Upregulation of rat Ccnd1 gene by exendin-4 in pancreatic beta cell line INS-1 : interaction of early growth response-1 with cis-regulatory element
The aim of this study was to investigate the effect of exendin-4 on the expression of cyclin D1 gene (Ccnd1), which is critical in regulating the progression of the cell cycle in INS-1 cells. INS-1 cells were stimulated with exendin-4 (10 nmol/l). Transient transfection and luciferase reporter assay...
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| Veröffentlicht in: | Diabetologia 2006-05, Vol.49 (5), p.969-979 |
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| creator | KANG, J.-H KIM, M.-J KO, S.-H JEONG, I.-K KOH, K.-H RHIE, D.-J YOON, S.-H HAHN, S.-J KIM, M.-S JO, Y.-H |
| description | The aim of this study was to investigate the effect of exendin-4 on the expression of cyclin D1 gene (Ccnd1), which is critical in regulating the progression of the cell cycle in INS-1 cells.
INS-1 cells were stimulated with exendin-4 (10 nmol/l). Transient transfection and luciferase reporter assays were performed to measure promoter activities of rat Ccnd1. Electrophoretic mobility shift and chromatin immunoprecipitation assays were used to examine the binding of transcription factors to sites responsive to exendin-4 in vitro and in vivo, respectively.
Exendin-4 increased both Ccnd1 mRNA and its protein levels in a time-dependent manner. The region from -174 to +130 of the promoter was found to contain cis-regulatory elements responsible for exendin-4-mediated gene induction. Early growth response-1 (EGR1) protein was bound to the region from -153 to -134, which includes the putative EGR1 binding site (5'-CACCCCCGC-3'). Moreover, exendin-4 recruited EGR1 protein to the promoter in vivo.
These findings suggest that exendin-4 activates Ccnd1 transcription through induction of EGR1 binding to a cis-regulatory element between -153 and -134 on the rat Ccnd1 promoter. These results provide an important indication that exendin-4 is a growth factor regulating beta cell proliferation. |
| doi_str_mv | 10.1007/s00125-006-0179-6 |
| format | Article |
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INS-1 cells were stimulated with exendin-4 (10 nmol/l). Transient transfection and luciferase reporter assays were performed to measure promoter activities of rat Ccnd1. Electrophoretic mobility shift and chromatin immunoprecipitation assays were used to examine the binding of transcription factors to sites responsive to exendin-4 in vitro and in vivo, respectively.
Exendin-4 increased both Ccnd1 mRNA and its protein levels in a time-dependent manner. The region from -174 to +130 of the promoter was found to contain cis-regulatory elements responsible for exendin-4-mediated gene induction. Early growth response-1 (EGR1) protein was bound to the region from -153 to -134, which includes the putative EGR1 binding site (5'-CACCCCCGC-3'). Moreover, exendin-4 recruited EGR1 protein to the promoter in vivo.
These findings suggest that exendin-4 activates Ccnd1 transcription through induction of EGR1 binding to a cis-regulatory element between -153 and -134 on the rat Ccnd1 promoter. These results provide an important indication that exendin-4 is a growth factor regulating beta cell proliferation.</description><identifier>ISSN: 0012-186X</identifier><identifier>EISSN: 1432-0428</identifier><identifier>DOI: 10.1007/s00125-006-0179-6</identifier><identifier>PMID: 16547599</identifier><language>eng</language><publisher>Berlin: Springer</publisher><subject>Animals ; Base Sequence ; Binding sites ; Biological and medical sciences ; Cell cycle ; Cell Division ; Cell growth ; Cell Line ; Cyclin D ; Cyclin-dependent kinases ; Cyclins - genetics ; Diabetes. Impaired glucose tolerance ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Gene Expression Regulation ; Genes ; Humans ; Insulinoma ; Internal medicine ; Islets of Langerhans - cytology ; Islets of Langerhans - physiology ; Kinases ; Medical sciences ; Medicine ; Molecular Sequence Data ; Pancreatic Neoplasms ; Peptides ; Peptides - physiology ; Promoter Regions, Genetic ; Proteins ; Rats ; Rats, Sprague-Dawley ; Regulatory Sequences, Nucleic Acid ; RNA, Messenger - genetics ; Sequence Alignment ; Sequence Homology, Nucleic Acid ; Transcription factors ; Transcription, Genetic ; Transcriptional Activation ; Venoms</subject><ispartof>Diabetologia, 2006-05, Vol.49 (5), p.969-979</ispartof><rights>2006 INIST-CNRS</rights><rights>Springer-Verlag 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c399t-542d7d1029322d5fedccc7b96f8733775c70d96488a57eda565cef1466e975bc3</citedby><cites>FETCH-LOGICAL-c399t-542d7d1029322d5fedccc7b96f8733775c70d96488a57eda565cef1466e975bc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17701286$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16547599$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>KANG, J.-H</creatorcontrib><creatorcontrib>KIM, M.-J</creatorcontrib><creatorcontrib>KO, S.-H</creatorcontrib><creatorcontrib>JEONG, I.-K</creatorcontrib><creatorcontrib>KOH, K.-H</creatorcontrib><creatorcontrib>RHIE, D.-J</creatorcontrib><creatorcontrib>YOON, S.-H</creatorcontrib><creatorcontrib>HAHN, S.-J</creatorcontrib><creatorcontrib>KIM, M.-S</creatorcontrib><creatorcontrib>JO, Y.-H</creatorcontrib><title>Upregulation of rat Ccnd1 gene by exendin-4 in pancreatic beta cell line INS-1 : interaction of early growth response-1 with cis-regulatory element</title><title>Diabetologia</title><addtitle>Diabetologia</addtitle><description>The aim of this study was to investigate the effect of exendin-4 on the expression of cyclin D1 gene (Ccnd1), which is critical in regulating the progression of the cell cycle in INS-1 cells.
INS-1 cells were stimulated with exendin-4 (10 nmol/l). Transient transfection and luciferase reporter assays were performed to measure promoter activities of rat Ccnd1. Electrophoretic mobility shift and chromatin immunoprecipitation assays were used to examine the binding of transcription factors to sites responsive to exendin-4 in vitro and in vivo, respectively.
Exendin-4 increased both Ccnd1 mRNA and its protein levels in a time-dependent manner. The region from -174 to +130 of the promoter was found to contain cis-regulatory elements responsible for exendin-4-mediated gene induction. Early growth response-1 (EGR1) protein was bound to the region from -153 to -134, which includes the putative EGR1 binding site (5'-CACCCCCGC-3'). Moreover, exendin-4 recruited EGR1 protein to the promoter in vivo.
These findings suggest that exendin-4 activates Ccnd1 transcription through induction of EGR1 binding to a cis-regulatory element between -153 and -134 on the rat Ccnd1 promoter. These results provide an important indication that exendin-4 is a growth factor regulating beta cell proliferation.</description><subject>Animals</subject><subject>Base Sequence</subject><subject>Binding sites</subject><subject>Biological and medical sciences</subject><subject>Cell cycle</subject><subject>Cell Division</subject><subject>Cell growth</subject><subject>Cell Line</subject><subject>Cyclin D</subject><subject>Cyclin-dependent kinases</subject><subject>Cyclins - genetics</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>Gene Expression Regulation</subject><subject>Genes</subject><subject>Humans</subject><subject>Insulinoma</subject><subject>Internal medicine</subject><subject>Islets of Langerhans - cytology</subject><subject>Islets of Langerhans - physiology</subject><subject>Kinases</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Molecular Sequence Data</subject><subject>Pancreatic Neoplasms</subject><subject>Peptides</subject><subject>Peptides - physiology</subject><subject>Promoter Regions, Genetic</subject><subject>Proteins</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Regulatory Sequences, Nucleic Acid</subject><subject>RNA, Messenger - genetics</subject><subject>Sequence Alignment</subject><subject>Sequence Homology, Nucleic Acid</subject><subject>Transcription factors</subject><subject>Transcription, Genetic</subject><subject>Transcriptional Activation</subject><subject>Venoms</subject><issn>0012-186X</issn><issn>1432-0428</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNpFkc1KJDEUhYPMoO3PA7iRMDDLOEnlr-JOmhkVxFmMgruQSm61JdWpMqnG6eeYF540XeLqcrnfPQfOQeic0UtGqf6RKWWVJJQqQpk2RB2gBRO8IlRU9Re02J0Jq9XzETrO-ZVSyqVQh-iIKSm0NGaB_j2NCVab3k3dEPHQ4uQmvPQxMLyCCLjZYvgLMXSRCNxFPLroExTa4wYmhz30Pe67Qt49_CEMXxVoguT8hx641G_xKg3v0wtOkMchZijge1d232Uy2w-pOPWwhjidoq-t6zOczfMEPf36-bi8Jfe_b-6W1_fEc2MmIkUVdGC0MryqgmwheO91Y1Rba861ll7TYJSoayc1BCeV9NAyoRQYLRvPT9C3ve6YhrcN5Mm-DpsUi6WtGK-FVIYWiO0hn4acE7R2TN3apa1l1O5asPsWbGnB7lqwqvxczMKbZg3h82OOvQDfZ8Bl7_o2lVS7_MlpXSRrxf8DiK2P5g</recordid><startdate>20060501</startdate><enddate>20060501</enddate><creator>KANG, J.-H</creator><creator>KIM, M.-J</creator><creator>KO, S.-H</creator><creator>JEONG, I.-K</creator><creator>KOH, K.-H</creator><creator>RHIE, D.-J</creator><creator>YOON, S.-H</creator><creator>HAHN, S.-J</creator><creator>KIM, M.-S</creator><creator>JO, Y.-H</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>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20060501</creationdate><title>Upregulation of rat Ccnd1 gene by exendin-4 in pancreatic beta cell line INS-1 : interaction of early growth response-1 with cis-regulatory element</title><author>KANG, J.-H ; KIM, M.-J ; KO, S.-H ; JEONG, I.-K ; KOH, K.-H ; RHIE, D.-J ; YOON, S.-H ; HAHN, S.-J ; KIM, M.-S ; JO, Y.-H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c399t-542d7d1029322d5fedccc7b96f8733775c70d96488a57eda565cef1466e975bc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Base Sequence</topic><topic>Binding sites</topic><topic>Biological and medical sciences</topic><topic>Cell cycle</topic><topic>Cell Division</topic><topic>Cell growth</topic><topic>Cell Line</topic><topic>Cyclin D</topic><topic>Cyclin-dependent kinases</topic><topic>Cyclins - genetics</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Etiopathogenesis. Screening. Investigations. Target tissue resistance</topic><topic>Gene Expression Regulation</topic><topic>Genes</topic><topic>Humans</topic><topic>Insulinoma</topic><topic>Internal medicine</topic><topic>Islets of Langerhans - cytology</topic><topic>Islets of Langerhans - physiology</topic><topic>Kinases</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Molecular Sequence Data</topic><topic>Pancreatic Neoplasms</topic><topic>Peptides</topic><topic>Peptides - physiology</topic><topic>Promoter Regions, Genetic</topic><topic>Proteins</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Regulatory Sequences, Nucleic Acid</topic><topic>RNA, Messenger - genetics</topic><topic>Sequence Alignment</topic><topic>Sequence Homology, Nucleic Acid</topic><topic>Transcription factors</topic><topic>Transcription, Genetic</topic><topic>Transcriptional Activation</topic><topic>Venoms</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>KANG, J.-H</creatorcontrib><creatorcontrib>KIM, M.-J</creatorcontrib><creatorcontrib>KO, S.-H</creatorcontrib><creatorcontrib>JEONG, I.-K</creatorcontrib><creatorcontrib>KOH, K.-H</creatorcontrib><creatorcontrib>RHIE, D.-J</creatorcontrib><creatorcontrib>YOON, S.-H</creatorcontrib><creatorcontrib>HAHN, S.-J</creatorcontrib><creatorcontrib>KIM, M.-S</creatorcontrib><creatorcontrib>JO, Y.-H</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>Immunology Abstracts</collection><collection>Health & 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>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</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical 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><jtitle>Diabetologia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>KANG, J.-H</au><au>KIM, M.-J</au><au>KO, S.-H</au><au>JEONG, I.-K</au><au>KOH, K.-H</au><au>RHIE, D.-J</au><au>YOON, S.-H</au><au>HAHN, S.-J</au><au>KIM, M.-S</au><au>JO, Y.-H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Upregulation of rat Ccnd1 gene by exendin-4 in pancreatic beta cell line INS-1 : interaction of early growth response-1 with cis-regulatory element</atitle><jtitle>Diabetologia</jtitle><addtitle>Diabetologia</addtitle><date>2006-05-01</date><risdate>2006</risdate><volume>49</volume><issue>5</issue><spage>969</spage><epage>979</epage><pages>969-979</pages><issn>0012-186X</issn><eissn>1432-0428</eissn><abstract>The aim of this study was to investigate the effect of exendin-4 on the expression of cyclin D1 gene (Ccnd1), which is critical in regulating the progression of the cell cycle in INS-1 cells.
INS-1 cells were stimulated with exendin-4 (10 nmol/l). Transient transfection and luciferase reporter assays were performed to measure promoter activities of rat Ccnd1. Electrophoretic mobility shift and chromatin immunoprecipitation assays were used to examine the binding of transcription factors to sites responsive to exendin-4 in vitro and in vivo, respectively.
Exendin-4 increased both Ccnd1 mRNA and its protein levels in a time-dependent manner. The region from -174 to +130 of the promoter was found to contain cis-regulatory elements responsible for exendin-4-mediated gene induction. Early growth response-1 (EGR1) protein was bound to the region from -153 to -134, which includes the putative EGR1 binding site (5'-CACCCCCGC-3'). Moreover, exendin-4 recruited EGR1 protein to the promoter in vivo.
These findings suggest that exendin-4 activates Ccnd1 transcription through induction of EGR1 binding to a cis-regulatory element between -153 and -134 on the rat Ccnd1 promoter. These results provide an important indication that exendin-4 is a growth factor regulating beta cell proliferation.</abstract><cop>Berlin</cop><pub>Springer</pub><pmid>16547599</pmid><doi>10.1007/s00125-006-0179-6</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Base Sequence Binding sites Biological and medical sciences Cell cycle Cell Division Cell growth Cell Line Cyclin D Cyclin-dependent kinases Cyclins - genetics Diabetes. Impaired glucose tolerance Endocrine pancreas. Apud cells (diseases) Endocrinopathies Etiopathogenesis. Screening. Investigations. Target tissue resistance Gene Expression Regulation Genes Humans Insulinoma Internal medicine Islets of Langerhans - cytology Islets of Langerhans - physiology Kinases Medical sciences Medicine Molecular Sequence Data Pancreatic Neoplasms Peptides Peptides - physiology Promoter Regions, Genetic Proteins Rats Rats, Sprague-Dawley Regulatory Sequences, Nucleic Acid RNA, Messenger - genetics Sequence Alignment Sequence Homology, Nucleic Acid Transcription factors Transcription, Genetic Transcriptional Activation Venoms |
| title | Upregulation of rat Ccnd1 gene by exendin-4 in pancreatic beta cell line INS-1 : interaction of early growth response-1 with cis-regulatory element |
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