proteins are essential to reverse masking in a specific way.',\n", - " 'author': ['Paul, J.',\n", - " 'Gilmour, R. S.',\n", - " 'Thomou, H.',\n", - " 'Threlfall, G.',\n", - " 'Kohl, D.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.jstor.org/stable/75921?origin=ads\"}'],\n", - " 'title': ['Organ-Specific Gene Masking in Mammalian Chromosomes']},\n", - " {'bibcode': '2018JBO....23i1407L',\n", - " 'abstract': 'We used intravital multiphoton microscopy to study the recovery of hepatobiliary metabolism following carbon tetrachloride (CCl4) induced hepatotoxicity in mice. The acquired images were processed by a first order kinetic model to generate rate constant resolved images of the mouse liver. We found that with progression of hepatotoxicity, the spatial gradient of hepatic function disappeared. A CCl4-induced damage mechanism involves the compromise of membrane functions, resulting in accumulation of processed 6-carboxyfluorescein molecules. At day 14 following induction, a restoration of the mouse hepatobiliary function was found. Our approach allows the study of the response of hepatic functions to chemical agents in real time and is useful for studying pharmacokinetics of drug molecules through optical microscopic imaging.',\n", - " 'author': ['Lin, Chih-Ju',\n", - " 'Lee, Sheng-Lin',\n", - " 'Lee, Hsuan-Shu',\n", - " 'Dong, Chen-Yuan'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1117%2F1.JBO.23.9.091407\"}'],\n", - " 'title': ['In vivo multiphoton kinetic imaging of the toxic effect of carbon tetrachloride on hepatobiliary metabolism']},\n", - " {'bibcode': '1989Natur.339..632L',\n", - " 'abstract': 'AS a family of structurally-related enzymes, cytochrome P450 (P450) monooxygenases exhibit paradoxical characteristics: although collectively the enzymes display a broad range of substrate specificities, individually they are characterized by a high degree of substrate and product selectivity. Mouse P45015α, and P450coh, for example, which are expressed in female liver and male kidney cells1,2, catalyse 15α-hydroxylation of Δ 4 3-ketone steroids, such as testosterone and 7-hydroxylation of coumarin, respectively3-6. In spite of their divergent catalytic activities, however, these enzymes differ by only 11 amino acids within their 494 residues5. To determine the structural basis of the different substrate specificities of P45015α and P450coh we therefore altered each of these 11 residues by site-directed mutagenesis, expressing the mutant cytochromes in COS-1 cells. We report that the activities of both cytochromes depend critically on the identities of the amino acids at positions 117, 209 and 365 and, moreover, that a single mutation in which Phe 209 is substituted by Leu is sufficient to convert the specificity of P450coh from coumarin to steroid hydroxylation.',\n", - " 'author': ['Lindberg, Raija L. P.', 'Negishi, Masahiko'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2F339632a0\"}'],\n", - " 'title': ['Alteration of mouse cytochrome P450coh substrate specificity by mutation of a single amino-acid residue']},\n", - " {'bibcode': '2020PNAS..117.2076W',\n", - " 'abstract': \"Wilson's disease is an autosomal recessive disorder that results in accumulation of toxic levels of copper in the liver, which can lead to cirrhosis and liver failure. Emerging evidence suggests that hepatic metabolic processes are altered in Wilson's disease patients and Wilson's disease animal models. Our studies revealed an unexpected improvement in glucose tolerance and insulin sensitivity in a Wilson's disease mouse model (Atp7b-/-) that correlate with activation of AMPK. These findings have the potential to uncover therapeutic options for patients with Wilson's disease, as well as for patients with metabolic disorders such as type 2 diabetes and fatty liver disease.\",\n", - " 'author': ['Wooton-Kee, Clavia Ruth',\n", - " 'Robertson, Matthew',\n", - " 'Zhou, Ying',\n", - " 'Dong, Bingning',\n", - " 'Sun, Zhen',\n", - " 'Kim, Kang Ho',\n", - " 'Liu, Hailan',\n", - " 'Xu, Yong',\n", - " 'Putluri, Nagireddy',\n", - " 'Saha, Pradip',\n", - " 'Coarfa, Cristian',\n", - " 'Moore, David D.',\n", - " 'Nuotio-Antar, Alli M.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1914267117\"}'],\n", - " 'title': [\"Metabolic dysregulation in the Atp7b-/- Wilson's disease mouse model\"]},\n", - " {'bibcode': '2013Natur.503..493O',\n", - " 'abstract': 'Adiponectin secreted from adipocytes binds to adiponectin receptors AdipoR1 and AdipoR2, and exerts antidiabetic effects via activation of AMPK and PPAR-α pathways, respectively. Levels of adiponectin in plasma are reduced in obesity, which causes insulin resistance and type 2 diabetes. Thus, orally active small molecules that bind to and activate AdipoR1 and AdipoR2 could ameliorate obesity-related diseases such as type 2 diabetes. Here we report the identification of orally active synthetic small-molecule AdipoR agonists. One of these compounds, AdipoR agonist (AdipoRon), bound to both AdipoR1 and AdipoR2 in vitro. AdipoRon showed very similar effects to adiponectin in muscle and liver, such as activation of AMPK and PPAR-α pathways, and ameliorated insulin resistance and glucose intolerance in mice fed a high-fat diet, which was completely obliterated in AdipoR1 and AdipoR2 double-knockout mice. Moreover, AdipoRon ameliorated diabetes of genetically obese rodent model db/db mice, and prolonged the shortened lifespan of db/db mice on a high-fat diet. Thus, orally active AdipoR agonists such as AdipoRon are a promising therapeutic approach for the treatment of obesity-related diseases such as type 2 diabetes.',\n", - " 'author': ['Okada-Iwabu, Miki',\n", - " 'Yamauchi, Toshimasa',\n", - " 'Iwabu, Masato',\n", - " 'Honma, Teruki',\n", - " 'Hamagami, Ken-Ichi',\n", - " 'Matsuda, Koichi',\n", - " 'Yamaguchi, Mamiko',\n", - " 'Tanabe, Hiroaki',\n", - " 'Kimura-Someya, Tomomi',\n", - " 'Shirouzu, Mikako',\n", - " 'Ogata, Hitomi',\n", - " 'Tokuyama, Kumpei',\n", - " 'Ueki, Kohjiro',\n", - " 'Nagano, Tetsuo',\n", - " 'Tanaka, Akiko',\n", - " 'Yokoyama, Shigeyuki',\n", - " 'Kadowaki, Takashi'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fnature12656\"}'],\n", - " 'title': ['A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity']},\n", - " {'bibcode': '2008PNAS..10514447A',\n", - " 'abstract': 'Here, we demonstrate a role for the mitochondrial NAD-dependent deacetylase Sirt3 in the maintenance of basal ATP levels and as a regulator of mitochondrial electron transport. We note that Sirt3−/− mouse embryonic fibroblasts have a reduction in basal ATP levels. Reconstitution with wild-type but not a deacetylase-deficient form of Sirt3 restored ATP levels in these cells. Furthermore in wild-type mice, the resting level of ATP correlates with organ-specific Sirt3 protein expression. Remarkably, in mice lacking Sirt3, basal levels of ATP in the heart, kidney, and liver were reduced >50%. We further demonstrate that mitochondrial protein acetylation is markedly elevated in Sirt3−/− tissues. In addition, in the absence of Sirt3, multiple components of Complex I of the electron transport chain demonstrate increased acetylation. Sirt3 can also physically interact with at least one of the known subunits of Complex I, the 39-kDa protein NDUFA9. Functional studies demonstrate that mitochondria from Sirt3−/− animals display a selective inhibition of Complex I activity. Furthermore, incubation of exogenous Sirt3 with mitochondria can augment Complex I activity. These results implicate protein acetylation as an important regulator of Complex I activity and demonstrate that Sirt3 functions in vivo to regulate and maintain basal ATP levels.',\n", - " 'author': ['Ahn, Bong-Hyun',\n", - " 'Kim, Hyun-Seok',\n", - " 'Song, Shiwei',\n", - " 'Lee, In Hye',\n", - " 'Liu, Jie',\n", - " 'Vassilopoulos, Athanassios',\n", - " 'Deng, Chu-Xia',\n", - " 'Finkel, Toren'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/105/38/14447\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/105/38/14447.full.pdf\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.0803790105\"}'],\n", - " 'title': ['A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis']},\n", - " {'bibcode': '2008Sci...322.1539S',\n", - " 'abstract': 'A high-fat diet causes activation of the regulatory protein c-Jun NH2-terminal kinase 1 (JNK1) and triggers development of insulin resistance. JNK1 is therefore a potential target for therapeutic treatment of metabolic syndrome. We explored the mechanism of JNK1 signaling by engineering mice in which the Jnk1 gene was ablated selectively in adipose tissue. JNK1 deficiency in adipose tissue suppressed high-fat diet-induced insulin resistance in the liver. JNK1-dependent secretion of the inflammatory cytokine interleukin-6 by adipose tissue caused increased expression of liver SOCS3, a protein that induces hepatic insulin resistance. Thus, JNK1 activation in adipose tissue can cause insulin resistance in the liver.',\n", - " 'author': ['Sabio, Guadalupe',\n", - " 'Das, Madhumita',\n", - " 'Mora, Alfonso',\n", - " 'Zhang, Zhiyou',\n", - " 'Jun, John Y.',\n", - " 'Ko, Hwi Jin',\n", - " 'Barrett, Tamera',\n", - " 'Kim, Jason K.',\n", - " 'Davis, Roger J.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.1160794\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.1160794\"}'],\n", - " 'title': ['A Stress Signaling Pathway in Adipose Tissue Regulates Hepatic Insulin Resistance']},\n", - " {'bibcode': '1999PNAS...9612816M',\n", - " 'abstract': 'The efficiency of first-generation adenoviral vectors as gene delivery tools is often limited by the short duration of transgene expression, which can be related to immune responses and to toxic effects of viral proteins. In addition, readministration is usually ineffective unless the animals are immunocompromised or a different adenovirus serotype is used. Recently, adenoviral vectors devoid of all viral coding sequences (helper-dependent or gutless vectors) have been developed to avoid expression of viral proteins. In mice, liver-directed gene transfer with AdSTK109, a helper-dependent adenoviral (Ad) vector containing the human α1-antitrypsin (hAAT) gene, resulted in sustained expression for longer than 10 months with negligible toxicity to the liver. In the present report, we have examined the duration of expression of AdSTK109 in the liver of baboons and compared it to first-generation vectors expressing hAAT. Transgene expression was limited to approximately 3-5 months with the first-generation vectors. In contrast, administration of AdSTK109 resulted in transgene expression for longer than a year in two of three baboons. We have also investigated the feasibility of circumventing the humoral response to the virus by sequential administration of vectors of different serotypes. We found that the ineffectiveness of readministration due to the humoral response to an Ad5 first-generation vector was overcome by use of an Ad2-based vector expressing hAAT. These data suggest that long-term expression of transgenes should be possible by combining the reduced immunogenicity and toxicity of helper-dependent vectors with sequential delivery of vectors of different serotypes.',\n", - " 'author': ['Morral, Núria',\n", - " \"O'Neal, Wanda\",\n", - " 'Rice, Karen',\n", - " 'Leland, Michele',\n", - " 'Kaplan, Johanne',\n", - " 'Piedra, Pedro A.',\n", - " 'Zhou, Heshan',\n", - " 'Parks, Robin J.',\n", - " 'Velji, Rizwan',\n", - " 'Aguilar-Córdova, Estuardo',\n", - " 'Wadsworth, Samuel',\n", - " 'Graham, Frank L.',\n", - " 'Kochanek, Stefan',\n", - " 'Carey, K. Dee',\n", - " 'Beaudet, Arthur L.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/96/22/12816\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/96/22/12816\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/96/22/12816\"}'],\n", - " 'title': ['Administration of Helper-Dependent Adenoviral Vectors and Sequential Delivery of Different Vector Serotype for Long-Term Liver-Directed Gene Transfer in Baboons']},\n", - " {'bibcode': '2002PNAS...99.6991G',\n", - " 'abstract': 'The role of the hepatitis B virus X protein (HBx) in the pathogenesis of hepatitis B virus (HBV) infection remains unclear. HBx exhibits pleiotropic biological effects, whose in vivo relevance is a matter for debate. In the present report, we have used a combination of HBx-expressing transgenic mice and liver cell transplantation to investigate the in vivo impact of HBx expression on liver cell proliferation and viability in a regenerative context. We show that moderate HBx expression inhibits liver regeneration after partial hepatectomy in HBx-expressing transgenic mice. We also demonstrate that the transplantation of HBx-expressing liver cells, isolated from HBx transgenic mice, is sufficient to inhibit overall recipient liver regeneration after partial hepatectomy. Moreover, the injection of serum samples drawn from HBx-expressing transgenic mice mimicked the inhibitory effect of HBx on liver regeneration. Finally, the incubation of primary rat hepatocytes with the supernatant of HBx-expressing liver cells inhibits cellular DNA synthesis. Taken together, our results demonstrate a paracrine inhibitory effect of HBx on liver cell proliferation and lead us to propose HBV as one of the few viruses implicated in human cancer which act, at least in part, through paracrine biological pathways.',\n", - " 'author': ['Guilherme Tralhao, J.',\n", - " 'Roudier, Jean',\n", - " 'Morosan, Serban',\n", - " 'Giannini, Carlo',\n", - " 'Tu, Hong',\n", - " 'Goulenok, Cyril',\n", - " 'Carnot, Françoise',\n", - " 'Zavala, Flora',\n", - " 'Joulin, Virginie',\n", - " 'Kremsdorf, Dina',\n", - " 'Bréchot, Christian'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/99/10/6991\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/99/10/6991\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/99/10/6991\"}'],\n", - " 'title': ['Paracrine in vivo inhibitory effects of hepatitis B virus X protein (HBx) on liver cell proliferation: An alternative mechanism of HBx-related pathogenesis']},\n", - " {'bibcode': '2015NatCo...6.7339B',\n", - " 'abstract': \"Diseases of lipid metabolism are a major cause of human morbidity, but no animal model entirely recapitulates human lipoprotein metabolism. Here we develop a xenograft mouse model using hepatocytes from a patient with familial hypercholesterolaemia caused by loss-of-function mutations in the low-density lipoprotein receptor (LDLR). Like familial hypercholesterolaemia patients, our familial hypercholesterolaemia liver chimeric mice develop hypercholesterolaemia and a 'humanized` serum profile, including expression of the emerging drug targets cholesteryl ester transfer protein and apolipoprotein (a), for which no genes exist in mice. We go on to replace the missing LDLR in familial hypercholesterolaemia liver chimeric mice using an adeno-associated virus 9-based gene therapy and restore normal lipoprotein profiles after administration of a single dose. Our study marks the first time a human metabolic disease is induced in an experimental animal model by human hepatocyte transplantation and treated by gene therapy. Such xenograft platforms offer the ability to validate human experimental therapies and may foster their rapid translation into the clinic.\",\n", - " 'author': ['Bissig-Choisat, Beatrice',\n", - " 'Wang, Lili',\n", - " 'Legras, Xavier',\n", - " 'Saha, Pradip K.',\n", - " 'Chen, Leon',\n", - " 'Bell, Peter',\n", - " 'Pankowicz, Francis P.',\n", - " 'Hill, Matthew C.',\n", - " 'Barzi, Mercedes',\n", - " 'Leyton, Claudia Kettlun',\n", - " 'Leung, Hon-Chiu Eastwood',\n", - " 'Kruse, Robert L.',\n", - " 'Himes, Ryan W.',\n", - " 'Goss, John A.',\n", - " 'Wilson, James M.',\n", - " 'Chan, Lawrence',\n", - " 'Lagor, William R.',\n", - " 'Bissig, Karl-Dimiter'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fncomms8339\"}'],\n", - " 'title': ['Development and rescue of human familial hypercholesterolaemia in a xenograft mouse model']},\n", - " {'bibcode': '2000PNAS...97.1281S',\n", - " 'abstract': 'Reelin regulates telencephalic and cerebellar lamination during mammalian development and is expressed in several structures of the adult brain; however, only traces of reelin were believed to be in peripheral tissues. Because reelin structurally resembles extracellular matrix proteins, and because many of these proteins are expressed in blood, we hypothesized that reelin also might be detectable in the circulation. Reelin (420 kDa) and two reelin-like immunoreactive bands (310 and 160 kDa) are expressed in serum and platelet-poor plasma of rats, mice, and humans, but these three bands were not detectable in serum of homozygous reeler (rl/rl) mice. Reelin plasma levels in heterozygous (rl/+) mice were half of those in wild-type littermates. Western blotting and immunocytochemistry using antireelin mAbs indicated that reelin-like immunoreactivity was expressed in a subset of chromaffin cells within the rat adrenal medulla and in a subset of cells coexpressing α-melanocyte-stimulating hormone within the pituitary pars intermedia. However, surgical removal of adrenal or pituitary failed to decrease the amount of reelin (420-kDa band) expressed in serum. Adult liver expressed one-third of the reelin mRNA concentration expressed in adult mouse cerebral cortex. Full-length reelin protein was detectable in liver extracts in situ; acutely isolated liver cells also secreted full-length reelin in vitro. Liver appears to be a prime candidate to produce and maintain the circulating reelin pool. It now becomes relevant to ask whether circulating reelin has a physiologic role on one or more peripheral target tissues.',\n", - " 'author': ['Smalheiser, Neil R.',\n", - " 'Costa, Erminio',\n", - " 'Guidotti, Alessandro',\n", - " 'Impagnatiello, Francesco',\n", - " 'Auta, James',\n", - " 'Lacor, Pascale',\n", - " 'Kriho, Virginia',\n", - " 'Pappas, George D.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/97/3/1281\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/97/3/1281\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/97/3/1281\"}'],\n", - " 'title': ['Expression of reelin in adult mammalian blood, liver, pituitary pars intermedia, and adrenal chromaffin cells']},\n", - " {'bibcode': '2019Sci...366.1029M',\n", - " 'abstract': 'The Hippo signaling pathway and its two downstream effectors, the YAP and TAZ transcriptional coactivators, are drivers of tumor growth in experimental models. Studying mouse models, we show that YAP and TAZ can also exert a tumor-suppressive function. We found that normal hepatocytes surrounding liver tumors displayed activation of YAP and TAZ and that deletion of Yap and Taz in these peritumoral hepatocytes accelerated tumor growth. Conversely, experimental hyperactivation of YAP in peritumoral hepatocytes triggered regression of primary liver tumors and melanoma-derived liver metastases. Furthermore, whereas tumor cells growing in wild-type livers required YAP and TAZ for their survival, those surrounded by Yap- and Taz-deficient hepatocytes were not dependent on YAP and TAZ. Tumor cell survival thus depends on the relative activity of YAP and TAZ in tumor cells and their surrounding tissue, suggesting that YAP and TAZ act through a mechanism of cell competition to eliminate tumor cells.',\n", - " 'author': ['Moya, Iván M.',\n", - " 'Castaldo, Stéphanie A.',\n", - " 'Van den Mooter, Laura',\n", - " 'Soheily, Soheil',\n", - " 'Sansores-Garcia, Leticia',\n", - " 'Jacobs, Jelle',\n", - " 'Mannaerts, Inge',\n", - " 'Xie, Jun',\n", - " 'Verboven, Elisabeth',\n", - " 'Hillen, Hanne',\n", - " 'Algueró-Nadal, Ana',\n", - " 'Karaman, Ruchan',\n", - " 'Van Haele, Matthias',\n", - " 'Kowalczyk, Weronika',\n", - " 'De Waegeneer, Maxime',\n", - " 'Verhulst, Stefaan',\n", - " 'Karras, Panagiotis',\n", - " 'van Huffel, Leen',\n", - " 'Zender, Lars',\n", - " 'Marine, Jean-Christophe',\n", - " 'Roskams, Tania',\n", - " 'Johnson, Randy',\n", - " 'Aerts, Stein',\n", - " 'van Grunsven, Leo A.',\n", - " 'Halder, Georg'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.science.org/doi/epdf/10.1126/science.aaw9886\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1126%2Fscience.aaw9886\"}'],\n", - " 'title': ['Peritumoral activation of the Hippo pathway effectors YAP and TAZ suppresses liver cancer in mice']},\n", - " {'bibcode': '1988EnvMM..11..523M',\n", - " 'abstract': 'Using the L5178Y mouse lymphoma cell thymidine kinase locus and the Salmonella his locus assays, the mutagenic potentials of several catecholamines and related compounds were examined. No supplementary metabolic activation systems were used. In the mouse lymphoma assay, the dihydroxybenzenes catechol and hydroquinone had similar and appreciable mutagenic potentials, whereas resorcinol was less active. Derivatives of catechol, such as dopamine and epinephrine, were mutagenic, whereas the related monohydroxylated compounds tyramine and synephrine were inactive. The primary amine, arterenol, and the corresponding secondary amine, epinephrine, induced similar mutagenic responses. Carboxylation of the side chain of dopamine, giving L‑dopa, reduced the maximum mutagenic response. The introduction of charged groups directly on to the aromatic ring also reduced mutagenic activity, while an intervening methylene reversed this effect. Thus, 3,4‑dihydroxyhydrocinnamic acid was more active than 3,4‑dihydroxybenzoic acid. The compound active at the lowest doses was 4‑tert‑butyl catechol. The activities of these compounds are highly dependent upon substituent groups. Experiments with superoxide dismutase gave circumstantial evidence for some of the mutagenic activity being due to superoxide anion. Active oxygen species might be responsible for some of the observed effects, but this cannot be concluded from the superoxide dismutase experiments. Mutagenic responses in Salmonella were very low but were significant for L‑dopa in three strains and for epinephrine and arterenol in one strain. Limited DNA association studies of 14C‑dopamine suggest interactions in L5178Y and Salmonella cells and in mouse liver. The mutagenicity of dopamine in L5178Y is reduced by high serum concentrations during the exposure period, while the apparent association with DNA is unaffected.',\n", - " 'author': ['McGregor, Douglas B.',\n", - " 'Riach, Colin G.',\n", - " 'Brown, Alison',\n", - " 'Edwards, Ian',\n", - " 'Reynolds, Deborah',\n", - " 'West, Katrine',\n", - " 'Willington, Sarah'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1002%2Fem.2850110413\"}'],\n", - " 'title': ['Reactivity of catecholamines and related substances in the mouse lymphoma L5178Y cell assay for mutagens']},\n", - " {'bibcode': '2008HETox..27...55P',\n", - " 'abstract': 'Diallyl sulfide, a sulfur-containing volatile compound present in garlic ( Allium sativum), exerts anticarcinogenic activity in various rodent tumor models. In the present study, apoptosis-inhibiting effects of diallyl sulfide against a carcinogenic polycyclic aromatic hydrocarbon, 7,12-dimethyl benz(a)anthracene (DMBA), in Swiss albino mice were observed. The animals were given either 250 μg/mouse or 500 μg/mouse of diallyl sulfide for 1 week after a single intragastric dose of 7,12-dimethyl benz(a)anthracene (50 mg/kg body weight). Results showed that diallyl sulfide supplementation effectively protects against 7,12-dimethyl benz(a)anthracene—induced oxidative stress, characterized by restored antioxidant enzyme levels (up to 64%) and lipid peroxidation (up to 25%). Flow cytometric analysis showed a reduction in apoptotic cell population in hypodiploid region in diallyl sulfide–supplemented animals. Inhibition of apoptosis was preceded by decrease in reactive oxygen species levels and restoration of mitochondrial transmembrane potential followed by decreased DNA fragmentation. In 7,12-dimethyl benz(a)anthracene–exposed animals, downregulation (~30%) of antiapoptotic Bcl-2 and upregulation (~60%) of pro-apoptotic Bax proteins were observed. These alterations were restored significantly by diallyl sulfide supplementation, indicating inhibition of apoptosis. Thus, these results show that diallyl sulfide provides protection against oxidative damage induced by 7,12-dimethyl benz(a)anthracene in mouse liver and may be an effective chemopreventive and therapeutic agent by modulating expression of cell-growth regulatory proteins.',\n", - " 'author': ['Prasad, S.', 'Kalra, N.', 'Srivastava, S.', 'Shukla, Y.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1177%2F0960327108088978\"}'],\n", - " 'title': ['Regulation of oxidative stress–mediated apoptosis by diallyl sulfide in DMBA-exposed Swiss mice']},\n", - " {'bibcode': '2020MiMic..26..997V',\n", - " 'abstract': 'Nonalcoholic fatty liver disease (NAFLD) represents a hepatic manifestation of metabolic syndrome. The aim of this study was to examine the effect of betaine on ultrastructural changes in the mouse liver with methionine- and choline-deficient (MCD) diet-induced NAFLD. Male C57BL/6 mice were divided into groups: Control—fed with standard chow, BET—standard chow supplemented with betaine (1.5% w/v drinking water), MCD—fed with MCD diet, and MCD + BET—MCD diet with betaine supplementation for 6 weeks. Liver samples were taken for pathohistology and transmission electron microscopy. The MCD diet-induced steatosis, inflammation, and balloon-altered hepatocytes were alleviated by betaine. MCD diet induced an increase in mitochondrial size versus the control group (p < 0.01), which was decreased in the betaine-treated group. In the MCD diet-fed group, the total mitochondrial count decreased versus the control group (p < 0.01), while it increased in the MCD + BET group versus MCD (p < 0.01). Electron microscopy showed an increase in the number of autophagosomes in the MCD and MCD + BET group versus control, and a significant difference in autophagosomes number was detected in the MCD + BET group by comparison with the MCD diet-treated group (p < 0.05). Betaine decreases the number of enlarged mitochondria, alleviates steatosis, and increases the number of autophagosomes in the liver of mice with NAFLD.',\n", - " 'author': ['Vesković, Milena',\n", - " 'Labudović-Borović, Milica',\n", - " 'Mladenović, Dušan',\n", - " 'Jadžić, Jelena',\n", - " 'Jorgačević, Bojan',\n", - " 'Vukićević, Dušan',\n", - " 'Vučević, Danijela',\n", - " 'Radosavljević, Tatjana'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1017%2FS1431927620024265\"}'],\n", - " 'title': ['Effect of Betaine Supplementation on Liver Tissue and Ultrastructural Changes in Methionine-Choline-Deficient Diet-Induced NAFLD']},\n", - " {'bibcode': '1982PNAS...79.1037E',\n", - " 'abstract': 'A previously unknown 5\\'nucleotidase (5\\'-ribonucleotide phosphohydrolase, EC 3.1.3.5) (5\\'-Nase) specific for orotidine 5\\'-monophosphate (OMP) hs been discovered. This enzyme orotidine 5\\'-monophosphate phosphohydrolase (OMPase), was isolated from mouse liver microsomes as a separate entity from the nonspecific 5\\'-Nase. OMPase was partially purified and is shown to cleave OMP to orotidine and inorganic phosphate. The enzyme has negligible activity towards UMP, CMP, dTMP, AMP, IMP, GMP, XMP, 6-azauridine 5\\'-monophosphate, 1-beta-D-ribofuranosylbarbituric acid 5\\'-monophosphate (BMF), 2\\'-UMP, 3\\'-UMP, 2\\'-AMP, 3\\'-AMP, ribose 5-phosphate and beta-glycerophosphate, all of which--with the exception of the 2\\' or 3\\' monophosphates, ribose 5\\'-phosphate, and beta-glycerophosphate--are substrates for 5\\'-Nase. Both enzymes are inhibited by NaF, but only OMPase is inhibited by SF reagents. OMPase is not inhibited by orotidine, orotate, BMP, concanavalin A, or tetramisole (an alkaline phosphatase inhibitor). OMPase had a Mr 53,000, Km value of 1 mM for OMP, and Vmax value of 49 nmol/min . mg of protein at the present stage of purification. OMPase activity has also been detected in various mammalian tissues including normal human tissues, human tumor xenografts, lymphocytes, and rat liver. OMPase may be responsible, in part, for the low levels of intracellular \"free\" OMP and for orotidine accumulation in cells treated with 6-azauridine and patients suffering from aortic aciduria.',\n", - " 'author': ['El Kouni, M. H.', 'Cha, S.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/79/4/1037\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/79/4/1037\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/79/4/1037\"}'],\n", - " 'title': [\"Isolation and partial characterization of a 5'-nucleotidase specific for orotidine-5'-monophosphate.\"]},\n", - " {'bibcode': '2015NatSR...512466S',\n", - " 'abstract': 'Nonalcoholic steatohepatitis (NASH) is a major health problem since it often leads to hepatocellular carcinoma. However, the underlying mechanisms of NASH development and subsequent fibrosis have yet to be clarified. We compared comprehensive lipidomic profiles between mice with high fat diet (HFD)-induced steatosis and STAM mice with NASH and subsequent fibrosis. The STAM mouse is a model that demonstrates NASH progression resembling the disease in humans: STAM mice manifest NASH at 8 weeks, which progresses to fibrosis at 12 weeks, and finally develop hepatocellular carcinoma. Overall, 250 lipid molecules were detected in the liver using liquid chromatography-mass spectrometry. We found that STAM mice with NASH presented a significantly higher abundance of sphingolipids and lower levels of triacylglycerols than the HFD-fed control mice. The abundance of certain fatty acids in phospholipid side chains was also significantly different between STAM and control mice, although global levels of phosphatidylcholines and phosphatidylethanolamines were comparable. Finally, increase in levels of acylcarnitines and some diacylglycerols was observed in STAM mice toward the fibrosis stage, but not in age-matched control mice. Our study provides insights into the lipid status of the steatotic, NASH, and fibrotic liver that would help elucidate the molecular pathophysiology of NASH progression.',\n", - " 'author': ['Saito, Kosuke',\n", - " 'Uebanso, Takashi',\n", - " 'Maekawa, Keiko',\n", - " 'Ishikawa, Masaki',\n", - " 'Taguchi, Ryo',\n", - " 'Nammo, Takao',\n", - " 'Nishimaki-Mogami, Tomoko',\n", - " 'Udagawa, Haruhide',\n", - " 'Fujii, Masato',\n", - " 'Shibazaki, Yuichiro',\n", - " 'Yoneyama, Hiroyuki',\n", - " 'Yasuda, Kazuki',\n", - " 'Saito, Yoshiro'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep12466\"}'],\n", - " 'title': ['Characterization of hepatic lipid profiles in a mouse model with nonalcoholic steatohepatitis and subsequent fibrosis']},\n", - " {'bibcode': '1999PNAS...96.2333G',\n", - " 'abstract': 'We are developing quantitative assays to repeatedly and noninvasively image expression of reporter genes in living animals, using positron emission tomography (PET). We synthesized positron-emitting 8-[18F]fluoroganciclovir (FGCV) and demonstrated that this compound is a substrate for the herpes simplex virus 1 thymidine kinase enzyme (HSV1-TK). Using positron-emitting FGCV as a PET reporter probe, we imaged adenovirus-directed hepatic expression of the HSV1-tk reporter gene in living mice. There is a significant positive correlation between the percent injected dose of FGCV retained per gram of liver and the levels of hepatic HSV1-tk reporter gene expression (r2 > 0.80). Over a similar range of HSV1-tk expression in vivo, the percent injected dose retained per gram of liver was 0-23% for ganciclovir and 0-3% for FGCV. Repeated, noninvasive, and quantitative imaging of PET reporter gene expression should be a valuable tool for studies of human gene therapy, of organ/cell transplantation, and of both environmental and behavioral modulation of gene expression in transgenic mice.',\n", - " 'author': ['Gambhir, Sanjiv S.',\n", - " 'Barrio, Jorge R.',\n", - " 'Phelps, Michael E.',\n", - " 'Iyer, Meera',\n", - " 'Namavari, Mohammad',\n", - " 'Satyamurthy, Nagichettiar',\n", - " 'Wu, Lily',\n", - " 'Green, Leeta A.',\n", - " 'Bauer, Eileen',\n", - " 'MacLaren, Duncan C.',\n", - " 'Nguyen, Khoi',\n", - " 'Berk, Arnold J.',\n", - " 'Cherry, Simon R.',\n", - " 'Herschman, Harvey R.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/96/5/2333\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/96/5/2333\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/96/5/2333\"}'],\n", - " 'title': ['Imaging Adenoviral-Directed Reporter Gene Expression in Living Animals with Positron Emission Tomography']},\n", - " {'bibcode': '1993PNAS...90.2812H',\n", - " 'abstract': 'We have explored the use of adenovirus-mediated gene transfer to transiently elicit production of low density lipoprotein (LDL) receptors in mice. A recombinant adenovirus carrying the human LDL receptor cDNA restored LDL receptor function in receptor-deficient cultured cells. Intravenous injection of recombinant virus acutely lowered plasma cholesterol levels and increased the rate of 125I-labeled LDL clearance from the circulation in normal mice. At 4 days after virus injection, the t1/2 of plasma LDL was reduced up to 10-fold. An estimated 90% of the parenchymal cells in liver expressed the adenovirus-transferred genes as judged by immunofluorescence of LDL receptors or by beta-galactosidase staining. These results demonstrate that adenovirus-mediated transfer of the LDL receptor gene provides an efficient way of augmenting LDL receptor gene function in the liver over the short term.',\n", - " 'author': ['Herz, Joachim', 'Gerard, Robert D.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/90/7/2812\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/90/7/2812\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/90/7/2812\"}'],\n", - " 'title': ['Adenovirus-mediated transfer of low density lipoprotein receptor gene acutely accelerates cholesterol clearance in normal mice.']},\n", - " {'bibcode': '2015ApNan...5..937A',\n", - " 'abstract': 'In this study, we report the biosynthesis of silver nanoparticles using the ethanolic leaf powder extract of Premna serratifolia L. and its anticancer activity in carbon tetra chloride (CCl4)-induced liver cancer in Swiss albino mice (Balb/c). The synthesized silver nanoparticles were characterized by SEM, FTIR and XRD analyses. The Debye-Scherrer equation was used to calculate particle size and the average size of silver nanoparticles synthesized from P. serratifolia leaf extract was 22.97 nm. The typical pattern revealed that the sample contained cubic structure of silver nanoparticles. FTIR analysis confirmed that the bioreduction of silver ions to silver nanoparticles is due to reduction by capping material of the plant extract. The silver nanoparticles of P. serratifolia leaf extract were effective in treating liver cancer in Swiss albino mice when compared with P. serratifolia leaf extract with isoleucine.',\n", - " 'author': ['Arockia John Paul, J.', 'Karunai Selvi, B.', 'Karmegam, N.'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1007%2Fs13204-014-0397-z\"}'],\n", - " 'title': ['Biosynthesis of silver nanoparticles from Premna serratifolia L. leaf and its anticancer activity in CCl4-induced hepato-cancerous Swiss albino mice']},\n", - " {'bibcode': '2024Heliy..1023561L',\n", - " 'abstract': 'Diabetes mellitus (DM) poses a significant global health burden, with hyperglycemia being a primary contributor to complications and high morbidity associated with this disorder. Existing glucose management strategies have shown suboptimal effectiveness, necessitating alternative approaches. In this study, we explored the role of high mobility group box 1 (HMGB1) in hyperglycemia, a protein implicated in initiating inflammation and strongly correlated with DM onset and progression. We hypothesized that HMGB1 knockdown will mitigate hyperglycemia severity and enhance glucose tolerance. To test this hypothesis, we utilized a novel inducible HMGB1 knockout (iHMGB1 KO) mouse model exhibiting systemic HMGB1 knockdown. Hyperglycemic phenotype was induced using low dose streptozotocin (STZ) injections, followed by longitudinal glucose measurements and oral glucose tolerance tests to evaluate the effect of HMGB1 knockdown on glucose metabolism. Our findings showed a substantial reduction in glucose levels and enhanced glucose tolerance in HMGB1 knockdown mice. Additionally, we performed RNA sequencing analyses, which identified potential alternations in genes and molecular pathways within the liver and skeletal muscle tissue that may account for the in vivo phenotypic changes observed in hyperglycemic mice following HMGB1 knockdown. In conclusion, our present study delivers the first direct evidence of a causal relationship between systemic HMGB1 knockdown and hyperglycemia in vivo, an association that had remained unexamined prior to this research. This discovery positions HMGB1 knockdown as a potentially efficacious therapeutic target for addressing hyperglycemia and, by extension, the DM epidemic. Furthermore, we have revealed potential underlying mechanisms, establishing the essential groundwork for subsequent in-depth mechanistic investigations focused on further elucidating and harnessing the promising therapeutic potential of HMGB1 in DM management.',\n", - " 'author': ['Liu, Zeyu',\n", - " 'Annarapu, Gowtham',\n", - " 'Yazdani, Hamza O.',\n", - " 'Wang, Qinge',\n", - " 'Liu, Silvia',\n", - " 'Luo, Jian-Hua',\n", - " 'Yu, Yan-Ping',\n", - " 'Ren, Baoguo',\n", - " 'Neal, Matthew D.',\n", - " 'Monga, Satdarshan P.',\n", - " 'Mota Alvidrez, Roberto Ivan'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.heliyon.2023.e23561\"}'],\n", - " 'title': ['Restoring glucose balance: Conditional HMGB1 knockdown mitigates hyperglycemia in a Streptozotocin induced mouse model']},\n", - " {'bibcode': '2016NatSR...619445W',\n", - " 'abstract': 'Adiponectin is an adipocyte-derived circulating protein with beneficial effects on injured livers. Adiponectin-deficient (adipo(-/-)) mice develop enhanced liver fibrosis, suggesting that adiponectin could be a therapeutic target for liver injury. In the present study, we investigated the protective role of ADP355, an adiponectin-based active short peptide, in thioacetamide (TAA)-induced acute injury and chronic liver fibrosis in mice. ADP355 remarkably reduced TAA-induced necroinflammation and liver fibrosis. ADP355 treatment increased liver glycogen, decreased serum alanine transaminase and alkaline phosphatase activity, and promoted body weight gain, hyper-proliferation and hypo-apoptosis. In addition, ADP355 administration suppressed the TAA-induced activation of hepatic stellate cells and macrophages in the liver. These were associated with the inactivation of TGF-β1/SMAD2 signaling and the promotion of AMPK and STAT3 signaling. Sensitivity of adipo(-/-) mice to chronic liver injury was decreased with ADP355. In conclusion, ADP355 could mimic adiponectin’s action and may be suitable for the preclinical or clinical therapy of chronic liver injury.',\n", - " 'author': ['Wang, Huafeng',\n", - " 'Zhang, Huan',\n", - " 'Zhang, Zimu',\n", - " 'Huang, Biao',\n", - " 'Cheng, Xixi',\n", - " 'Wang, Dan',\n", - " 'La Gahu, Zha',\n", - " 'Xue, Zhenyi',\n", - " 'da, Yurong',\n", - " 'Li, Daiqing',\n", - " 'Yao, Zhi',\n", - " 'Gao, Fei',\n", - " 'Xu, Aimin',\n", - " 'Zhang, Rongxin'],\n", - " 'links_data': ['{\"access\": \"open\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fsrep19445\"}'],\n", - " 'title': ['Adiponectin-derived active peptide ADP355 exerts anti-inflammatory and anti-fibrotic activities in thioacetamide-induced liver injury']},\n", - " {'bibcode': '2020SPIE11228E..2CA',\n", - " 'abstract': 'We present a new OCT-based tissue dynamics/subcellular motion analysis method to visualize tissue dynamics, where we increase the functionality of OCT to be sensitive for tissue dynamics by utilizing rapid-time-sequence analysis of OCT signals. These analysis includes log intensity variance (LIV) and OCT time-correlation analysis (OCT decorrelation speed; OCDS). In addition to LIV and OCDS methods, attenuation coefficient (AC), birefringence, and degree of polarization uniformity (DOPU) analysis were performed. These methods used to visualize and quantify long-term tissue dynamics degradation of different tissue types such as dissected mouse liver and tumor spheroids. These methods were quantitative, so the time-course tissue dynamics degradation has been not only visualized as an image, but also quantitative analysis of the dynamics degradation were performed.',\n", - " 'author': ['Abd El-Sadek, I. G.',\n", - " 'Miyazawa, A.',\n", - " 'Shen, L. T. W.',\n", - " 'Fukuda, S.',\n", - " 'Yamashita, T.',\n", - " 'Oka, Y.',\n", - " 'Mukherjee, P.',\n", - " 'Makita, S.',\n", - " 'Matsusaka, S.',\n", - " 'Oshika, T.',\n", - " 'Kano, H.',\n", - " 'Yasuno, Y.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"video\", \"url\": \"https://doi.org/10.1117/12.2548541\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1117%2F12.2548541\"}'],\n", - " 'title': ['Quantification of ex vivo tissue activity by short and long time-course analysis of multifunctional OCT signals']},\n", - " {'bibcode': '2008AcAC..618..116S',\n", - " 'abstract': 'We detected mouse liver malate, sorbitol and aldehyde dehydrogenases by negative staining, analysis of malate and sorbitol dehydrogenase activities using each substrate, and electron transfers including nicotinamide adenine dinucleotide (NAD) and nitroblue tetrazolium in non-denaturing two-dimensional electrophoresis (2-DE) gel. Dehydrogenases were also identified by electrospray ionization tandem mass spectrometry (ESI-MS/MS) after 2-DE separation and protein detection by negative staining. Spots of dehydrogenases separated by 2-DE were excised, and simultaneously transferred and immobilized on polyvinylidene difuoride (PVDF) resin by electrophoresis. The dehydrogenase activities remained intact after immobilization . In conclusion, resin-immobilized dehydrogenases can be simultaneously obtained after separation by non-denaturing 2-DE, detection by negative staining and transferring to resins.',\n", - " 'author': ['Shimazaki, Youji', 'Kadota, Mariko'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1016%2Fj.aca.2008.04.046\"}'],\n", - " 'title': ['Simultaneous immobilization of dehydrogenases on polyvinylidene difluoride resin after separation by non-denaturing two-dimensional electrophoresis']},\n", - " {'bibcode': '2006AIPC..832..498K',\n", - " 'abstract': 'Throughout the life span, complex physiological systems are regulated by specific age related mechanisms, thus maintaining the age axis homeostasis. Our efforts for understanding the underlying mechanisms began about a decade ago, successfully discovering the very fist such a mechanism, we called the ASE/AIE-mediated age-related regulatory mechanism of gene expression. This mechanism can explain the major feature of the age-related increase profile of blood coagulation activity. Global analyses of the mouse liver genes and proteins revealed heir highly dynamic and complex age-related regulation, suggesting the existence of several major phases over the life span. These studies facilitate a systematic investigation into the regulatory mechanisms of age-axis homeostasis, a slow dynamics system of the complex biological systems.',\n", - " 'author': ['Kurachi, K.',\n", - " 'Yasui, M.',\n", - " 'Isobe, T.',\n", - " 'Suenaga, E.',\n", - " 'Kurachi, S.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1063%2F1.2204547\"}'],\n", - " 'title': ['Age Dimension Homeostasis of Physiological Systems, a Slow Dynamics Model in Biology']},\n", - " {'bibcode': '1982PNAS...79.1163C',\n", - " 'abstract': 'The turnover of DNA and histones in the livers and brains of mice has been determined. These mice had been exposed to constant levels of tritiated water from conception until they were 8 months old. At this point, exposure to tritium was discontinued, and the tritium remaining in DNA and histones was measured at various intervals afterward. The half-lives calculated for these components (with 95% confidence limits given in parentheses) were 117 (85-188) days for liver histone, 318 (241-466) days for liver DNA, 159 (129-208) days for brain histone and 593 (376-1406) days for brain DNA. The difference between histone and DNA turnover is statistically significant for both tissues and indicates that histone turnover within tissues cannot be solely accounted for by cell turnover within the tissue but also must include histone turnover within living cells. The half-life of histone within cells is estimated to be 117 (88-178) days in liver and 223 (187-277) days in brain.',\n", - " 'author': ['Commerford, S. L.', 'Carsten, A. L.', 'Cronkite, E. P.'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/79/4/1163\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/79/4/1163\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/79/4/1163\"}'],\n", - " 'title': ['Histone Turnover within Nonproliferating Cells']},\n", - " {'bibcode': '1994PNAS...91..614T',\n", - " 'abstract': 'Interferon-gamma may play an important role in the immune response and in inflammatory diseases, including chronic active hepatitis. To understand the role of interferon-gamma in the regulation of inflammation and to establish a mouse model of chronic active hepatitis, we produced transgenic mice in which the mouse interferon-gamma gene was regulated by a liver-specific promoter, the serum amyloid P component gene promoter. Four transgenic mouse lines were generated, and two of these lines expressed mRNA of interferon-gamma in the liver. Levels of serum transaminases increased gradually as a function of age and were significantly higher than those of interferon-gamma-negative littermates after 4 weeks after birth. One transgenic mouse line showed a histology of chronic active hepatitis similar to that found in human patients, although cirrhotic changes such as fibrosis were scarce. Thus, the liver-specific production of interferon-gamma is sufficient to induce chronic inflammatory disease and this mouse is a transgenic model of chronic active hepatitis.',\n", - " 'author': ['Toyonaga, Tetsushi',\n", - " 'Hino, Okio',\n", - " 'Sugai, Satoshi',\n", - " 'Wakasug, Shoji',\n", - " 'Abe, Kuniya',\n", - " 'Shichiri, Motoaki',\n", - " 'Yamamura, Ken-Ichi'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/cgi/reprint/91/2/614\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/91/2/614\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"http://www.pnas.org/cgi/content/abstract/91/2/614\"}'],\n", - " 'title': ['Chronic Active Hepatitis in Transgenic Mice Expressing Interferon-γ in the Liver']},\n", - " {'bibcode': '2020Natur.588..479L',\n", - " 'abstract': 'Cholesterol is an essential lipid and its synthesis is nutritionally and energetically costly1,2. In mammals, cholesterol biosynthesis increases after feeding and is inhibited under fasting conditions3. However, the regulatory mechanisms of cholesterol biosynthesis at the fasting-feeding transition remain poorly understood. Here we show that the deubiquitylase ubiquitin-specific peptidase 20 (USP20) stabilizes HMG-CoA reductase (HMGCR), the rate-limiting enzyme in the cholesterol biosynthetic pathway, in the feeding state. The post-prandial increase in insulin and glucose concentration stimulates mTORC1 to phosphorylate USP20 at S132 and S134; USP20 is recruited to the HMGCR complex and antagonizes its degradation. The feeding-induced stabilization of HMGCR is abolished in mice with liver-specific Usp20 deletion and in USP20(S132A/S134A) knock-in mice. Genetic deletion or pharmacological inhibition of USP20 markedly decreases diet-induced body weight gain, reduces lipid levels in the serum and liver, improves insulin sensitivity and increases energy expenditure. These metabolic changes are reversed by expression of the constitutively stable HMGCR(K248R). This study reveals an unexpected regulatory axis from mTORC1 to HMGCR via USP20 phosphorylation and suggests that inhibitors of USP20 could be used to lower cholesterol levels to treat metabolic diseases including hyperlipidaemia, liver steatosis, obesity and diabetes.',\n", - " 'author': ['Lu, Xiao-Yi',\n", - " 'Shi, Xiong-Jie',\n", - " 'Hu, Ao',\n", - " 'Wang, Ju-Qiong',\n", - " 'Ding, Yi',\n", - " 'Jiang, Wei',\n", - " 'Sun, Ming',\n", - " 'Zhao, Xiaolu',\n", - " 'Luo, Jie',\n", - " 'Qi, Wei',\n", - " 'Song, Bao-Liang'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1038%2Fs41586-020-2928-y\"}'],\n", - " 'title': ['Feeding induces cholesterol biosynthesis via the mTORC1-USP20-HMGCR axis']},\n", - " {'bibcode': '2015PNAS..11211282K',\n", - " 'abstract': 'The liver is rich in mitochondria and has an exceptional regenerative capacity after partial hepatectomy or transplantation, viral infections, or chemical injuries; however, relatively little is known about the genetic factors for mitochondrial DNA (mtDNA) replication during liver regeneration. Here, we show that liver regeneration is markedly reduced in mice lacking mitochondrial topoisomerase I (TOP1mt). This defect is linked with reduced production of mtDNA and defective mitochondrial functions during acute energy demand for liver regeneration. Additionally, TOP1mt KO primary hepatocytes from CCl4-treated mice showed reduced and damaged mitochondria, decreased O2 consumption, and ATP production. Together with mtDNA depletion and regeneration experiments with ethidium bromide, these results demonstrate that Top1mt is required for mtDNA synthesis and appropriate liver regeneration.',\n", - " 'author': ['Khiati, Salim',\n", - " 'Baechler, Simone A.',\n", - " 'Factor, Valentina M.',\n", - " 'Zhang, Hongliang',\n", - " 'Huang, Shar-yin N.',\n", - " 'Dalla Rosa, Ilaria',\n", - " 'Sourbier, Carole',\n", - " 'Neckers, Leonard',\n", - " 'Thorgeirsson, Snorri S.',\n", - " 'Pommier, Yves'],\n", - " 'links_data': ['{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"pdf\", \"url\": \"https://www.pnas.org/content/112/36/11282\"}',\n", - " '{\"access\": \"\", \"instances\": \"\", \"title\": \"\", \"type\": \"electr\", \"url\": \"https://doi.org/10.1073%2Fpnas.1511016112\"}'],\n", - " 'title': ['Lack of mitochondrial topoisomerase I (TOP1mt) impairs liver regeneration']},\n", - " ...]}}" - ] - }, - "execution_count": 14, - "metadata": {}, - "output_type": "execute_result" - 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"id": "9f720c76-85e2-40ad-b18a-3859202736b6", - "metadata": {}, - "outputs": [ - { - "data": { - "text/plain": [ - "'https://baas.aas.org/pub/2023n2i265p03'" - ] - }, - "execution_count": 11, - "metadata": {}, - "output_type": "execute_result" - } - ], - "source": [ - "#Construct a URL to access the original source of a given document\n", - "url = json.loads(results['response']['docs'][doc_num]['links_data'][0])['url']\n", - "url" - ] - }, - { - "cell_type": "code", - "execution_count": 8, - "id": "b5a083d3-8862-4927-8dc3-91d0342941fc", - "metadata": {}, - "outputs": [ - { - "data": { - "text/plain": [ - "{'responseHeader': {'status': 0,\n", - " 'QTime': 22,\n", - " 'params': {'q': '*:*',\n", - " 'fl': 'bibcode,title',\n", - " 'start': '0',\n", - " 'internal_logging_params': 'X-Amzn-Trace-Id=Root=1-65a96c5b-50bd41ca443d7b136d1564cc',\n", - " 'fq': '{!bitset}',\n", - " 'rows': '2000',\n", - " 'wt': 'json'}},\n", - " 'response': {'numFound': 3,\n", - " 'start': 0,\n", - " 'docs': [{'bibcode': '1989LNP...334..242S',\n", - " 'title': ['The Optical and Radio Properties of X-Ray Selected Bl-Lacertae Objects']},\n", - " {'bibcode': '1907AN....174...59.', 'title': ['Kleine Mitteilungen']},\n", - " {'bibcode': '1908PA.....16..445.', 'title': ['Variable Stars']}]}}" - ] - }, - "execution_count": 8, - "metadata": {}, - "output_type": "execute_result" - } - ], - "source": [ - "encoded_query = urlencode({\"q\": \"*:*\",\n", - " \"fl\": \"bibcode,title\",\n", - " \"rows\": 2000\n", - " })\n", - "payload = \"bibcode\\n1907AN....174...59.\\n1908PA.....16..445.\\n1989LNP...334..242S\"\n", - "results = requests.post(\"https://api.adsabs.harvard.edu/v1/search/bigquery?{}\".format(encoded_query), \\\n", - " headers={'Authorization': 'Bearer ' + token}, \\\n", - " data=payload)\n", - "\n", - "results.json()" - ] - }, - { - "cell_type": "code", - "execution_count": null, - "id": "f00288b6-eeda-4c8f-9b64-e9e18f622754", - "metadata": {}, - "outputs": [], - "source": [] - } - ], - "metadata": { - "kernelspec": { - "display_name": "Python 3 (ipykernel)", - "language": "python", - "name": "python3" - }, - "language_info": { - "codemirror_mode": { - "name": "ipython", - "version": 3 - }, - "file_extension": ".py", - "mimetype": "text/x-python", - "name": "python", - "nbconvert_exporter": "python", - "pygments_lexer": "ipython3", - "version": "3.11.5" - } - }, - "nbformat": 4, - "nbformat_minor": 5 -} From eed894e453555cc93ad84d6227fba70b34456569 Mon Sep 17 00:00:00 2001 From: Bishwas Praveen Date: Thu, 25 Jan 2024 10:50:26 -0600 Subject: [PATCH 6/7] added blank=true to source field --- feedback/models.py | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/feedback/models.py b/feedback/models.py index f1e475f6..e286e395 100644 --- a/feedback/models.py +++ b/feedback/models.py @@ -6,7 +6,7 @@ class Feedback(models.Model): email = models.EmailField() subject = models.CharField(max_length=400) comments = models.TextField() - source = models.CharField(max_length=50, default="SDE") + source = models.CharField(max_length=50, default="SDE", blank=True) class Meta: verbose_name = "Feedback Response" From 7b6412498dc0c7859e00f3df19cf7ad45ff55726 Mon Sep 17 00:00:00 2001 From: Bishwas Praveen Date: Thu, 25 Jan 2024 10:51:04 -0600 Subject: [PATCH 7/7] deleted older migration file and added the latest one --- feedback/migrations/0003_feedback_source.py | 4 ++-- 1 file changed, 2 insertions(+), 2 deletions(-) diff --git a/feedback/migrations/0003_feedback_source.py b/feedback/migrations/0003_feedback_source.py index 604a2c68..b4b66de4 100644 --- a/feedback/migrations/0003_feedback_source.py +++ b/feedback/migrations/0003_feedback_source.py @@ -1,4 +1,4 @@ -# Generated by Django 4.2.6 on 2024-01-22 17:00 +# Generated by Django 4.2.6 on 2024-01-25 16:48 from django.db import migrations, models @@ -12,6 +12,6 @@ class Migration(migrations.Migration): migrations.AddField( model_name="feedback", name="source", - field=models.CharField(default="SDE", max_length=50), + field=models.CharField(blank=True, default="SDE", max_length=50), ), ]