Loading…

Downregulation of Maize Cinnamoyl‐Coenzyme A Reductase via RNA Interference Technology Causes Brown Midrib and Improves Ammonia Fiber Expansion‐Pretreated Conversion into Fermentable Sugars for Biofuels

ABSTRACT Conversion of lignocellulosic biomass into fermentable sugars for biofuels requires expensive pretreatment processes involving the breakdown of the cell wall structure and/or removal of lignin to increase accessibility of enzymes to the crop structural carbohydrates. Lignin is synthesized f...

Full description

Saved in:
Bibliographic Details
Published in:Crop science 2012-11, Vol.52 (6), p.2687-2701
Main Authors: Park, Sang‐Hyuck, Mei, Chuansheng, Pauly, Markus, Ong, Rebecca Garlock, Dale, Bruce E., Sabzikar, Robab, Fotoh, Hussien, Nguyen, Thang, Sticklen, Mariam
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-c3703-e361b3e7498edfb77c455d6841d7f325439bd8612415bfbc12cd9448c92ea87c3
cites cdi_FETCH-LOGICAL-c3703-e361b3e7498edfb77c455d6841d7f325439bd8612415bfbc12cd9448c92ea87c3
container_end_page 2701
container_issue 6
container_start_page 2687
container_title Crop science
container_volume 52
creator Park, Sang‐Hyuck
Mei, Chuansheng
Pauly, Markus
Ong, Rebecca Garlock
Dale, Bruce E.
Sabzikar, Robab
Fotoh, Hussien
Nguyen, Thang
Sticklen, Mariam
description ABSTRACT Conversion of lignocellulosic biomass into fermentable sugars for biofuels requires expensive pretreatment processes involving the breakdown of the cell wall structure and/or removal of lignin to increase accessibility of enzymes to the crop structural carbohydrates. Lignin is synthesized from precursors through a complex biosynthesis pathway. One of the important enzymes in this pathway is cinnamoyl‐coenzyme A reductase (CCR), which catalyzes the transformation of feruloyl and p‐coumaryl thioesters to their respective aldehydes. In an attempt to reduce lignin content and potentially accelerate deconstruction of maize (Zea mays L.) stover structural carbohydrates into fermentable sugars, expression of maize CCR (ZmCCR1; EC 1.2.1.44) was downregulated via ribonucleic acid interference (RNAi). Thirty first generation independent ZmCCR1_RNAi transgenic lines were produced. Among 10 out of 30 randomly tested, six lines showed significantly reduced ZmCCR1 transcription. The second generation of these ZmCCR1 downregulated transgenic plants exhibited brown coloration of midribs, husk, and stems and 7.0 to 8.7% reduction in Klason lignin. Also, crystalline cellulose was slightly increased in the lignin downregulated maize stover and further increased conversion of the ammonia fiber expansion (AFEX)‐pretreated maize stover into fermentable sugars. The third generation of CCR downregulated plants showed further reduced CCR transcription as compared to their second generation of transgenic (T1) plants.
doi_str_mv 10.2135/cropsci2012.04.0253
format article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_1285243651</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2887156421</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3703-e361b3e7498edfb77c455d6841d7f325439bd8612415bfbc12cd9448c92ea87c3</originalsourceid><addsrcrecordid>eNqNUctuE0EQXCGQMIEv4NIS4mhnnvs4OkscLCUksoPEbTU722sm2p0xM7sOzimfwJfxEXwJYxwhjpxaqq6uqlYlyVtKZoxyeaq92wZtGKFsRsSMMMmfJRMquJySVPLnyYQQSqc0519eJq9CuCOEZEUmJ8nPD-7eetyMnRqMs-BauFLmAaE01qre7btfjz9Kh_Zh3yPMYYXNqAcVEHZGwerTHJZ2QN-iR6sRblF_ta5zmz2UagwY4MxHA7gyjTc1KNvAst96t4ubed87G0UWpkYP59-3yoYYIfrdeBw8qgEbKJ3doT_gYOzgYIG-RzuoukNYjxvlA7TOw5lx7YhdeJ28aFUX8M3TPEk-L85vy4_Ty-uLZTm_nGqeET5FntKaYyaKHJu2zjItpGzSXNAmazmTghd1k6eUCSrrttaU6aYQItcFQ5Vnmp8k74668ZdvI4ahunOjt9GyoiyXTPBU0sjiR1bsJwSPbbX1pld-X1FSHYqr_imuIqI6FBev3j9pq6BV13pltQl_T1kqRYxWRN7iyLs3He7_R7oq1yUrV9c363J5wIn4Y_gb3sS2FQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1285243651</pqid></control><display><type>article</type><title>Downregulation of Maize Cinnamoyl‐Coenzyme A Reductase via RNA Interference Technology Causes Brown Midrib and Improves Ammonia Fiber Expansion‐Pretreated Conversion into Fermentable Sugars for Biofuels</title><source>Wiley-Blackwell Read &amp; Publish Collection</source><creator>Park, Sang‐Hyuck ; Mei, Chuansheng ; Pauly, Markus ; Ong, Rebecca Garlock ; Dale, Bruce E. ; Sabzikar, Robab ; Fotoh, Hussien ; Nguyen, Thang ; Sticklen, Mariam</creator><creatorcontrib>Park, Sang‐Hyuck ; Mei, Chuansheng ; Pauly, Markus ; Ong, Rebecca Garlock ; Dale, Bruce E. ; Sabzikar, Robab ; Fotoh, Hussien ; Nguyen, Thang ; Sticklen, Mariam</creatorcontrib><description>ABSTRACT Conversion of lignocellulosic biomass into fermentable sugars for biofuels requires expensive pretreatment processes involving the breakdown of the cell wall structure and/or removal of lignin to increase accessibility of enzymes to the crop structural carbohydrates. Lignin is synthesized from precursors through a complex biosynthesis pathway. One of the important enzymes in this pathway is cinnamoyl‐coenzyme A reductase (CCR), which catalyzes the transformation of feruloyl and p‐coumaryl thioesters to their respective aldehydes. In an attempt to reduce lignin content and potentially accelerate deconstruction of maize (Zea mays L.) stover structural carbohydrates into fermentable sugars, expression of maize CCR (ZmCCR1; EC 1.2.1.44) was downregulated via ribonucleic acid interference (RNAi). Thirty first generation independent ZmCCR1_RNAi transgenic lines were produced. Among 10 out of 30 randomly tested, six lines showed significantly reduced ZmCCR1 transcription. The second generation of these ZmCCR1 downregulated transgenic plants exhibited brown coloration of midribs, husk, and stems and 7.0 to 8.7% reduction in Klason lignin. Also, crystalline cellulose was slightly increased in the lignin downregulated maize stover and further increased conversion of the ammonia fiber expansion (AFEX)‐pretreated maize stover into fermentable sugars. The third generation of CCR downregulated plants showed further reduced CCR transcription as compared to their second generation of transgenic (T1) plants.</description><identifier>ISSN: 0011-183X</identifier><identifier>EISSN: 1435-0653</identifier><identifier>DOI: 10.2135/cropsci2012.04.0253</identifier><identifier>CODEN: CRPSAY</identifier><language>eng</language><publisher>Madison, WI: The Crop Science Society of America, Inc</publisher><subject>Agronomy. Soil science and plant productions ; Aldehydes ; Ammonia ; Biodiesel fuels ; Biofuels ; Biological and medical sciences ; Biomass ; Biosynthesis ; Carbohydrates ; Cellulose ; Colleges &amp; universities ; Conversion ; Corn ; Enzymes ; Ethanol ; Expansion ; Fundamental and applied biological sciences. Psychology ; Plant growth ; Seeds ; Stover ; Sugar ; Transgenic plants</subject><ispartof>Crop science, 2012-11, Vol.52 (6), p.2687-2701</ispartof><rights>Copyright © by the Crop Science Society of America, Inc.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright American Society of Agronomy Nov/Dec 2012</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3703-e361b3e7498edfb77c455d6841d7f325439bd8612415bfbc12cd9448c92ea87c3</citedby><cites>FETCH-LOGICAL-c3703-e361b3e7498edfb77c455d6841d7f325439bd8612415bfbc12cd9448c92ea87c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=26548619$$DView record in Pascal Francis$$Hfree_for_read</backlink></links><search><creatorcontrib>Park, Sang‐Hyuck</creatorcontrib><creatorcontrib>Mei, Chuansheng</creatorcontrib><creatorcontrib>Pauly, Markus</creatorcontrib><creatorcontrib>Ong, Rebecca Garlock</creatorcontrib><creatorcontrib>Dale, Bruce E.</creatorcontrib><creatorcontrib>Sabzikar, Robab</creatorcontrib><creatorcontrib>Fotoh, Hussien</creatorcontrib><creatorcontrib>Nguyen, Thang</creatorcontrib><creatorcontrib>Sticklen, Mariam</creatorcontrib><title>Downregulation of Maize Cinnamoyl‐Coenzyme A Reductase via RNA Interference Technology Causes Brown Midrib and Improves Ammonia Fiber Expansion‐Pretreated Conversion into Fermentable Sugars for Biofuels</title><title>Crop science</title><description>ABSTRACT Conversion of lignocellulosic biomass into fermentable sugars for biofuels requires expensive pretreatment processes involving the breakdown of the cell wall structure and/or removal of lignin to increase accessibility of enzymes to the crop structural carbohydrates. Lignin is synthesized from precursors through a complex biosynthesis pathway. One of the important enzymes in this pathway is cinnamoyl‐coenzyme A reductase (CCR), which catalyzes the transformation of feruloyl and p‐coumaryl thioesters to their respective aldehydes. In an attempt to reduce lignin content and potentially accelerate deconstruction of maize (Zea mays L.) stover structural carbohydrates into fermentable sugars, expression of maize CCR (ZmCCR1; EC 1.2.1.44) was downregulated via ribonucleic acid interference (RNAi). Thirty first generation independent ZmCCR1_RNAi transgenic lines were produced. Among 10 out of 30 randomly tested, six lines showed significantly reduced ZmCCR1 transcription. The second generation of these ZmCCR1 downregulated transgenic plants exhibited brown coloration of midribs, husk, and stems and 7.0 to 8.7% reduction in Klason lignin. Also, crystalline cellulose was slightly increased in the lignin downregulated maize stover and further increased conversion of the ammonia fiber expansion (AFEX)‐pretreated maize stover into fermentable sugars. The third generation of CCR downregulated plants showed further reduced CCR transcription as compared to their second generation of transgenic (T1) plants.</description><subject>Agronomy. Soil science and plant productions</subject><subject>Aldehydes</subject><subject>Ammonia</subject><subject>Biodiesel fuels</subject><subject>Biofuels</subject><subject>Biological and medical sciences</subject><subject>Biomass</subject><subject>Biosynthesis</subject><subject>Carbohydrates</subject><subject>Cellulose</subject><subject>Colleges &amp; universities</subject><subject>Conversion</subject><subject>Corn</subject><subject>Enzymes</subject><subject>Ethanol</subject><subject>Expansion</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Plant growth</subject><subject>Seeds</subject><subject>Stover</subject><subject>Sugar</subject><subject>Transgenic plants</subject><issn>0011-183X</issn><issn>1435-0653</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNqNUctuE0EQXCGQMIEv4NIS4mhnnvs4OkscLCUksoPEbTU722sm2p0xM7sOzimfwJfxEXwJYxwhjpxaqq6uqlYlyVtKZoxyeaq92wZtGKFsRsSMMMmfJRMquJySVPLnyYQQSqc0519eJq9CuCOEZEUmJ8nPD-7eetyMnRqMs-BauFLmAaE01qre7btfjz9Kh_Zh3yPMYYXNqAcVEHZGwerTHJZ2QN-iR6sRblF_ta5zmz2UagwY4MxHA7gyjTc1KNvAst96t4ubed87G0UWpkYP59-3yoYYIfrdeBw8qgEbKJ3doT_gYOzgYIG-RzuoukNYjxvlA7TOw5lx7YhdeJ28aFUX8M3TPEk-L85vy4_Ty-uLZTm_nGqeET5FntKaYyaKHJu2zjItpGzSXNAmazmTghd1k6eUCSrrttaU6aYQItcFQ5Vnmp8k74668ZdvI4ahunOjt9GyoiyXTPBU0sjiR1bsJwSPbbX1pld-X1FSHYqr_imuIqI6FBev3j9pq6BV13pltQl_T1kqRYxWRN7iyLs3He7_R7oq1yUrV9c363J5wIn4Y_gb3sS2FQ</recordid><startdate>201211</startdate><enddate>201211</enddate><creator>Park, Sang‐Hyuck</creator><creator>Mei, Chuansheng</creator><creator>Pauly, Markus</creator><creator>Ong, Rebecca Garlock</creator><creator>Dale, Bruce E.</creator><creator>Sabzikar, Robab</creator><creator>Fotoh, Hussien</creator><creator>Nguyen, Thang</creator><creator>Sticklen, Mariam</creator><general>The Crop Science Society of America, Inc</general><general>Crop Science Society of America</general><general>American Society of Agronomy</general><scope>IQODW</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X2</scope><scope>7XB</scope><scope>88I</scope><scope>8AF</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>L6V</scope><scope>M0K</scope><scope>M2O</scope><scope>M2P</scope><scope>M7S</scope><scope>MBDVC</scope><scope>PATMY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>R05</scope><scope>S0X</scope></search><sort><creationdate>201211</creationdate><title>Downregulation of Maize Cinnamoyl‐Coenzyme A Reductase via RNA Interference Technology Causes Brown Midrib and Improves Ammonia Fiber Expansion‐Pretreated Conversion into Fermentable Sugars for Biofuels</title><author>Park, Sang‐Hyuck ; Mei, Chuansheng ; Pauly, Markus ; Ong, Rebecca Garlock ; Dale, Bruce E. ; Sabzikar, Robab ; Fotoh, Hussien ; Nguyen, Thang ; Sticklen, Mariam</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3703-e361b3e7498edfb77c455d6841d7f325439bd8612415bfbc12cd9448c92ea87c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Agronomy. Soil science and plant productions</topic><topic>Aldehydes</topic><topic>Ammonia</topic><topic>Biodiesel fuels</topic><topic>Biofuels</topic><topic>Biological and medical sciences</topic><topic>Biomass</topic><topic>Biosynthesis</topic><topic>Carbohydrates</topic><topic>Cellulose</topic><topic>Colleges &amp; universities</topic><topic>Conversion</topic><topic>Corn</topic><topic>Enzymes</topic><topic>Ethanol</topic><topic>Expansion</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Plant growth</topic><topic>Seeds</topic><topic>Stover</topic><topic>Sugar</topic><topic>Transgenic plants</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Park, Sang‐Hyuck</creatorcontrib><creatorcontrib>Mei, Chuansheng</creatorcontrib><creatorcontrib>Pauly, Markus</creatorcontrib><creatorcontrib>Ong, Rebecca Garlock</creatorcontrib><creatorcontrib>Dale, Bruce E.</creatorcontrib><creatorcontrib>Sabzikar, Robab</creatorcontrib><creatorcontrib>Fotoh, Hussien</creatorcontrib><creatorcontrib>Nguyen, Thang</creatorcontrib><creatorcontrib>Sticklen, Mariam</creatorcontrib><collection>Pascal-Francis</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Agricultural Science Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>Materials Science &amp; Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central</collection><collection>Agricultural &amp; Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Engineering Collection</collection><collection>Agricultural Science Database</collection><collection>Research Library</collection><collection>ProQuest Science Journals</collection><collection>Engineering Database</collection><collection>Research Library (Corporate)</collection><collection>Environmental Science 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>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>ProQuest Central Basic</collection><collection>University of Michigan</collection><collection>SIRS Editorial</collection><jtitle>Crop science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Park, Sang‐Hyuck</au><au>Mei, Chuansheng</au><au>Pauly, Markus</au><au>Ong, Rebecca Garlock</au><au>Dale, Bruce E.</au><au>Sabzikar, Robab</au><au>Fotoh, Hussien</au><au>Nguyen, Thang</au><au>Sticklen, Mariam</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Downregulation of Maize Cinnamoyl‐Coenzyme A Reductase via RNA Interference Technology Causes Brown Midrib and Improves Ammonia Fiber Expansion‐Pretreated Conversion into Fermentable Sugars for Biofuels</atitle><jtitle>Crop science</jtitle><date>2012-11</date><risdate>2012</risdate><volume>52</volume><issue>6</issue><spage>2687</spage><epage>2701</epage><pages>2687-2701</pages><issn>0011-183X</issn><eissn>1435-0653</eissn><coden>CRPSAY</coden><abstract>ABSTRACT Conversion of lignocellulosic biomass into fermentable sugars for biofuels requires expensive pretreatment processes involving the breakdown of the cell wall structure and/or removal of lignin to increase accessibility of enzymes to the crop structural carbohydrates. Lignin is synthesized from precursors through a complex biosynthesis pathway. One of the important enzymes in this pathway is cinnamoyl‐coenzyme A reductase (CCR), which catalyzes the transformation of feruloyl and p‐coumaryl thioesters to their respective aldehydes. In an attempt to reduce lignin content and potentially accelerate deconstruction of maize (Zea mays L.) stover structural carbohydrates into fermentable sugars, expression of maize CCR (ZmCCR1; EC 1.2.1.44) was downregulated via ribonucleic acid interference (RNAi). Thirty first generation independent ZmCCR1_RNAi transgenic lines were produced. Among 10 out of 30 randomly tested, six lines showed significantly reduced ZmCCR1 transcription. The second generation of these ZmCCR1 downregulated transgenic plants exhibited brown coloration of midribs, husk, and stems and 7.0 to 8.7% reduction in Klason lignin. Also, crystalline cellulose was slightly increased in the lignin downregulated maize stover and further increased conversion of the ammonia fiber expansion (AFEX)‐pretreated maize stover into fermentable sugars. The third generation of CCR downregulated plants showed further reduced CCR transcription as compared to their second generation of transgenic (T1) plants.</abstract><cop>Madison, WI</cop><pub>The Crop Science Society of America, Inc</pub><doi>10.2135/cropsci2012.04.0253</doi><tpages>15</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0011-183X
ispartof Crop science, 2012-11, Vol.52 (6), p.2687-2701
issn 0011-183X
1435-0653
language eng
recordid cdi_proquest_journals_1285243651
source Wiley-Blackwell Read & Publish Collection
subjects Agronomy. Soil science and plant productions
Aldehydes
Ammonia
Biodiesel fuels
Biofuels
Biological and medical sciences
Biomass
Biosynthesis
Carbohydrates
Cellulose
Colleges & universities
Conversion
Corn
Enzymes
Ethanol
Expansion
Fundamental and applied biological sciences. Psychology
Plant growth
Seeds
Stover
Sugar
Transgenic plants
title Downregulation of Maize Cinnamoyl‐Coenzyme A Reductase via RNA Interference Technology Causes Brown Midrib and Improves Ammonia Fiber Expansion‐Pretreated Conversion into Fermentable Sugars for Biofuels
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T00%3A55%3A39IST&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=Downregulation%20of%20Maize%20Cinnamoyl%E2%80%90Coenzyme%20A%20Reductase%20via%20RNA%20Interference%20Technology%20Causes%20Brown%20Midrib%20and%20Improves%20Ammonia%20Fiber%20Expansion%E2%80%90Pretreated%20Conversion%20into%20Fermentable%20Sugars%20for%20Biofuels&rft.jtitle=Crop%20science&rft.au=Park,%20Sang%E2%80%90Hyuck&rft.date=2012-11&rft.volume=52&rft.issue=6&rft.spage=2687&rft.epage=2701&rft.pages=2687-2701&rft.issn=0011-183X&rft.eissn=1435-0653&rft.coden=CRPSAY&rft_id=info:doi/10.2135/cropsci2012.04.0253&rft_dat=%3Cproquest_cross%3E2887156421%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c3703-e361b3e7498edfb77c455d6841d7f325439bd8612415bfbc12cd9448c92ea87c3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1285243651&rft_id=info:pmid/&rfr_iscdi=true