A Genome-Wide Longitudinal Transcriptome Analysis of the Aging Model Podospora anserine

Aging of biological systems is controlled by various processes which have a potential impact on gene expression. Here we report a genome-wide transcriptome analysis of the fungal aging model Podospora anserina. Total RNA of three individuals of defined age were pooled and analyzed by SuperSAGE (seri...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:PloS one 2013-12, Vol.8 (12), p.e83109
Hauptverfasser: Philipp, Oliver, Hamann, Andrea, Servos, Jörg, Werner, Alexandra, Koch, Ina, Osiewacz, Heinz D
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page
container_issue 12
container_start_page e83109
container_title PloS one
container_volume 8
creator Philipp, Oliver
Hamann, Andrea
Servos, Jörg
Werner, Alexandra
Koch, Ina
Osiewacz, Heinz D
description Aging of biological systems is controlled by various processes which have a potential impact on gene expression. Here we report a genome-wide transcriptome analysis of the fungal aging model Podospora anserina. Total RNA of three individuals of defined age were pooled and analyzed by SuperSAGE (serial analysis of gene expression). A bioinformatics analysis identified different molecular pathways to be affected during aging. While the abundance of transcripts linked to ribosomes and to the proteasome quality control system were found to decrease during aging, those associated with autophagy increase, suggesting that autophagy may act as a compensatory quality control pathway. Transcript profiles associated with the energy metabolism including mitochondrial functions were identified to fluctuate during aging. Comparison of wild-type transcripts, which are continuously down-regulated during aging, with those down-regulated in the long-lived, copper-uptake mutant grisea, validated the relevance of age-related changes in cellular copper metabolism. Overall, we (i) present a unique age-related data set of a longitudinal study of the experimental aging model P. anserina which represents a reference resource for future investigations in a variety of organisms, (ii) suggest autophagy to be a key quality control pathway that becomes active once other pathways fail, and (iii) present testable predictions for subsequent experimental investigations.
doi_str_mv 10.1371/journal.pone.0083109
format Article
fullrecord <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1470083079</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A478204254</galeid><sourcerecordid>A478204254</sourcerecordid><originalsourceid>FETCH-LOGICAL-c570t-a55b4c716f2995a93a7484470d59e4e5b65d39a83801e496032efe6c7a3abdb23</originalsourceid><addsrcrecordid>eNqNktFr1TAUxoMobk7_A8GCIPjQa9qkSfMiXIbOwZWJTvcY0ua0N6NNapKK--_NZd1YQUHykOSc3_cFvhyEXhZ4UxBevLt2s7dq2EzOwgbjmhRYPELHhSBlzkpMHj84H6FnIVxjXJGasafoqKSEM0bZMbraZmdg3Qj5ldGQ7ZztTZy1Sc7ZpVc2tN5MMfWzbSrdBBMy12Vxn-69sX322WkYsi9OuzA5r7KkAG8sPEdPOjUEeLHsJ-j7xw-Xp5_y3cXZ-el2l7cVxzFXVdXQlhesK4WolCCK05pSjnUlgELVsEoToWpS4wKoYJiU0AFruSKq0U1JTtCrW99pcEEumQRZJIsUCeYiEe8XYm5G0C3Y6NUgJ29G5W-kU0auO9bsZe9-yZSV4Jwmg9eLgXc_ZwjxH88sVK8GkMZ2Lpm1owmt3FJel5iW1cFr8xcqLQ2jadNPdibVV4K3K0FiIvyOvZpDkOffvv4_e_Fjzb55wO5BDXEf3DBH42xYg_QWbL0LwUN3n1yB5WEQ79KQh0GUyyCSP0K1zms</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1470083079</pqid></control><display><type>article</type><title>A Genome-Wide Longitudinal Transcriptome Analysis of the Aging Model Podospora anserine</title><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><source>Public Library of Science (PLoS)</source><creator>Philipp, Oliver ; Hamann, Andrea ; Servos, Jörg ; Werner, Alexandra ; Koch, Ina ; Osiewacz, Heinz D</creator><creatorcontrib>Philipp, Oliver ; Hamann, Andrea ; Servos, Jörg ; Werner, Alexandra ; Koch, Ina ; Osiewacz, Heinz D</creatorcontrib><description>Aging of biological systems is controlled by various processes which have a potential impact on gene expression. Here we report a genome-wide transcriptome analysis of the fungal aging model Podospora anserina. Total RNA of three individuals of defined age were pooled and analyzed by SuperSAGE (serial analysis of gene expression). A bioinformatics analysis identified different molecular pathways to be affected during aging. While the abundance of transcripts linked to ribosomes and to the proteasome quality control system were found to decrease during aging, those associated with autophagy increase, suggesting that autophagy may act as a compensatory quality control pathway. Transcript profiles associated with the energy metabolism including mitochondrial functions were identified to fluctuate during aging. Comparison of wild-type transcripts, which are continuously down-regulated during aging, with those down-regulated in the long-lived, copper-uptake mutant grisea, validated the relevance of age-related changes in cellular copper metabolism. Overall, we (i) present a unique age-related data set of a longitudinal study of the experimental aging model P. anserina which represents a reference resource for future investigations in a variety of organisms, (ii) suggest autophagy to be a key quality control pathway that becomes active once other pathways fail, and (iii) present testable predictions for subsequent experimental investigations.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0083109</identifier><identifier>PMID: 24376646</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Active control ; Age ; Aging ; Analysis ; Autophagy ; Bioinformatics ; Cell death ; Computer science ; Control systems ; Copper ; Correlation analysis ; Developmental biology ; Disease ; Energy metabolism ; Fungi ; Gene expression ; Genes ; Genetic engineering ; Genomes ; Genomics ; Kinases ; Metabolism ; Mitochondria ; Neurodegeneration ; Phagocytosis ; Physiological aspects ; Proteasomes ; Quality control ; Quality management ; Ribonucleic acid ; Ribosomes ; RNA ; Serial analysis of gene expression ; Transcription</subject><ispartof>PloS one, 2013-12, Vol.8 (12), p.e83109</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Philipp et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Philipp et al 2013 Philipp et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c570t-a55b4c716f2995a93a7484470d59e4e5b65d39a83801e496032efe6c7a3abdb23</citedby><cites>FETCH-LOGICAL-c570t-a55b4c716f2995a93a7484470d59e4e5b65d39a83801e496032efe6c7a3abdb23</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/PMC3869774/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3869774/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids></links><search><creatorcontrib>Philipp, Oliver</creatorcontrib><creatorcontrib>Hamann, Andrea</creatorcontrib><creatorcontrib>Servos, Jörg</creatorcontrib><creatorcontrib>Werner, Alexandra</creatorcontrib><creatorcontrib>Koch, Ina</creatorcontrib><creatorcontrib>Osiewacz, Heinz D</creatorcontrib><title>A Genome-Wide Longitudinal Transcriptome Analysis of the Aging Model Podospora anserine</title><title>PloS one</title><description>Aging of biological systems is controlled by various processes which have a potential impact on gene expression. Here we report a genome-wide transcriptome analysis of the fungal aging model Podospora anserina. Total RNA of three individuals of defined age were pooled and analyzed by SuperSAGE (serial analysis of gene expression). A bioinformatics analysis identified different molecular pathways to be affected during aging. While the abundance of transcripts linked to ribosomes and to the proteasome quality control system were found to decrease during aging, those associated with autophagy increase, suggesting that autophagy may act as a compensatory quality control pathway. Transcript profiles associated with the energy metabolism including mitochondrial functions were identified to fluctuate during aging. Comparison of wild-type transcripts, which are continuously down-regulated during aging, with those down-regulated in the long-lived, copper-uptake mutant grisea, validated the relevance of age-related changes in cellular copper metabolism. Overall, we (i) present a unique age-related data set of a longitudinal study of the experimental aging model P. anserina which represents a reference resource for future investigations in a variety of organisms, (ii) suggest autophagy to be a key quality control pathway that becomes active once other pathways fail, and (iii) present testable predictions for subsequent experimental investigations.</description><subject>Active control</subject><subject>Age</subject><subject>Aging</subject><subject>Analysis</subject><subject>Autophagy</subject><subject>Bioinformatics</subject><subject>Cell death</subject><subject>Computer science</subject><subject>Control systems</subject><subject>Copper</subject><subject>Correlation analysis</subject><subject>Developmental biology</subject><subject>Disease</subject><subject>Energy metabolism</subject><subject>Fungi</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic engineering</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Kinases</subject><subject>Metabolism</subject><subject>Mitochondria</subject><subject>Neurodegeneration</subject><subject>Phagocytosis</subject><subject>Physiological aspects</subject><subject>Proteasomes</subject><subject>Quality control</subject><subject>Quality management</subject><subject>Ribonucleic acid</subject><subject>Ribosomes</subject><subject>RNA</subject><subject>Serial analysis of gene expression</subject><subject>Transcription</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNqNktFr1TAUxoMobk7_A8GCIPjQa9qkSfMiXIbOwZWJTvcY0ua0N6NNapKK--_NZd1YQUHykOSc3_cFvhyEXhZ4UxBevLt2s7dq2EzOwgbjmhRYPELHhSBlzkpMHj84H6FnIVxjXJGasafoqKSEM0bZMbraZmdg3Qj5ldGQ7ZztTZy1Sc7ZpVc2tN5MMfWzbSrdBBMy12Vxn-69sX322WkYsi9OuzA5r7KkAG8sPEdPOjUEeLHsJ-j7xw-Xp5_y3cXZ-el2l7cVxzFXVdXQlhesK4WolCCK05pSjnUlgELVsEoToWpS4wKoYJiU0AFruSKq0U1JTtCrW99pcEEumQRZJIsUCeYiEe8XYm5G0C3Y6NUgJ29G5W-kU0auO9bsZe9-yZSV4Jwmg9eLgXc_ZwjxH88sVK8GkMZ2Lpm1owmt3FJel5iW1cFr8xcqLQ2jadNPdibVV4K3K0FiIvyOvZpDkOffvv4_e_Fjzb55wO5BDXEf3DBH42xYg_QWbL0LwUN3n1yB5WEQ79KQh0GUyyCSP0K1zms</recordid><startdate>20131220</startdate><enddate>20131220</enddate><creator>Philipp, Oliver</creator><creator>Hamann, Andrea</creator><creator>Servos, Jörg</creator><creator>Werner, Alexandra</creator><creator>Koch, Ina</creator><creator>Osiewacz, Heinz D</creator><general>Public Library of Science</general><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20131220</creationdate><title>A Genome-Wide Longitudinal Transcriptome Analysis of the Aging Model Podospora anserine</title><author>Philipp, Oliver ; Hamann, Andrea ; Servos, Jörg ; Werner, Alexandra ; Koch, Ina ; Osiewacz, Heinz D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c570t-a55b4c716f2995a93a7484470d59e4e5b65d39a83801e496032efe6c7a3abdb23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Active control</topic><topic>Age</topic><topic>Aging</topic><topic>Analysis</topic><topic>Autophagy</topic><topic>Bioinformatics</topic><topic>Cell death</topic><topic>Computer science</topic><topic>Control systems</topic><topic>Copper</topic><topic>Correlation analysis</topic><topic>Developmental biology</topic><topic>Disease</topic><topic>Energy metabolism</topic><topic>Fungi</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Genetic engineering</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Kinases</topic><topic>Metabolism</topic><topic>Mitochondria</topic><topic>Neurodegeneration</topic><topic>Phagocytosis</topic><topic>Physiological aspects</topic><topic>Proteasomes</topic><topic>Quality control</topic><topic>Quality management</topic><topic>Ribonucleic acid</topic><topic>Ribosomes</topic><topic>RNA</topic><topic>Serial analysis of gene expression</topic><topic>Transcription</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Philipp, Oliver</creatorcontrib><creatorcontrib>Hamann, Andrea</creatorcontrib><creatorcontrib>Servos, Jörg</creatorcontrib><creatorcontrib>Werner, Alexandra</creatorcontrib><creatorcontrib>Koch, Ina</creatorcontrib><creatorcontrib>Osiewacz, Heinz D</creatorcontrib><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing &amp; Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological &amp; Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science &amp; Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies &amp; Aerospace Collection</collection><collection>Agricultural &amp; Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Philipp, Oliver</au><au>Hamann, Andrea</au><au>Servos, Jörg</au><au>Werner, Alexandra</au><au>Koch, Ina</au><au>Osiewacz, Heinz D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Genome-Wide Longitudinal Transcriptome Analysis of the Aging Model Podospora anserine</atitle><jtitle>PloS one</jtitle><date>2013-12-20</date><risdate>2013</risdate><volume>8</volume><issue>12</issue><spage>e83109</spage><pages>e83109-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Aging of biological systems is controlled by various processes which have a potential impact on gene expression. Here we report a genome-wide transcriptome analysis of the fungal aging model Podospora anserina. Total RNA of three individuals of defined age were pooled and analyzed by SuperSAGE (serial analysis of gene expression). A bioinformatics analysis identified different molecular pathways to be affected during aging. While the abundance of transcripts linked to ribosomes and to the proteasome quality control system were found to decrease during aging, those associated with autophagy increase, suggesting that autophagy may act as a compensatory quality control pathway. Transcript profiles associated with the energy metabolism including mitochondrial functions were identified to fluctuate during aging. Comparison of wild-type transcripts, which are continuously down-regulated during aging, with those down-regulated in the long-lived, copper-uptake mutant grisea, validated the relevance of age-related changes in cellular copper metabolism. Overall, we (i) present a unique age-related data set of a longitudinal study of the experimental aging model P. anserina which represents a reference resource for future investigations in a variety of organisms, (ii) suggest autophagy to be a key quality control pathway that becomes active once other pathways fail, and (iii) present testable predictions for subsequent experimental investigations.</abstract><cop>San Francisco</cop><pub>Public Library of Science</pub><pmid>24376646</pmid><doi>10.1371/journal.pone.0083109</doi><tpages>e83109</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1932-6203
ispartof PloS one, 2013-12, Vol.8 (12), p.e83109
issn 1932-6203
1932-6203
language eng
recordid cdi_plos_journals_1470083079
source DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS)
subjects Active control
Age
Aging
Analysis
Autophagy
Bioinformatics
Cell death
Computer science
Control systems
Copper
Correlation analysis
Developmental biology
Disease
Energy metabolism
Fungi
Gene expression
Genes
Genetic engineering
Genomes
Genomics
Kinases
Metabolism
Mitochondria
Neurodegeneration
Phagocytosis
Physiological aspects
Proteasomes
Quality control
Quality management
Ribonucleic acid
Ribosomes
RNA
Serial analysis of gene expression
Transcription
title A Genome-Wide Longitudinal Transcriptome Analysis of the Aging Model Podospora anserine
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T23%3A50%3A30IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20Genome-Wide%20Longitudinal%20Transcriptome%20Analysis%20of%20the%20Aging%20Model%20Podospora%20anserine&rft.jtitle=PloS%20one&rft.au=Philipp,%20Oliver&rft.date=2013-12-20&rft.volume=8&rft.issue=12&rft.spage=e83109&rft.pages=e83109-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0083109&rft_dat=%3Cgale_plos_%3EA478204254%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1470083079&rft_id=info:pmid/24376646&rft_galeid=A478204254&rfr_iscdi=true