Adaptive and Specialised Transcriptional Responses to Xenobiotic Stress in Caenorhabditis elegans Are Regulated by Nuclear Hormone Receptors
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{"title"=>"Adaptive and Specialised Transcriptional Responses to Xenobiotic Stress in Caenorhabditis elegans Are Regulated by Nuclear Hormone Receptors", "type"=>"journal", "authors"=>[{"first_name"=>"Laura M.", "last_name"=>"Jones", "scopus_author_id"=>"36168186900"}, {"first_name"=>"Samantha J.", "last_name"=>"Rayson", "scopus_author_id"=>"55029480800"}, {"first_name"=>"Anthony J.", "last_name"=>"Flemming", "scopus_author_id"=>"7003951909"}, {"first_name"=>"Peter E.", "last_name"=>"Urwin", "scopus_author_id"=>"7004487861"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84880822705", "issn"=>"19326203", "pui"=>"369439166", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "sgr"=>"84880822705", "pmid"=>"23922869", "doi"=>"10.1371/journal.pone.0069956"}, "id"=>"7ebbd552-f977-3503-8395-509e3b3c9b67", "abstract"=>"Characterisation of the pathways by which xenobiotics are metabolised and excreted in both target and non-target organisms is crucial for the rational design of effective and specific novel bioactive molecules. Consequently, we have investigated the induced responses of the model nematode Caenorhabditis elegans to a variety of xenobiotics which represent a range of putative modes of action. The majority of genes that were specifically induced in preliminary microarray analyses encoded enzymes from Phase I and II metabolism, including cytochrome P450s, short chain dehydrogenases, UDP-glucuronosyl transferases and glutathione transferases. Changes in gene expression were confirmed by quantitative PCR and GFP induction in reporter strains driven by promoters for transcription of twelve induced enzymes was investigated. The particular complement of metabolic genes induced was found to be highly contingent on the xenobiotic applied. The known regulators of responses to applied chemicals ahr-1, hif-1, mdt-15 and nhr-8 were not required for any of these inducible responses and skn-1 regulated GFP expression from only two of the promoters. Reporter strains were used in conjunction with systematic RNAi screens to identify transcription factors which drive expression of these genes under xenobiotic exposure. These transcription factors appeared to regulate specific xenobiotic responses and have no reported phenotypes under standard conditions. Focussing on nhr-176 we demonstrate the role of this transcription factor in mediating the resistance to thiabendazole.", "link"=>"http://www.mendeley.com/research/adaptive-specialised-transcriptional-responses-xenobiotic-stress-caenorhabditis-elegans-regulated-nu", "reader_count"=>30, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>11, "Student > Ph. D. Student"=>8, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>11, "Student > Ph. D. Student"=>8, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>1, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>7, "Agricultural and Biological Sciences"=>17, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Chemistry"=>1, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>17}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}, "Unspecified"=>{"Unspecified"=>1}, "Environmental Science"=>{"Environmental Science"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Netherlands"=>1, "United States"=>1, "United Kingdom"=>1, "Germany"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1133499"], "description"=>"<p>Images with UV and visible illumination of <i>cyp-35b3::GFP</i>, <i>cyp-35d1::GFP</i>, <i>gst-31::GFP</i> and <i>ugt-25::GFP</i> reporter strains in adult stage under exposure to 1.0 mM chloroquine, 0.25 mM thiabendazole, 0.5 mM dazomet and 2.0 mM imidacloprid, respectively. An example of each of the spatial expression patterns observed is shown; intestine (<i>cyp-35b3::GFP</i> and <i>cyp-35d1::GFP</i>) pharynx/hypodermis/vulva (<i>gst-31::GFP</i>) and hypodermis/vulva (<i>ugt-25::GFP</i>). Scale bar represents 100 µm in all images.</p>", "links"=>[], "tags"=>["agrochemicals", "Pest control", "Sustainable agriculture", "Biochemistry", "enzymes", "Enzyme metabolism", "Computational biology", "microarrays", "Model organisms", "Molecular cell biology", "Synthetic Biology", "toxicology", "Veterinary medicine", "gfp", "strains", "driven", "promoters", "genes", "encoding", "gst"], "article_id"=>757030, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Laura M. Jones", "Samantha J. Rayson", "Anthony J. Flemming", "Peter E. Urwin"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0069956.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_GFP_in_a_selection_of_reporter_strains_driven_by_promoters_for_genes_encoding_CYP_GST_and_UGTs_/757030", "title"=>"Expression of GFP in a selection of reporter strains driven by promoters for genes encoding CYP, GST and UGTs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-26 03:00:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/1133515"], "description"=>"<p>Low magnification images with UV illumination of <i>cyp-35b3::GFP</i>, <i>cyp-35d1::GFP</i>, <i>gst-31::GFP</i> and <i>ugt-25::GFP</i> reporter strains in adult stage under exposure to 0.25 mM beta-napthoflavone, 1.0 mM chloroquine, 0.5 mM dazomet, 0.25 mM juglone, 2.0 mM imidacloprid and 0.25 mM thiabendazole. Scale bar represents 500 µm in all images.</p>", "links"=>[], "tags"=>["agrochemicals", "Pest control", "Sustainable agriculture", "Biochemistry", "enzymes", "Enzyme metabolism", "Computational biology", "microarrays", "Model organisms", "Molecular cell biology", "Synthetic Biology", "toxicology", "Veterinary medicine", "gfp", "strains", "xenobiotic"], "article_id"=>757037, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Laura M. Jones", "Samantha J. Rayson", "Anthony J. Flemming", "Peter E. Urwin"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0069956.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_response_of_GFP_reporter_strains_under_xenobiotic_exposure_/757037", "title"=>"The response of GFP reporter strains under xenobiotic exposure.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-26 03:00:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/1133521"], "description"=>"<p>Xenobiotic exposures were A) and B) 0.5 mM dazomet, C) 1.0 mM chloroquine, D) 0.25 mM thiabendazole and E) 2.0 mM imidacloprid. The mean of three biological replicates is plotted with standard error of the mean. *<i>p</i><0.05, **<i>p</i><0.01 and ***<i>p</i><0.001 from one-way Analysis of Variance.</p>", "links"=>[], "tags"=>["agrochemicals", "Pest control", "Sustainable agriculture", "Biochemistry", "enzymes", "Enzyme metabolism", "Computational biology", "microarrays", "Model organisms", "Molecular cell biology", "Synthetic Biology", "toxicology", "Veterinary medicine", "xenobiotic", "induction", "strains", "driven", "promoters", "dsrna", "knockdown", "transcription"], "article_id"=>757043, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Laura M. Jones", "Samantha J. Rayson", "Anthony J. Flemming", "Peter E. Urwin"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0069956.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_GFP_expression_upon_xenobiotic_induction_in_reporter_strains_driven_by_promoters_for_A_gst_31_B_ugt_13_C_cyp_35b3_D_cyp_35d1_E_ugt_25_following_exposure_to_dsRNA_to_knockdown_transcription_factors_/757043", "title"=>"GFP expression upon xenobiotic induction in reporter strains driven by promoters for A) <i>gst-31</i> B) <i>ugt-13</i> C) <i>cyp-35b3</i> D) <i>cyp-35d1</i> E) <i>ugt-25</i> following exposure to dsRNA to knockdown transcription factors.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-26 03:00:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/1133528"], "description"=>"<p>GFP expression in <i>cyp-35d1::GFP</i> adult stage upon induction by 0.25 mM thiabendazole when fed on <i>E. coli</i> HT115 (DE3) containing <i>pl4440</i> (control; A and C) and when fed on <i>E. coli</i> HT115 (DE3) containing <i>pl4440::nhr-176</i> (B and D). Low magnification images showing GFP expression in <i>cyp-35d1::GFP</i> adult stage under UV illumination (E) upon induction by 0.5% DMSO when fed on <i>E. coli</i> HT115 (DE3) containing <i>pl4440</i> (F) upon induction by 0.25 mM thiabendazole when fed on <i>E. coli</i> HT115 (DE3) containing <i>pl4440</i> (G) upon induction by 0.25 mM thiabendazole when fed on <i>E. coli</i> HT115 (DE3) containing <i>pl4440::nhr-176</i> (F). Scale bar represents 100 µm in A-D.</p>", "links"=>[], "tags"=>["agrochemicals", "Pest control", "Sustainable agriculture", "Biochemistry", "enzymes", "Enzyme metabolism", "Computational biology", "microarrays", "Model organisms", "Molecular cell biology", "Synthetic Biology", "toxicology", "Veterinary medicine", "lines", "nhr-176", "knocked", "rnai"], "article_id"=>757050, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Laura M. Jones", "Samantha J. Rayson", "Anthony J. Flemming", "Peter E. Urwin"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0069956.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_GFP_expression_of_reporter_lines_when_NHR_176_was_knocked_down_by_RNAi_prior_to_chemical_induction_/757050", "title"=>"GFP expression of reporter lines when NHR-176 was knocked down by RNAi prior to chemical induction.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-26 03:00:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/1133531"], "description"=>"<p>The mean of three biological replicates is plotted with standard error of the mean. *p<0.05, **p<0.01 and ***p<0.001 from one-way Analysis of Variance.</p>", "links"=>[], "tags"=>["agrochemicals", "Pest control", "Sustainable agriculture", "Biochemistry", "enzymes", "Enzyme metabolism", "Computational biology", "microarrays", "Model organisms", "Molecular cell biology", "Synthetic Biology", "toxicology", "Veterinary medicine", "eggs", "laid", "nematodes", "grown", "rnai", "thiabendazole", "l1"], "article_id"=>757053, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Laura M. Jones", "Samantha J. Rayson", "Anthony J. Flemming", "Peter E. Urwin"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0069956.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Total_number_of_eggs_laid_by_nematodes_grown_under_RNAi_and_thiabendazole_exposure_from_L1_stage_for_four_days_/757053", "title"=>"Total number of eggs laid by nematodes grown under RNAi and thiabendazole exposure from L1 stage for four days.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-26 03:00:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/1133532"], "description"=>"<p>(0 = no expression, 5 = strong expression).</p>", "links"=>[], "tags"=>["agrochemicals", "Pest control", "Sustainable agriculture", "Biochemistry", "enzymes", "Enzyme metabolism", "Computational biology", "microarrays", "Model organisms", "Molecular cell biology", "Synthetic Biology", "toxicology", "Veterinary medicine", "strains", "driven", "promoters", "genes", "upregulated", "xenobiotic", "qpcr"], "article_id"=>757054, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Laura M. Jones", "Samantha J. Rayson", "Anthony J. Flemming", "Peter E. Urwin"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0069956.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_GFP_expression_in_reporter_strains_driven_by_promoters_for_genes_significantly_upregulated_p_8804_0_01_under_xenobiotic_exposure_in_qPCR_analyses_/757054", "title"=>"GFP expression in reporter strains driven by promoters for genes significantly upregulated (p≤0.01) under xenobiotic exposure in qPCR analyses.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-07-26 03:00:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/1133533", "https://ndownloader.figshare.com/files/1133539", "https://ndownloader.figshare.com/files/1133546", "https://ndownloader.figshare.com/files/1133552", "https://ndownloader.figshare.com/files/1133556"], "description"=>"<div><p>Characterisation of the pathways by which xenobiotics are metabolised and excreted in both target and non-target organisms is crucial for the rational design of effective and specific novel bioactive molecules. Consequently, we have investigated the induced responses of the model nematode <i>Caenorhabditis elegans</i> to a variety of xenobiotics which represent a range of putative modes of action. The majority of genes that were specifically induced in preliminary microarray analyses encoded enzymes from Phase I and II metabolism, including cytochrome P450s, short chain dehydrogenases, UDP-glucuronosyl transferases and glutathione transferases. Changes in gene expression were confirmed by quantitative PCR and GFP induction in reporter strains driven by promoters for transcription of twelve induced enzymes was investigated. The particular complement of metabolic genes induced was found to be highly contingent on the xenobiotic applied. The known regulators of responses to applied chemicals <i>ahr-1, hif-1, mdt-15</i> and <i>nhr-8</i> were not required for any of these inducible responses and <i>skn-1</i> regulated GFP expression from only two of the promoters. Reporter strains were used in conjunction with systematic RNAi screens to identify transcription factors which drive expression of these genes under xenobiotic exposure. These transcription factors appeared to regulate specific xenobiotic responses and have no reported phenotypes under standard conditions. Focussing on <i>nhr-176</i> we demonstrate the role of this transcription factor in mediating the resistance to thiabendazole.</p></div>", "links"=>[], "tags"=>["agrochemicals", "Pest control", "Sustainable agriculture", "Biochemistry", "enzymes", "Enzyme metabolism", "Computational biology", "microarrays", "Model organisms", "Molecular cell biology", "Synthetic Biology", "toxicology", "Veterinary medicine", "adaptive", "specialised", "transcriptional", "responses", "xenobiotic", "regulated", "receptors"], "article_id"=>757055, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Laura M. Jones", "Samantha J. Rayson", "Anthony J. Flemming", "Peter E. Urwin"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0069956.s001", "https://dx.doi.org/10.1371/journal.pone.0069956.s002", "https://dx.doi.org/10.1371/journal.pone.0069956.s003", "https://dx.doi.org/10.1371/journal.pone.0069956.s004", "https://dx.doi.org/10.1371/journal.pone.0069956.s005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Adaptive_and_Specialised_Transcriptional_Responses_to_Xenobiotic_Stress_in_Caenorhabditis_elegans_Are_Regulated_by_Nuclear_Hormone_Receptors/757055", "title"=>"Adaptive and Specialised Transcriptional Responses to Xenobiotic Stress in <i>Caenorhabditis elegans</i> Are Regulated by Nuclear Hormone Receptors", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-07-26 03:00:29"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"11", "full-text"=>"10", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"8", "full-text"=>"10", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"9", "full-text"=>"7", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"12", "full-text"=>"12", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"16", "full-text"=>"11", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}

Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[269, 466, 588, 697, 800, 896, 988, 1076, 1165, 1254, 1340, 1417]}, {"subject_area"=>"/Biology and life sciences/Biochemistry", "average_usage"=>[266, 468, 593, 703, 804, 903, 993, 1084, 1171, 1256, 1339, 1422, 1492]}, {"subject_area"=>"/Biology and life sciences/Genetics", "average_usage"=>[284, 491, 620, 738, 843, 945, 1043, 1137, 1225, 1315, 1400, 1479, 1555]}, {"subject_area"=>"/Biology and life sciences/Organisms", "average_usage"=>[281, 484, 611, 728, 835, 934, 1030, 1123, 1214, 1299, 1383, 1464]}, {"subject_area"=>"/Medicine and health sciences", "average_usage"=>[264, 460, 584, 692, 794, 887, 978, 1067, 1154, 1241, 1328, 1408, 1474]}, {"subject_area"=>"/Medicine and health sciences/Pharmacology", "average_usage"=>[265, 471, 604, 723, 827, 926, 1022, 1113, 1210, 1290, 1377, 1454, 1532]}]}
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