CiteULike

Mendeley | Further Information

{"title"=>"Retinoic Acid Receptor-Dependent, Cell-Autonomous, Endogenous Retinoic Acid Signaling and Its Target Genes in Mouse Collecting Duct Cells", "type"=>"journal", "authors"=>[{"first_name"=>"Yuen Fei", "last_name"=>"Wong", "scopus_author_id"=>"56245141400"}, {"first_name"=>"Patricia D.", "last_name"=>"Wilson", "scopus_author_id"=>"35395923900"}, {"first_name"=>"Robert J.", "last_name"=>"Unwin", "scopus_author_id"=>"8234615900"}, {"first_name"=>"Jill T.", "last_name"=>"Norman", "scopus_author_id"=>"7402491487"}, {"first_name"=>"Matthew", "last_name"=>"Arno", "scopus_author_id"=>"7003596762"}, {"first_name"=>"Bruce M.", "last_name"=>"Hendry", "scopus_author_id"=>"7005100278"}, {"first_name"=>"Qihe", "last_name"=>"Xu", "scopus_author_id"=>"7403743653"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84866873327", "sgr"=>"84866873327", "pui"=>"365742299", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"23049847", "doi"=>"10.1371/journal.pone.0045725"}, "id"=>"55c71e24-a0c2-3978-afe5-6995a2f22870", "abstract"=>"BACKGROUND: Vitamin A is necessary for kidney development and has also been linked to regulation of solute and water homeostasis and to protection against kidney stone disease, infection, inflammation, and scarring. Most functions of vitamin A are mediated by its main active form, all-trans retinoic acid (tRA), which binds retinoic acid receptors (RARs) to modulate gene expression. We and others have recently reported that renal tRA/RAR activity is confined to the ureteric bud (UB) and collecting duct (CD) cell lineage, suggesting that endogenous tRA/RARs primarily act through regulating gene expression in these cells in embryonic and adult kidney, respectively.\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: To explore target genes of endogenous tRA/RARs, we employed the mIMCD-3 mouse inner medullary CD cell line, which is a model of CD principal cells and exhibits constitutive tRA/RAR activity as CD principal cells do in vivo. Combining antagonism of RARs, inhibition of tRA synthesis, exposure to exogenous tRA, and gene expression profiling techniques, we have identified 125 genes as candidate targets and validated 20 genes that were highly regulated (Dhrs3, Sprr1a, and Ppbp were the top three). Endogenous tRA/RARs were more important in maintaining, rather than suppressing, constitutive gene expression. Although many identified genes were expressed in UBs and/or CDs, their exact functions in this cell lineage are still poorly defined. Nevertheless, gene ontology analysis suggests that these genes are involved in kidney development, renal functioning, and regulation of tRA signaling.\\n\\nCONCLUSIONS/SIGNIFICANCE: A rigorous approach to defining target genes for endogenous tRA/RARs has been established. At the pan-genomic level, genes regulated by endogenous tRA/RARs in a CD cell line have been catalogued for the first time. Such a catalogue will guide further studies on molecular mediators of endogenous tRA/RARs during kidney development and in relation to renal defects associated with vitamin A deficiency.", "link"=>"http://www.mendeley.com/research/retinoic-acid-receptordependent-cellautonomous-endogenous-retinoic-acid-signaling-target-genes-mouse", "reader_count"=>13, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>8, "Student > Master"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>8, "Student > Master"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>6, "Medicine and Dentistry"=>1, "Arts and Humanities"=>1, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>6}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>1}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "reader_count_by_country"=>{"United States"=>1, "Germany"=>1}, "group_count"=>0}

ORCID

CrossRef

• http://doi.org/10.1242/dev.181560
• http://doi.org/10.1089/dna.2018.4426
• http://doi.org/10.1096/fj.201600319R
• http://doi.org/10.1016/j.diff.2016.10.001
• http://doi.org/10.1096/fj.13-227967
• http://doi.org/10.1016/j.jcmgh.2019.06.001

DataCite

Europe PMC Citations | Further Information

Europe PMC Database Citations | Further Information

{"UNIPROT"=>5}

PubMed Central

• 3834788

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84866873327"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84866873327?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84866873327&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84866873327&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/84866873327", "dc:identifier"=>"SCOPUS_ID:84866873327", "eid"=>"2-s2.0-84866873327", "dc:title"=>"Retinoic Acid Receptor-Dependent, Cell-Autonomous, Endogenous Retinoic Acid Signaling and Its Target Genes in Mouse Collecting Duct Cells", "dc:creator"=>"Wong Y.", "prism:publicationName"=>"PLoS ONE", "prism:eIssn"=>"19326203", "prism:volume"=>"7", "prism:issueIdentifier"=>"9", "prism:pageRange"=>nil, "prism:coverDate"=>"2012-09-26", "prism:coverDisplayDate"=>"26 September 2012", "prism:doi"=>"10.1371/journal.pone.0045725", "citedby-count"=>"9", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"King's College London", "affiliation-city"=>"London", "affiliation-country"=>"United Kingdom"}], "pubmed-id"=>"23049847", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "article-number"=>"e45725", "source-id"=>"10600153309", "openaccess"=>"1", "openaccessFlag"=>true}

Web of Science® | Further Information

Article Coverage

Article Coverage Curated

Facebook

• {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplosone%2Farticle%3Fid%3D10.1371%252Fjournal.pone.0045725", "share_count"=>0, "like_count"=>0, "comment_count"=>0, "click_count"=>0, "total_count"=>0}

Journal Comments

Nature

Reddit

Research Blogging

ScienceSeeker | Further Information

Twitter

• {"id"=>"253033497525104640", "text"=>"New reference!!! \nFind out more at http://t.co/sSArzLfE", "created_at"=>"2012-10-02T07:27:41Z", "user"=>"Qlucore", "user_name"=>"Qlucore", "user_profile_image"=>"http://a0.twimg.com/profile_images/2016658689/bollar_filtrerade__PCA_data_analysis_normal.jpg"}

Wikipedia

Wordpress.com | Further Information

Counter

• {"month"=>"9", "year"=>"2012", "pdf_views"=>"10", "xml_views"=>"3", "html_views"=>"162"}
• {"month"=>"10", "year"=>"2012", "pdf_views"=>"36", "xml_views"=>"2", "html_views"=>"233"}
• {"month"=>"11", "year"=>"2012", "pdf_views"=>"14", "xml_views"=>"1", "html_views"=>"60"}
• {"month"=>"12", "year"=>"2012", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"44"}
• {"month"=>"1", "year"=>"2013", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"39"}
• {"month"=>"2", "year"=>"2013", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"49"}
• {"month"=>"3", "year"=>"2013", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"57"}
• {"month"=>"4", "year"=>"2013", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"26"}
• {"month"=>"5", "year"=>"2013", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"44"}
• {"month"=>"6", "year"=>"2013", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"53"}
• {"month"=>"7", "year"=>"2013", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"90"}
• {"month"=>"8", "year"=>"2013", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"55"}
• {"month"=>"9", "year"=>"2013", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"29"}
• {"month"=>"10", "year"=>"2013", "pdf_views"=>"13", "xml_views"=>"2", "html_views"=>"51"}
• {"month"=>"11", "year"=>"2013", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"30"}
• {"month"=>"12", "year"=>"2013", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"67"}
• {"month"=>"1", "year"=>"2014", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"55"}
• {"month"=>"2", "year"=>"2014", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"47"}
• {"month"=>"3", "year"=>"2014", "pdf_views"=>"4", "xml_views"=>"2", "html_views"=>"53"}
• {"month"=>"4", "year"=>"2014", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"48"}
• {"month"=>"5", "year"=>"2014", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"40"}
• {"month"=>"6", "year"=>"2014", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"52"}
• {"month"=>"7", "year"=>"2014", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"53"}
• {"month"=>"8", "year"=>"2014", "pdf_views"=>"3", "xml_views"=>"2", "html_views"=>"33"}
• {"month"=>"9", "year"=>"2014", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"35"}
• {"month"=>"10", "year"=>"2014", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"54"}
• {"month"=>"11", "year"=>"2014", "pdf_views"=>"2", "xml_views"=>"1", "html_views"=>"28"}
• {"month"=>"12", "year"=>"2014", "pdf_views"=>"3", "xml_views"=>"1", "html_views"=>"29"}
• {"month"=>"1", "year"=>"2015", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"58"}
• {"month"=>"2", "year"=>"2015", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"29"}
• {"month"=>"3", "year"=>"2015", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"32"}
• {"month"=>"4", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"40"}
• {"month"=>"5", "year"=>"2015", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"60"}
• {"month"=>"6", "year"=>"2015", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"23"}
• {"month"=>"7", "year"=>"2015", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"35"}
• {"month"=>"8", "year"=>"2015", "pdf_views"=>"1", "xml_views"=>"1", "html_views"=>"23"}
• {"month"=>"9", "year"=>"2015", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"59"}
• {"month"=>"10", "year"=>"2015", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"79"}
• {"month"=>"11", "year"=>"2015", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"107"}
• {"month"=>"12", "year"=>"2015", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"106"}
• {"month"=>"1", "year"=>"2016", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"76"}
• {"month"=>"2", "year"=>"2016", "pdf_views"=>"0", "xml_views"=>"0", "html_views"=>"32"}
• {"month"=>"3", "year"=>"2016", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"66"}
• {"month"=>"4", "year"=>"2016", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"31"}
• {"month"=>"5", "year"=>"2016", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"18"}
• {"month"=>"6", "year"=>"2016", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"20"}
• {"month"=>"7", "year"=>"2016", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"23"}
• {"month"=>"8", "year"=>"2016", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"22"}
• {"month"=>"9", "year"=>"2016", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"36"}
• {"month"=>"10", "year"=>"2016", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"21"}
• {"month"=>"11", "year"=>"2016", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"32"}
• {"month"=>"12", "year"=>"2016", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"20"}
• {"month"=>"1", "year"=>"2017", "pdf_views"=>"0", "xml_views"=>"0", "html_views"=>"19"}
• {"month"=>"2", "year"=>"2017", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"31"}
• {"month"=>"3", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"35"}
• {"month"=>"4", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"26"}
• {"month"=>"5", "year"=>"2017", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"30"}
• {"month"=>"6", "year"=>"2017", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"36"}
• {"month"=>"7", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"12"}
• {"month"=>"8", "year"=>"2017", "pdf_views"=>"3", "xml_views"=>"1", "html_views"=>"17"}
• {"month"=>"9", "year"=>"2017", "pdf_views"=>"11", "xml_views"=>"1", "html_views"=>"21"}
• {"month"=>"10", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"31"}
• {"month"=>"11", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"72"}
• {"month"=>"12", "year"=>"2017", "pdf_views"=>"2", "xml_views"=>"1", "html_views"=>"30"}
• {"month"=>"1", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"18"}
• {"month"=>"2", "year"=>"2018", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"9"}
• {"month"=>"3", "year"=>"2018", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"7"}
• {"month"=>"4", "year"=>"2018", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"10"}
• {"month"=>"5", "year"=>"2018", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"9"}
• {"month"=>"6", "year"=>"2018", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"3"}
• {"month"=>"7", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"3", "html_views"=>"5"}
• {"month"=>"8", "year"=>"2018", "pdf_views"=>"1", "xml_views"=>"1", "html_views"=>"7"}
• {"month"=>"9", "year"=>"2018", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"3"}
• {"month"=>"10", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"7"}
• {"month"=>"11", "year"=>"2018", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"20"}
• {"month"=>"12", "year"=>"2018", "pdf_views"=>"0", "xml_views"=>"0", "html_views"=>"7"}
• {"month"=>"1", "year"=>"2019", "pdf_views"=>"1", "xml_views"=>"1", "html_views"=>"2"}
• {"month"=>"2", "year"=>"2019", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"7"}
• {"month"=>"3", "year"=>"2019", "pdf_views"=>"6", "xml_views"=>"2", "html_views"=>"4"}
• {"month"=>"4", "year"=>"2019", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"1"}
• {"month"=>"5", "year"=>"2019", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"2"}
• {"month"=>"6", "year"=>"2019", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"3"}
• {"month"=>"7", "year"=>"2019", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"3"}
• {"month"=>"8", "year"=>"2019", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"12"}
• {"month"=>"9", "year"=>"2019", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"3"}
• {"month"=>"10", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"1"}
• {"month"=>"11", "year"=>"2019", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"5"}
• {"month"=>"12", "year"=>"2019", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"2"}
• {"month"=>"1", "year"=>"2020", "pdf_views"=>"11", "xml_views"=>"1", "html_views"=>"4"}
• {"month"=>"2", "year"=>"2020", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"14"}
• {"month"=>"3", "year"=>"2020", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"4"}

Figshare

• {"files"=>["https://ndownloader.figshare.com/files/569295"], "description"=>"<p>Enrichment analysis on the 125 candidate target genes showed that they are associated with many biological processes (green box) and diseases (red box), some of which are highly relevant to renal physiology and pathology. Those marked with an asterisk were reported to be associated with tRA/RAR signaling. The full list of gene ontologies for the 125 candidate target genes are in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045725#pone.0045725.s007\" target=\"_blank\">Table S4</a>. <b>B.</b> (<b>i</b>) The 20 validated target genes of endogenous tRA/RARs were reported to be involved in retinol metabolism (A), cell-cell, cell-substrate interaction (B), ureteric bud branching (C), immune/inflammatory processes (D), oxidative stress (E), repair/regeneration (F), ion/solute/water transport and metabolism (G), and gene transcription/translation (H); functions of 9930023K05Rik, Klhdc7a, Sorcs2, and 2310007B03Rik are not yet known. Pink: GeneGO Metacore™, Yellow: DAVID <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045725#pone.0045725-Huang1\" target=\"_blank\">[50]</a>, Green: GeneGO Metacore™ and DAVID, Blue: additional literature review <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045725#pone.0045725-Zeisberg1\" target=\"_blank\">[20]</a>, <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045725#pone.0045725-Behr1\" target=\"_blank\">[22]</a>, <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045725#pone.0045725-Levashova1\" target=\"_blank\">[45]</a>, <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045725#pone.0045725-Starkey1\" target=\"_blank\">[48]</a>, <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045725#pone.0045725-Pradervand1\" target=\"_blank\">[51]</a>, <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045725#pone.0045725-Bonilla1\" target=\"_blank\">[52]</a>, <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045725#pone.0045725-Zhang1\" target=\"_blank\">[53]</a>. The full list of gene ontologies for the 20 validate target genes are in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045725#pone.0045725.s008\" target=\"_blank\">Table S5</a>. (<b>ii</b>) Expression of the validated genes in native samples, available through Gene Expression Omnibus datasets (Ω: GSE6290, θ: GSE7891), was reviewed. E11.5 UB: embryonic day 11.5 ureteric bud cells from mice (three samples), E15.5 mCD: embryonic day 15.5 medullary collecting duct cells from mice (three samples), rat IMCD: inner medullary collecting duct cells from rat (one sample from 6-week-old and two samples from 10-week-old). +: present, −: absent, ud: undetermined; ?: present in 6-week-old sample but absent from 10-week-old samples. (<b>iii</b>) The number of direct-repeat 5 (DR5) RARE that are present in the validated genes in whole mouse genome is summarized here, based on report from Lalevee et al. <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045725#pone.0045725-Lalevee1\" target=\"_blank\">[4]</a>. *: At least one of the DR5 RAREs is present within 10 kb from transcriptional start site and from gene end.</p>", "links"=>[], "tags"=>["retinoic"], "article_id"=>239789, "categories"=>["Physiology", "Marine Biology", "Cancer", "Genetics"], "users"=>["Yuen Fei Wong", "Patricia D. Wilson", "Robert J. Unwin", "Jill T. Norman", "Matthew Arno", "Bruce M. Hendry", "Qihe Xu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0045725.g006", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gene_ontologies_expression_in_native_tissues_and_presence_of_retinoic_acid_response_element_RARE_A_/239789", "title"=>"Gene ontologies, expression in native tissues, and presence of retinoic acid response element (RARE). A.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-26 02:43:09"}
• {"files"=>["https://ndownloader.figshare.com/files/569013"], "description"=>"<p>mRNA expression of Bmp7 (<b>Ai</b>) and Foxa1 (<b>Aii</b>) was suppressed by AGN193109; the suppression was at least partially abolished in the presence of 0.2 µM tRA. <b>Bi.</b> Bmp7 mRNA was suppressed by DEAB; the suppression was reversed to a level slightly higher than basal level in the presence of 0.01 µM tRA. <b>Bii.</b> Expression of Foxa1 mRNA was suppressed by DEAB; the suppression was partially abolished in the presence of 0.01 µM tRA. Each dot represents mean value of three technical replicates from a single biological experiment. *, **, and ***: p<0.05, p<0.01, and p<0.001, respectively.</p>", "links"=>[], "tags"=>["bmp7", "foxa1", "agn193109"], "article_id"=>239499, "categories"=>["Physiology", "Marine Biology", "Cancer", "Genetics"], "users"=>["Yuen Fei Wong", "Patricia D. Wilson", "Robert J. Unwin", "Jill T. Norman", "Matthew Arno", "Bruce M. Hendry", "Qihe Xu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0045725.g003", "stats"=>{"downloads"=>2, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Regulation_of_Bmp7_and_Foxa1_by_AGN193109_and_4_diethylamino_benzaldehyde_DEAB_in_pilot_study_/239499", "title"=>"Regulation of Bmp7 and Foxa1 by AGN193109 and 4-(diethylamino)benzaldehyde (DEAB) in pilot study.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-26 02:38:19"}
• {"files"=>["https://ndownloader.figshare.com/files/568797"], "description"=>"<p>In cells, all-<i>trans</i> retinol (tRol), i.e., vitamin A, is oxidized reversibly to all-<i>trans</i> retinaldehyde (tRal), catalyzed by the enzymes retinol dehydrogenases (Rdhs) or alcohol dehydrogenases (Adhs). tRal is then oxidized irreversibly to all-<i>trans</i> retinoic acid (tRA), catalyzed by retinaldehyde dehydrogenases (Raldhs). tRA translocates into cell nucleus to bind and activate retinoic acid receptors (RARs), modulating gene transcription. AGN193109 (purple) and 4-(diethylamino)benzaldehyde (DEAB, orange) were used to compete with tRA for RAR binding and to inhibit Raldhs in the conversion of tRal into tRA, respectively. Specificity of inhibition was confirmed by adding exogenous tRA (red) simultaneously to examine if the effects of AGN193109 and DEAB could be at least partially abolished.</p>", "links"=>[], "tags"=>["employed", "endogenous", "signaling"], "article_id"=>239287, "categories"=>["Physiology", "Marine Biology", "Cancer", "Genetics"], "users"=>["Yuen Fei Wong", "Patricia D. Wilson", "Robert J. Unwin", "Jill T. Norman", "Matthew Arno", "Bruce M. Hendry", "Qihe Xu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0045725.g001", "stats"=>{"downloads"=>2, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Strategy_employed_to_examine_endogenous_tRA_RAR_signaling_and_its_target_genes_/239287", "title"=>"Strategy employed to examine endogenous tRA/RAR signaling and its target genes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-26 02:34:47"}
• {"files"=>["https://ndownloader.figshare.com/files/569498"], "description"=>"<p>Assay ID and amplicon length of Taqman® Gene Expression Assays used.</p>", "links"=>[], "tags"=>["id", "amplicon", "assays"], "article_id"=>239988, "categories"=>["Physiology", "Marine Biology", "Cancer", "Genetics"], "users"=>["Yuen Fei Wong", "Patricia D. Wilson", "Robert J. Unwin", "Jill T. Norman", "Matthew Arno", "Bruce M. Hendry", "Qihe Xu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0045725.t004", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Assay_ID_and_amplicon_length_of_Taqman_174_Gene_Expression_Assays_used_/239988", "title"=>"Assay ID and amplicon length of Taqman® Gene Expression Assays used.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-09-26 02:46:28"}
• {"files"=>["https://ndownloader.figshare.com/files/569402"], "description"=>"<p>Shown here are mean fold-changes of gene expression compared to vehicle control from three experimental groups. Genes were sorted by fold-changes of AGN193109 group compared to vehicle group. Minus and plus numbers indicate folds of suppression and induction, respectively, in comparison to the vehicle control group, which was normalized as 1.</p>", "links"=>[], "tags"=>["20", "down-regulated"], "article_id"=>239889, "categories"=>["Physiology", "Marine Biology", "Cancer", "Genetics"], "users"=>["Yuen Fei Wong", "Patricia D. Wilson", "Robert J. Unwin", "Jill T. Norman", "Matthew Arno", "Bruce M. Hendry", "Qihe Xu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0045725.t001", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Top_20_most_down_regulated_genes_/239889", "title"=>"Top 20 most down-regulated genes.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-09-26 02:44:49"}
• {"files"=>["https://ndownloader.figshare.com/files/569096"], "description"=>"<p>A total of 403 and 439 unique genes were short-listed from AGN193109 experiment and DEAB experiment, respectively. 133 genes were regulated by AGN193109 and DEAB; among them, 125 genes (designated as group 1 genes), were regulated by AGN193109 and DEAB at similar directions, which the regulation was at least partially abolished in the simultaneous presence of exogenous tRA. 270 genes were regulated only by AGN193109, of which regulation of 213 genes (designated as group 2 genes) was at least partially abolished in the simultaneous presence of exogenous tRA; 306 genes were regulated only by DEAB, of which regulation of 266 genes (designated as group 3 genes) was at least partially abolished in the simultaneous presence of exogenous tRA. Note that the fold-changes of intersected genes were higher than those of non-intersected genes. When ranked based on fold-changes, 80% of the top 20 most regulated genes (<b>B</b>) and 90% of the top 10 most regulated genes were overlapped (<b>C</b>).</p>", "links"=>[], "tags"=>["genes", "short-listed", "microarray"], "article_id"=>239586, "categories"=>["Physiology", "Marine Biology", "Cancer", "Genetics"], "users"=>["Yuen Fei Wong", "Patricia D. Wilson", "Robert J. Unwin", "Jill T. Norman", "Matthew Arno", "Bruce M. Hendry", "Qihe Xu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0045725.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Candidate_target_genes_short_listed_from_microarray_experiments_A_/239586", "title"=>"Candidate target genes short-listed from microarray experiments. A.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-26 02:39:46"}
• {"files"=>["https://ndownloader.figshare.com/files/569471"], "description"=>"<p>Shown here are mean fold-changes of gene expression compared to vehicle control from three experimental groups. Genes were sorted by fold-changes of AGN193109 group compared to vehicle group. Minus and plus numbers indicate folds of suppression and induction, respectively, in comparison to the vehicle control group, which was normalized as 1.</p>", "links"=>[], "tags"=>["20", "up-regulated"], "article_id"=>239965, "categories"=>["Physiology", "Marine Biology", "Cancer", "Genetics"], "users"=>["Yuen Fei Wong", "Patricia D. Wilson", "Robert J. Unwin", "Jill T. Norman", "Matthew Arno", "Bruce M. Hendry", "Qihe Xu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0045725.t002", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Top_20_most_up_regulated_genes_/239965", "title"=>"Top 20 most up-regulated genes.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-09-26 02:46:05"}
• {"files"=>["https://ndownloader.figshare.com/files/569171"], "description"=>"<p>A total of 31 and 94 genes were up-(red) and down-(green) regulated, respectively, by AGN193109 and by DEAB; regulation of these genes were at least partially abolished in the presence of tRA. Of the 31 up-regulated genes, 24 were up-regulated by AGN193109 by less than 1.5-fold, 7 by more than 1.5-fold but less than 2-fold, and none by 2-fold and more; none of the genes were up-regulated by DEAB by 1.5-fold and more. Of the 94 down-regulated genes, 38 were down-regulated by AGN193109 by less than 1.5-fold, 37 by more than 1.5-fold but less than 2-fold, and 19 by 2-fold and more; 68 were down-regulated by DEAB by less than 1.5-fold, 14 by more than 1.5-fold but less than 2-fold, and 12 by 2-fold and more.</p>", "links"=>[], "tags"=>["genes", "endogenous", "induced", "suppressed"], "article_id"=>239659, "categories"=>["Physiology", "Marine Biology", "Cancer", "Genetics"], "users"=>["Yuen Fei Wong", "Patricia D. Wilson", "Robert J. Unwin", "Jill T. Norman", "Matthew Arno", "Bruce M. Hendry", "Qihe Xu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0045725.g005", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Candidate_target_genes_of_endogenous_tRA_RARs_number_of_induced_and_suppressed_genes_/239659", "title"=>"Candidate target genes of endogenous tRA/RARs: number of induced and suppressed genes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-26 02:40:59"}
• {"files"=>["https://ndownloader.figshare.com/files/301933", "https://ndownloader.figshare.com/files/301990", "https://ndownloader.figshare.com/files/302046", "https://ndownloader.figshare.com/files/302083", "https://ndownloader.figshare.com/files/302107", "https://ndownloader.figshare.com/files/302131", "https://ndownloader.figshare.com/files/302155", "https://ndownloader.figshare.com/files/302178"], "description"=>"<div><h3>Background</h3><p>Vitamin A is necessary for kidney development and has also been linked to regulation of solute and water homeostasis and to protection against kidney stone disease, infection, inflammation, and scarring. Most functions of vitamin A are mediated by its main active form, all-<em>trans</em> retinoic acid (tRA), which binds retinoic acid receptors (RARs) to modulate gene expression. We and others have recently reported that renal tRA/RAR activity is confined to the ureteric bud (UB) and collecting duct (CD) cell lineage, suggesting that endogenous tRA/RARs primarily act through regulating gene expression in these cells in embryonic and adult kidney, respectively.</p> <h3>Methodology/Principal Findings</h3><p>To explore target genes of endogenous tRA/RARs, we employed the mIMCD-3 mouse inner medullary CD cell line, which is a model of CD principal cells and exhibits constitutive tRA/RAR activity as CD principal cells do in vivo. Combining antagonism of RARs, inhibition of tRA synthesis, exposure to exogenous tRA, and gene expression profiling techniques, we have identified 125 genes as candidate targets and validated 20 genes that were highly regulated (Dhrs3, Sprr1a, and Ppbp were the top three). Endogenous tRA/RARs were more important in maintaining, rather than suppressing, constitutive gene expression. Although many identified genes were expressed in UBs and/or CDs, their exact functions in this cell lineage are still poorly defined. Nevertheless, gene ontology analysis suggests that these genes are involved in kidney development, renal functioning, and regulation of tRA signaling.</p> <h3>Conclusions/Significance</h3><p>A rigorous approach to defining target genes for endogenous tRA/RARs has been established. At the pan-genomic level, genes regulated by endogenous tRA/RARs in a CD cell line have been catalogued for the first time. Such a catalogue will guide further studies on molecular mediators of endogenous tRA/RARs during kidney development and in relation to renal defects associated with vitamin A deficiency.</p> </div>", "links"=>[], "tags"=>["retinoic", "endogenous", "signaling", "genes", "collecting", "duct", "cells"], "article_id"=>119545, "categories"=>["Physiology", "Marine Biology", "Cancer", "Genetics"], "users"=>["Yuen Fei Wong", "Patricia D. Wilson", "Robert J. Unwin", "Jill T. Norman", "Matthew Arno", "Bruce M. Hendry", "Qihe Xu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0045725.s001", "https://dx.doi.org/10.1371/journal.pone.0045725.s002", "https://dx.doi.org/10.1371/journal.pone.0045725.s003", "https://dx.doi.org/10.1371/journal.pone.0045725.s004", "https://dx.doi.org/10.1371/journal.pone.0045725.s005", "https://dx.doi.org/10.1371/journal.pone.0045725.s006", "https://dx.doi.org/10.1371/journal.pone.0045725.s007", "https://dx.doi.org/10.1371/journal.pone.0045725.s008"], "stats"=>{"downloads"=>18, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Retinoic_Acid_Receptor_Dependent_Cell_Autonomous_Endogenous_Retinoic_Acid_Signaling_and_Its_Target_Genes_in_Mouse_Collecting_Duct_Cells/119545", "title"=>"Retinoic Acid Receptor-Dependent, Cell-Autonomous, Endogenous Retinoic Acid Signaling and Its Target Genes in Mouse Collecting Duct Cells", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-09-26 02:39:05"}
• {"files"=>["https://ndownloader.figshare.com/files/569435"], "description"=>"<p>Shown here are means of gene expression levels relative to vehicle control group ± standard errors (SE); the vehicle control group was normalized as 1. Taking Dhrs3 expression as an example, 0.01 and 2.88 in the AGN193109 group and the DEAB+tRA group indicate 100-fold reduction and 2.88-fold induction relative to the vehicle group, respectively.</p>*<p>p<0.05 vs vehicle,</p>**<p>p<0.01 vs vehicle,</p>***<p>p<0.001 vs vehicle;</p>∧<p>p<0.05 vs AGN193109,</p>∧∧<p>p<0.01 vs AGN193109,</p>∧∧∧<p>p<0.001 vs AGN193109;</p>+<p>p<0.05 vs DEAB,</p>++<p>p<0.01 vs DEAB,</p>+++<p>p<0.001 vs DEAB; NA: Not amplified.</p>", "links"=>[], "tags"=>["20", "down-regulated"], "article_id"=>239927, "categories"=>["Physiology", "Marine Biology", "Cancer", "Genetics"], "users"=>["Yuen Fei Wong", "Patricia D. Wilson", "Robert J. Unwin", "Jill T. Norman", "Matthew Arno", "Bruce M. Hendry", "Qihe Xu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0045725.t003", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Validation_of_top_20_most_down_regulated_genes_/239927", "title"=>"Validation of top 20 most down-regulated genes.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-09-26 02:45:27"}
• {"files"=>["https://ndownloader.figshare.com/files/568883"], "description"=>"<p>mIMCD-3 cells expressed E-cadherin (E-cad) (<b>Ai</b>) and aquaporin 2 (AQP2) (<b>Aii</b>) proteins. Left panels showed positive staining of specific antibodies, whereas right panels showed negative controls of cells stained with the respective non-immune IgGs. Original magnification was 200×. <b>Bi.</b> Treating cells with 1 µM AGN193109 for 24 h resulted in a decrease of RARE-luciferase activity to about 50% of that of the vehicle control group; the reduction was at least partially abolished with simultaneous addition of exogenous tRA at 0.01–1 µM, in a dose-dependent manner. ** and ***: p<0.01 and p<0.001, respectively. <b>Bii.</b> Treating cells with 25 µM DEAB for 72 h resulted in a suppression of RARE-luciferase activity to about 50% of that of vehicle control group; when exogenous tRA was added during the last 24 h, the suppression of RARE-luciferase activity was reversed in a dose-dependent manner, saturated at 1 nM tRA. # and ##: p<0.05 and 0<0.01 vs vehicle control group, respectively; ** and ***: p<0.01 and p<0.001 vs DEAB-only group, respectively. <b>Biii.</b> When cells were treated with exogenous tRA alone at 0.001–0.1 µM for 24 h, a slight trend of dose-dependent increase of RARE-luciferase activity was noted but the difference was not statistically significant. Each dot represents mean value of triplicates or quadruplicates from a single biological experiment.</p>", "links"=>[], "tags"=>["cells", "genes", "endogenous"], "article_id"=>239371, "categories"=>["Physiology", "Marine Biology", "Cancer", "Genetics"], "users"=>["Yuen Fei Wong", "Patricia D. Wilson", "Robert J. Unwin", "Jill T. Norman", "Matthew Arno", "Bruce M. Hendry", "Qihe Xu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0045725.g002", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_mIMCD_3_cells_as_an_in_vitro_model_to_examine_target_genes_of_endogenous_tRA_RARs_/239371", "title"=>"mIMCD-3 cells as an <i>in vitro</i> model to examine target genes of endogenous tRA/RARs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-26 02:36:11"}

PMC Usage Stats | Further Information

• {"unique-ip"=>"41", "full-text"=>"32", "pdf"=>"20", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"18", "supp-data"=>"9", "cited-by"=>"0", "year"=>"2012", "month"=>"10"}
• {"unique-ip"=>"15", "full-text"=>"13", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2012", "month"=>"12"}
• {"unique-ip"=>"24", "full-text"=>"22", "pdf"=>"6", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"12", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"1"}
• {"unique-ip"=>"14", "full-text"=>"13", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"3"}
• {"unique-ip"=>"16", "full-text"=>"21", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"2"}
• {"unique-ip"=>"10", "full-text"=>"6", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2013", "month"=>"4"}
• {"unique-ip"=>"28", "full-text"=>"28", "pdf"=>"13", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"12", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"11"}
• {"unique-ip"=>"16", "full-text"=>"11", "pdf"=>"5", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"18", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"5"}
• {"unique-ip"=>"14", "full-text"=>"8", "pdf"=>"12", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"8", "cited-by"=>"0", "year"=>"2013", "month"=>"6"}
• {"unique-ip"=>"10", "full-text"=>"19", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"20", "supp-data"=>"8", "cited-by"=>"0", "year"=>"2013", "month"=>"7"}
• {"unique-ip"=>"11", "full-text"=>"10", "pdf"=>"3", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"8", "cited-by"=>"0", "year"=>"2013", "month"=>"8"}
• {"unique-ip"=>"7", "full-text"=>"9", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"9"}
• {"unique-ip"=>"12", "full-text"=>"9", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"10"}
• {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"11"}
• {"unique-ip"=>"10", "full-text"=>"7", "pdf"=>"7", "abstract"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"12"}
• {"unique-ip"=>"2", "full-text"=>"1", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"1"}
• {"unique-ip"=>"3", "full-text"=>"4", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"2"}
• {"unique-ip"=>"13", "full-text"=>"10", "pdf"=>"5", "abstract"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"3"}
• {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"5"}
• {"unique-ip"=>"4", "full-text"=>"1", "pdf"=>"0", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"6"}
• {"unique-ip"=>"9", "full-text"=>"6", "pdf"=>"1", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"4"}
• {"unique-ip"=>"5", "full-text"=>"8", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"4"}
• {"unique-ip"=>"16", "full-text"=>"12", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"5"}
• {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"6"}
• {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"7"}
• {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"3"}
• {"unique-ip"=>"2", "full-text"=>"1", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"2"}
• {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
• {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"9"}
• {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"10"}
• {"unique-ip"=>"8", "full-text"=>"4", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"7"}
• {"unique-ip"=>"5", "full-text"=>"0", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"8"}
• {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"9"}
• {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"2", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"10"}
• {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
• {"unique-ip"=>"19", "full-text"=>"11", "pdf"=>"5", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2014", "month"=>"11"}
• {"unique-ip"=>"3", "full-text"=>"5", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2014", "month"=>"12"}
• {"unique-ip"=>"13", "full-text"=>"14", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2015", "month"=>"1"}
• {"unique-ip"=>"10", "full-text"=>"8", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"2", "year"=>"2015", "month"=>"11"}
• {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
• {"unique-ip"=>"13", "full-text"=>"7", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2016", "month"=>"1"}
• {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
• {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
• {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
• {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2016", "month"=>"6"}
• {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
• {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
• {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
• {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
• {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
• {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
• {"unique-ip"=>"9", "full-text"=>"7", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"9", "cited-by"=>"0", "year"=>"2017", "month"=>"1"}
• {"unique-ip"=>"7", "full-text"=>"3", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
• {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
• {"unique-ip"=>"1", "full-text"=>"0", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
• {"unique-ip"=>"7", "full-text"=>"4", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
• {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
• {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
• {"unique-ip"=>"11", "full-text"=>"23", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"10", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
• {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
• {"unique-ip"=>"6", "full-text"=>"1", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
• {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
• {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
• {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"10", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
• {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"6", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
• {"unique-ip"=>"6", "full-text"=>"7", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
• {"unique-ip"=>"7", "full-text"=>"5", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
• {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
• {"unique-ip"=>"4", "full-text"=>"0", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
• {"unique-ip"=>"5", "full-text"=>"3", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
• {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
• {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
• {"unique-ip"=>"1", "full-text"=>"0", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
• {"unique-ip"=>"6", "full-text"=>"7", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
• {"unique-ip"=>"10", "full-text"=>"12", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
• {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
• {"unique-ip"=>"11", "full-text"=>"15", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
• {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
• {"unique-ip"=>"9", "full-text"=>"5", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
• {"unique-ip"=>"5", "full-text"=>"3", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
• {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"8", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}
• {"unique-ip"=>"10", "full-text"=>"4", "pdf"=>"9", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}
• {"unique-ip"=>"12", "full-text"=>"10", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"7", "cited-by"=>"0", "year"=>"2020", "month"=>"2"}

Relative Metric

{"start_date"=>"2012-01-01T00:00:00Z", "end_date"=>"2012-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[322, 550, 671, 773, 864, 955, 1048, 1135, 1223, 1308, 1387, 1465, 1534, 1602, 1673, 1744, 1813, 1885, 1955, 2026, 2093, 2160, 2228, 2290, 2349]}, {"subject_area"=>"/Biology and life sciences/Anatomy", "average_usage"=>[308, 530, 649, 751, 844, 933, 1021, 1107, 1194, 1277, 1357, 1426, 1501, 1572, 1634, 1702, 1768, 1838, 1910, 1976, 2046, 2114, 2181, 2241, 2298]}, {"subject_area"=>"/Biology and life sciences/Cell biology", "average_usage"=>[319, 556, 679, 785, 881, 970, 1062, 1149, 1236, 1323, 1402, 1474, 1545, 1617, 1681, 1754, 1822, 1892, 1963, 2031, 2099, 2165, 2233, 2299, 2359]}, {"subject_area"=>"/Biology and life sciences/Computational biology", "average_usage"=>[375, 629, 760, 889, 1000, 1110, 1203, 1298, 1399, 1492, 1603, 1699, 1774, 1855, 1918, 1998, 2062, 2152, 2227, 2312, 2378, 2461, 2528, 2600, 2664]}, {"subject_area"=>"/Biology and life sciences/Genetics", "average_usage"=>[333, 576, 707, 814, 908, 1004, 1104, 1197, 1280, 1370, 1449, 1531, 1603, 1673, 1742, 1817, 1886, 1954, 2025, 2098, 2171, 2234, 2304, 2365, 2431]}, {"subject_area"=>"/Biology and life sciences/Molecular biology", "average_usage"=>[324, 551, 679, 782, 879, 971, 1064, 1154, 1245, 1328, 1406, 1476, 1541, 1617, 1683, 1754, 1818, 1893, 1962, 2025, 2092, 2164, 2227, 2294, 2355]}, {"subject_area"=>"/Medicine and health sciences/Anatomy", "average_usage"=>[307, 529, 649, 751, 845, 936, 1025, 1113, 1197, 1284, 1360, 1432, 1501, 1570, 1632, 1697, 1765, 1834, 1904, 1972, 2041, 2107, 2170, 2231, 2292]}]}

F1000Prime