Synergistic interaction of two independent genetic loci causes extreme elevation of serum IgA in mice
Understanding the molecular regulation of immunoglobulin A (IgA) expression is important as it plays an essential role in the first-line defence through mucosal secretions. Using inbred mouse strains, we identified two independent and dominant acting genetic loci that synergistically cause a 40-fold...
Gespeichert in:
| Veröffentlicht in: | Genes and immunity 2004-07, Vol.5 (5), p.375-380 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 380 |
|---|---|
| container_issue | 5 |
| container_start_page | 375 |
| container_title | Genes and immunity |
| container_volume | 5 |
| creator | Schneider, B Hanke, P Jagla, W Wattler, S Nehls, M Grosse, J Schröder, A Laufs, J |
| description | Understanding the molecular regulation of immunoglobulin A (IgA) expression is important as it plays an essential role in the first-line defence through mucosal secretions. Using inbred mouse strains, we identified two independent and dominant acting genetic loci that synergistically cause a 40-fold upregulation in serum IgA levels when introduced into the murine strain C57Bl/6J (B6). The first locus on chromosome 12 appears to be mainly responsible for the natural four-fold higher IgA levels in C3HeB/FeJ (C3H) compared to B6 mice. A second independent, chemically induced mutation on chromosome 5 caused a two-fold elevation when transferred from C3H into B6 mice. Both loci in concert effect a 40-fold elevation against the B6 genetic background. We determined the chromosomal localization of the two loci simultaneously by a one-step mapping process. The chemically induced mutation was identified within the immunoglobulin joining chain (IgJ) gene on chromosome 5. The major serum IgA modifier between the C3H and B6 was located on chromosome 12. This modifier region was mapped to a 350 kb region containing several immunoglobulin heavy-chain genes and the Igα germline switch gene. We speculate that by interfering with both IgA expression and distribution, synergistic regulation of IgA is achieved. |
| doi_str_mv | 10.1038/sj.gene.6364105 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_journals_2641728711</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A182930137</galeid><sourcerecordid>A182930137</sourcerecordid><originalsourceid>FETCH-LOGICAL-c512t-900d0ecf9ab394d3af8ddd101ecdff4857c4a6e0394ad4709f63d588563fe9bc3</originalsourceid><addsrcrecordid>eNp1kd-LEzEQxxdRvPP02Scl6JMP20u6u8nmsRz-KBwInj6HNJksKd2kJln1_ntnac9S8AgkYebz_Q4zU1WvGV0w2vTXebsYIMCCN7xltHtSXbJW8LprBX06_zmv217Ii-pFzltKGWdcPq8uWMdEx1txWcHdfYA0-Fy8IT4USNoUHwOJjpTfEUMW9oBXKGSuNGO7aDwxesqQCfwpCUYgsINf-kGYIU0jWQ8rlJPRG3hZPXN6l-HV8b2qfnz6-P3mS3379fP6ZnVbm44tSy0ptRSMk3rTyNY22vXWWkYZGOtc23fCtJoDxaS22KJ0vLFd33e8cSA3prmq3h989yn-nCAXtY1TClhSLXFAYtkLxpB69yjFeklZS_nJatA7UD64WHA0o89GrVi_lA1ljUBq8R8KjwXsOwZwHuNngg9nAmQKznDAaWa1vvt2zl4fWJNizgmc2ic_6nSvGFXz-lXeqnkp6rh-VLw9djZtRrAn_rhvBOgByJgKA6RT6497vjlIgi5Tgn-eD_m_jZTEWw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>218901406</pqid></control><display><type>article</type><title>Synergistic interaction of two independent genetic loci causes extreme elevation of serum IgA in mice</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>SpringerLink Journals - AutoHoldings</source><creator>Schneider, B ; Hanke, P ; Jagla, W ; Wattler, S ; Nehls, M ; Grosse, J ; Schröder, A ; Laufs, J</creator><creatorcontrib>Schneider, B ; Hanke, P ; Jagla, W ; Wattler, S ; Nehls, M ; Grosse, J ; Schröder, A ; Laufs, J</creatorcontrib><description>Understanding the molecular regulation of immunoglobulin A (IgA) expression is important as it plays an essential role in the first-line defence through mucosal secretions. Using inbred mouse strains, we identified two independent and dominant acting genetic loci that synergistically cause a 40-fold upregulation in serum IgA levels when introduced into the murine strain C57Bl/6J (B6). The first locus on chromosome 12 appears to be mainly responsible for the natural four-fold higher IgA levels in C3HeB/FeJ (C3H) compared to B6 mice. A second independent, chemically induced mutation on chromosome 5 caused a two-fold elevation when transferred from C3H into B6 mice. Both loci in concert effect a 40-fold elevation against the B6 genetic background. We determined the chromosomal localization of the two loci simultaneously by a one-step mapping process. The chemically induced mutation was identified within the immunoglobulin joining chain (IgJ) gene on chromosome 5. The major serum IgA modifier between the C3H and B6 was located on chromosome 12. This modifier region was mapped to a 350 kb region containing several immunoglobulin heavy-chain genes and the Igα germline switch gene. We speculate that by interfering with both IgA expression and distribution, synergistic regulation of IgA is achieved.</description><identifier>ISSN: 1466-4879</identifier><identifier>EISSN: 1476-5470</identifier><identifier>DOI: 10.1038/sj.gene.6364105</identifier><identifier>PMID: 15175647</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Amino Acid Transport Systems, Neutral - genetics ; Animals ; Base Sequence ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Chromosome 12 ; Chromosome 5 ; Chromosome Mapping ; Chromosomes ; Chromosomes - genetics ; DNA Mutational Analysis ; Ethylnitrosourea - pharmacology ; full-paper ; Gene Expression ; Gene loci ; Gene mapping ; Genetic aspects ; Genetic regulation ; Health aspects ; Human Genetics ; Immunoglobulin A ; Immunoglobulin A - blood ; Immunoglobulin A - genetics ; Immunoglobulin J-Chains - genetics ; Immunoglobulins ; Immunology ; Inbreeding ; Localization ; Male ; Mice ; Mice, Inbred C3H ; Molecular Sequence Data ; Mucosa ; Mutagenesis - drug effects ; Mutagenesis - genetics ; Mutation ; Physiological aspects ; Point Mutation - genetics ; Quantitative Trait Loci ; Secretions ; Up-Regulation - genetics</subject><ispartof>Genes and immunity, 2004-07, Vol.5 (5), p.375-380</ispartof><rights>Springer Nature Limited 2004</rights><rights>COPYRIGHT 2004 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jul 2004</rights><rights>Nature Publishing Group 2004.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c512t-900d0ecf9ab394d3af8ddd101ecdff4857c4a6e0394ad4709f63d588563fe9bc3</citedby><cites>FETCH-LOGICAL-c512t-900d0ecf9ab394d3af8ddd101ecdff4857c4a6e0394ad4709f63d588563fe9bc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/sj.gene.6364105$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/sj.gene.6364105$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15175647$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schneider, B</creatorcontrib><creatorcontrib>Hanke, P</creatorcontrib><creatorcontrib>Jagla, W</creatorcontrib><creatorcontrib>Wattler, S</creatorcontrib><creatorcontrib>Nehls, M</creatorcontrib><creatorcontrib>Grosse, J</creatorcontrib><creatorcontrib>Schröder, A</creatorcontrib><creatorcontrib>Laufs, J</creatorcontrib><title>Synergistic interaction of two independent genetic loci causes extreme elevation of serum IgA in mice</title><title>Genes and immunity</title><addtitle>Genes Immun</addtitle><addtitle>Genes Immun</addtitle><description>Understanding the molecular regulation of immunoglobulin A (IgA) expression is important as it plays an essential role in the first-line defence through mucosal secretions. Using inbred mouse strains, we identified two independent and dominant acting genetic loci that synergistically cause a 40-fold upregulation in serum IgA levels when introduced into the murine strain C57Bl/6J (B6). The first locus on chromosome 12 appears to be mainly responsible for the natural four-fold higher IgA levels in C3HeB/FeJ (C3H) compared to B6 mice. A second independent, chemically induced mutation on chromosome 5 caused a two-fold elevation when transferred from C3H into B6 mice. Both loci in concert effect a 40-fold elevation against the B6 genetic background. We determined the chromosomal localization of the two loci simultaneously by a one-step mapping process. The chemically induced mutation was identified within the immunoglobulin joining chain (IgJ) gene on chromosome 5. The major serum IgA modifier between the C3H and B6 was located on chromosome 12. This modifier region was mapped to a 350 kb region containing several immunoglobulin heavy-chain genes and the Igα germline switch gene. We speculate that by interfering with both IgA expression and distribution, synergistic regulation of IgA is achieved.</description><subject>Amino Acid Transport Systems, Neutral - genetics</subject><subject>Animals</subject><subject>Base Sequence</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Chromosome 12</subject><subject>Chromosome 5</subject><subject>Chromosome Mapping</subject><subject>Chromosomes</subject><subject>Chromosomes - genetics</subject><subject>DNA Mutational Analysis</subject><subject>Ethylnitrosourea - pharmacology</subject><subject>full-paper</subject><subject>Gene Expression</subject><subject>Gene loci</subject><subject>Gene mapping</subject><subject>Genetic aspects</subject><subject>Genetic regulation</subject><subject>Health aspects</subject><subject>Human Genetics</subject><subject>Immunoglobulin A</subject><subject>Immunoglobulin A - blood</subject><subject>Immunoglobulin A - genetics</subject><subject>Immunoglobulin J-Chains - genetics</subject><subject>Immunoglobulins</subject><subject>Immunology</subject><subject>Inbreeding</subject><subject>Localization</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C3H</subject><subject>Molecular Sequence Data</subject><subject>Mucosa</subject><subject>Mutagenesis - drug effects</subject><subject>Mutagenesis - genetics</subject><subject>Mutation</subject><subject>Physiological aspects</subject><subject>Point Mutation - genetics</subject><subject>Quantitative Trait Loci</subject><subject>Secretions</subject><subject>Up-Regulation - genetics</subject><issn>1466-4879</issn><issn>1476-5470</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</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>eNp1kd-LEzEQxxdRvPP02Scl6JMP20u6u8nmsRz-KBwInj6HNJksKd2kJln1_ntnac9S8AgkYebz_Q4zU1WvGV0w2vTXebsYIMCCN7xltHtSXbJW8LprBX06_zmv217Ii-pFzltKGWdcPq8uWMdEx1txWcHdfYA0-Fy8IT4USNoUHwOJjpTfEUMW9oBXKGSuNGO7aDwxesqQCfwpCUYgsINf-kGYIU0jWQ8rlJPRG3hZPXN6l-HV8b2qfnz6-P3mS3379fP6ZnVbm44tSy0ptRSMk3rTyNY22vXWWkYZGOtc23fCtJoDxaS22KJ0vLFd33e8cSA3prmq3h989yn-nCAXtY1TClhSLXFAYtkLxpB69yjFeklZS_nJatA7UD64WHA0o89GrVi_lA1ljUBq8R8KjwXsOwZwHuNngg9nAmQKznDAaWa1vvt2zl4fWJNizgmc2ic_6nSvGFXz-lXeqnkp6rh-VLw9djZtRrAn_rhvBOgByJgKA6RT6497vjlIgi5Tgn-eD_m_jZTEWw</recordid><startdate>20040701</startdate><enddate>20040701</enddate><creator>Schneider, B</creator><creator>Hanke, P</creator><creator>Jagla, W</creator><creator>Wattler, S</creator><creator>Nehls, M</creator><creator>Grosse, J</creator><creator>Schröder, A</creator><creator>Laufs, J</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><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>ISR</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</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>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope></search><sort><creationdate>20040701</creationdate><title>Synergistic interaction of two independent genetic loci causes extreme elevation of serum IgA in mice</title><author>Schneider, B ; Hanke, P ; Jagla, W ; Wattler, S ; Nehls, M ; Grosse, J ; Schröder, A ; Laufs, J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c512t-900d0ecf9ab394d3af8ddd101ecdff4857c4a6e0394ad4709f63d588563fe9bc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Amino Acid Transport Systems, Neutral - genetics</topic><topic>Animals</topic><topic>Base Sequence</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Chromosome 12</topic><topic>Chromosome 5</topic><topic>Chromosome Mapping</topic><topic>Chromosomes</topic><topic>Chromosomes - genetics</topic><topic>DNA Mutational Analysis</topic><topic>Ethylnitrosourea - pharmacology</topic><topic>full-paper</topic><topic>Gene Expression</topic><topic>Gene loci</topic><topic>Gene mapping</topic><topic>Genetic aspects</topic><topic>Genetic regulation</topic><topic>Health aspects</topic><topic>Human Genetics</topic><topic>Immunoglobulin A</topic><topic>Immunoglobulin A - blood</topic><topic>Immunoglobulin A - genetics</topic><topic>Immunoglobulin J-Chains - genetics</topic><topic>Immunoglobulins</topic><topic>Immunology</topic><topic>Inbreeding</topic><topic>Localization</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C3H</topic><topic>Molecular Sequence Data</topic><topic>Mucosa</topic><topic>Mutagenesis - drug effects</topic><topic>Mutagenesis - genetics</topic><topic>Mutation</topic><topic>Physiological aspects</topic><topic>Point Mutation - genetics</topic><topic>Quantitative Trait Loci</topic><topic>Secretions</topic><topic>Up-Regulation - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schneider, B</creatorcontrib><creatorcontrib>Hanke, P</creatorcontrib><creatorcontrib>Jagla, W</creatorcontrib><creatorcontrib>Wattler, S</creatorcontrib><creatorcontrib>Nehls, M</creatorcontrib><creatorcontrib>Grosse, J</creatorcontrib><creatorcontrib>Schröder, A</creatorcontrib><creatorcontrib>Laufs, J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</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 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>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</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 & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</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>Genetics Abstracts</collection><jtitle>Genes and immunity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schneider, B</au><au>Hanke, P</au><au>Jagla, W</au><au>Wattler, S</au><au>Nehls, M</au><au>Grosse, J</au><au>Schröder, A</au><au>Laufs, J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synergistic interaction of two independent genetic loci causes extreme elevation of serum IgA in mice</atitle><jtitle>Genes and immunity</jtitle><stitle>Genes Immun</stitle><addtitle>Genes Immun</addtitle><date>2004-07-01</date><risdate>2004</risdate><volume>5</volume><issue>5</issue><spage>375</spage><epage>380</epage><pages>375-380</pages><issn>1466-4879</issn><eissn>1476-5470</eissn><abstract>Understanding the molecular regulation of immunoglobulin A (IgA) expression is important as it plays an essential role in the first-line defence through mucosal secretions. Using inbred mouse strains, we identified two independent and dominant acting genetic loci that synergistically cause a 40-fold upregulation in serum IgA levels when introduced into the murine strain C57Bl/6J (B6). The first locus on chromosome 12 appears to be mainly responsible for the natural four-fold higher IgA levels in C3HeB/FeJ (C3H) compared to B6 mice. A second independent, chemically induced mutation on chromosome 5 caused a two-fold elevation when transferred from C3H into B6 mice. Both loci in concert effect a 40-fold elevation against the B6 genetic background. We determined the chromosomal localization of the two loci simultaneously by a one-step mapping process. The chemically induced mutation was identified within the immunoglobulin joining chain (IgJ) gene on chromosome 5. The major serum IgA modifier between the C3H and B6 was located on chromosome 12. This modifier region was mapped to a 350 kb region containing several immunoglobulin heavy-chain genes and the Igα germline switch gene. We speculate that by interfering with both IgA expression and distribution, synergistic regulation of IgA is achieved.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>15175647</pmid><doi>10.1038/sj.gene.6364105</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1466-4879 |
| ispartof | Genes and immunity, 2004-07, Vol.5 (5), p.375-380 |
| issn | 1466-4879 1476-5470 |
| language | eng |
| recordid | cdi_proquest_journals_2641728711 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; SpringerLink Journals - AutoHoldings |
| subjects | Amino Acid Transport Systems, Neutral - genetics Animals Base Sequence Biomedical and Life Sciences Biomedicine Cancer Research Chromosome 12 Chromosome 5 Chromosome Mapping Chromosomes Chromosomes - genetics DNA Mutational Analysis Ethylnitrosourea - pharmacology full-paper Gene Expression Gene loci Gene mapping Genetic aspects Genetic regulation Health aspects Human Genetics Immunoglobulin A Immunoglobulin A - blood Immunoglobulin A - genetics Immunoglobulin J-Chains - genetics Immunoglobulins Immunology Inbreeding Localization Male Mice Mice, Inbred C3H Molecular Sequence Data Mucosa Mutagenesis - drug effects Mutagenesis - genetics Mutation Physiological aspects Point Mutation - genetics Quantitative Trait Loci Secretions Up-Regulation - genetics |
| title | Synergistic interaction of two independent genetic loci causes extreme elevation of serum IgA in mice |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-17T11%3A43%3A36IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Synergistic%20interaction%20of%20two%20independent%20genetic%20loci%20causes%20extreme%20elevation%20of%20serum%20IgA%20in%20mice&rft.jtitle=Genes%20and%20immunity&rft.au=Schneider,%20B&rft.date=2004-07-01&rft.volume=5&rft.issue=5&rft.spage=375&rft.epage=380&rft.pages=375-380&rft.issn=1466-4879&rft.eissn=1476-5470&rft_id=info:doi/10.1038/sj.gene.6364105&rft_dat=%3Cgale_proqu%3EA182930137%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=218901406&rft_id=info:pmid/15175647&rft_galeid=A182930137&rfr_iscdi=true |