Suppression of phenylalanine ammonia lyase expression in sugar beet by the fungal pathogen Cercospora beticola is mediated at the core promoter of the gene

The suppression of plant defence reactions plays a crucial role in causing plant diseases. In this report, we show that inducible plant defences are repressed during the development of Cercospora leaf spot disease. In the early phase of infection of sugar beet (Beta vulgaris L.) leaves with the phyt...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Plant molecular biology 2004-08, Vol.55 (6), p.835-852
Hauptverfasser: Schmidt, K, Heberle, B, Kurrasch, J, Nehls, R, Stahl, D.J
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 852
container_issue 6
container_start_page 835
container_title Plant molecular biology
container_volume 55
creator Schmidt, K
Heberle, B
Kurrasch, J
Nehls, R
Stahl, D.J
description The suppression of plant defence reactions plays a crucial role in causing plant diseases. In this report, we show that inducible plant defences are repressed during the development of Cercospora leaf spot disease. In the early phase of infection of sugar beet (Beta vulgaris L.) leaves with the phytopathogenic fungus Cercospora beticola, a reduction in the expression of the phenylalanine ammonia lyase (BvPAL) and cinnamic acid 4-hydroxylase (BvC4H) genes was observed. BvPAL reduction was found at the transcript and enzyme activity levels. In order to analyse the signal transduction process responsible for suppression, the BvPAL promoter was isolated. An abbreviated 5'- and 3'-deletion series of the promoter was effected using transient biolistic assays, which showed that the activity of a truncated promoter from positions -34 to +246, relative to the transcriptional starting site, retains approximately 30% of the activity of the full-length promoter. The region within the BvPAL promoter required for the reduction in transcription was identified as being positions -34 to +45, with respect to the start of the transcription. This region is equivalent to the core promoter, characterised by the TATA-box, an initiator (Inr) and an unknown downstream element in the region between +7 and +45. These data indicate that (1) plant defence responses are repressed during the development of Cercospora leaf spot disease and (2) the PAL core promoter is involved in the detection of the repression signal.
doi_str_mv 10.1007/s11103-005-2141-2
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_17552458</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>17552458</sourcerecordid><originalsourceid>FETCH-LOGICAL-c366t-bb270c933510d9ed04c2859d20b8458bf4f75718f1041d7d6d3e071c091e16243</originalsourceid><addsrcrecordid>eNqNkcuO1DAQRS0EYpqBD2ADXrELVPkRJ0vU4iWNxGKYteUklW6jJA62I9Hfws_ipluwxRtL1rnXpTqMvUR4iwDmXUJEkBWArgQqrMQjtkNtZKVBNI_ZDrA2lVIobtizlL4DlJSsn7Ib1DUoI2DHft1v6xopJR8WHka-Hmk5TW5yi1-Iu3kOi3d8OrlEnH7-Jf3C03ZwkXdEmXcnno_Ex205uImvLh_DgRa-p9iHtIboCpZ9HybHfeIzDd5lGrjLf2J9iMTXGOaQKZ5nOD-WPD1nT0Y3JXpxvW_Zw8cP3_afq7uvn77s399VvazrXHWdMNC3UmqEoaUBVC8a3Q4CukbpphvVaLTBZkRQOJihHiSBwR5aJKyFkrfszaW3DPFjo5Tt7FNPU1kChS1ZNFqL0vQ_oGw1YAHxAvYxpBRptGv0s4sni2DP6uxFnS3q7FmdFSXz6lq-dWVF_xJXVwV4fQFGF6w7RJ_sw70ovwG0dVOO_A1P4Z86</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17539501</pqid></control><display><type>article</type><title>Suppression of phenylalanine ammonia lyase expression in sugar beet by the fungal pathogen Cercospora beticola is mediated at the core promoter of the gene</title><source>MEDLINE</source><source>SpringerLink Journals</source><creator>Schmidt, K ; Heberle, B ; Kurrasch, J ; Nehls, R ; Stahl, D.J</creator><creatorcontrib>Schmidt, K ; Heberle, B ; Kurrasch, J ; Nehls, R ; Stahl, D.J</creatorcontrib><description>The suppression of plant defence reactions plays a crucial role in causing plant diseases. In this report, we show that inducible plant defences are repressed during the development of Cercospora leaf spot disease. In the early phase of infection of sugar beet (Beta vulgaris L.) leaves with the phytopathogenic fungus Cercospora beticola, a reduction in the expression of the phenylalanine ammonia lyase (BvPAL) and cinnamic acid 4-hydroxylase (BvC4H) genes was observed. BvPAL reduction was found at the transcript and enzyme activity levels. In order to analyse the signal transduction process responsible for suppression, the BvPAL promoter was isolated. An abbreviated 5'- and 3'-deletion series of the promoter was effected using transient biolistic assays, which showed that the activity of a truncated promoter from positions -34 to +246, relative to the transcriptional starting site, retains approximately 30% of the activity of the full-length promoter. The region within the BvPAL promoter required for the reduction in transcription was identified as being positions -34 to +45, with respect to the start of the transcription. This region is equivalent to the core promoter, characterised by the TATA-box, an initiator (Inr) and an unknown downstream element in the region between +7 and +45. These data indicate that (1) plant defence responses are repressed during the development of Cercospora leaf spot disease and (2) the PAL core promoter is involved in the detection of the repression signal.</description><identifier>ISSN: 0167-4412</identifier><identifier>EISSN: 1573-5028</identifier><identifier>DOI: 10.1007/s11103-005-2141-2</identifier><identifier>PMID: 15604720</identifier><language>eng</language><publisher>Netherlands</publisher><subject>5' Flanking Region - genetics ; Amino Acid Sequence ; Ascomycota - growth &amp; development ; Base Sequence ; Beta vulgaris ; Beta vulgaris - enzymology ; Beta vulgaris - genetics ; Beta vulgaris - microbiology ; Beta vulgaris subsp. vulgaris ; Cercospora ; Cercospora beticola ; Cytochrome P-450 Enzyme System - genetics ; Cytochrome P-450 Enzyme System - metabolism ; defense mechanisms ; disease resistance ; DNA, Plant - chemistry ; DNA, Plant - genetics ; DNA, Plant - isolation &amp; purification ; gene expression ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Plant ; gene silencing ; leaf spotting ; leaves ; luciferase ; Luciferases - genetics ; Luciferases - metabolism ; messenger RNA ; Mixed Function Oxygenases - genetics ; Mixed Function Oxygenases - metabolism ; Molecular Sequence Data ; Mutagenesis, Insertional ; nucleotide sequences ; phenylalanine ammonia-lyase ; Phenylalanine Ammonia-Lyase - genetics ; Phenylalanine Ammonia-Lyase - metabolism ; Plant Leaves - enzymology ; Plant Leaves - genetics ; Plant Leaves - microbiology ; plant pathogenic fungi ; promoter regions ; Promoter Regions, Genetic - genetics ; Recombinant Fusion Proteins - genetics ; Recombinant Fusion Proteins - metabolism ; Regulatory Sequences, Nucleic Acid - genetics ; reporter genes ; Sequence Analysis, DNA ; Sequence Deletion ; Sequence Homology, Nucleic Acid ; signal transduction ; sugar beet ; Time Factors ; Trans-Cinnamate 4-Monooxygenase ; transcription (genetics) ; Transcription, Genetic - genetics ; Transformation, Genetic ; transgenic plants</subject><ispartof>Plant molecular biology, 2004-08, Vol.55 (6), p.835-852</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c366t-bb270c933510d9ed04c2859d20b8458bf4f75718f1041d7d6d3e071c091e16243</citedby><cites>FETCH-LOGICAL-c366t-bb270c933510d9ed04c2859d20b8458bf4f75718f1041d7d6d3e071c091e16243</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15604720$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schmidt, K</creatorcontrib><creatorcontrib>Heberle, B</creatorcontrib><creatorcontrib>Kurrasch, J</creatorcontrib><creatorcontrib>Nehls, R</creatorcontrib><creatorcontrib>Stahl, D.J</creatorcontrib><title>Suppression of phenylalanine ammonia lyase expression in sugar beet by the fungal pathogen Cercospora beticola is mediated at the core promoter of the gene</title><title>Plant molecular biology</title><addtitle>Plant Mol Biol</addtitle><description>The suppression of plant defence reactions plays a crucial role in causing plant diseases. In this report, we show that inducible plant defences are repressed during the development of Cercospora leaf spot disease. In the early phase of infection of sugar beet (Beta vulgaris L.) leaves with the phytopathogenic fungus Cercospora beticola, a reduction in the expression of the phenylalanine ammonia lyase (BvPAL) and cinnamic acid 4-hydroxylase (BvC4H) genes was observed. BvPAL reduction was found at the transcript and enzyme activity levels. In order to analyse the signal transduction process responsible for suppression, the BvPAL promoter was isolated. An abbreviated 5'- and 3'-deletion series of the promoter was effected using transient biolistic assays, which showed that the activity of a truncated promoter from positions -34 to +246, relative to the transcriptional starting site, retains approximately 30% of the activity of the full-length promoter. The region within the BvPAL promoter required for the reduction in transcription was identified as being positions -34 to +45, with respect to the start of the transcription. This region is equivalent to the core promoter, characterised by the TATA-box, an initiator (Inr) and an unknown downstream element in the region between +7 and +45. These data indicate that (1) plant defence responses are repressed during the development of Cercospora leaf spot disease and (2) the PAL core promoter is involved in the detection of the repression signal.</description><subject>5' Flanking Region - genetics</subject><subject>Amino Acid Sequence</subject><subject>Ascomycota - growth &amp; development</subject><subject>Base Sequence</subject><subject>Beta vulgaris</subject><subject>Beta vulgaris - enzymology</subject><subject>Beta vulgaris - genetics</subject><subject>Beta vulgaris - microbiology</subject><subject>Beta vulgaris subsp. vulgaris</subject><subject>Cercospora</subject><subject>Cercospora beticola</subject><subject>Cytochrome P-450 Enzyme System - genetics</subject><subject>Cytochrome P-450 Enzyme System - metabolism</subject><subject>defense mechanisms</subject><subject>disease resistance</subject><subject>DNA, Plant - chemistry</subject><subject>DNA, Plant - genetics</subject><subject>DNA, Plant - isolation &amp; purification</subject><subject>gene expression</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>Gene Expression Regulation, Plant</subject><subject>gene silencing</subject><subject>leaf spotting</subject><subject>leaves</subject><subject>luciferase</subject><subject>Luciferases - genetics</subject><subject>Luciferases - metabolism</subject><subject>messenger RNA</subject><subject>Mixed Function Oxygenases - genetics</subject><subject>Mixed Function Oxygenases - metabolism</subject><subject>Molecular Sequence Data</subject><subject>Mutagenesis, Insertional</subject><subject>nucleotide sequences</subject><subject>phenylalanine ammonia-lyase</subject><subject>Phenylalanine Ammonia-Lyase - genetics</subject><subject>Phenylalanine Ammonia-Lyase - metabolism</subject><subject>Plant Leaves - enzymology</subject><subject>Plant Leaves - genetics</subject><subject>Plant Leaves - microbiology</subject><subject>plant pathogenic fungi</subject><subject>promoter regions</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Recombinant Fusion Proteins - genetics</subject><subject>Recombinant Fusion Proteins - metabolism</subject><subject>Regulatory Sequences, Nucleic Acid - genetics</subject><subject>reporter genes</subject><subject>Sequence Analysis, DNA</subject><subject>Sequence Deletion</subject><subject>Sequence Homology, Nucleic Acid</subject><subject>signal transduction</subject><subject>sugar beet</subject><subject>Time Factors</subject><subject>Trans-Cinnamate 4-Monooxygenase</subject><subject>transcription (genetics)</subject><subject>Transcription, Genetic - genetics</subject><subject>Transformation, Genetic</subject><subject>transgenic plants</subject><issn>0167-4412</issn><issn>1573-5028</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkcuO1DAQRS0EYpqBD2ADXrELVPkRJ0vU4iWNxGKYteUklW6jJA62I9Hfws_ipluwxRtL1rnXpTqMvUR4iwDmXUJEkBWArgQqrMQjtkNtZKVBNI_ZDrA2lVIobtizlL4DlJSsn7Ib1DUoI2DHft1v6xopJR8WHka-Hmk5TW5yi1-Iu3kOi3d8OrlEnH7-Jf3C03ZwkXdEmXcnno_Ex205uImvLh_DgRa-p9iHtIboCpZ9HybHfeIzDd5lGrjLf2J9iMTXGOaQKZ5nOD-WPD1nT0Y3JXpxvW_Zw8cP3_afq7uvn77s399VvazrXHWdMNC3UmqEoaUBVC8a3Q4CukbpphvVaLTBZkRQOJihHiSBwR5aJKyFkrfszaW3DPFjo5Tt7FNPU1kChS1ZNFqL0vQ_oGw1YAHxAvYxpBRptGv0s4sni2DP6uxFnS3q7FmdFSXz6lq-dWVF_xJXVwV4fQFGF6w7RJ_sw70ovwG0dVOO_A1P4Z86</recordid><startdate>20040801</startdate><enddate>20040801</enddate><creator>Schmidt, K</creator><creator>Heberle, B</creator><creator>Kurrasch, J</creator><creator>Nehls, R</creator><creator>Stahl, D.J</creator><scope>FBQ</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>7TM</scope><scope>7T7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20040801</creationdate><title>Suppression of phenylalanine ammonia lyase expression in sugar beet by the fungal pathogen Cercospora beticola is mediated at the core promoter of the gene</title><author>Schmidt, K ; Heberle, B ; Kurrasch, J ; Nehls, R ; Stahl, D.J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c366t-bb270c933510d9ed04c2859d20b8458bf4f75718f1041d7d6d3e071c091e16243</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>5' Flanking Region - genetics</topic><topic>Amino Acid Sequence</topic><topic>Ascomycota - growth &amp; development</topic><topic>Base Sequence</topic><topic>Beta vulgaris</topic><topic>Beta vulgaris - enzymology</topic><topic>Beta vulgaris - genetics</topic><topic>Beta vulgaris - microbiology</topic><topic>Beta vulgaris subsp. vulgaris</topic><topic>Cercospora</topic><topic>Cercospora beticola</topic><topic>Cytochrome P-450 Enzyme System - genetics</topic><topic>Cytochrome P-450 Enzyme System - metabolism</topic><topic>defense mechanisms</topic><topic>disease resistance</topic><topic>DNA, Plant - chemistry</topic><topic>DNA, Plant - genetics</topic><topic>DNA, Plant - isolation &amp; purification</topic><topic>gene expression</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>Gene Expression Regulation, Plant</topic><topic>gene silencing</topic><topic>leaf spotting</topic><topic>leaves</topic><topic>luciferase</topic><topic>Luciferases - genetics</topic><topic>Luciferases - metabolism</topic><topic>messenger RNA</topic><topic>Mixed Function Oxygenases - genetics</topic><topic>Mixed Function Oxygenases - metabolism</topic><topic>Molecular Sequence Data</topic><topic>Mutagenesis, Insertional</topic><topic>nucleotide sequences</topic><topic>phenylalanine ammonia-lyase</topic><topic>Phenylalanine Ammonia-Lyase - genetics</topic><topic>Phenylalanine Ammonia-Lyase - metabolism</topic><topic>Plant Leaves - enzymology</topic><topic>Plant Leaves - genetics</topic><topic>Plant Leaves - microbiology</topic><topic>plant pathogenic fungi</topic><topic>promoter regions</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Recombinant Fusion Proteins - genetics</topic><topic>Recombinant Fusion Proteins - metabolism</topic><topic>Regulatory Sequences, Nucleic Acid - genetics</topic><topic>reporter genes</topic><topic>Sequence Analysis, DNA</topic><topic>Sequence Deletion</topic><topic>Sequence Homology, Nucleic Acid</topic><topic>signal transduction</topic><topic>sugar beet</topic><topic>Time Factors</topic><topic>Trans-Cinnamate 4-Monooxygenase</topic><topic>transcription (genetics)</topic><topic>Transcription, Genetic - genetics</topic><topic>Transformation, Genetic</topic><topic>transgenic plants</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schmidt, K</creatorcontrib><creatorcontrib>Heberle, B</creatorcontrib><creatorcontrib>Kurrasch, J</creatorcontrib><creatorcontrib>Nehls, R</creatorcontrib><creatorcontrib>Stahl, D.J</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Plant molecular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schmidt, K</au><au>Heberle, B</au><au>Kurrasch, J</au><au>Nehls, R</au><au>Stahl, D.J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Suppression of phenylalanine ammonia lyase expression in sugar beet by the fungal pathogen Cercospora beticola is mediated at the core promoter of the gene</atitle><jtitle>Plant molecular biology</jtitle><addtitle>Plant Mol Biol</addtitle><date>2004-08-01</date><risdate>2004</risdate><volume>55</volume><issue>6</issue><spage>835</spage><epage>852</epage><pages>835-852</pages><issn>0167-4412</issn><eissn>1573-5028</eissn><abstract>The suppression of plant defence reactions plays a crucial role in causing plant diseases. In this report, we show that inducible plant defences are repressed during the development of Cercospora leaf spot disease. In the early phase of infection of sugar beet (Beta vulgaris L.) leaves with the phytopathogenic fungus Cercospora beticola, a reduction in the expression of the phenylalanine ammonia lyase (BvPAL) and cinnamic acid 4-hydroxylase (BvC4H) genes was observed. BvPAL reduction was found at the transcript and enzyme activity levels. In order to analyse the signal transduction process responsible for suppression, the BvPAL promoter was isolated. An abbreviated 5'- and 3'-deletion series of the promoter was effected using transient biolistic assays, which showed that the activity of a truncated promoter from positions -34 to +246, relative to the transcriptional starting site, retains approximately 30% of the activity of the full-length promoter. The region within the BvPAL promoter required for the reduction in transcription was identified as being positions -34 to +45, with respect to the start of the transcription. This region is equivalent to the core promoter, characterised by the TATA-box, an initiator (Inr) and an unknown downstream element in the region between +7 and +45. These data indicate that (1) plant defence responses are repressed during the development of Cercospora leaf spot disease and (2) the PAL core promoter is involved in the detection of the repression signal.</abstract><cop>Netherlands</cop><pmid>15604720</pmid><doi>10.1007/s11103-005-2141-2</doi><tpages>18</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0167-4412
ispartof Plant molecular biology, 2004-08, Vol.55 (6), p.835-852
issn 0167-4412
1573-5028
language eng
recordid cdi_proquest_miscellaneous_17552458
source MEDLINE; SpringerLink Journals
subjects 5' Flanking Region - genetics
Amino Acid Sequence
Ascomycota - growth & development
Base Sequence
Beta vulgaris
Beta vulgaris - enzymology
Beta vulgaris - genetics
Beta vulgaris - microbiology
Beta vulgaris subsp. vulgaris
Cercospora
Cercospora beticola
Cytochrome P-450 Enzyme System - genetics
Cytochrome P-450 Enzyme System - metabolism
defense mechanisms
disease resistance
DNA, Plant - chemistry
DNA, Plant - genetics
DNA, Plant - isolation & purification
gene expression
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Plant
gene silencing
leaf spotting
leaves
luciferase
Luciferases - genetics
Luciferases - metabolism
messenger RNA
Mixed Function Oxygenases - genetics
Mixed Function Oxygenases - metabolism
Molecular Sequence Data
Mutagenesis, Insertional
nucleotide sequences
phenylalanine ammonia-lyase
Phenylalanine Ammonia-Lyase - genetics
Phenylalanine Ammonia-Lyase - metabolism
Plant Leaves - enzymology
Plant Leaves - genetics
Plant Leaves - microbiology
plant pathogenic fungi
promoter regions
Promoter Regions, Genetic - genetics
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
Regulatory Sequences, Nucleic Acid - genetics
reporter genes
Sequence Analysis, DNA
Sequence Deletion
Sequence Homology, Nucleic Acid
signal transduction
sugar beet
Time Factors
Trans-Cinnamate 4-Monooxygenase
transcription (genetics)
Transcription, Genetic - genetics
Transformation, Genetic
transgenic plants
title Suppression of phenylalanine ammonia lyase expression in sugar beet by the fungal pathogen Cercospora beticola is mediated at the core promoter of the gene
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-26T17%3A39%3A19IST&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=Suppression%20of%20phenylalanine%20ammonia%20lyase%20expression%20in%20sugar%20beet%20by%20the%20fungal%20pathogen%20Cercospora%20beticola%20is%20mediated%20at%20the%20core%20promoter%20of%20the%20gene&rft.jtitle=Plant%20molecular%20biology&rft.au=Schmidt,%20K&rft.date=2004-08-01&rft.volume=55&rft.issue=6&rft.spage=835&rft.epage=852&rft.pages=835-852&rft.issn=0167-4412&rft.eissn=1573-5028&rft_id=info:doi/10.1007/s11103-005-2141-2&rft_dat=%3Cproquest_cross%3E17552458%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=17539501&rft_id=info:pmid/15604720&rfr_iscdi=true