A novel actinomycete strain de-replication approach based on the diversity of polyketide synthase and nonribosomal peptide synthetase biosynthetic pathways
The actinomycetes traditionally represent one of the most important sources for the discovery of new metabolites with biological activity; and many of these are described as being produced by polyketide synthases (PKS) and nonribosomal peptide synthetases (NRPS). We present a strain characterization...
Gespeichert in:
| Veröffentlicht in: | Applied microbiology and biotechnology 2005-06, Vol.67 (6), p.795-806 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 806 |
|---|---|
| container_issue | 6 |
| container_start_page | 795 |
| container_title | Applied microbiology and biotechnology |
| container_volume | 67 |
| creator | AYUSO, Angel CLARK, Desmond GONZALEZ, Ignacio SALAZAR, Oscar ANDERSON, Annaliesa GENILLOUD, Olga |
| description | The actinomycetes traditionally represent one of the most important sources for the discovery of new metabolites with biological activity; and many of these are described as being produced by polyketide synthases (PKS) and nonribosomal peptide synthetases (NRPS). We present a strain characterization system based on the metabolic potential of microbial strains by targeting these biosynthetic genes. After an initial evaluation of the existing bias derived from the PCR detection in a well defined biosynthetic systems, we developed a new fingerprinting approach based on the restriction analysis of these PKS and NRPS amplified sequences. This method was applied to study the distribution of PKS and NRPS biosynthetic systems in a collection of wild-type actinomycetes isolated from tropical soil samples that were evaluated for the production of antimicrobial activities. We discuss the application of this tool as an alternative characterization approach for actinomycetes and we comment on the relationship observed between the presence of PKS-I, PKS-II and NRPS sequences and the antimicrobial activities observed in some of the microbial groups tested. |
| doi_str_mv | 10.1007/s00253-004-1828-7 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_67951406</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2087340011</sourcerecordid><originalsourceid>FETCH-LOGICAL-c490t-e9b5e7cb4d7bc0b2a1857926b3542213c4dc938c475e507d2b31d644147140873</originalsourceid><addsrcrecordid>eNqF0cmKFDEABuAgitOOPoAXCYLeSrOnchwGNxjwoueQremM1UmZpGeoZ_FlTdEFDV48hYQvf5YfgNcYfcAIyY8VIcLpgBAb8EjGQT4BO8woGZDA7CnYISz5ILkar8CLWu8RwmQU4jm4wlwwqajYgT83MOWHMEHjWkz5uLjQAqytmJigD0MJ8xSdaTEnaOa5ZOMO0JoaPOwr7RCgjw-h1NgWmPdwztPyK7Toe8aS2qFDaJLvZ6QSba75aCY4h_kiQluNjXmbRQdn0w6PZqkvwbO9mWp4tY3X4OfnTz9uvw533798u725GxxTqA1BWR6ks8xL65AlBo9cKiIs5YwQTB3zTtHRMckDR9ITS7EXjGEmMUOjpNfg_Tm3P-_3KdSmj7G6ME0mhXyqWkjFuxT_hf27JcOcdPj2H3ifTyX1R2hBEJVIyTUNn5ErudYS9nou8WjKojHSa7_63K_u_eq1X71e9c0WfLLH4C87tkI7eLcBU52Z9sUkF-vFCYWJEoz-BX_UsFI</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>620370976</pqid></control><display><type>article</type><title>A novel actinomycete strain de-replication approach based on the diversity of polyketide synthase and nonribosomal peptide synthetase biosynthetic pathways</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>AYUSO, Angel ; CLARK, Desmond ; GONZALEZ, Ignacio ; SALAZAR, Oscar ; ANDERSON, Annaliesa ; GENILLOUD, Olga</creator><creatorcontrib>AYUSO, Angel ; CLARK, Desmond ; GONZALEZ, Ignacio ; SALAZAR, Oscar ; ANDERSON, Annaliesa ; GENILLOUD, Olga</creatorcontrib><description>The actinomycetes traditionally represent one of the most important sources for the discovery of new metabolites with biological activity; and many of these are described as being produced by polyketide synthases (PKS) and nonribosomal peptide synthetases (NRPS). We present a strain characterization system based on the metabolic potential of microbial strains by targeting these biosynthetic genes. After an initial evaluation of the existing bias derived from the PCR detection in a well defined biosynthetic systems, we developed a new fingerprinting approach based on the restriction analysis of these PKS and NRPS amplified sequences. This method was applied to study the distribution of PKS and NRPS biosynthetic systems in a collection of wild-type actinomycetes isolated from tropical soil samples that were evaluated for the production of antimicrobial activities. We discuss the application of this tool as an alternative characterization approach for actinomycetes and we comment on the relationship observed between the presence of PKS-I, PKS-II and NRPS sequences and the antimicrobial activities observed in some of the microbial groups tested.</description><identifier>ISSN: 0175-7598</identifier><identifier>EISSN: 1432-0614</identifier><identifier>DOI: 10.1007/s00253-004-1828-7</identifier><identifier>PMID: 15647936</identifier><identifier>CODEN: AMBIDG</identifier><language>eng</language><publisher>Berlin: Springer</publisher><subject>Actinobacteria - genetics ; Actinobacteria - metabolism ; Anti-Bacterial Agents - biosynthesis ; Anti-Bacterial Agents - pharmacology ; Antifungal Agents - metabolism ; Antifungal Agents - pharmacology ; Bacteria - drug effects ; Biological and medical sciences ; Biology of microorganisms of confirmed or potential industrial interest ; Biotechnology ; Candida albicans - drug effects ; DNA Fingerprinting ; Fundamental and applied biological sciences. Psychology ; Genes, Bacterial ; Genetic Variation ; Metabolites ; Microbial Sensitivity Tests ; Microbiology ; Miscellaneous ; Mission oriented research ; Molecular Sequence Data ; Peptide Synthases - biosynthesis ; Peptide Synthases - genetics ; Peptides ; Polyketide Synthases - biosynthesis ; Polyketide Synthases - genetics ; Polymerase Chain Reaction ; Soil Microbiology ; Tropical Climate ; Tropical environments</subject><ispartof>Applied microbiology and biotechnology, 2005-06, Vol.67 (6), p.795-806</ispartof><rights>2005 INIST-CNRS</rights><rights>Springer-Verlag 2005</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c490t-e9b5e7cb4d7bc0b2a1857926b3542213c4dc938c475e507d2b31d644147140873</citedby><cites>FETCH-LOGICAL-c490t-e9b5e7cb4d7bc0b2a1857926b3542213c4dc938c475e507d2b31d644147140873</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16912964$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15647936$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>AYUSO, Angel</creatorcontrib><creatorcontrib>CLARK, Desmond</creatorcontrib><creatorcontrib>GONZALEZ, Ignacio</creatorcontrib><creatorcontrib>SALAZAR, Oscar</creatorcontrib><creatorcontrib>ANDERSON, Annaliesa</creatorcontrib><creatorcontrib>GENILLOUD, Olga</creatorcontrib><title>A novel actinomycete strain de-replication approach based on the diversity of polyketide synthase and nonribosomal peptide synthetase biosynthetic pathways</title><title>Applied microbiology and biotechnology</title><addtitle>Appl Microbiol Biotechnol</addtitle><description>The actinomycetes traditionally represent one of the most important sources for the discovery of new metabolites with biological activity; and many of these are described as being produced by polyketide synthases (PKS) and nonribosomal peptide synthetases (NRPS). We present a strain characterization system based on the metabolic potential of microbial strains by targeting these biosynthetic genes. After an initial evaluation of the existing bias derived from the PCR detection in a well defined biosynthetic systems, we developed a new fingerprinting approach based on the restriction analysis of these PKS and NRPS amplified sequences. This method was applied to study the distribution of PKS and NRPS biosynthetic systems in a collection of wild-type actinomycetes isolated from tropical soil samples that were evaluated for the production of antimicrobial activities. We discuss the application of this tool as an alternative characterization approach for actinomycetes and we comment on the relationship observed between the presence of PKS-I, PKS-II and NRPS sequences and the antimicrobial activities observed in some of the microbial groups tested.</description><subject>Actinobacteria - genetics</subject><subject>Actinobacteria - metabolism</subject><subject>Anti-Bacterial Agents - biosynthesis</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Antifungal Agents - metabolism</subject><subject>Antifungal Agents - pharmacology</subject><subject>Bacteria - drug effects</subject><subject>Biological and medical sciences</subject><subject>Biology of microorganisms of confirmed or potential industrial interest</subject><subject>Biotechnology</subject><subject>Candida albicans - drug effects</subject><subject>DNA Fingerprinting</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genes, Bacterial</subject><subject>Genetic Variation</subject><subject>Metabolites</subject><subject>Microbial Sensitivity Tests</subject><subject>Microbiology</subject><subject>Miscellaneous</subject><subject>Mission oriented research</subject><subject>Molecular Sequence Data</subject><subject>Peptide Synthases - biosynthesis</subject><subject>Peptide Synthases - genetics</subject><subject>Peptides</subject><subject>Polyketide Synthases - biosynthesis</subject><subject>Polyketide Synthases - genetics</subject><subject>Polymerase Chain Reaction</subject><subject>Soil Microbiology</subject><subject>Tropical Climate</subject><subject>Tropical environments</subject><issn>0175-7598</issn><issn>1432-0614</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqF0cmKFDEABuAgitOOPoAXCYLeSrOnchwGNxjwoueQremM1UmZpGeoZ_FlTdEFDV48hYQvf5YfgNcYfcAIyY8VIcLpgBAb8EjGQT4BO8woGZDA7CnYISz5ILkar8CLWu8RwmQU4jm4wlwwqajYgT83MOWHMEHjWkz5uLjQAqytmJigD0MJ8xSdaTEnaOa5ZOMO0JoaPOwr7RCgjw-h1NgWmPdwztPyK7Toe8aS2qFDaJLvZ6QSba75aCY4h_kiQluNjXmbRQdn0w6PZqkvwbO9mWp4tY3X4OfnTz9uvw533798u725GxxTqA1BWR6ks8xL65AlBo9cKiIs5YwQTB3zTtHRMckDR9ITS7EXjGEmMUOjpNfg_Tm3P-_3KdSmj7G6ME0mhXyqWkjFuxT_hf27JcOcdPj2H3ifTyX1R2hBEJVIyTUNn5ErudYS9nou8WjKojHSa7_63K_u_eq1X71e9c0WfLLH4C87tkI7eLcBU52Z9sUkF-vFCYWJEoz-BX_UsFI</recordid><startdate>20050601</startdate><enddate>20050601</enddate><creator>AYUSO, Angel</creator><creator>CLARK, Desmond</creator><creator>GONZALEZ, Ignacio</creator><creator>SALAZAR, Oscar</creator><creator>ANDERSON, Annaliesa</creator><creator>GENILLOUD, Olga</creator><general>Springer</general><general>Springer Nature B.V</general><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>3V.</scope><scope>7QL</scope><scope>7T7</scope><scope>7WY</scope><scope>7WZ</scope><scope>7X7</scope><scope>7XB</scope><scope>87Z</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8FL</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BEZIV</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FRNLG</scope><scope>FYUFA</scope><scope>F~G</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K60</scope><scope>K6~</scope><scope>K9.</scope><scope>L.-</scope><scope>LK8</scope><scope>M0C</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQBIZ</scope><scope>PQBZA</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20050601</creationdate><title>A novel actinomycete strain de-replication approach based on the diversity of polyketide synthase and nonribosomal peptide synthetase biosynthetic pathways</title><author>AYUSO, Angel ; CLARK, Desmond ; GONZALEZ, Ignacio ; SALAZAR, Oscar ; ANDERSON, Annaliesa ; GENILLOUD, Olga</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c490t-e9b5e7cb4d7bc0b2a1857926b3542213c4dc938c475e507d2b31d644147140873</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Actinobacteria - genetics</topic><topic>Actinobacteria - metabolism</topic><topic>Anti-Bacterial Agents - biosynthesis</topic><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Antifungal Agents - metabolism</topic><topic>Antifungal Agents - pharmacology</topic><topic>Bacteria - drug effects</topic><topic>Biological and medical sciences</topic><topic>Biology of microorganisms of confirmed or potential industrial interest</topic><topic>Biotechnology</topic><topic>Candida albicans - drug effects</topic><topic>DNA Fingerprinting</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genes, Bacterial</topic><topic>Genetic Variation</topic><topic>Metabolites</topic><topic>Microbial Sensitivity Tests</topic><topic>Microbiology</topic><topic>Miscellaneous</topic><topic>Mission oriented research</topic><topic>Molecular Sequence Data</topic><topic>Peptide Synthases - biosynthesis</topic><topic>Peptide Synthases - genetics</topic><topic>Peptides</topic><topic>Polyketide Synthases - biosynthesis</topic><topic>Polyketide Synthases - genetics</topic><topic>Polymerase Chain Reaction</topic><topic>Soil Microbiology</topic><topic>Tropical Climate</topic><topic>Tropical environments</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>AYUSO, Angel</creatorcontrib><creatorcontrib>CLARK, Desmond</creatorcontrib><creatorcontrib>GONZALEZ, Ignacio</creatorcontrib><creatorcontrib>SALAZAR, Oscar</creatorcontrib><creatorcontrib>ANDERSON, Annaliesa</creatorcontrib><creatorcontrib>GENILLOUD, Olga</creatorcontrib><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>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>ABI/INFORM Collection</collection><collection>ABI/INFORM Global (PDF only)</collection><collection>Health & Medical Collection (Proquest)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ABI/INFORM Collection</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech 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>ABI/INFORM Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Business Premium Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Business Premium Collection (Alumni)</collection><collection>Health Research Premium Collection</collection><collection>ABI/INFORM Global (Corporate)</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Business Collection (Alumni Edition)</collection><collection>ProQuest Business Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ABI/INFORM Professional Advanced</collection><collection>ProQuest Biological Science Collection</collection><collection>ABI/INFORM Global</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Science Journals</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>One Business</collection><collection>ProQuest One Business (Alumni)</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 Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Applied microbiology and biotechnology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>AYUSO, Angel</au><au>CLARK, Desmond</au><au>GONZALEZ, Ignacio</au><au>SALAZAR, Oscar</au><au>ANDERSON, Annaliesa</au><au>GENILLOUD, Olga</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A novel actinomycete strain de-replication approach based on the diversity of polyketide synthase and nonribosomal peptide synthetase biosynthetic pathways</atitle><jtitle>Applied microbiology and biotechnology</jtitle><addtitle>Appl Microbiol Biotechnol</addtitle><date>2005-06-01</date><risdate>2005</risdate><volume>67</volume><issue>6</issue><spage>795</spage><epage>806</epage><pages>795-806</pages><issn>0175-7598</issn><eissn>1432-0614</eissn><coden>AMBIDG</coden><abstract>The actinomycetes traditionally represent one of the most important sources for the discovery of new metabolites with biological activity; and many of these are described as being produced by polyketide synthases (PKS) and nonribosomal peptide synthetases (NRPS). We present a strain characterization system based on the metabolic potential of microbial strains by targeting these biosynthetic genes. After an initial evaluation of the existing bias derived from the PCR detection in a well defined biosynthetic systems, we developed a new fingerprinting approach based on the restriction analysis of these PKS and NRPS amplified sequences. This method was applied to study the distribution of PKS and NRPS biosynthetic systems in a collection of wild-type actinomycetes isolated from tropical soil samples that were evaluated for the production of antimicrobial activities. We discuss the application of this tool as an alternative characterization approach for actinomycetes and we comment on the relationship observed between the presence of PKS-I, PKS-II and NRPS sequences and the antimicrobial activities observed in some of the microbial groups tested.</abstract><cop>Berlin</cop><pub>Springer</pub><pmid>15647936</pmid><doi>10.1007/s00253-004-1828-7</doi><tpages>12</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0175-7598 |
| ispartof | Applied microbiology and biotechnology, 2005-06, Vol.67 (6), p.795-806 |
| issn | 0175-7598 1432-0614 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_67951406 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Actinobacteria - genetics Actinobacteria - metabolism Anti-Bacterial Agents - biosynthesis Anti-Bacterial Agents - pharmacology Antifungal Agents - metabolism Antifungal Agents - pharmacology Bacteria - drug effects Biological and medical sciences Biology of microorganisms of confirmed or potential industrial interest Biotechnology Candida albicans - drug effects DNA Fingerprinting Fundamental and applied biological sciences. Psychology Genes, Bacterial Genetic Variation Metabolites Microbial Sensitivity Tests Microbiology Miscellaneous Mission oriented research Molecular Sequence Data Peptide Synthases - biosynthesis Peptide Synthases - genetics Peptides Polyketide Synthases - biosynthesis Polyketide Synthases - genetics Polymerase Chain Reaction Soil Microbiology Tropical Climate Tropical environments |
| title | A novel actinomycete strain de-replication approach based on the diversity of polyketide synthase and nonribosomal peptide synthetase biosynthetic pathways |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-24T20%3A45%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20novel%20actinomycete%20strain%20de-replication%20approach%20based%20on%20the%20diversity%20of%20polyketide%20synthase%20and%20nonribosomal%20peptide%20synthetase%20biosynthetic%20pathways&rft.jtitle=Applied%20microbiology%20and%20biotechnology&rft.au=AYUSO,%20Angel&rft.date=2005-06-01&rft.volume=67&rft.issue=6&rft.spage=795&rft.epage=806&rft.pages=795-806&rft.issn=0175-7598&rft.eissn=1432-0614&rft.coden=AMBIDG&rft_id=info:doi/10.1007/s00253-004-1828-7&rft_dat=%3Cproquest_cross%3E2087340011%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=620370976&rft_id=info:pmid/15647936&rfr_iscdi=true |