Global Gene Expression Patterns in Clostridium thermocellum as Determined by Microarray Analysis of Chemostat Cultures on Cellulose or Cellobiose
A microarray study of chemostat growth on insoluble cellulose or soluble cellobiose has provided substantial new information on Clostridium thermocellum gene expression. This is the first comprehensive examination of gene expression in C. thermocellum under defined growth conditions. Expression was...
Gespeichert in:
Veröffentlicht in: | Applied and Environmental Microbiology 2011-02, Vol.77 (4), p.1243-1253 |
---|---|
Hauptverfasser: | , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 1253 |
---|---|
container_issue | 4 |
container_start_page | 1243 |
container_title | Applied and Environmental Microbiology |
container_volume | 77 |
creator | Riederer, Allison Takasuka, Taichi E Makino, Shin-ichi Stevenson, David M Bukhman, Yury V Elsen, Nathaniel L Fox, Brian G |
description | A microarray study of chemostat growth on insoluble cellulose or soluble cellobiose has provided substantial new information on Clostridium thermocellum gene expression. This is the first comprehensive examination of gene expression in C. thermocellum under defined growth conditions. Expression was detected from 2,846 of 3,189 genes, and regression analysis revealed 348 genes whose changes in expression patterns were growth rate and/or substrate dependent. Successfully modeled genes included those for scaffoldin and cellulosomal enzymes, intracellular metabolic enzymes, transcriptional regulators, sigma factors, signal transducers, transporters, and hypothetical proteins. Unique genes encoding glycolytic pathway and ethanol fermentation enzymes expressed at high levels simultaneously with previously established maximal ethanol production were also identified. Ranking of normalized expression intensities revealed significant changes in transcriptional levels of these genes. The pattern of expression of transcriptional regulators, sigma factors, and signal transducers indicates that response to growth rate is the dominant global mechanism used for control of gene expression in C. thermocellum. |
doi_str_mv | 10.1128/AEM.02008-10 |
format | Article |
fullrecord | <record><control><sourceid>proquest_osti_</sourceid><recordid>TN_cdi_osti_scitechconnect_1153073</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>851226717</sourcerecordid><originalsourceid>FETCH-LOGICAL-c624t-661a6275bbc3cf6e5ffacd76c652c0da18203c9f6ad05bda1ae997bbc811cf453</originalsourceid><addsrcrecordid>eNqNks1u1DAUhSMEoqWwYw0GCbEh5dqOf7JBGoVhQGoFEnRtOY4z4yqJBzsB5jF4Y5zOMIUVrKxjfzrXPj5Z9hjDOcZEvl4sL8-BAMgcw53sFEMpc0Ypv5udApRlTkgBJ9mDGK8BoAAu72cnBGNeFoydZj9Xna91h1Z2sGj5YxtsjM4P6JMeRxuGiNyAqs7HMbjGTT0aNzb03tiuS0JH9NYmrHeDbVC9Q5fOBK9D0Du0GHS3iy4i36JqY_tkoUdUTd04pRkojahmk2RtkQ83wtcuqYfZvVZ30T46rGfZ1bvll-p9fvFx9aFaXOSGk2LMOceaE8Hq2lDTcsvaVptGcMMZMdBoLAlQU7ZcN8DqpLUtS5FoibFpC0bPsjd73-1U97YxdhiD7tQ2uF6HnfLaqb9PBrdRa_9NUeCCAEkGz_cG6WlOReNGazbGD4M1o8KYURA0QS8PU4L_Otk4qt7FOT49WD9FVYLADBiV_0EWhQAG8E9SMkwIF1jcXvFIXvsppJ-ZIV4wAnK2e7WH0t_FGGx7zACDmiumUsXUTcXSTsKf_JnbEf7dqQS8OAA6Gt21QQ_GxVuOSoEpKxL3bM9t3Hrz3QWrdOyVtr0SQhUKk2KO7-meabVXeh2Sz9VnApgCLgugUtJfZ2Pviw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>856452080</pqid></control><display><type>article</type><title>Global Gene Expression Patterns in Clostridium thermocellum as Determined by Microarray Analysis of Chemostat Cultures on Cellulose or Cellobiose</title><source>American Society for Microbiology</source><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Riederer, Allison ; Takasuka, Taichi E ; Makino, Shin-ichi ; Stevenson, David M ; Bukhman, Yury V ; Elsen, Nathaniel L ; Fox, Brian G</creator><creatorcontrib>Riederer, Allison ; Takasuka, Taichi E ; Makino, Shin-ichi ; Stevenson, David M ; Bukhman, Yury V ; Elsen, Nathaniel L ; Fox, Brian G ; Great Lakes Bioenergy Research Center (GLBRC)</creatorcontrib><description>A microarray study of chemostat growth on insoluble cellulose or soluble cellobiose has provided substantial new information on Clostridium thermocellum gene expression. This is the first comprehensive examination of gene expression in C. thermocellum under defined growth conditions. Expression was detected from 2,846 of 3,189 genes, and regression analysis revealed 348 genes whose changes in expression patterns were growth rate and/or substrate dependent. Successfully modeled genes included those for scaffoldin and cellulosomal enzymes, intracellular metabolic enzymes, transcriptional regulators, sigma factors, signal transducers, transporters, and hypothetical proteins. Unique genes encoding glycolytic pathway and ethanol fermentation enzymes expressed at high levels simultaneously with previously established maximal ethanol production were also identified. Ranking of normalized expression intensities revealed significant changes in transcriptional levels of these genes. The pattern of expression of transcriptional regulators, sigma factors, and signal transducers indicates that response to growth rate is the dominant global mechanism used for control of gene expression in C. thermocellum.</description><identifier>ISSN: 0099-2240</identifier><identifier>EISSN: 1098-5336</identifier><identifier>EISSN: 1098-6596</identifier><identifier>DOI: 10.1128/AEM.02008-10</identifier><identifier>PMID: 21169455</identifier><identifier>CODEN: AEMIDF</identifier><language>eng</language><publisher>Washington, DC: American Society for Microbiology</publisher><subject>Bacteria ; Bacterial Proteins - genetics ; Bacterial Proteins - metabolism ; Biological and medical sciences ; Biotechnology ; Carrier Proteins - genetics ; Cell culture ; Cell growth ; Cellobiose - metabolism ; Cellulase - genetics ; Cellulose ; Cellulose - metabolism ; Clostridium thermocellum ; Clostridium thermocellum - enzymology ; Clostridium thermocellum - genetics ; Clostridium thermocellum - growth & development ; Clostridium thermocellum - metabolism ; Culture Media ; Enzymes ; Ethanol - metabolism ; Fermentation - genetics ; Fundamental and applied biological sciences. Psychology ; Gene expression ; Gene Expression Profiling ; Gene Expression Regulation, Bacterial ; Glycolysis ; Microarray Analysis ; Microbiology ; Multienzyme Complexes - genetics ; Multigene Family ; Proteins ; Regulatory Elements, Transcriptional ; Sigma Factor - genetics ; Signal Transduction ; Transcription, Genetic</subject><ispartof>Applied and Environmental Microbiology, 2011-02, Vol.77 (4), p.1243-1253</ispartof><rights>2015 INIST-CNRS</rights><rights>Copyright American Society for Microbiology Feb 2011</rights><rights>Copyright © 2011, American Society for Microbiology 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c624t-661a6275bbc3cf6e5ffacd76c652c0da18203c9f6ad05bda1ae997bbc811cf453</citedby><cites>FETCH-LOGICAL-c624t-661a6275bbc3cf6e5ffacd76c652c0da18203c9f6ad05bda1ae997bbc811cf453</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3067202/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3067202/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,3188,3189,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23871354$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21169455$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/1153073$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Riederer, Allison</creatorcontrib><creatorcontrib>Takasuka, Taichi E</creatorcontrib><creatorcontrib>Makino, Shin-ichi</creatorcontrib><creatorcontrib>Stevenson, David M</creatorcontrib><creatorcontrib>Bukhman, Yury V</creatorcontrib><creatorcontrib>Elsen, Nathaniel L</creatorcontrib><creatorcontrib>Fox, Brian G</creatorcontrib><creatorcontrib>Great Lakes Bioenergy Research Center (GLBRC)</creatorcontrib><title>Global Gene Expression Patterns in Clostridium thermocellum as Determined by Microarray Analysis of Chemostat Cultures on Cellulose or Cellobiose</title><title>Applied and Environmental Microbiology</title><addtitle>Appl Environ Microbiol</addtitle><description>A microarray study of chemostat growth on insoluble cellulose or soluble cellobiose has provided substantial new information on Clostridium thermocellum gene expression. This is the first comprehensive examination of gene expression in C. thermocellum under defined growth conditions. Expression was detected from 2,846 of 3,189 genes, and regression analysis revealed 348 genes whose changes in expression patterns were growth rate and/or substrate dependent. Successfully modeled genes included those for scaffoldin and cellulosomal enzymes, intracellular metabolic enzymes, transcriptional regulators, sigma factors, signal transducers, transporters, and hypothetical proteins. Unique genes encoding glycolytic pathway and ethanol fermentation enzymes expressed at high levels simultaneously with previously established maximal ethanol production were also identified. Ranking of normalized expression intensities revealed significant changes in transcriptional levels of these genes. The pattern of expression of transcriptional regulators, sigma factors, and signal transducers indicates that response to growth rate is the dominant global mechanism used for control of gene expression in C. thermocellum.</description><subject>Bacteria</subject><subject>Bacterial Proteins - genetics</subject><subject>Bacterial Proteins - metabolism</subject><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>Carrier Proteins - genetics</subject><subject>Cell culture</subject><subject>Cell growth</subject><subject>Cellobiose - metabolism</subject><subject>Cellulase - genetics</subject><subject>Cellulose</subject><subject>Cellulose - metabolism</subject><subject>Clostridium thermocellum</subject><subject>Clostridium thermocellum - enzymology</subject><subject>Clostridium thermocellum - genetics</subject><subject>Clostridium thermocellum - growth & development</subject><subject>Clostridium thermocellum - metabolism</subject><subject>Culture Media</subject><subject>Enzymes</subject><subject>Ethanol - metabolism</subject><subject>Fermentation - genetics</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Bacterial</subject><subject>Glycolysis</subject><subject>Microarray Analysis</subject><subject>Microbiology</subject><subject>Multienzyme Complexes - genetics</subject><subject>Multigene Family</subject><subject>Proteins</subject><subject>Regulatory Elements, Transcriptional</subject><subject>Sigma Factor - genetics</subject><subject>Signal Transduction</subject><subject>Transcription, Genetic</subject><issn>0099-2240</issn><issn>1098-5336</issn><issn>1098-6596</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNks1u1DAUhSMEoqWwYw0GCbEh5dqOf7JBGoVhQGoFEnRtOY4z4yqJBzsB5jF4Y5zOMIUVrKxjfzrXPj5Z9hjDOcZEvl4sL8-BAMgcw53sFEMpc0Ypv5udApRlTkgBJ9mDGK8BoAAu72cnBGNeFoydZj9Xna91h1Z2sGj5YxtsjM4P6JMeRxuGiNyAqs7HMbjGTT0aNzb03tiuS0JH9NYmrHeDbVC9Q5fOBK9D0Du0GHS3iy4i36JqY_tkoUdUTd04pRkojahmk2RtkQ83wtcuqYfZvVZ30T46rGfZ1bvll-p9fvFx9aFaXOSGk2LMOceaE8Hq2lDTcsvaVptGcMMZMdBoLAlQU7ZcN8DqpLUtS5FoibFpC0bPsjd73-1U97YxdhiD7tQ2uF6HnfLaqb9PBrdRa_9NUeCCAEkGz_cG6WlOReNGazbGD4M1o8KYURA0QS8PU4L_Otk4qt7FOT49WD9FVYLADBiV_0EWhQAG8E9SMkwIF1jcXvFIXvsppJ-ZIV4wAnK2e7WH0t_FGGx7zACDmiumUsXUTcXSTsKf_JnbEf7dqQS8OAA6Gt21QQ_GxVuOSoEpKxL3bM9t3Hrz3QWrdOyVtr0SQhUKk2KO7-meabVXeh2Sz9VnApgCLgugUtJfZ2Pviw</recordid><startdate>20110201</startdate><enddate>20110201</enddate><creator>Riederer, Allison</creator><creator>Takasuka, Taichi E</creator><creator>Makino, Shin-ichi</creator><creator>Stevenson, David M</creator><creator>Bukhman, Yury V</creator><creator>Elsen, Nathaniel L</creator><creator>Fox, Brian G</creator><general>American Society for Microbiology</general><general>American Society for Microbiology (ASM)</general><scope>FBQ</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QO</scope><scope>7SN</scope><scope>7SS</scope><scope>7ST</scope><scope>7T7</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>SOI</scope><scope>7X8</scope><scope>OTOTI</scope><scope>5PM</scope></search><sort><creationdate>20110201</creationdate><title>Global Gene Expression Patterns in Clostridium thermocellum as Determined by Microarray Analysis of Chemostat Cultures on Cellulose or Cellobiose</title><author>Riederer, Allison ; Takasuka, Taichi E ; Makino, Shin-ichi ; Stevenson, David M ; Bukhman, Yury V ; Elsen, Nathaniel L ; Fox, Brian G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c624t-661a6275bbc3cf6e5ffacd76c652c0da18203c9f6ad05bda1ae997bbc811cf453</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Bacteria</topic><topic>Bacterial Proteins - genetics</topic><topic>Bacterial Proteins - metabolism</topic><topic>Biological and medical sciences</topic><topic>Biotechnology</topic><topic>Carrier Proteins - genetics</topic><topic>Cell culture</topic><topic>Cell growth</topic><topic>Cellobiose - metabolism</topic><topic>Cellulase - genetics</topic><topic>Cellulose</topic><topic>Cellulose - metabolism</topic><topic>Clostridium thermocellum</topic><topic>Clostridium thermocellum - enzymology</topic><topic>Clostridium thermocellum - genetics</topic><topic>Clostridium thermocellum - growth & development</topic><topic>Clostridium thermocellum - metabolism</topic><topic>Culture Media</topic><topic>Enzymes</topic><topic>Ethanol - metabolism</topic><topic>Fermentation - genetics</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Bacterial</topic><topic>Glycolysis</topic><topic>Microarray Analysis</topic><topic>Microbiology</topic><topic>Multienzyme Complexes - genetics</topic><topic>Multigene Family</topic><topic>Proteins</topic><topic>Regulatory Elements, Transcriptional</topic><topic>Sigma Factor - genetics</topic><topic>Signal Transduction</topic><topic>Transcription, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Riederer, Allison</creatorcontrib><creatorcontrib>Takasuka, Taichi E</creatorcontrib><creatorcontrib>Makino, Shin-ichi</creatorcontrib><creatorcontrib>Stevenson, David M</creatorcontrib><creatorcontrib>Bukhman, Yury V</creatorcontrib><creatorcontrib>Elsen, Nathaniel L</creatorcontrib><creatorcontrib>Fox, Brian G</creatorcontrib><creatorcontrib>Great Lakes Bioenergy Research Center (GLBRC)</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Environment Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>Environment Abstracts</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Applied and Environmental Microbiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Riederer, Allison</au><au>Takasuka, Taichi E</au><au>Makino, Shin-ichi</au><au>Stevenson, David M</au><au>Bukhman, Yury V</au><au>Elsen, Nathaniel L</au><au>Fox, Brian G</au><aucorp>Great Lakes Bioenergy Research Center (GLBRC)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Global Gene Expression Patterns in Clostridium thermocellum as Determined by Microarray Analysis of Chemostat Cultures on Cellulose or Cellobiose</atitle><jtitle>Applied and Environmental Microbiology</jtitle><addtitle>Appl Environ Microbiol</addtitle><date>2011-02-01</date><risdate>2011</risdate><volume>77</volume><issue>4</issue><spage>1243</spage><epage>1253</epage><pages>1243-1253</pages><issn>0099-2240</issn><eissn>1098-5336</eissn><eissn>1098-6596</eissn><coden>AEMIDF</coden><abstract>A microarray study of chemostat growth on insoluble cellulose or soluble cellobiose has provided substantial new information on Clostridium thermocellum gene expression. This is the first comprehensive examination of gene expression in C. thermocellum under defined growth conditions. Expression was detected from 2,846 of 3,189 genes, and regression analysis revealed 348 genes whose changes in expression patterns were growth rate and/or substrate dependent. Successfully modeled genes included those for scaffoldin and cellulosomal enzymes, intracellular metabolic enzymes, transcriptional regulators, sigma factors, signal transducers, transporters, and hypothetical proteins. Unique genes encoding glycolytic pathway and ethanol fermentation enzymes expressed at high levels simultaneously with previously established maximal ethanol production were also identified. Ranking of normalized expression intensities revealed significant changes in transcriptional levels of these genes. The pattern of expression of transcriptional regulators, sigma factors, and signal transducers indicates that response to growth rate is the dominant global mechanism used for control of gene expression in C. thermocellum.</abstract><cop>Washington, DC</cop><pub>American Society for Microbiology</pub><pmid>21169455</pmid><doi>10.1128/AEM.02008-10</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0099-2240 |
ispartof | Applied and Environmental Microbiology, 2011-02, Vol.77 (4), p.1243-1253 |
issn | 0099-2240 1098-5336 1098-6596 |
language | eng |
recordid | cdi_osti_scitechconnect_1153073 |
source | American Society for Microbiology; MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection |
subjects | Bacteria Bacterial Proteins - genetics Bacterial Proteins - metabolism Biological and medical sciences Biotechnology Carrier Proteins - genetics Cell culture Cell growth Cellobiose - metabolism Cellulase - genetics Cellulose Cellulose - metabolism Clostridium thermocellum Clostridium thermocellum - enzymology Clostridium thermocellum - genetics Clostridium thermocellum - growth & development Clostridium thermocellum - metabolism Culture Media Enzymes Ethanol - metabolism Fermentation - genetics Fundamental and applied biological sciences. Psychology Gene expression Gene Expression Profiling Gene Expression Regulation, Bacterial Glycolysis Microarray Analysis Microbiology Multienzyme Complexes - genetics Multigene Family Proteins Regulatory Elements, Transcriptional Sigma Factor - genetics Signal Transduction Transcription, Genetic |
title | Global Gene Expression Patterns in Clostridium thermocellum as Determined by Microarray Analysis of Chemostat Cultures on Cellulose or Cellobiose |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-30T18%3A53%3A49IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_osti_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Global%20Gene%20Expression%20Patterns%20in%20Clostridium%20thermocellum%20as%20Determined%20by%20Microarray%20Analysis%20of%20Chemostat%20Cultures%20on%20Cellulose%20or%20Cellobiose&rft.jtitle=Applied%20and%20Environmental%20Microbiology&rft.au=Riederer,%20Allison&rft.aucorp=Great%20Lakes%20Bioenergy%20Research%20Center%20(GLBRC)&rft.date=2011-02-01&rft.volume=77&rft.issue=4&rft.spage=1243&rft.epage=1253&rft.pages=1243-1253&rft.issn=0099-2240&rft.eissn=1098-5336&rft.coden=AEMIDF&rft_id=info:doi/10.1128/AEM.02008-10&rft_dat=%3Cproquest_osti_%3E851226717%3C/proquest_osti_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=856452080&rft_id=info:pmid/21169455&rfr_iscdi=true |