Loading…
Perceptual variation in umami taste and polymorphisms in TAS1R taste receptor genes
The TAS1R1 and TAS1R3 G protein-coupled receptors are believed to function in combination as a heteromeric glutamate taste receptor in humans. We hypothesized that variations in the umami perception of glutamate would correlate with variations in the sequence of these 2 genes, if they contribute dir...
Saved in:
Published in: | The American journal of clinical nutrition 2009-09, Vol.90 (3), p.770S-779S |
---|---|
Main Authors: | , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
cited_by | cdi_FETCH-LOGICAL-c462t-f515a7bdf3cd9f308e8f761c79ce322d0725a1653c739f7c0b1c88d68a19d7b73 |
---|---|
cites | cdi_FETCH-LOGICAL-c462t-f515a7bdf3cd9f308e8f761c79ce322d0725a1653c739f7c0b1c88d68a19d7b73 |
container_end_page | 779S |
container_issue | 3 |
container_start_page | 770S |
container_title | The American journal of clinical nutrition |
container_volume | 90 |
creator | CHEN, Qing-Ying ALARCON, Suzanne THARP, Anilet AHMED, Osama M ESTRELLA, Nelsa L GREENE, Tiffani A RUCKER, Joseph BRESLIN, Paul As |
description | The TAS1R1 and TAS1R3 G protein-coupled receptors are believed to function in combination as a heteromeric glutamate taste receptor in humans.
We hypothesized that variations in the umami perception of glutamate would correlate with variations in the sequence of these 2 genes, if they contribute directly to umami taste.
In this study, we first characterized the general sensitivity to glutamate in a sample population of 242 subjects. We performed these experiments by sequencing the coding regions of the genomic TAS1R1 and TAS1R3 genes in a separate set of 87 individuals who were tested repeatedly with monopotassium glutamate (MPG) solutions. Last, we tested the role of the candidate umami taste receptor hTAS1R1-hTAS1R3 in a functional expression assay.
A subset of subjects displays extremes of sensitivity, and a battery of different psychophysical tests validated this observation. Statistical analysis showed that the rare T allele of single nucleotide polymorphism (SNP) R757C in TAS1R3 led to a doubling of umami ratings of 25 mmol MPG/L. Other suggestive SNPs of TAS1R3 include the A allele of A5T and the A allele of R247H, which both resulted in an approximate doubling of umami ratings of 200 mmol MPG/L. We confirmed the potential role of the human TAS1R1-TAS1R3 heteromer receptor in umami taste by recording responses, specifically to l-glutamate and inosine 5'-monophosphate (IMP) mixtures in a heterologous expression assay in HEK (human embryonic kidney) T cells.
There is a reliable and valid variation in human umami taste of l-glutamate. Variations in perception of umami taste correlated with variations in the human TAS1R3 gene. The putative human taste receptor TAS1R1-TAS1R3 responds specifically to l-glutamate mixed with the ribonucleotide IMP. Thus, this receptor likely contributes to human umami taste perception. |
doi_str_mv | 10.3945/ajcn.2009.27462n |
format | article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_67594465</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1847243551</sourcerecordid><originalsourceid>FETCH-LOGICAL-c462t-f515a7bdf3cd9f308e8f761c79ce322d0725a1653c739f7c0b1c88d68a19d7b73</originalsourceid><addsrcrecordid>eNpdkM1LwzAYxoMobk7vnqQIeuvMR9skxzH8gqHi5jmkaaIdbVqTVth_b-qKgqf38nsenvcHwDmCc8KT9EZulZ1jCPkc0yTD9gBMEScsJhjSQzCFEOKYoyydgBPvtxAinLDsGEwQTxmFLJ2C9Yt2SrddL6voS7pSdmVjo9JGfS3rMuqk73QkbRG1TbWrG9d-lL72A7BZrNHrCDg9dDQuetdW-1NwZGTl9dl4Z-Dt7nazfIhXz_ePy8UqVmFrF5sUpZLmhSGq4IZAppmhGVKUK00wLiDFqQzjiaKEG6pgjhRjRcYk4gXNKZmB631v65rPXvtO1KVXuqqk1U3vRUZTniShYAYu_4Hbpnc2bBOYBGEwyVCA4B5SrvHeaSNaV9bS7QSCYrAtBttisC1-bD-FyMXY2-e1Lv4Co94AXI2A9EpWxkmrSv_LYcQzHt4k3x5LiDY</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>231930461</pqid></control><display><type>article</type><title>Perceptual variation in umami taste and polymorphisms in TAS1R taste receptor genes</title><source>ScienceDirect (Online service)</source><creator>CHEN, Qing-Ying ; ALARCON, Suzanne ; THARP, Anilet ; AHMED, Osama M ; ESTRELLA, Nelsa L ; GREENE, Tiffani A ; RUCKER, Joseph ; BRESLIN, Paul As</creator><creatorcontrib>CHEN, Qing-Ying ; ALARCON, Suzanne ; THARP, Anilet ; AHMED, Osama M ; ESTRELLA, Nelsa L ; GREENE, Tiffani A ; RUCKER, Joseph ; BRESLIN, Paul As</creatorcontrib><description>The TAS1R1 and TAS1R3 G protein-coupled receptors are believed to function in combination as a heteromeric glutamate taste receptor in humans.
We hypothesized that variations in the umami perception of glutamate would correlate with variations in the sequence of these 2 genes, if they contribute directly to umami taste.
In this study, we first characterized the general sensitivity to glutamate in a sample population of 242 subjects. We performed these experiments by sequencing the coding regions of the genomic TAS1R1 and TAS1R3 genes in a separate set of 87 individuals who were tested repeatedly with monopotassium glutamate (MPG) solutions. Last, we tested the role of the candidate umami taste receptor hTAS1R1-hTAS1R3 in a functional expression assay.
A subset of subjects displays extremes of sensitivity, and a battery of different psychophysical tests validated this observation. Statistical analysis showed that the rare T allele of single nucleotide polymorphism (SNP) R757C in TAS1R3 led to a doubling of umami ratings of 25 mmol MPG/L. Other suggestive SNPs of TAS1R3 include the A allele of A5T and the A allele of R247H, which both resulted in an approximate doubling of umami ratings of 200 mmol MPG/L. We confirmed the potential role of the human TAS1R1-TAS1R3 heteromer receptor in umami taste by recording responses, specifically to l-glutamate and inosine 5'-monophosphate (IMP) mixtures in a heterologous expression assay in HEK (human embryonic kidney) T cells.
There is a reliable and valid variation in human umami taste of l-glutamate. Variations in perception of umami taste correlated with variations in the human TAS1R3 gene. The putative human taste receptor TAS1R1-TAS1R3 responds specifically to l-glutamate mixed with the ribonucleotide IMP. Thus, this receptor likely contributes to human umami taste perception.</description><identifier>ISSN: 0002-9165</identifier><identifier>EISSN: 1938-3207</identifier><identifier>DOI: 10.3945/ajcn.2009.27462n</identifier><identifier>PMID: 19587085</identifier><identifier>CODEN: AJCNAC</identifier><language>eng</language><publisher>Bethesda, MD: American Society for Nutrition</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alleles ; Biological and medical sciences ; Feeding. Feeding behavior ; Female ; Fundamental and applied biological sciences. Psychology ; Genes ; Genetic Variation ; Genomics ; Glutamic Acid ; Humans ; Inosine Monophosphate ; Male ; Middle Aged ; Polymorphism ; Polymorphism, Single Nucleotide ; Receptors, G-Protein-Coupled - genetics ; Receptors, G-Protein-Coupled - metabolism ; Receptors, G-Protein-Coupled - physiology ; Receptors, Glutamate - genetics ; Receptors, Glutamate - physiology ; Sensory perception ; Studies ; T cell receptors ; T-Lymphocytes - metabolism ; Taste ; Taste - genetics ; Taste - physiology ; Taste Perception - genetics ; Taste Perception - physiology ; Taste Threshold - genetics ; Taste Threshold - physiology ; Vertebrates: anatomy and physiology, studies on body, several organs or systems ; Young Adult</subject><ispartof>The American journal of clinical nutrition, 2009-09, Vol.90 (3), p.770S-779S</ispartof><rights>2009 INIST-CNRS</rights><rights>Copyright American Society for Clinical Nutrition, Inc. Sep 1, 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c462t-f515a7bdf3cd9f308e8f761c79ce322d0725a1653c739f7c0b1c88d68a19d7b73</citedby><cites>FETCH-LOGICAL-c462t-f515a7bdf3cd9f308e8f761c79ce322d0725a1653c739f7c0b1c88d68a19d7b73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>309,310,314,780,784,789,790,23930,23931,25140,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21969072$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19587085$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>CHEN, Qing-Ying</creatorcontrib><creatorcontrib>ALARCON, Suzanne</creatorcontrib><creatorcontrib>THARP, Anilet</creatorcontrib><creatorcontrib>AHMED, Osama M</creatorcontrib><creatorcontrib>ESTRELLA, Nelsa L</creatorcontrib><creatorcontrib>GREENE, Tiffani A</creatorcontrib><creatorcontrib>RUCKER, Joseph</creatorcontrib><creatorcontrib>BRESLIN, Paul As</creatorcontrib><title>Perceptual variation in umami taste and polymorphisms in TAS1R taste receptor genes</title><title>The American journal of clinical nutrition</title><addtitle>Am J Clin Nutr</addtitle><description>The TAS1R1 and TAS1R3 G protein-coupled receptors are believed to function in combination as a heteromeric glutamate taste receptor in humans.
We hypothesized that variations in the umami perception of glutamate would correlate with variations in the sequence of these 2 genes, if they contribute directly to umami taste.
In this study, we first characterized the general sensitivity to glutamate in a sample population of 242 subjects. We performed these experiments by sequencing the coding regions of the genomic TAS1R1 and TAS1R3 genes in a separate set of 87 individuals who were tested repeatedly with monopotassium glutamate (MPG) solutions. Last, we tested the role of the candidate umami taste receptor hTAS1R1-hTAS1R3 in a functional expression assay.
A subset of subjects displays extremes of sensitivity, and a battery of different psychophysical tests validated this observation. Statistical analysis showed that the rare T allele of single nucleotide polymorphism (SNP) R757C in TAS1R3 led to a doubling of umami ratings of 25 mmol MPG/L. Other suggestive SNPs of TAS1R3 include the A allele of A5T and the A allele of R247H, which both resulted in an approximate doubling of umami ratings of 200 mmol MPG/L. We confirmed the potential role of the human TAS1R1-TAS1R3 heteromer receptor in umami taste by recording responses, specifically to l-glutamate and inosine 5'-monophosphate (IMP) mixtures in a heterologous expression assay in HEK (human embryonic kidney) T cells.
There is a reliable and valid variation in human umami taste of l-glutamate. Variations in perception of umami taste correlated with variations in the human TAS1R3 gene. The putative human taste receptor TAS1R1-TAS1R3 responds specifically to l-glutamate mixed with the ribonucleotide IMP. Thus, this receptor likely contributes to human umami taste perception.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alleles</subject><subject>Biological and medical sciences</subject><subject>Feeding. Feeding behavior</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genes</subject><subject>Genetic Variation</subject><subject>Genomics</subject><subject>Glutamic Acid</subject><subject>Humans</subject><subject>Inosine Monophosphate</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Polymorphism</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Receptors, G-Protein-Coupled - genetics</subject><subject>Receptors, G-Protein-Coupled - metabolism</subject><subject>Receptors, G-Protein-Coupled - physiology</subject><subject>Receptors, Glutamate - genetics</subject><subject>Receptors, Glutamate - physiology</subject><subject>Sensory perception</subject><subject>Studies</subject><subject>T cell receptors</subject><subject>T-Lymphocytes - metabolism</subject><subject>Taste</subject><subject>Taste - genetics</subject><subject>Taste - physiology</subject><subject>Taste Perception - genetics</subject><subject>Taste Perception - physiology</subject><subject>Taste Threshold - genetics</subject><subject>Taste Threshold - physiology</subject><subject>Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><subject>Young Adult</subject><issn>0002-9165</issn><issn>1938-3207</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><recordid>eNpdkM1LwzAYxoMobk7vnqQIeuvMR9skxzH8gqHi5jmkaaIdbVqTVth_b-qKgqf38nsenvcHwDmCc8KT9EZulZ1jCPkc0yTD9gBMEScsJhjSQzCFEOKYoyydgBPvtxAinLDsGEwQTxmFLJ2C9Yt2SrddL6voS7pSdmVjo9JGfS3rMuqk73QkbRG1TbWrG9d-lL72A7BZrNHrCDg9dDQuetdW-1NwZGTl9dl4Z-Dt7nazfIhXz_ePy8UqVmFrF5sUpZLmhSGq4IZAppmhGVKUK00wLiDFqQzjiaKEG6pgjhRjRcYk4gXNKZmB631v65rPXvtO1KVXuqqk1U3vRUZTniShYAYu_4Hbpnc2bBOYBGEwyVCA4B5SrvHeaSNaV9bS7QSCYrAtBttisC1-bD-FyMXY2-e1Lv4Co94AXI2A9EpWxkmrSv_LYcQzHt4k3x5LiDY</recordid><startdate>20090901</startdate><enddate>20090901</enddate><creator>CHEN, Qing-Ying</creator><creator>ALARCON, Suzanne</creator><creator>THARP, Anilet</creator><creator>AHMED, Osama M</creator><creator>ESTRELLA, Nelsa L</creator><creator>GREENE, Tiffani A</creator><creator>RUCKER, Joseph</creator><creator>BRESLIN, Paul As</creator><general>American Society for Nutrition</general><general>American Society for Clinical Nutrition, Inc</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>7QP</scope><scope>7T7</scope><scope>7TS</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20090901</creationdate><title>Perceptual variation in umami taste and polymorphisms in TAS1R taste receptor genes</title><author>CHEN, Qing-Ying ; ALARCON, Suzanne ; THARP, Anilet ; AHMED, Osama M ; ESTRELLA, Nelsa L ; GREENE, Tiffani A ; RUCKER, Joseph ; BRESLIN, Paul As</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c462t-f515a7bdf3cd9f308e8f761c79ce322d0725a1653c739f7c0b1c88d68a19d7b73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alleles</topic><topic>Biological and medical sciences</topic><topic>Feeding. Feeding behavior</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genes</topic><topic>Genetic Variation</topic><topic>Genomics</topic><topic>Glutamic Acid</topic><topic>Humans</topic><topic>Inosine Monophosphate</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Polymorphism</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Receptors, G-Protein-Coupled - genetics</topic><topic>Receptors, G-Protein-Coupled - metabolism</topic><topic>Receptors, G-Protein-Coupled - physiology</topic><topic>Receptors, Glutamate - genetics</topic><topic>Receptors, Glutamate - physiology</topic><topic>Sensory perception</topic><topic>Studies</topic><topic>T cell receptors</topic><topic>T-Lymphocytes - metabolism</topic><topic>Taste</topic><topic>Taste - genetics</topic><topic>Taste - physiology</topic><topic>Taste Perception - genetics</topic><topic>Taste Perception - physiology</topic><topic>Taste Threshold - genetics</topic><topic>Taste Threshold - physiology</topic><topic>Vertebrates: anatomy and physiology, studies on body, several organs or systems</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>CHEN, Qing-Ying</creatorcontrib><creatorcontrib>ALARCON, Suzanne</creatorcontrib><creatorcontrib>THARP, Anilet</creatorcontrib><creatorcontrib>AHMED, Osama M</creatorcontrib><creatorcontrib>ESTRELLA, Nelsa L</creatorcontrib><creatorcontrib>GREENE, Tiffani A</creatorcontrib><creatorcontrib>RUCKER, Joseph</creatorcontrib><creatorcontrib>BRESLIN, Paul As</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>Calcium & Calcified Tissue Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Physical Education Index</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The American journal of clinical nutrition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>CHEN, Qing-Ying</au><au>ALARCON, Suzanne</au><au>THARP, Anilet</au><au>AHMED, Osama M</au><au>ESTRELLA, Nelsa L</au><au>GREENE, Tiffani A</au><au>RUCKER, Joseph</au><au>BRESLIN, Paul As</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Perceptual variation in umami taste and polymorphisms in TAS1R taste receptor genes</atitle><jtitle>The American journal of clinical nutrition</jtitle><addtitle>Am J Clin Nutr</addtitle><date>2009-09-01</date><risdate>2009</risdate><volume>90</volume><issue>3</issue><spage>770S</spage><epage>779S</epage><pages>770S-779S</pages><issn>0002-9165</issn><eissn>1938-3207</eissn><coden>AJCNAC</coden><abstract>The TAS1R1 and TAS1R3 G protein-coupled receptors are believed to function in combination as a heteromeric glutamate taste receptor in humans.
We hypothesized that variations in the umami perception of glutamate would correlate with variations in the sequence of these 2 genes, if they contribute directly to umami taste.
In this study, we first characterized the general sensitivity to glutamate in a sample population of 242 subjects. We performed these experiments by sequencing the coding regions of the genomic TAS1R1 and TAS1R3 genes in a separate set of 87 individuals who were tested repeatedly with monopotassium glutamate (MPG) solutions. Last, we tested the role of the candidate umami taste receptor hTAS1R1-hTAS1R3 in a functional expression assay.
A subset of subjects displays extremes of sensitivity, and a battery of different psychophysical tests validated this observation. Statistical analysis showed that the rare T allele of single nucleotide polymorphism (SNP) R757C in TAS1R3 led to a doubling of umami ratings of 25 mmol MPG/L. Other suggestive SNPs of TAS1R3 include the A allele of A5T and the A allele of R247H, which both resulted in an approximate doubling of umami ratings of 200 mmol MPG/L. We confirmed the potential role of the human TAS1R1-TAS1R3 heteromer receptor in umami taste by recording responses, specifically to l-glutamate and inosine 5'-monophosphate (IMP) mixtures in a heterologous expression assay in HEK (human embryonic kidney) T cells.
There is a reliable and valid variation in human umami taste of l-glutamate. Variations in perception of umami taste correlated with variations in the human TAS1R3 gene. The putative human taste receptor TAS1R1-TAS1R3 responds specifically to l-glutamate mixed with the ribonucleotide IMP. Thus, this receptor likely contributes to human umami taste perception.</abstract><cop>Bethesda, MD</cop><pub>American Society for Nutrition</pub><pmid>19587085</pmid><doi>10.3945/ajcn.2009.27462n</doi><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0002-9165 |
ispartof | The American journal of clinical nutrition, 2009-09, Vol.90 (3), p.770S-779S |
issn | 0002-9165 1938-3207 |
language | eng |
recordid | cdi_proquest_miscellaneous_67594465 |
source | ScienceDirect (Online service) |
subjects | Adolescent Adult Aged Aged, 80 and over Alleles Biological and medical sciences Feeding. Feeding behavior Female Fundamental and applied biological sciences. Psychology Genes Genetic Variation Genomics Glutamic Acid Humans Inosine Monophosphate Male Middle Aged Polymorphism Polymorphism, Single Nucleotide Receptors, G-Protein-Coupled - genetics Receptors, G-Protein-Coupled - metabolism Receptors, G-Protein-Coupled - physiology Receptors, Glutamate - genetics Receptors, Glutamate - physiology Sensory perception Studies T cell receptors T-Lymphocytes - metabolism Taste Taste - genetics Taste - physiology Taste Perception - genetics Taste Perception - physiology Taste Threshold - genetics Taste Threshold - physiology Vertebrates: anatomy and physiology, studies on body, several organs or systems Young Adult |
title | Perceptual variation in umami taste and polymorphisms in TAS1R taste receptor genes |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T06%3A35%3A55IST&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=Perceptual%20variation%20in%20umami%20taste%20and%20polymorphisms%20in%20TAS1R%20taste%20receptor%20genes&rft.jtitle=The%20American%20journal%20of%20clinical%20nutrition&rft.au=CHEN,%20Qing-Ying&rft.date=2009-09-01&rft.volume=90&rft.issue=3&rft.spage=770S&rft.epage=779S&rft.pages=770S-779S&rft.issn=0002-9165&rft.eissn=1938-3207&rft.coden=AJCNAC&rft_id=info:doi/10.3945/ajcn.2009.27462n&rft_dat=%3Cproquest_cross%3E1847243551%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c462t-f515a7bdf3cd9f308e8f761c79ce322d0725a1653c739f7c0b1c88d68a19d7b73%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=231930461&rft_id=info:pmid/19587085&rfr_iscdi=true |