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class="data"><span class="js-profile-view-count"></span></p></div></span></div><div class="ri-section"><div class="ri-section-header"><span>Interests</span></div><div class="ri-tags-container"><a data-click-track="profile-user-info-expand-research-interests" data-has-card-for-ri-list="39344319" href="https://www.academia.edu/Documents/in/Mycobacterium_tuberculosis"><div id="js-react-on-rails-context" style="display:none" data-rails-context="{"inMailer":false,"i18nLocale":"en","i18nDefaultLocale":"en","href":"https://independent.academia.edu/GraceChappell","location":"/GraceChappell","scheme":"https","host":"independent.academia.edu","port":null,"pathname":"/GraceChappell","search":null,"httpAcceptLanguage":null,"serverSide":false}"></div> <div class="js-react-on-rails-component" style="display:none" data-component-name="Pill" data-props="{"color":"gray","children":["Mycobacterium tuberculosis"]}" data-trace="false" data-dom-id="Pill-react-component-95ac323a-441f-4811-bd3d-89b864a16f08"></div> <div id="Pill-react-component-95ac323a-441f-4811-bd3d-89b864a16f08"></div> </a><a data-click-track="profile-user-info-expand-research-interests" data-has-card-for-ri-list="39344319" href="https://www.academia.edu/Documents/in/DNA_methylation"><div class="js-react-on-rails-component" style="display:none" data-component-name="Pill" data-props="{"color":"gray","children":["DNA methylation"]}" data-trace="false" data-dom-id="Pill-react-component-c1b14148-37ef-4958-8ac3-13daa916cc18"></div> <div id="Pill-react-component-c1b14148-37ef-4958-8ac3-13daa916cc18"></div> </a><a data-click-track="profile-user-info-expand-research-interests" data-has-card-for-ri-list="39344319" href="https://www.academia.edu/Documents/in/Liver_Cirrhosis"><div class="js-react-on-rails-component" style="display:none" data-component-name="Pill" data-props="{"color":"gray","children":["Liver Cirrhosis"]}" data-trace="false" data-dom-id="Pill-react-component-bdb8b79d-9d8c-4334-bdc8-95d56469ca0b"></div> <div id="Pill-react-component-bdb8b79d-9d8c-4334-bdc8-95d56469ca0b"></div> </a><a data-click-track="profile-user-info-expand-research-interests" data-has-card-for-ri-list="39344319" href="https://www.academia.edu/Documents/in/Plant_extracts"><div class="js-react-on-rails-component" style="display:none" data-component-name="Pill" data-props="{"color":"gray","children":["Plant extracts"]}" data-trace="false" data-dom-id="Pill-react-component-da06bbaf-7b5c-4339-ad85-5068e77bc323"></div> <div id="Pill-react-component-da06bbaf-7b5c-4339-ad85-5068e77bc323"></div> </a><a data-click-track="profile-user-info-expand-research-interests" data-has-card-for-ri-list="39344319" href="https://www.academia.edu/Documents/in/Veterinary_Sciences"><div class="js-react-on-rails-component" style="display:none" data-component-name="Pill" data-props="{"color":"gray","children":["Veterinary Sciences"]}" data-trace="false" data-dom-id="Pill-react-component-0f436a61-468b-4f24-9c9c-5c375ed239f7"></div> <div id="Pill-react-component-0f436a61-468b-4f24-9c9c-5c375ed239f7"></div> </a></div></div></div></div><div class="right-panel-container"><div class="user-content-wrapper"><div class="uploads-container" id="social-redesign-work-container"><div class="upload-header"><h2 class="ds2-5-heading-sans-serif-xs">Uploads</h2></div><div class="documents-container backbone-social-profile-documents" style="width: 100%;"><div class="u-taCenter"></div><div class="profile--tab_content_container js-tab-pane tab-pane active" id="all"><div class="profile--tab_heading_container js-section-heading" data-section="Papers" id="Papers"><h3 class="profile--tab_heading_container">Papers by Grace Chappell</h3></div><div class="js-work-strip profile--work_container" data-work-id="19147560"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/19147560/Differentially_expressed_microRNAs_provide_mechanistic_insight_into_fibrosis_associated_liver_carcinogenesis_in_mice"><img alt="Research paper thumbnail of Differentially expressed microRNAs provide mechanistic insight into fibrosis-associated liver carcinogenesis in mice" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/19147560/Differentially_expressed_microRNAs_provide_mechanistic_insight_into_fibrosis_associated_liver_carcinogenesis_in_mice">Differentially expressed microRNAs provide mechanistic insight into fibrosis-associated liver carcinogenesis in mice</a></div><div class="wp-workCard_item wp-workCard--coauthors"><span>by </span><span><a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/GraceChappell">Grace Chappell</a> and <a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/TakekiUehara">Takeki Uehara</a></span></div><div class="wp-workCard_item"><span>Molecular carcinogenesis</span><span>, Jan 11, 2015</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Hepatocellular carcinoma (HCC) is one of the most prevalent human cancers, with rising incidence ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Hepatocellular carcinoma (HCC) is one of the most prevalent human cancers, with rising incidence worldwide. The molecular mechanisms associated with the development of HCC are complex and include multiple interconnected molecular alterations with mounting evidence indicating an important role of microRNAs (miRNAs) in the pathogenesis of HCC. In humans, the development of HCC is commonly associated with liver cirrhosis. To study fibrosis-associated liver carcinogenesis, we used a mouse model designed to emulate the development of HCC in cirrhotic liver. Specifically, we were interested in evaluating the role of miRNAs in the molecular pathogenesis of liver carcinogenesis in male B6C3F1/J mice treated with N-nitrosodiethylamine (DEN) or carbon tetrachloride (CCl4 ) alone or a combination of DEN and CCl4 and characterized by a differential tumor incidence that increased in the following order: DEN&lt;CCl4 &lt;DEN+CCl4 . Treatment with DEN alone had negligible effect on hepatic miRNA ex...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="19147560"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="19147560"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 19147560; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=19147560]").text(description); $(".js-view-count[data-work-id=19147560]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 19147560; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='19147560']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 19147560, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=19147560]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":19147560,"title":"Differentially expressed microRNAs provide mechanistic insight into fibrosis-associated liver carcinogenesis in mice","translated_title":"","metadata":{"abstract":"Hepatocellular carcinoma (HCC) is one of the most prevalent human cancers, with rising incidence worldwide. The molecular mechanisms associated with the development of HCC are complex and include multiple interconnected molecular alterations with mounting evidence indicating an important role of microRNAs (miRNAs) in the pathogenesis of HCC. In humans, the development of HCC is commonly associated with liver cirrhosis. To study fibrosis-associated liver carcinogenesis, we used a mouse model designed to emulate the development of HCC in cirrhotic liver. Specifically, we were interested in evaluating the role of miRNAs in the molecular pathogenesis of liver carcinogenesis in male B6C3F1/J mice treated with N-nitrosodiethylamine (DEN) or carbon tetrachloride (CCl4 ) alone or a combination of DEN and CCl4 and characterized by a differential tumor incidence that increased in the following order: DEN\u0026lt;CCl4 \u0026lt;DEN+CCl4 . Treatment with DEN alone had negligible effect on hepatic miRNA ex...","publication_date":{"day":11,"month":1,"year":2015,"errors":{}},"publication_name":"Molecular carcinogenesis"},"translated_abstract":"Hepatocellular carcinoma (HCC) is one of the most prevalent human cancers, with rising incidence worldwide. The molecular mechanisms associated with the development of HCC are complex and include multiple interconnected molecular alterations with mounting evidence indicating an important role of microRNAs (miRNAs) in the pathogenesis of HCC. In humans, the development of HCC is commonly associated with liver cirrhosis. To study fibrosis-associated liver carcinogenesis, we used a mouse model designed to emulate the development of HCC in cirrhotic liver. Specifically, we were interested in evaluating the role of miRNAs in the molecular pathogenesis of liver carcinogenesis in male B6C3F1/J mice treated with N-nitrosodiethylamine (DEN) or carbon tetrachloride (CCl4 ) alone or a combination of DEN and CCl4 and characterized by a differential tumor incidence that increased in the following order: DEN\u0026lt;CCl4 \u0026lt;DEN+CCl4 . Treatment with DEN alone had negligible effect on hepatic miRNA ex...","internal_url":"https://www.academia.edu/19147560/Differentially_expressed_microRNAs_provide_mechanistic_insight_into_fibrosis_associated_liver_carcinogenesis_in_mice","translated_internal_url":"","created_at":"2015-11-28T11:26:33.816-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":39344319,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[{"id":11151065,"work_id":19147560,"tagging_user_id":39344319,"tagged_user_id":39296401,"co_author_invite_id":null,"email":"t***a@shionogi.co.jp","display_order":0,"name":"Takeki Uehara","title":"Differentially expressed microRNAs provide mechanistic insight into fibrosis-associated liver carcinogenesis in mice"},{"id":11151066,"work_id":19147560,"tagging_user_id":39344319,"tagged_user_id":null,"co_author_invite_id":2551626,"email":"f***d@fda.hhs.gov","display_order":4194304,"name":"Frederick Beland","title":"Differentially expressed microRNAs provide mechanistic insight into fibrosis-associated liver carcinogenesis in mice"},{"id":11151067,"work_id":19147560,"tagging_user_id":39344319,"tagged_user_id":null,"co_author_invite_id":1386162,"email":"i***n@cvm.tamu.edu","display_order":6291456,"name":"Ivan Rusyn","title":"Differentially expressed microRNAs provide mechanistic insight into fibrosis-associated liver carcinogenesis in mice"},{"id":11151070,"work_id":19147560,"tagging_user_id":39344319,"tagged_user_id":null,"co_author_invite_id":2551627,"email":"i***y@fda.hhs.gov","display_order":7340032,"name":"Igor Pogribny","title":"Differentially expressed microRNAs provide mechanistic insight into fibrosis-associated liver carcinogenesis in mice"}],"downloadable_attachments":[],"slug":"Differentially_expressed_microRNAs_provide_mechanistic_insight_into_fibrosis_associated_liver_carcinogenesis_in_mice","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":39344319,"first_name":"Grace","middle_initials":null,"last_name":"Chappell","page_name":"GraceChappell","domain_name":"independent","created_at":"2015-11-28T11:25:45.377-08:00","display_name":"Grace Chappell","url":"https://independent.academia.edu/GraceChappell"},"attachments":[],"research_interests":[{"id":536979,"name":"MOLECULAR CARC陌NOGENES陌S","url":"https://www.academia.edu/Documents/in/MOLECULAR_CARC%C4%B0NOGENES%C4%B0S"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="19147559"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/19147559/Epigenetic_Events_Determine_Tissue_Specific_Toxicity_of_Inhalational_Exposure_to_the_Genotoxic_Chemical_1_3_Butadiene_in_Male_C57BL_6J_Mice"><img alt="Research paper thumbnail of Epigenetic Events Determine Tissue-Specific Toxicity of Inhalational Exposure to the Genotoxic Chemical 1,3-Butadiene in Male C57BL/6J Mice" class="work-thumbnail" src="https://attachments.academia-assets.com/40457567/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/19147559/Epigenetic_Events_Determine_Tissue_Specific_Toxicity_of_Inhalational_Exposure_to_the_Genotoxic_Chemical_1_3_Butadiene_in_Male_C57BL_6J_Mice">Epigenetic Events Determine Tissue-Specific Toxicity of Inhalational Exposure to the Genotoxic Chemical 1,3-Butadiene in Male C57BL/6J Mice</a></div><div class="wp-workCard_item wp-workCard--coauthors"><span>by </span><span><a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/GraceChappell">Grace Chappell</a> and <a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/BodnarW">W. Bodnar</a></span></div><div class="wp-workCard_item"><span>Toxicological Sciences</span><span>, 2014</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="dfdf092404c348f4d7d91dc1c9c93a2e" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":40457567,"asset_id":19147559,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/40457567/download_file?st=MTczMjc5MDQxNSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="19147559"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="19147559"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 19147559; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=19147559]").text(description); $(".js-view-count[data-work-id=19147559]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 19147559; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='19147559']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 19147559, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "dfdf092404c348f4d7d91dc1c9c93a2e" } } $('.js-work-strip[data-work-id=19147559]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":19147559,"title":"Epigenetic Events Determine Tissue-Specific Toxicity of Inhalational Exposure to the Genotoxic Chemical 1,3-Butadiene in Male C57BL/6J Mice","translated_title":"","metadata":{"grobid_abstract":"1,3-Butadiene (BD), a widely used industrial chemical and a ubiquitous environmental pollutant, is a known human carcinogen. Although genotoxicity is an established mechanism of the tumorigenicity of BD, epigenetic effects have also been observed in livers of mice exposed to the chemical. To better characterize the diverse molecular mechanisms of BD tumorigenicity, we evaluated genotoxic and epigenotoxic effects of BD exposure in mouse tissues that are target (lung and liver) and non-target (kidney) for BD-induced tumors. We hypothesized that epigenetic alterations may explain, at least in part, the tissue-specific differences in BD tumorigenicity in mice. We evaluated the level of N-7-(2,3,4-trihydroxybut-1-yl)guanine (THB-Gua) adducts and 1,4-bis-(guan-7-yl)-2,3-butanediol (bis-N7G-BD) crosslinks, DNA methylation, and histone modifications in male C57BL/6 mice exposed to filtered air or 425 ppm of BD by inhalation (6 hr/day, 5 days/week) for two weeks. While DNA damage was observed in all three tissues of BD-exposed mice, variation in epigenetic effects clearly existed between the kidneys, liver and lungs. Epigenetic alterations indicative of genomic instability, including demethylation of repetitive DNA sequences and alterations in histone-lysine acetylation, were evident in the liver and lung tissues of BD-exposed mice. Changes in DNA methylation were insignificant in the kidneys of treated mice, while marks of condensed heterochromatin and transcriptional silencing (histone-lysine trimethylation) were increased. These modifications may represent a potential mechanistic explanation for the lack of tumorigenesis in the kidney. Our results indicate that differential tissue susceptibility to chemical-induced tumorigenesis may be attributed to tissue-specific epigenetic alterations.","publication_date":{"day":null,"month":null,"year":2014,"errors":{}},"publication_name":"Toxicological Sciences","grobid_abstract_attachment_id":40457567},"translated_abstract":null,"internal_url":"https://www.academia.edu/19147559/Epigenetic_Events_Determine_Tissue_Specific_Toxicity_of_Inhalational_Exposure_to_the_Genotoxic_Chemical_1_3_Butadiene_in_Male_C57BL_6J_Mice","translated_internal_url":"","created_at":"2015-11-28T11:26:33.736-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":39344319,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[{"id":11151068,"work_id":19147559,"tagging_user_id":39344319,"tagged_user_id":null,"co_author_invite_id":1386162,"email":"i***n@cvm.tamu.edu","display_order":0,"name":"Ivan Rusyn","title":"Epigenetic Events Determine Tissue-Specific Toxicity of Inhalational Exposure to the Genotoxic Chemical 1,3-Butadiene in Male C57BL/6J Mice"},{"id":11151071,"work_id":19147559,"tagging_user_id":39344319,"tagged_user_id":null,"co_author_invite_id":2551627,"email":"i***y@fda.hhs.gov","display_order":4194304,"name":"Igor Pogribny","title":"Epigenetic Events Determine Tissue-Specific Toxicity of Inhalational Exposure to the Genotoxic Chemical 1,3-Butadiene in Male C57BL/6J Mice"},{"id":11151072,"work_id":19147559,"tagging_user_id":39344319,"tagged_user_id":null,"co_author_invite_id":2608561,"email":"b***n@gmail.com","display_order":6291456,"name":"B. O'Brien","title":"Epigenetic Events Determine Tissue-Specific Toxicity of Inhalational Exposure to the Genotoxic Chemical 1,3-Butadiene in Male C57BL/6J Mice"},{"id":11151073,"work_id":19147559,"tagging_user_id":39344319,"tagged_user_id":null,"co_author_invite_id":2608562,"email":"o***k@med.unc.edu","display_order":7340032,"name":"O. Kosyk","title":"Epigenetic Events Determine Tissue-Specific Toxicity of Inhalational Exposure to the Genotoxic Chemical 1,3-Butadiene in Male C57BL/6J Mice"},{"id":11151075,"work_id":19147559,"tagging_user_id":39344319,"tagged_user_id":null,"co_author_invite_id":2608563,"email":"k***n@ncsu.edu","display_order":7864320,"name":"K. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="19147558"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/19147558/In_Vitro_Screening_for_Population_Variability_in_Chemical_Toxicity"><img alt="Research paper thumbnail of In Vitro Screening for Population Variability in Chemical Toxicity" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/19147558/In_Vitro_Screening_for_Population_Variability_in_Chemical_Toxicity">In Vitro Screening for Population Variability in Chemical Toxicity</a></div><div class="wp-workCard_item"><span>Toxicological Sciences</span><span>, 2011</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Immortalized human lymphoblastoid cell lines have been used to demonstrate that it is possible to...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Immortalized human lymphoblastoid cell lines have been used to demonstrate that it is possible to use an in vitro model system to identify genetic factors that affect responses to xenobiotics. To extend the application of such studies to investigative toxicology by assessing interindividual and population-wide variability and heritability of chemical-induced toxicity phenotypes, we have used cell lines from the Centre d&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;Etude du Polymorphisme Humain (CEPH) trios assembled by the HapMap Consortium. Our goal is to aid in the development of predictive in vitro genetics-anchored models of chemical-induced toxicity. Cell lines from the CEPH trios were exposed to three concentrations of 14 environmental chemicals. We assessed ATP production and caspase-3/7 activity 24 h after treatment. Replicate analyses were used to evaluate experimental variability and classify responses. We show that variability of response across the cell lines exists for some, but not all, chemicals, with perfluorooctanoic acid (PFOA) and phenobarbital eliciting the greatest degree of interindividual variability. Although the data for the chemicals used here do not show evidence for broad-sense heritability of toxicity response phenotypes, substantial cell line variation was found, and candidate genetic factors contributing to the variability in response to PFOA were investigated using genome-wide association analysis. The approach of screening chemicals for toxicity in a genetically defined yet diverse in vitro human cell-based system is potentially useful for identification of chemicals that may pose a highest risk, the extent of within-species variability in the population, and genetic loci of interest that potentially contribute to chemical susceptibility.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="19147558"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="19147558"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 19147558; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=19147558]").text(description); $(".js-view-count[data-work-id=19147558]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 19147558; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='19147558']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 19147558, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=19147558]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":19147558,"title":"In Vitro Screening for Population Variability in Chemical Toxicity","translated_title":"","metadata":{"abstract":"Immortalized human lymphoblastoid cell lines have been used to demonstrate that it is possible to use an in vitro model system to identify genetic factors that affect responses to xenobiotics. To extend the application of such studies to investigative toxicology by assessing interindividual and population-wide variability and heritability of chemical-induced toxicity phenotypes, we have used cell lines from the Centre d\u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;Etude du Polymorphisme Humain (CEPH) trios assembled by the HapMap Consortium. Our goal is to aid in the development of predictive in vitro genetics-anchored models of chemical-induced toxicity. Cell lines from the CEPH trios were exposed to three concentrations of 14 environmental chemicals. We assessed ATP production and caspase-3/7 activity 24 h after treatment. Replicate analyses were used to evaluate experimental variability and classify responses. We show that variability of response across the cell lines exists for some, but not all, chemicals, with perfluorooctanoic acid (PFOA) and phenobarbital eliciting the greatest degree of interindividual variability. Although the data for the chemicals used here do not show evidence for broad-sense heritability of toxicity response phenotypes, substantial cell line variation was found, and candidate genetic factors contributing to the variability in response to PFOA were investigated using genome-wide association analysis. The approach of screening chemicals for toxicity in a genetically defined yet diverse in vitro human cell-based system is potentially useful for identification of chemicals that may pose a highest risk, the extent of within-species variability in the population, and genetic loci of interest that potentially contribute to chemical susceptibility.","publication_date":{"day":null,"month":null,"year":2011,"errors":{}},"publication_name":"Toxicological Sciences"},"translated_abstract":"Immortalized human lymphoblastoid cell lines have been used to demonstrate that it is possible to use an in vitro model system to identify genetic factors that affect responses to xenobiotics. To extend the application of such studies to investigative toxicology by assessing interindividual and population-wide variability and heritability of chemical-induced toxicity phenotypes, we have used cell lines from the Centre d\u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;Etude du Polymorphisme Humain (CEPH) trios assembled by the HapMap Consortium. Our goal is to aid in the development of predictive in vitro genetics-anchored models of chemical-induced toxicity. Cell lines from the CEPH trios were exposed to three concentrations of 14 environmental chemicals. We assessed ATP production and caspase-3/7 activity 24 h after treatment. Replicate analyses were used to evaluate experimental variability and classify responses. We show that variability of response across the cell lines exists for some, but not all, chemicals, with perfluorooctanoic acid (PFOA) and phenobarbital eliciting the greatest degree of interindividual variability. Although the data for the chemicals used here do not show evidence for broad-sense heritability of toxicity response phenotypes, substantial cell line variation was found, and candidate genetic factors contributing to the variability in response to PFOA were investigated using genome-wide association analysis. The approach of screening chemicals for toxicity in a genetically defined yet diverse in vitro human cell-based system is potentially useful for identification of chemicals that may pose a highest risk, the extent of within-species variability in the population, and genetic loci of interest that potentially contribute to chemical susceptibility.","internal_url":"https://www.academia.edu/19147558/In_Vitro_Screening_for_Population_Variability_in_Chemical_Toxicity","translated_internal_url":"","created_at":"2015-11-28T11:26:33.654-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":39344319,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[{"id":11151069,"work_id":19147558,"tagging_user_id":39344319,"tagged_user_id":null,"co_author_invite_id":1386162,"email":"i***n@cvm.tamu.edu","display_order":0,"name":"Ivan Rusyn","title":"In Vitro Screening for Population Variability in Chemical Toxicity"},{"id":11151074,"work_id":19147558,"tagging_user_id":39344319,"tagged_user_id":null,"co_author_invite_id":2608562,"email":"o***k@med.unc.edu","display_order":4194304,"name":"O. Kosyk","title":"In Vitro Screening for Population Variability in Chemical Toxicity"},{"id":11151078,"work_id":19147558,"tagging_user_id":39344319,"tagged_user_id":141528129,"co_author_invite_id":511506,"email":"j***z@vassar.edu","affiliation":"Vassar College","display_order":6291456,"name":"Jodi Schwarz","title":"In Vitro Screening for Population Variability in Chemical Toxicity"},{"id":11151079,"work_id":19147558,"tagging_user_id":39344319,"tagged_user_id":null,"co_author_invite_id":609548,"email":"p***s@ufl.edu","display_order":7340032,"name":"P. Ross","title":"In Vitro Screening for Population Variability in Chemical Toxicity"},{"id":11151080,"work_id":19147558,"tagging_user_id":39344319,"tagged_user_id":null,"co_author_invite_id":2254822,"email":"f***t@ncsu.edu","display_order":7864320,"name":"F. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="19147557"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/19147557/Inbreeding_Depression_and_Inbreeding_Avoidance_in_a_Natural_Population_of_Guppies_Poecilia_reticulata_"><img alt="Research paper thumbnail of Inbreeding Depression and Inbreeding Avoidance in a Natural Population of Guppies ( Poecilia reticulata )" class="work-thumbnail" src="https://attachments.academia-assets.com/40457569/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/19147557/Inbreeding_Depression_and_Inbreeding_Avoidance_in_a_Natural_Population_of_Guppies_Poecilia_reticulata_">Inbreeding Depression and Inbreeding Avoidance in a Natural Population of Guppies ( Poecilia reticulata )</a></div><div class="wp-workCard_item"><span>Ethology</span><span>, 2010</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="bc59a0b947bc9315486b73d0530f9950" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":40457569,"asset_id":19147557,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/40457569/download_file?st=MTczMjc5MDQxNSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="19147557"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="19147557"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 19147557; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=19147557]").text(description); $(".js-view-count[data-work-id=19147557]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 19147557; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='19147557']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 19147557, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "bc59a0b947bc9315486b73d0530f9950" } } $('.js-work-strip[data-work-id=19147557]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":19147557,"title":"Inbreeding Depression and Inbreeding Avoidance in a Natural Population of Guppies ( Poecilia reticulata )","translated_title":"","metadata":{"grobid_abstract":"Maintenance of genetic variation in the face of strong natural selection is a long-standing problem in evolutionary biology. One of the most extreme examples of within-population variation is the polymorphic, genetically determined color pattern of male Trinidad guppies (Poecilia reticulata). Female mating preference for rare or novel patterns has been implicated as a factor in maintaining this variation. The origin of this preference is not understood, although inbreeding avoidance has been proposed as a mechanism. Inbreeding avoidance is advantageous when populations exhibit inbreeding depression and the opportunity for mating between relatives exists. To determine whether these conditions are met in a natural guppy population, we assessed mating and reproductive patterns using polymorphic molecular markers. Females produced more offspring with less-related males than with more-related ones. In addition, females were more likely to have mated with lessrelated males, but this trend was only marginally significant. Male heterozygosity was positively correlated with mating success and with the number of offspring sired, consistent with strong inbreeding depression for adult male fitness. These results provide substantial insight into mating patterns of a wild guppy population: strong inbreeding depression occurs, and individuals tend to avoid mating with relatives.","publication_date":{"day":null,"month":null,"year":2010,"errors":{}},"publication_name":"Ethology","grobid_abstract_attachment_id":40457569},"translated_abstract":null,"internal_url":"https://www.academia.edu/19147557/Inbreeding_Depression_and_Inbreeding_Avoidance_in_a_Natural_Population_of_Guppies_Poecilia_reticulata_","translated_internal_url":"","created_at":"2015-11-28T11:26:33.556-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":39344319,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[{"id":11151081,"work_id":19147557,"tagging_user_id":39344319,"tagged_user_id":null,"co_author_invite_id":2608565,"email":"a***j@gmail.com","display_order":0,"name":"Ashley Johnson","title":"Inbreeding Depression and Inbreeding Avoidance in a Natural 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class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/19013758/Genetic_and_epigenetic_changes_in_fibrosis_associated_hepatocarcinogenesis_in_mice"><img alt="Research paper thumbnail of Genetic and epigenetic changes in fibrosis-associated hepatocarcinogenesis in mice" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/19013758/Genetic_and_epigenetic_changes_in_fibrosis_associated_hepatocarcinogenesis_in_mice">Genetic and epigenetic changes in fibrosis-associated hepatocarcinogenesis in mice</a></div><div class="wp-workCard_item wp-workCard--coauthors"><span>by </span><span><a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/GraceChappell">Grace Chappell</a>, <a class="" data-click-track="profile-work-strip-authors" href="https://umich.academia.edu/MarkHoenerhoff">Mark Hoenerhoff</a>, and <a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/TakekiUehara">Takeki Uehara</a></span></div><div class="wp-workCard_item"><span>International Journal of Cancer</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Hepatocellular carcinoma (HCC) is one of the most prevalent cancers and is rising in incidence wo...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Hepatocellular carcinoma (HCC) is one of the most prevalent cancers and is rising in incidence worldwide. The molecular mechanisms leading to the development of HCC are complex and include both genetic and epigenetic events. To determine the relative contribution of these alterations in liver tumorigenesis, we evaluated epigenetic modifications at both global and gene specific levels, as well as the mutational profile of genes commonly altered in liver tumors. A mouse model of fibrosis-associated liver cancer that was designed to emulate cirrhotic liver, a prevailing disease state observed in most humans with HCC, was used. Tumor and non-tumor liver samples from B6C3F1 mice treated with N-nitrosodiethylamine (DEN; a single ip injection of 1 mg/kg at 14 days of age) and carbon tetrachloride (CCl4 ; 0.2 ml/kg, 2 times/week ip starting at 8 weeks of age for 14 weeks), as well as corresponding vehicle control animals, were analyzed for genetic and epigenetic alterations. H-ras, Ctnnb1, ...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="19013758"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="19013758"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 19013758; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=19013758]").text(description); $(".js-view-count[data-work-id=19013758]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 19013758; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='19013758']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 19013758, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=19013758]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":19013758,"title":"Genetic and epigenetic changes in fibrosis-associated hepatocarcinogenesis in mice","translated_title":"","metadata":{"abstract":"Hepatocellular carcinoma (HCC) is one of the most prevalent cancers and is rising in incidence worldwide. The molecular mechanisms leading to the development of HCC are complex and include both genetic and epigenetic events. To determine the relative contribution of these alterations in liver tumorigenesis, we evaluated epigenetic modifications at both global and gene specific levels, as well as the mutational profile of genes commonly altered in liver tumors. A mouse model of fibrosis-associated liver cancer that was designed to emulate cirrhotic liver, a prevailing disease state observed in most humans with HCC, was used. Tumor and non-tumor liver samples from B6C3F1 mice treated with N-nitrosodiethylamine (DEN; a single ip injection of 1 mg/kg at 14 days of age) and carbon tetrachloride (CCl4 ; 0.2 ml/kg, 2 times/week ip starting at 8 weeks of age for 14 weeks), as well as corresponding vehicle control animals, were analyzed for genetic and epigenetic alterations. H-ras, Ctnnb1, ...","publication_name":"International Journal of Cancer"},"translated_abstract":"Hepatocellular carcinoma (HCC) is one of the most prevalent cancers and is rising in incidence worldwide. The molecular mechanisms leading to the development of HCC are complex and include both genetic and epigenetic events. To determine the relative contribution of these alterations in liver tumorigenesis, we evaluated epigenetic modifications at both global and gene specific levels, as well as the mutational profile of genes commonly altered in liver tumors. A mouse model of fibrosis-associated liver cancer that was designed to emulate cirrhotic liver, a prevailing disease state observed in most humans with HCC, was used. Tumor and non-tumor liver samples from B6C3F1 mice treated with N-nitrosodiethylamine (DEN; a single ip injection of 1 mg/kg at 14 days of age) and carbon tetrachloride (CCl4 ; 0.2 ml/kg, 2 times/week ip starting at 8 weeks of age for 14 weeks), as well as corresponding vehicle control animals, were analyzed for genetic and epigenetic alterations. H-ras, Ctnnb1, ...","internal_url":"https://www.academia.edu/19013758/Genetic_and_epigenetic_changes_in_fibrosis_associated_hepatocarcinogenesis_in_mice","translated_internal_url":"","created_at":"2015-11-25T14:21:24.485-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":39163719,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[{"id":10933907,"work_id":19013758,"tagging_user_id":39163719,"tagged_user_id":39344319,"co_author_invite_id":2551624,"email":"g***p@live.unc.edu","display_order":0,"name":"Grace Chappell","title":"Genetic and epigenetic changes in fibrosis-associated hepatocarcinogenesis in mice"},{"id":10933909,"work_id":19013758,"tagging_user_id":39163719,"tagged_user_id":39296401,"co_author_invite_id":2551625,"email":"t***a@shionogi.co.jp","display_order":4194304,"name":"Takeki Uehara","title":"Genetic and epigenetic changes in fibrosis-associated hepatocarcinogenesis in mice"},{"id":16295351,"work_id":19013758,"tagging_user_id":39163719,"tagged_user_id":null,"co_author_invite_id":1386162,"email":"i***n@cvm.tamu.edu","display_order":6291456,"name":"Ivan Rusyn","title":"Genetic and epigenetic changes in fibrosis-associated hepatocarcinogenesis in mice"},{"id":16295352,"work_id":19013758,"tagging_user_id":39163719,"tagged_user_id":null,"co_author_invite_id":2551627,"email":"i***y@fda.hhs.gov","display_order":7340032,"name":"Igor Pogribny","title":"Genetic and epigenetic changes in fibrosis-associated hepatocarcinogenesis in mice"},{"id":16295353,"work_id":19013758,"tagging_user_id":39163719,"tagged_user_id":null,"co_author_invite_id":2551626,"email":"f***d@fda.hhs.gov","display_order":7864320,"name":"Frederick Beland","title":"Genetic and epigenetic changes in fibrosis-associated hepatocarcinogenesis in mice"},{"id":16295414,"work_id":19013758,"tagging_user_id":39163719,"tagged_user_id":44314857,"co_author_invite_id":615768,"email":"h***5@niehs.nih.gov","display_order":8126464,"name":"Hue-hua Hong","title":"Genetic and epigenetic changes in fibrosis-associated hepatocarcinogenesis in mice"}],"downloadable_attachments":[],"slug":"Genetic_and_epigenetic_changes_in_fibrosis_associated_hepatocarcinogenesis_in_mice","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":39163719,"first_name":"Mark","middle_initials":"","last_name":"Hoenerhoff","page_name":"MarkHoenerhoff","domain_name":"umich","created_at":"2015-11-25T14:20:13.310-08:00","display_name":"Mark Hoenerhoff","url":"https://umich.academia.edu/MarkHoenerhoff"},"attachments":[],"research_interests":[{"id":6021,"name":"Cancer","url":"https://www.academia.edu/Documents/in/Cancer"},{"id":23323,"name":"Transcription Factors","url":"https://www.academia.edu/Documents/in/Transcription_Factors"},{"id":71343,"name":"Liver Cirrhosis","url":"https://www.academia.edu/Documents/in/Liver_Cirrhosis"},{"id":71437,"name":"Liver","url":"https://www.academia.edu/Documents/in/Liver"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":111972,"name":"Hepatocellular Carcinoma","url":"https://www.academia.edu/Documents/in/Hepatocellular_Carcinoma"},{"id":121665,"name":"DNA methylation","url":"https://www.academia.edu/Documents/in/DNA_methylation"},{"id":164354,"name":"Beta-Catenin","url":"https://www.academia.edu/Documents/in/Beta-Catenin"},{"id":238813,"name":"Chromatin","url":"https://www.academia.edu/Documents/in/Chromatin"},{"id":317185,"name":"Histones","url":"https://www.academia.edu/Documents/in/Histones"},{"id":390063,"name":"Carbon Tetrachloride","url":"https://www.academia.edu/Documents/in/Carbon_Tetrachloride"},{"id":537661,"name":"Genomic instability","url":"https://www.academia.edu/Documents/in/Genomic_instability"},{"id":1261254,"name":"Diethylnitrosamine","url":"https://www.academia.edu/Documents/in/Diethylnitrosamine"},{"id":2039739,"name":"Down-Regulation","url":"https://www.academia.edu/Documents/in/Down-Regulation"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> </div><div class="profile--tab_content_container js-tab-pane tab-pane" data-section-id="4171076" id="papers"><div class="js-work-strip profile--work_container" data-work-id="19147560"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/19147560/Differentially_expressed_microRNAs_provide_mechanistic_insight_into_fibrosis_associated_liver_carcinogenesis_in_mice"><img alt="Research paper thumbnail of Differentially expressed microRNAs provide mechanistic insight into fibrosis-associated liver carcinogenesis in mice" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/19147560/Differentially_expressed_microRNAs_provide_mechanistic_insight_into_fibrosis_associated_liver_carcinogenesis_in_mice">Differentially expressed microRNAs provide mechanistic insight into fibrosis-associated liver carcinogenesis in mice</a></div><div class="wp-workCard_item wp-workCard--coauthors"><span>by </span><span><a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/GraceChappell">Grace Chappell</a> and <a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/TakekiUehara">Takeki Uehara</a></span></div><div class="wp-workCard_item"><span>Molecular carcinogenesis</span><span>, Jan 11, 2015</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Hepatocellular carcinoma (HCC) is one of the most prevalent human cancers, with rising incidence ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Hepatocellular carcinoma (HCC) is one of the most prevalent human cancers, with rising incidence worldwide. The molecular mechanisms associated with the development of HCC are complex and include multiple interconnected molecular alterations with mounting evidence indicating an important role of microRNAs (miRNAs) in the pathogenesis of HCC. In humans, the development of HCC is commonly associated with liver cirrhosis. To study fibrosis-associated liver carcinogenesis, we used a mouse model designed to emulate the development of HCC in cirrhotic liver. Specifically, we were interested in evaluating the role of miRNAs in the molecular pathogenesis of liver carcinogenesis in male B6C3F1/J mice treated with N-nitrosodiethylamine (DEN) or carbon tetrachloride (CCl4 ) alone or a combination of DEN and CCl4 and characterized by a differential tumor incidence that increased in the following order: DEN&lt;CCl4 &lt;DEN+CCl4 . Treatment with DEN alone had negligible effect on hepatic miRNA ex...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="19147560"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="19147560"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 19147560; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=19147560]").text(description); $(".js-view-count[data-work-id=19147560]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 19147560; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='19147560']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 19147560, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=19147560]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":19147560,"title":"Differentially expressed microRNAs provide mechanistic insight into fibrosis-associated liver carcinogenesis in mice","translated_title":"","metadata":{"abstract":"Hepatocellular carcinoma (HCC) is one of the most prevalent human cancers, with rising incidence worldwide. The molecular mechanisms associated with the development of HCC are complex and include multiple interconnected molecular alterations with mounting evidence indicating an important role of microRNAs (miRNAs) in the pathogenesis of HCC. In humans, the development of HCC is commonly associated with liver cirrhosis. To study fibrosis-associated liver carcinogenesis, we used a mouse model designed to emulate the development of HCC in cirrhotic liver. Specifically, we were interested in evaluating the role of miRNAs in the molecular pathogenesis of liver carcinogenesis in male B6C3F1/J mice treated with N-nitrosodiethylamine (DEN) or carbon tetrachloride (CCl4 ) alone or a combination of DEN and CCl4 and characterized by a differential tumor incidence that increased in the following order: DEN\u0026lt;CCl4 \u0026lt;DEN+CCl4 . Treatment with DEN alone had negligible effect on hepatic miRNA ex...","publication_date":{"day":11,"month":1,"year":2015,"errors":{}},"publication_name":"Molecular carcinogenesis"},"translated_abstract":"Hepatocellular carcinoma (HCC) is one of the most prevalent human cancers, with rising incidence worldwide. The molecular mechanisms associated with the development of HCC are complex and include multiple interconnected molecular alterations with mounting evidence indicating an important role of microRNAs (miRNAs) in the pathogenesis of HCC. In humans, the development of HCC is commonly associated with liver cirrhosis. To study fibrosis-associated liver carcinogenesis, we used a mouse model designed to emulate the development of HCC in cirrhotic liver. Specifically, we were interested in evaluating the role of miRNAs in the molecular pathogenesis of liver carcinogenesis in male B6C3F1/J mice treated with N-nitrosodiethylamine (DEN) or carbon tetrachloride (CCl4 ) alone or a combination of DEN and CCl4 and characterized by a differential tumor incidence that increased in the following order: DEN\u0026lt;CCl4 \u0026lt;DEN+CCl4 . Treatment with DEN alone had negligible effect on hepatic miRNA ex...","internal_url":"https://www.academia.edu/19147560/Differentially_expressed_microRNAs_provide_mechanistic_insight_into_fibrosis_associated_liver_carcinogenesis_in_mice","translated_internal_url":"","created_at":"2015-11-28T11:26:33.816-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":39344319,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[{"id":11151065,"work_id":19147560,"tagging_user_id":39344319,"tagged_user_id":39296401,"co_author_invite_id":null,"email":"t***a@shionogi.co.jp","display_order":0,"name":"Takeki Uehara","title":"Differentially expressed microRNAs provide mechanistic insight into fibrosis-associated liver carcinogenesis in mice"},{"id":11151066,"work_id":19147560,"tagging_user_id":39344319,"tagged_user_id":null,"co_author_invite_id":2551626,"email":"f***d@fda.hhs.gov","display_order":4194304,"name":"Frederick Beland","title":"Differentially expressed microRNAs provide mechanistic insight into fibrosis-associated liver carcinogenesis in mice"},{"id":11151067,"work_id":19147560,"tagging_user_id":39344319,"tagged_user_id":null,"co_author_invite_id":1386162,"email":"i***n@cvm.tamu.edu","display_order":6291456,"name":"Ivan Rusyn","title":"Differentially expressed microRNAs provide mechanistic insight into fibrosis-associated liver carcinogenesis in mice"},{"id":11151070,"work_id":19147560,"tagging_user_id":39344319,"tagged_user_id":null,"co_author_invite_id":2551627,"email":"i***y@fda.hhs.gov","display_order":7340032,"name":"Igor Pogribny","title":"Differentially expressed microRNAs provide mechanistic insight into fibrosis-associated liver carcinogenesis in mice"}],"downloadable_attachments":[],"slug":"Differentially_expressed_microRNAs_provide_mechanistic_insight_into_fibrosis_associated_liver_carcinogenesis_in_mice","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":39344319,"first_name":"Grace","middle_initials":null,"last_name":"Chappell","page_name":"GraceChappell","domain_name":"independent","created_at":"2015-11-28T11:25:45.377-08:00","display_name":"Grace Chappell","url":"https://independent.academia.edu/GraceChappell"},"attachments":[],"research_interests":[{"id":536979,"name":"MOLECULAR CARC陌NOGENES陌S","url":"https://www.academia.edu/Documents/in/MOLECULAR_CARC%C4%B0NOGENES%C4%B0S"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="19147559"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/19147559/Epigenetic_Events_Determine_Tissue_Specific_Toxicity_of_Inhalational_Exposure_to_the_Genotoxic_Chemical_1_3_Butadiene_in_Male_C57BL_6J_Mice"><img alt="Research paper thumbnail of Epigenetic Events Determine Tissue-Specific Toxicity of Inhalational Exposure to the Genotoxic Chemical 1,3-Butadiene in Male C57BL/6J Mice" class="work-thumbnail" src="https://attachments.academia-assets.com/40457567/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/19147559/Epigenetic_Events_Determine_Tissue_Specific_Toxicity_of_Inhalational_Exposure_to_the_Genotoxic_Chemical_1_3_Butadiene_in_Male_C57BL_6J_Mice">Epigenetic Events Determine Tissue-Specific Toxicity of Inhalational Exposure to the Genotoxic Chemical 1,3-Butadiene in Male C57BL/6J Mice</a></div><div class="wp-workCard_item wp-workCard--coauthors"><span>by </span><span><a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/GraceChappell">Grace Chappell</a> and <a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/BodnarW">W. Bodnar</a></span></div><div class="wp-workCard_item"><span>Toxicological Sciences</span><span>, 2014</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="dfdf092404c348f4d7d91dc1c9c93a2e" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":40457567,"asset_id":19147559,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/40457567/download_file?st=MTczMjc5MDQxNSw4LjIyMi4yMDguMTQ2&st=MTczMjc5MDQxNSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="19147559"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="19147559"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 19147559; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=19147559]").text(description); $(".js-view-count[data-work-id=19147559]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 19147559; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='19147559']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 19147559, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "dfdf092404c348f4d7d91dc1c9c93a2e" } } $('.js-work-strip[data-work-id=19147559]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":19147559,"title":"Epigenetic Events Determine Tissue-Specific Toxicity of Inhalational Exposure to the Genotoxic Chemical 1,3-Butadiene in Male C57BL/6J Mice","translated_title":"","metadata":{"grobid_abstract":"1,3-Butadiene (BD), a widely used industrial chemical and a ubiquitous environmental pollutant, is a known human carcinogen. Although genotoxicity is an established mechanism of the tumorigenicity of BD, epigenetic effects have also been observed in livers of mice exposed to the chemical. To better characterize the diverse molecular mechanisms of BD tumorigenicity, we evaluated genotoxic and epigenotoxic effects of BD exposure in mouse tissues that are target (lung and liver) and non-target (kidney) for BD-induced tumors. We hypothesized that epigenetic alterations may explain, at least in part, the tissue-specific differences in BD tumorigenicity in mice. We evaluated the level of N-7-(2,3,4-trihydroxybut-1-yl)guanine (THB-Gua) adducts and 1,4-bis-(guan-7-yl)-2,3-butanediol (bis-N7G-BD) crosslinks, DNA methylation, and histone modifications in male C57BL/6 mice exposed to filtered air or 425 ppm of BD by inhalation (6 hr/day, 5 days/week) for two weeks. While DNA damage was observed in all three tissues of BD-exposed mice, variation in epigenetic effects clearly existed between the kidneys, liver and lungs. Epigenetic alterations indicative of genomic instability, including demethylation of repetitive DNA sequences and alterations in histone-lysine acetylation, were evident in the liver and lung tissues of BD-exposed mice. Changes in DNA methylation were insignificant in the kidneys of treated mice, while marks of condensed heterochromatin and transcriptional silencing (histone-lysine trimethylation) were increased. These modifications may represent a potential mechanistic explanation for the lack of tumorigenesis in the kidney. Our results indicate that differential tissue susceptibility to chemical-induced tumorigenesis may be attributed to tissue-specific epigenetic alterations.","publication_date":{"day":null,"month":null,"year":2014,"errors":{}},"publication_name":"Toxicological Sciences","grobid_abstract_attachment_id":40457567},"translated_abstract":null,"internal_url":"https://www.academia.edu/19147559/Epigenetic_Events_Determine_Tissue_Specific_Toxicity_of_Inhalational_Exposure_to_the_Genotoxic_Chemical_1_3_Butadiene_in_Male_C57BL_6J_Mice","translated_internal_url":"","created_at":"2015-11-28T11:26:33.736-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":39344319,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[{"id":11151068,"work_id":19147559,"tagging_user_id":39344319,"tagged_user_id":null,"co_author_invite_id":1386162,"email":"i***n@cvm.tamu.edu","display_order":0,"name":"Ivan Rusyn","title":"Epigenetic Events Determine Tissue-Specific Toxicity of Inhalational Exposure to the Genotoxic Chemical 1,3-Butadiene in Male C57BL/6J Mice"},{"id":11151071,"work_id":19147559,"tagging_user_id":39344319,"tagged_user_id":null,"co_author_invite_id":2551627,"email":"i***y@fda.hhs.gov","display_order":4194304,"name":"Igor Pogribny","title":"Epigenetic Events Determine Tissue-Specific Toxicity of Inhalational Exposure to the Genotoxic Chemical 1,3-Butadiene in Male C57BL/6J Mice"},{"id":11151072,"work_id":19147559,"tagging_user_id":39344319,"tagged_user_id":null,"co_author_invite_id":2608561,"email":"b***n@gmail.com","display_order":6291456,"name":"B. O'Brien","title":"Epigenetic Events Determine Tissue-Specific Toxicity of Inhalational Exposure to the Genotoxic Chemical 1,3-Butadiene in Male C57BL/6J Mice"},{"id":11151073,"work_id":19147559,"tagging_user_id":39344319,"tagged_user_id":null,"co_author_invite_id":2608562,"email":"o***k@med.unc.edu","display_order":7340032,"name":"O. Kosyk","title":"Epigenetic Events Determine Tissue-Specific Toxicity of Inhalational Exposure to the Genotoxic Chemical 1,3-Butadiene in Male C57BL/6J Mice"},{"id":11151075,"work_id":19147559,"tagging_user_id":39344319,"tagged_user_id":null,"co_author_invite_id":2608563,"email":"k***n@ncsu.edu","display_order":7864320,"name":"K. Sexton","title":"Epigenetic Events Determine Tissue-Specific Toxicity of Inhalational Exposure to the Genotoxic Chemical 1,3-Butadiene in Male C57BL/6J Mice"},{"id":11151076,"work_id":19147559,"tagging_user_id":39344319,"tagged_user_id":39463530,"co_author_invite_id":2608564,"email":"w***r@unc.edu","display_order":8126464,"name":"W. Bodnar","title":"Epigenetic Events Determine Tissue-Specific Toxicity of Inhalational Exposure to the Genotoxic Chemical 1,3-Butadiene in Male C57BL/6J Mice"},{"id":11151077,"work_id":19147559,"tagging_user_id":39344319,"tagged_user_id":59888875,"co_author_invite_id":2526199,"email":"b***n@uts.edu.au","display_order":8257536,"name":"B. Obrien","title":"Epigenetic Events Determine Tissue-Specific Toxicity of Inhalational Exposure to the Genotoxic Chemical 1,3-Butadiene in Male C57BL/6J Mice"}],"downloadable_attachments":[{"id":40457567,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/40457567/thumbnails/1.jpg","file_name":"Epigenetic_Events_Determine_Tissue-Speci20151128-17659-1124gr5.pdf","download_url":"https://www.academia.edu/attachments/40457567/download_file?st=MTczMjc5MDQxNSw4LjIyMi4yMDguMTQ2&st=MTczMjc5MDQxNSw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Epigenetic_Events_Determine_Tissue_Speci.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/40457567/Epigenetic_Events_Determine_Tissue-Speci20151128-17659-1124gr5-libre.pdf?1448739090=\u0026response-content-disposition=attachment%3B+filename%3DEpigenetic_Events_Determine_Tissue_Speci.pdf\u0026Expires=1732794015\u0026Signature=KhaQ~AIGS0rzUkfZPu82cAyNmtLd1otoAu0SHS6vh6UiPxuCWXRWbobKp9zr0vax-vngyFNBVtlIAAqSe3u4kCRYnXmC7AeJ0DPGIDcdtjROUwf3JcdzjFz2HPemWNruxPJ102tLntFJsSJx5i8uuzTuYJsUxq~wDhydMZVLvnsxuRZuY4ECvUDyar6iduLZD7bu5J2s85YPvrSj4OntWlpiWiT73MF63o4-ipffXtiZqkB3Sd-TIRIcUxbzybWGy-oGSplzRlqROQYbuoOvsrE2HUPa9eUr5IacDE32xDevTQGwXvwF6ZtOROljNBGwFv1826nofRe5sp2JTWOYHA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Epigenetic_Events_Determine_Tissue_Specific_Toxicity_of_Inhalational_Exposure_to_the_Genotoxic_Chemical_1_3_Butadiene_in_Male_C57BL_6J_Mice","translated_slug":"","page_count":32,"language":"en","content_type":"Work","owner":{"id":39344319,"first_name":"Grace","middle_initials":null,"last_name":"Chappell","page_name":"GraceChappell","domain_name":"independent","created_at":"2015-11-28T11:25:45.377-08:00","display_name":"Grace Chappell","url":"https://independent.academia.edu/GraceChappell"},"attachments":[{"id":40457567,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/40457567/thumbnails/1.jpg","file_name":"Epigenetic_Events_Determine_Tissue-Speci20151128-17659-1124gr5.pdf","download_url":"https://www.academia.edu/attachments/40457567/download_file?st=MTczMjc5MDQxNSw4LjIyMi4yMDguMTQ2&st=MTczMjc5MDQxNSw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Epigenetic_Events_Determine_Tissue_Speci.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/40457567/Epigenetic_Events_Determine_Tissue-Speci20151128-17659-1124gr5-libre.pdf?1448739090=\u0026response-content-disposition=attachment%3B+filename%3DEpigenetic_Events_Determine_Tissue_Speci.pdf\u0026Expires=1732794015\u0026Signature=KhaQ~AIGS0rzUkfZPu82cAyNmtLd1otoAu0SHS6vh6UiPxuCWXRWbobKp9zr0vax-vngyFNBVtlIAAqSe3u4kCRYnXmC7AeJ0DPGIDcdtjROUwf3JcdzjFz2HPemWNruxPJ102tLntFJsSJx5i8uuzTuYJsUxq~wDhydMZVLvnsxuRZuY4ECvUDyar6iduLZD7bu5J2s85YPvrSj4OntWlpiWiT73MF63o4-ipffXtiZqkB3Sd-TIRIcUxbzybWGy-oGSplzRlqROQYbuoOvsrE2HUPa9eUr5IacDE32xDevTQGwXvwF6ZtOROljNBGwFv1826nofRe5sp2JTWOYHA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":37834,"name":"Western blotting","url":"https://www.academia.edu/Documents/in/Western_blotting"},{"id":71294,"name":"Kidney","url":"https://www.academia.edu/Documents/in/Kidney"},{"id":71437,"name":"Liver","url":"https://www.academia.edu/Documents/in/Liver"},{"id":121665,"name":"DNA methylation","url":"https://www.academia.edu/Documents/in/DNA_methylation"},{"id":197297,"name":"Lung","url":"https://www.academia.edu/Documents/in/Lung"},{"id":317185,"name":"Histones","url":"https://www.academia.edu/Documents/in/Histones"},{"id":537661,"name":"Genomic instability","url":"https://www.academia.edu/Documents/in/Genomic_instability"},{"id":1656539,"name":"Air Pollutants","url":"https://www.academia.edu/Documents/in/Air_Pollutants"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="19147558"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/19147558/In_Vitro_Screening_for_Population_Variability_in_Chemical_Toxicity"><img alt="Research paper thumbnail of In Vitro Screening for Population Variability in Chemical Toxicity" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/19147558/In_Vitro_Screening_for_Population_Variability_in_Chemical_Toxicity">In Vitro Screening for Population Variability in Chemical Toxicity</a></div><div class="wp-workCard_item"><span>Toxicological Sciences</span><span>, 2011</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Immortalized human lymphoblastoid cell lines have been used to demonstrate that it is possible to...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Immortalized human lymphoblastoid cell lines have been used to demonstrate that it is possible to use an in vitro model system to identify genetic factors that affect responses to xenobiotics. To extend the application of such studies to investigative toxicology by assessing interindividual and population-wide variability and heritability of chemical-induced toxicity phenotypes, we have used cell lines from the Centre d&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;Etude du Polymorphisme Humain (CEPH) trios assembled by the HapMap Consortium. Our goal is to aid in the development of predictive in vitro genetics-anchored models of chemical-induced toxicity. Cell lines from the CEPH trios were exposed to three concentrations of 14 environmental chemicals. We assessed ATP production and caspase-3/7 activity 24 h after treatment. Replicate analyses were used to evaluate experimental variability and classify responses. We show that variability of response across the cell lines exists for some, but not all, chemicals, with perfluorooctanoic acid (PFOA) and phenobarbital eliciting the greatest degree of interindividual variability. Although the data for the chemicals used here do not show evidence for broad-sense heritability of toxicity response phenotypes, substantial cell line variation was found, and candidate genetic factors contributing to the variability in response to PFOA were investigated using genome-wide association analysis. The approach of screening chemicals for toxicity in a genetically defined yet diverse in vitro human cell-based system is potentially useful for identification of chemicals that may pose a highest risk, the extent of within-species variability in the population, and genetic loci of interest that potentially contribute to chemical susceptibility.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="19147558"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="19147558"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 19147558; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=19147558]").text(description); $(".js-view-count[data-work-id=19147558]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 19147558; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='19147558']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 19147558, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=19147558]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":19147558,"title":"In Vitro Screening for Population Variability in Chemical Toxicity","translated_title":"","metadata":{"abstract":"Immortalized human lymphoblastoid cell lines have been used to demonstrate that it is possible to use an in vitro model system to identify genetic factors that affect responses to xenobiotics. To extend the application of such studies to investigative toxicology by assessing interindividual and population-wide variability and heritability of chemical-induced toxicity phenotypes, we have used cell lines from the Centre d\u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;Etude du Polymorphisme Humain (CEPH) trios assembled by the HapMap Consortium. Our goal is to aid in the development of predictive in vitro genetics-anchored models of chemical-induced toxicity. Cell lines from the CEPH trios were exposed to three concentrations of 14 environmental chemicals. We assessed ATP production and caspase-3/7 activity 24 h after treatment. Replicate analyses were used to evaluate experimental variability and classify responses. We show that variability of response across the cell lines exists for some, but not all, chemicals, with perfluorooctanoic acid (PFOA) and phenobarbital eliciting the greatest degree of interindividual variability. Although the data for the chemicals used here do not show evidence for broad-sense heritability of toxicity response phenotypes, substantial cell line variation was found, and candidate genetic factors contributing to the variability in response to PFOA were investigated using genome-wide association analysis. The approach of screening chemicals for toxicity in a genetically defined yet diverse in vitro human cell-based system is potentially useful for identification of chemicals that may pose a highest risk, the extent of within-species variability in the population, and genetic loci of interest that potentially contribute to chemical susceptibility.","publication_date":{"day":null,"month":null,"year":2011,"errors":{}},"publication_name":"Toxicological Sciences"},"translated_abstract":"Immortalized human lymphoblastoid cell lines have been used to demonstrate that it is possible to use an in vitro model system to identify genetic factors that affect responses to xenobiotics. To extend the application of such studies to investigative toxicology by assessing interindividual and population-wide variability and heritability of chemical-induced toxicity phenotypes, we have used cell lines from the Centre d\u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;Etude du Polymorphisme Humain (CEPH) trios assembled by the HapMap Consortium. Our goal is to aid in the development of predictive in vitro genetics-anchored models of chemical-induced toxicity. Cell lines from the CEPH trios were exposed to three concentrations of 14 environmental chemicals. We assessed ATP production and caspase-3/7 activity 24 h after treatment. Replicate analyses were used to evaluate experimental variability and classify responses. We show that variability of response across the cell lines exists for some, but not all, chemicals, with perfluorooctanoic acid (PFOA) and phenobarbital eliciting the greatest degree of interindividual variability. Although the data for the chemicals used here do not show evidence for broad-sense heritability of toxicity response phenotypes, substantial cell line variation was found, and candidate genetic factors contributing to the variability in response to PFOA were investigated using genome-wide association analysis. The approach of screening chemicals for toxicity in a genetically defined yet diverse in vitro human cell-based system is potentially useful for identification of chemicals that may pose a highest risk, the extent of within-species variability in the population, and genetic loci of interest that potentially contribute to chemical susceptibility.","internal_url":"https://www.academia.edu/19147558/In_Vitro_Screening_for_Population_Variability_in_Chemical_Toxicity","translated_internal_url":"","created_at":"2015-11-28T11:26:33.654-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":39344319,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[{"id":11151069,"work_id":19147558,"tagging_user_id":39344319,"tagged_user_id":null,"co_author_invite_id":1386162,"email":"i***n@cvm.tamu.edu","display_order":0,"name":"Ivan Rusyn","title":"In Vitro Screening for Population Variability in Chemical Toxicity"},{"id":11151074,"work_id":19147558,"tagging_user_id":39344319,"tagged_user_id":null,"co_author_invite_id":2608562,"email":"o***k@med.unc.edu","display_order":4194304,"name":"O. Kosyk","title":"In Vitro Screening for Population Variability in Chemical Toxicity"},{"id":11151078,"work_id":19147558,"tagging_user_id":39344319,"tagged_user_id":141528129,"co_author_invite_id":511506,"email":"j***z@vassar.edu","affiliation":"Vassar College","display_order":6291456,"name":"Jodi Schwarz","title":"In Vitro Screening for Population Variability in Chemical Toxicity"},{"id":11151079,"work_id":19147558,"tagging_user_id":39344319,"tagged_user_id":null,"co_author_invite_id":609548,"email":"p***s@ufl.edu","display_order":7340032,"name":"P. Ross","title":"In Vitro Screening for Population Variability in Chemical Toxicity"},{"id":11151080,"work_id":19147558,"tagging_user_id":39344319,"tagged_user_id":null,"co_author_invite_id":2254822,"email":"f***t@ncsu.edu","display_order":7864320,"name":"F. Wright","title":"In Vitro Screening for Population Variability in Chemical Toxicity"}],"downloadable_attachments":[],"slug":"In_Vitro_Screening_for_Population_Variability_in_Chemical_Toxicity","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":39344319,"first_name":"Grace","middle_initials":null,"last_name":"Chappell","page_name":"GraceChappell","domain_name":"independent","created_at":"2015-11-28T11:25:45.377-08:00","display_name":"Grace Chappell","url":"https://independent.academia.edu/GraceChappell"},"attachments":[],"research_interests":[{"id":194916,"name":"ROC Curve","url":"https://www.academia.edu/Documents/in/ROC_Curve"},{"id":213897,"name":"Phenotype","url":"https://www.academia.edu/Documents/in/Phenotype"},{"id":372410,"name":"Genotype","url":"https://www.academia.edu/Documents/in/Genotype"},{"id":666927,"name":"Toxicity Tests","url":"https://www.academia.edu/Documents/in/Toxicity_Tests"},{"id":1816594,"name":"Adenosine Triphosphate","url":"https://www.academia.edu/Documents/in/Adenosine_Triphosphate"},{"id":1957240,"name":"ENVIRONMENTAL SCIENCE AND MANAGEMENT","url":"https://www.academia.edu/Documents/in/ENVIRONMENTAL_SCIENCE_AND_MANAGEMENT"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="19147557"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/19147557/Inbreeding_Depression_and_Inbreeding_Avoidance_in_a_Natural_Population_of_Guppies_Poecilia_reticulata_"><img alt="Research paper thumbnail of Inbreeding Depression and Inbreeding Avoidance in a Natural Population of Guppies ( Poecilia reticulata )" class="work-thumbnail" src="https://attachments.academia-assets.com/40457569/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/19147557/Inbreeding_Depression_and_Inbreeding_Avoidance_in_a_Natural_Population_of_Guppies_Poecilia_reticulata_">Inbreeding Depression and Inbreeding Avoidance in a Natural Population of Guppies ( Poecilia reticulata )</a></div><div class="wp-workCard_item"><span>Ethology</span><span>, 2010</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="bc59a0b947bc9315486b73d0530f9950" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":40457569,"asset_id":19147557,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/40457569/download_file?st=MTczMjc5MDQxNSw4LjIyMi4yMDguMTQ2&st=MTczMjc5MDQxNSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="19147557"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="19147557"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 19147557; 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One of the most extreme examples of within-population variation is the polymorphic, genetically determined color pattern of male Trinidad guppies (Poecilia reticulata). Female mating preference for rare or novel patterns has been implicated as a factor in maintaining this variation. The origin of this preference is not understood, although inbreeding avoidance has been proposed as a mechanism. Inbreeding avoidance is advantageous when populations exhibit inbreeding depression and the opportunity for mating between relatives exists. To determine whether these conditions are met in a natural guppy population, we assessed mating and reproductive patterns using polymorphic molecular markers. Females produced more offspring with less-related males than with more-related ones. In addition, females were more likely to have mated with lessrelated males, but this trend was only marginally significant. Male heterozygosity was positively correlated with mating success and with the number of offspring sired, consistent with strong inbreeding depression for adult male fitness. These results provide substantial insight into mating patterns of a wild guppy population: strong inbreeding depression occurs, and individuals tend to avoid mating with relatives.","publication_date":{"day":null,"month":null,"year":2010,"errors":{}},"publication_name":"Ethology","grobid_abstract_attachment_id":40457569},"translated_abstract":null,"internal_url":"https://www.academia.edu/19147557/Inbreeding_Depression_and_Inbreeding_Avoidance_in_a_Natural_Population_of_Guppies_Poecilia_reticulata_","translated_internal_url":"","created_at":"2015-11-28T11:26:33.556-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":39344319,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[{"id":11151081,"work_id":19147557,"tagging_user_id":39344319,"tagged_user_id":null,"co_author_invite_id":2608565,"email":"a***j@gmail.com","display_order":0,"name":"Ashley Johnson","title":"Inbreeding Depression and Inbreeding Avoidance in a Natural Population of Guppies ( Poecilia reticulata )"},{"id":11151082,"work_id":19147557,"tagging_user_id":39344319,"tagged_user_id":null,"co_author_invite_id":2608566,"email":"a***e@gmail.com","display_order":4194304,"name":"Anna Price","title":"Inbreeding Depression and Inbreeding Avoidance in a Natural Population of Guppies ( Poecilia reticulata )"},{"id":11151083,"work_id":19147557,"tagging_user_id":39344319,"tagged_user_id":null,"co_author_invite_id":2608567,"email":"o***f@unm.edu","display_order":6291456,"name":"Robert Olendorf","title":"Inbreeding Depression and Inbreeding Avoidance in a Natural Population of Guppies ( Poecilia reticulata )"},{"id":11151084,"work_id":19147557,"tagging_user_id":39344319,"tagged_user_id":null,"co_author_invite_id":632903,"email":"k***s@bio.fsu.edu","display_order":7340032,"name":"Kimberly Hughes","title":"Inbreeding Depression and Inbreeding Avoidance in a Natural Population of Guppies ( Poecilia reticulata 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Chappell","url":"https://independent.academia.edu/GraceChappell"},"attachments":[{"id":40457569,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/40457569/thumbnails/1.jpg","file_name":"Inbreeding_Depression_and_Inbreeding_Avo20151128-16148-1br5yon.pdf","download_url":"https://www.academia.edu/attachments/40457569/download_file?st=MTczMjc5MDQxNSw4LjIyMi4yMDguMTQ2&st=MTczMjc5MDQxNSw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Inbreeding_Depression_and_Inbreeding_Avo.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/40457569/Inbreeding_Depression_and_Inbreeding_Avo20151128-16148-1br5yon-libre.pdf?1448739684=\u0026response-content-disposition=attachment%3B+filename%3DInbreeding_Depression_and_Inbreeding_Avo.pdf\u0026Expires=1732794015\u0026Signature=MIXTLmOMuFNPH81kagocCTtrAfb2mxnr9iX~1yAGdESDGIZHLE4r7GH-jtJYLqPK8OuX8gzYk4LBwcis3z~7UJiM7v5vHJ6hdbwPcb41Vn19mK9XlxSrTUouy3zYuvIdR0J3d0vW4kPhasWg1C71-CsVfmV7kgEC4HKmDOkYKZyubHuhx3KZR6qxjxzdVysthui5IWRnVlehrPhG73xOVhqmzx2LR~BqDkgK8u3Cc4Qt4s6WA4C9CDFAS1zDEHFvswF~3vRa0vh6wA3nuzZsrqQxYw3mvZP2en6ydLs2~J3ntZLfFkScgaK5bpXRDXEopMlHTfd8bulHWjhtnNHFSQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":155,"name":"Evolutionary Biology","url":"https://www.academia.edu/Documents/in/Evolutionary_Biology"},{"id":173,"name":"Zoology","url":"https://www.academia.edu/Documents/in/Zoology"},{"id":179,"name":"Ethology","url":"https://www.academia.edu/Documents/in/Ethology"},{"id":221,"name":"Psychology","url":"https://www.academia.edu/Documents/in/Psychology"},{"id":60635,"name":"Guppy","url":"https://www.academia.edu/Documents/in/Guppy"},{"id":151932,"name":"Inbreeding Avoidance","url":"https://www.academia.edu/Documents/in/Inbreeding_Avoidance"},{"id":175711,"name":"Poecilia Reticulata","url":"https://www.academia.edu/Documents/in/Poecilia_Reticulata"},{"id":485998,"name":"Inbreeding Depression","url":"https://www.academia.edu/Documents/in/Inbreeding_Depression"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="19013758"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/19013758/Genetic_and_epigenetic_changes_in_fibrosis_associated_hepatocarcinogenesis_in_mice"><img alt="Research paper thumbnail of Genetic and epigenetic changes in fibrosis-associated hepatocarcinogenesis in mice" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/19013758/Genetic_and_epigenetic_changes_in_fibrosis_associated_hepatocarcinogenesis_in_mice">Genetic and epigenetic changes in fibrosis-associated hepatocarcinogenesis in mice</a></div><div class="wp-workCard_item wp-workCard--coauthors"><span>by </span><span><a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/GraceChappell">Grace Chappell</a>, <a class="" data-click-track="profile-work-strip-authors" href="https://umich.academia.edu/MarkHoenerhoff">Mark Hoenerhoff</a>, and <a class="" data-click-track="profile-work-strip-authors" href="https://independent.academia.edu/TakekiUehara">Takeki Uehara</a></span></div><div class="wp-workCard_item"><span>International Journal of Cancer</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Hepatocellular carcinoma (HCC) is one of the most prevalent cancers and is rising in incidence wo...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Hepatocellular carcinoma (HCC) is one of the most prevalent cancers and is rising in incidence worldwide. The molecular mechanisms leading to the development of HCC are complex and include both genetic and epigenetic events. To determine the relative contribution of these alterations in liver tumorigenesis, we evaluated epigenetic modifications at both global and gene specific levels, as well as the mutational profile of genes commonly altered in liver tumors. A mouse model of fibrosis-associated liver cancer that was designed to emulate cirrhotic liver, a prevailing disease state observed in most humans with HCC, was used. Tumor and non-tumor liver samples from B6C3F1 mice treated with N-nitrosodiethylamine (DEN; a single ip injection of 1 mg/kg at 14 days of age) and carbon tetrachloride (CCl4 ; 0.2 ml/kg, 2 times/week ip starting at 8 weeks of age for 14 weeks), as well as corresponding vehicle control animals, were analyzed for genetic and epigenetic alterations. H-ras, Ctnnb1, ...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="19013758"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="19013758"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 19013758; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=19013758]").text(description); $(".js-view-count[data-work-id=19013758]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 19013758; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='19013758']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 19013758, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=19013758]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":19013758,"title":"Genetic and epigenetic changes in fibrosis-associated hepatocarcinogenesis in mice","translated_title":"","metadata":{"abstract":"Hepatocellular carcinoma (HCC) is one of the most prevalent cancers and is rising in incidence worldwide. The molecular mechanisms leading to the development of HCC are complex and include both genetic and epigenetic events. To determine the relative contribution of these alterations in liver tumorigenesis, we evaluated epigenetic modifications at both global and gene specific levels, as well as the mutational profile of genes commonly altered in liver tumors. A mouse model of fibrosis-associated liver cancer that was designed to emulate cirrhotic liver, a prevailing disease state observed in most humans with HCC, was used. Tumor and non-tumor liver samples from B6C3F1 mice treated with N-nitrosodiethylamine (DEN; a single ip injection of 1 mg/kg at 14 days of age) and carbon tetrachloride (CCl4 ; 0.2 ml/kg, 2 times/week ip starting at 8 weeks of age for 14 weeks), as well as corresponding vehicle control animals, were analyzed for genetic and epigenetic alterations. H-ras, Ctnnb1, ...","publication_name":"International Journal of Cancer"},"translated_abstract":"Hepatocellular carcinoma (HCC) is one of the most prevalent cancers and is rising in incidence worldwide. The molecular mechanisms leading to the development of HCC are complex and include both genetic and epigenetic events. To determine the relative contribution of these alterations in liver tumorigenesis, we evaluated epigenetic modifications at both global and gene specific levels, as well as the mutational profile of genes commonly altered in liver tumors. A mouse model of fibrosis-associated liver cancer that was designed to emulate cirrhotic liver, a prevailing disease state observed in most humans with HCC, was used. Tumor and non-tumor liver samples from B6C3F1 mice treated with N-nitrosodiethylamine (DEN; a single ip injection of 1 mg/kg at 14 days of age) and carbon tetrachloride (CCl4 ; 0.2 ml/kg, 2 times/week ip starting at 8 weeks of age for 14 weeks), as well as corresponding vehicle control animals, were analyzed for genetic and epigenetic alterations. H-ras, Ctnnb1, ...","internal_url":"https://www.academia.edu/19013758/Genetic_and_epigenetic_changes_in_fibrosis_associated_hepatocarcinogenesis_in_mice","translated_internal_url":"","created_at":"2015-11-25T14:21:24.485-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":39163719,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[{"id":10933907,"work_id":19013758,"tagging_user_id":39163719,"tagged_user_id":39344319,"co_author_invite_id":2551624,"email":"g***p@live.unc.edu","display_order":0,"name":"Grace Chappell","title":"Genetic and epigenetic changes in fibrosis-associated hepatocarcinogenesis in mice"},{"id":10933909,"work_id":19013758,"tagging_user_id":39163719,"tagged_user_id":39296401,"co_author_invite_id":2551625,"email":"t***a@shionogi.co.jp","display_order":4194304,"name":"Takeki Uehara","title":"Genetic and epigenetic changes in fibrosis-associated hepatocarcinogenesis in mice"},{"id":16295351,"work_id":19013758,"tagging_user_id":39163719,"tagged_user_id":null,"co_author_invite_id":1386162,"email":"i***n@cvm.tamu.edu","display_order":6291456,"name":"Ivan Rusyn","title":"Genetic and epigenetic changes in fibrosis-associated hepatocarcinogenesis in mice"},{"id":16295352,"work_id":19013758,"tagging_user_id":39163719,"tagged_user_id":null,"co_author_invite_id":2551627,"email":"i***y@fda.hhs.gov","display_order":7340032,"name":"Igor Pogribny","title":"Genetic and epigenetic changes in fibrosis-associated hepatocarcinogenesis in mice"},{"id":16295353,"work_id":19013758,"tagging_user_id":39163719,"tagged_user_id":null,"co_author_invite_id":2551626,"email":"f***d@fda.hhs.gov","display_order":7864320,"name":"Frederick Beland","title":"Genetic and epigenetic changes in fibrosis-associated hepatocarcinogenesis in mice"},{"id":16295414,"work_id":19013758,"tagging_user_id":39163719,"tagged_user_id":44314857,"co_author_invite_id":615768,"email":"h***5@niehs.nih.gov","display_order":8126464,"name":"Hue-hua Hong","title":"Genetic and epigenetic changes in fibrosis-associated hepatocarcinogenesis in mice"}],"downloadable_attachments":[],"slug":"Genetic_and_epigenetic_changes_in_fibrosis_associated_hepatocarcinogenesis_in_mice","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":39163719,"first_name":"Mark","middle_initials":"","last_name":"Hoenerhoff","page_name":"MarkHoenerhoff","domain_name":"umich","created_at":"2015-11-25T14:20:13.310-08:00","display_name":"Mark Hoenerhoff","url":"https://umich.academia.edu/MarkHoenerhoff"},"attachments":[],"research_interests":[{"id":6021,"name":"Cancer","url":"https://www.academia.edu/Documents/in/Cancer"},{"id":23323,"name":"Transcription Factors","url":"https://www.academia.edu/Documents/in/Transcription_Factors"},{"id":71343,"name":"Liver Cirrhosis","url":"https://www.academia.edu/Documents/in/Liver_Cirrhosis"},{"id":71437,"name":"Liver","url":"https://www.academia.edu/Documents/in/Liver"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":111972,"name":"Hepatocellular Carcinoma","url":"https://www.academia.edu/Documents/in/Hepatocellular_Carcinoma"},{"id":121665,"name":"DNA methylation","url":"https://www.academia.edu/Documents/in/DNA_methylation"},{"id":164354,"name":"Beta-Catenin","url":"https://www.academia.edu/Documents/in/Beta-Catenin"},{"id":238813,"name":"Chromatin","url":"https://www.academia.edu/Documents/in/Chromatin"},{"id":317185,"name":"Histones","url":"https://www.academia.edu/Documents/in/Histones"},{"id":390063,"name":"Carbon Tetrachloride","url":"https://www.academia.edu/Documents/in/Carbon_Tetrachloride"},{"id":537661,"name":"Genomic instability","url":"https://www.academia.edu/Documents/in/Genomic_instability"},{"id":1261254,"name":"Diethylnitrosamine","url":"https://www.academia.edu/Documents/in/Diethylnitrosamine"},{"id":2039739,"name":"Down-Regulation","url":"https://www.academia.edu/Documents/in/Down-Regulation"}],"urls":[]}, dispatcherData: dispatcherData }); 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