Transcriptome analysis of tetrodotoxin sensing and tetrodotoxin action in the central nervous system of tiger puffer Takifugu rubripes juveniles

To reveal the sensing of tetrodotoxin (TTX) by tiger puffer Takifugu rubripes juveniles and its action in the central nervous system (CNS), we conducted transcriptome analysis using next-generation sequencing for the olfactory system and brain of non-toxic cultured juveniles administered TTX. Sixty-...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Fisheries science 2017-05, Vol.83 (3), p.401-412
Hauptverfasser: Okita, Kogen, Tan, Engkong, Satone, Hina, Kinoshita, Shigeharu, Asakawa, Shuichi, Ojima, Daisuke, Yamazaki, Hideki, Sakiyama, Kazutaka, Takatani, Tomohiro, Arakawa, Osamu, Hagiwara, Atsushi, Sakakura, Yoshitaka
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 412
container_issue 3
container_start_page 401
container_title Fisheries science
container_volume 83
creator Okita, Kogen
Tan, Engkong
Satone, Hina
Kinoshita, Shigeharu
Asakawa, Shuichi
Ojima, Daisuke
Yamazaki, Hideki
Sakiyama, Kazutaka
Takatani, Tomohiro
Arakawa, Osamu
Hagiwara, Atsushi
Sakakura, Yoshitaka
description To reveal the sensing of tetrodotoxin (TTX) by tiger puffer Takifugu rubripes juveniles and its action in the central nervous system (CNS), we conducted transcriptome analysis using next-generation sequencing for the olfactory system and brain of non-toxic cultured juveniles administered TTX. Sixty-seven million reads from the nasal region (olfactory epithelium and skin) and the brain of each of three individuals of the control, TTX-sensing and TTX-administered juveniles were assembled into 153,958 contigs. Mapping raw reads from each sample onto the nucleotide sequences of predicted transcripts in the T. rubripes genome (FUGU version 4) and the de novo assembled contigs to investigate their frequency of expression revealed that the expression of 21 and 81 known genes significantly changed in TTX-sensing and TTX-administered juveniles in comparison with control juveniles, respectively. These genes included those related to feeding regulation and a reward system, and indicated that TTX ingestion of T. rubripes juveniles is controlled in the feeding center in the brain, that T. rubripes may sense TTX as a reward, and that accumulated TTX directly acts on the central nervous system to adjust TTX ingestion.
doi_str_mv 10.1007/s12562-017-1079-z
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_1899614325</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1899614325</sourcerecordid><originalsourceid>FETCH-LOGICAL-c453t-e05209a54ab5bfd21b0c852cb1d6b9fe836ab077ac62d2455906f54c63aff7393</originalsourceid><addsrcrecordid>eNp1kM1OAyEUhYnRxPrzAO5IXI8CMzDD0jT-JSZu6powDFRqC5XLNNan8JFF60IXru5N7jnn5nwInVFyQQlpL4EyLlhFaFtR0srqfQ9NaNM0FZNE7KMJkVRWkonuEB0BLAghgpNugj5mSQcwya9zXFmsg15uwQOODmebUxxijm8-YLABfJgXwfD3oE32MeCy5WeLjQ056SUONm3iCBi2kO3qO83PbcLr0bkyZvrFu3E-4jT25bUFvBg3NvilhRN04PQS7OnPPEZPN9ez6V318Hh7P716qEzD61xZwhmRmje6570bGO2J6TgzPR1EL53taqF70rbaCDawhvOCwfHGiFo719ayPkbnu9x1iq-jhawWcUylPijaSSloUzNeVHSnMikCJOvUOvmVTltFifoCr3bgVQGvvsCr9-JhOw8UbSitfyX_a_oE2g6LSA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1899614325</pqid></control><display><type>article</type><title>Transcriptome analysis of tetrodotoxin sensing and tetrodotoxin action in the central nervous system of tiger puffer Takifugu rubripes juveniles</title><source>Springer Nature - Complete Springer Journals</source><creator>Okita, Kogen ; Tan, Engkong ; Satone, Hina ; Kinoshita, Shigeharu ; Asakawa, Shuichi ; Ojima, Daisuke ; Yamazaki, Hideki ; Sakiyama, Kazutaka ; Takatani, Tomohiro ; Arakawa, Osamu ; Hagiwara, Atsushi ; Sakakura, Yoshitaka</creator><creatorcontrib>Okita, Kogen ; Tan, Engkong ; Satone, Hina ; Kinoshita, Shigeharu ; Asakawa, Shuichi ; Ojima, Daisuke ; Yamazaki, Hideki ; Sakiyama, Kazutaka ; Takatani, Tomohiro ; Arakawa, Osamu ; Hagiwara, Atsushi ; Sakakura, Yoshitaka</creatorcontrib><description>To reveal the sensing of tetrodotoxin (TTX) by tiger puffer Takifugu rubripes juveniles and its action in the central nervous system (CNS), we conducted transcriptome analysis using next-generation sequencing for the olfactory system and brain of non-toxic cultured juveniles administered TTX. Sixty-seven million reads from the nasal region (olfactory epithelium and skin) and the brain of each of three individuals of the control, TTX-sensing and TTX-administered juveniles were assembled into 153,958 contigs. Mapping raw reads from each sample onto the nucleotide sequences of predicted transcripts in the T. rubripes genome (FUGU version 4) and the de novo assembled contigs to investigate their frequency of expression revealed that the expression of 21 and 81 known genes significantly changed in TTX-sensing and TTX-administered juveniles in comparison with control juveniles, respectively. These genes included those related to feeding regulation and a reward system, and indicated that TTX ingestion of T. rubripes juveniles is controlled in the feeding center in the brain, that T. rubripes may sense TTX as a reward, and that accumulated TTX directly acts on the central nervous system to adjust TTX ingestion.</description><identifier>ISSN: 0919-9268</identifier><identifier>EISSN: 1444-2906</identifier><identifier>DOI: 10.1007/s12562-017-1079-z</identifier><language>eng</language><publisher>Tokyo: Springer Japan</publisher><subject>Biomedical and Life Sciences ; Brain ; Central nervous system ; Detection ; Epithelium ; Feeding ; Fish &amp; Wildlife Biology &amp; Management ; Fish culture ; Fish skin ; Fisheries ; Food Science ; Freshwater &amp; Marine Ecology ; Gene expression ; Gene mapping ; Gene sequencing ; Genes ; Ingestion ; Juveniles ; Life Sciences ; Mapping ; Minors ; Nervous system ; Nucleotides ; Odour ; Olfaction ; Olfactory epithelium ; Olfactory system ; Original Article ; Reinforcement ; Sampling ; Smell ; Takifugu rubripes ; Tetrodotoxin ; Toxins</subject><ispartof>Fisheries science, 2017-05, Vol.83 (3), p.401-412</ispartof><rights>Japanese Society of Fisheries Science 2017</rights><rights>Fisheries Science is a copyright of Springer, 2017.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c453t-e05209a54ab5bfd21b0c852cb1d6b9fe836ab077ac62d2455906f54c63aff7393</citedby><cites>FETCH-LOGICAL-c453t-e05209a54ab5bfd21b0c852cb1d6b9fe836ab077ac62d2455906f54c63aff7393</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12562-017-1079-z$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12562-017-1079-z$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids></links><search><creatorcontrib>Okita, Kogen</creatorcontrib><creatorcontrib>Tan, Engkong</creatorcontrib><creatorcontrib>Satone, Hina</creatorcontrib><creatorcontrib>Kinoshita, Shigeharu</creatorcontrib><creatorcontrib>Asakawa, Shuichi</creatorcontrib><creatorcontrib>Ojima, Daisuke</creatorcontrib><creatorcontrib>Yamazaki, Hideki</creatorcontrib><creatorcontrib>Sakiyama, Kazutaka</creatorcontrib><creatorcontrib>Takatani, Tomohiro</creatorcontrib><creatorcontrib>Arakawa, Osamu</creatorcontrib><creatorcontrib>Hagiwara, Atsushi</creatorcontrib><creatorcontrib>Sakakura, Yoshitaka</creatorcontrib><title>Transcriptome analysis of tetrodotoxin sensing and tetrodotoxin action in the central nervous system of tiger puffer Takifugu rubripes juveniles</title><title>Fisheries science</title><addtitle>Fish Sci</addtitle><description>To reveal the sensing of tetrodotoxin (TTX) by tiger puffer Takifugu rubripes juveniles and its action in the central nervous system (CNS), we conducted transcriptome analysis using next-generation sequencing for the olfactory system and brain of non-toxic cultured juveniles administered TTX. Sixty-seven million reads from the nasal region (olfactory epithelium and skin) and the brain of each of three individuals of the control, TTX-sensing and TTX-administered juveniles were assembled into 153,958 contigs. Mapping raw reads from each sample onto the nucleotide sequences of predicted transcripts in the T. rubripes genome (FUGU version 4) and the de novo assembled contigs to investigate their frequency of expression revealed that the expression of 21 and 81 known genes significantly changed in TTX-sensing and TTX-administered juveniles in comparison with control juveniles, respectively. These genes included those related to feeding regulation and a reward system, and indicated that TTX ingestion of T. rubripes juveniles is controlled in the feeding center in the brain, that T. rubripes may sense TTX as a reward, and that accumulated TTX directly acts on the central nervous system to adjust TTX ingestion.</description><subject>Biomedical and Life Sciences</subject><subject>Brain</subject><subject>Central nervous system</subject><subject>Detection</subject><subject>Epithelium</subject><subject>Feeding</subject><subject>Fish &amp; Wildlife Biology &amp; Management</subject><subject>Fish culture</subject><subject>Fish skin</subject><subject>Fisheries</subject><subject>Food Science</subject><subject>Freshwater &amp; Marine Ecology</subject><subject>Gene expression</subject><subject>Gene mapping</subject><subject>Gene sequencing</subject><subject>Genes</subject><subject>Ingestion</subject><subject>Juveniles</subject><subject>Life Sciences</subject><subject>Mapping</subject><subject>Minors</subject><subject>Nervous system</subject><subject>Nucleotides</subject><subject>Odour</subject><subject>Olfaction</subject><subject>Olfactory epithelium</subject><subject>Olfactory system</subject><subject>Original Article</subject><subject>Reinforcement</subject><subject>Sampling</subject><subject>Smell</subject><subject>Takifugu rubripes</subject><subject>Tetrodotoxin</subject><subject>Toxins</subject><issn>0919-9268</issn><issn>1444-2906</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp1kM1OAyEUhYnRxPrzAO5IXI8CMzDD0jT-JSZu6powDFRqC5XLNNan8JFF60IXru5N7jnn5nwInVFyQQlpL4EyLlhFaFtR0srqfQ9NaNM0FZNE7KMJkVRWkonuEB0BLAghgpNugj5mSQcwya9zXFmsg15uwQOODmebUxxijm8-YLABfJgXwfD3oE32MeCy5WeLjQ056SUONm3iCBi2kO3qO83PbcLr0bkyZvrFu3E-4jT25bUFvBg3NvilhRN04PQS7OnPPEZPN9ez6V318Hh7P716qEzD61xZwhmRmje6570bGO2J6TgzPR1EL53taqF70rbaCDawhvOCwfHGiFo719ayPkbnu9x1iq-jhawWcUylPijaSSloUzNeVHSnMikCJOvUOvmVTltFifoCr3bgVQGvvsCr9-JhOw8UbSitfyX_a_oE2g6LSA</recordid><startdate>20170501</startdate><enddate>20170501</enddate><creator>Okita, Kogen</creator><creator>Tan, Engkong</creator><creator>Satone, Hina</creator><creator>Kinoshita, Shigeharu</creator><creator>Asakawa, Shuichi</creator><creator>Ojima, Daisuke</creator><creator>Yamazaki, Hideki</creator><creator>Sakiyama, Kazutaka</creator><creator>Takatani, Tomohiro</creator><creator>Arakawa, Osamu</creator><creator>Hagiwara, Atsushi</creator><creator>Sakakura, Yoshitaka</creator><general>Springer Japan</general><general>Springer Nature B.V</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TN</scope><scope>7U7</scope><scope>7WY</scope><scope>7WZ</scope><scope>7XB</scope><scope>87Z</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8FL</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BEZIV</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>F1W</scope><scope>FRNLG</scope><scope>F~G</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H95</scope><scope>H98</scope><scope>HCIFZ</scope><scope>K60</scope><scope>K6~</scope><scope>L.-</scope><scope>L.G</scope><scope>LK8</scope><scope>M0C</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PCBAR</scope><scope>PQBIZ</scope><scope>PQBZA</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope></search><sort><creationdate>20170501</creationdate><title>Transcriptome analysis of tetrodotoxin sensing and tetrodotoxin action in the central nervous system of tiger puffer Takifugu rubripes juveniles</title><author>Okita, Kogen ; Tan, Engkong ; Satone, Hina ; Kinoshita, Shigeharu ; Asakawa, Shuichi ; Ojima, Daisuke ; Yamazaki, Hideki ; Sakiyama, Kazutaka ; Takatani, Tomohiro ; Arakawa, Osamu ; Hagiwara, Atsushi ; Sakakura, Yoshitaka</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c453t-e05209a54ab5bfd21b0c852cb1d6b9fe836ab077ac62d2455906f54c63aff7393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Biomedical and Life Sciences</topic><topic>Brain</topic><topic>Central nervous system</topic><topic>Detection</topic><topic>Epithelium</topic><topic>Feeding</topic><topic>Fish &amp; Wildlife Biology &amp; Management</topic><topic>Fish culture</topic><topic>Fish skin</topic><topic>Fisheries</topic><topic>Food Science</topic><topic>Freshwater &amp; Marine Ecology</topic><topic>Gene expression</topic><topic>Gene mapping</topic><topic>Gene sequencing</topic><topic>Genes</topic><topic>Ingestion</topic><topic>Juveniles</topic><topic>Life Sciences</topic><topic>Mapping</topic><topic>Minors</topic><topic>Nervous system</topic><topic>Nucleotides</topic><topic>Odour</topic><topic>Olfaction</topic><topic>Olfactory epithelium</topic><topic>Olfactory system</topic><topic>Original Article</topic><topic>Reinforcement</topic><topic>Sampling</topic><topic>Smell</topic><topic>Takifugu rubripes</topic><topic>Tetrodotoxin</topic><topic>Toxins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Okita, Kogen</creatorcontrib><creatorcontrib>Tan, Engkong</creatorcontrib><creatorcontrib>Satone, Hina</creatorcontrib><creatorcontrib>Kinoshita, Shigeharu</creatorcontrib><creatorcontrib>Asakawa, Shuichi</creatorcontrib><creatorcontrib>Ojima, Daisuke</creatorcontrib><creatorcontrib>Yamazaki, Hideki</creatorcontrib><creatorcontrib>Sakiyama, Kazutaka</creatorcontrib><creatorcontrib>Takatani, Tomohiro</creatorcontrib><creatorcontrib>Arakawa, Osamu</creatorcontrib><creatorcontrib>Hagiwara, Atsushi</creatorcontrib><creatorcontrib>Sakakura, Yoshitaka</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oceanic Abstracts</collection><collection>Toxicology Abstracts</collection><collection>ABI/INFORM Collection</collection><collection>ABI/INFORM Global (PDF only)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ABI/INFORM Global (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ABI/INFORM Collection (Alumni Edition)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Business Premium Collection</collection><collection>Natural Science Collection</collection><collection>Earth, Atmospheric &amp; Aquatic Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Business Premium Collection (Alumni)</collection><collection>ABI/INFORM Global (Corporate)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>Aquatic Science &amp; Fisheries Abstracts (ASFA) 1: Biological Sciences &amp; Living Resources</collection><collection>Aquatic Science &amp; Fisheries Abstracts (ASFA) Aquaculture Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Business Collection (Alumni Edition)</collection><collection>ProQuest Business Collection</collection><collection>ABI/INFORM Professional Advanced</collection><collection>Aquatic Science &amp; Fisheries Abstracts (ASFA) Professional</collection><collection>ProQuest Biological Science Collection</collection><collection>ABI/INFORM Global</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Earth, Atmospheric &amp; Aquatic Science Database</collection><collection>ProQuest One Business</collection><collection>ProQuest One Business (Alumni)</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 Basic</collection><jtitle>Fisheries science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Okita, Kogen</au><au>Tan, Engkong</au><au>Satone, Hina</au><au>Kinoshita, Shigeharu</au><au>Asakawa, Shuichi</au><au>Ojima, Daisuke</au><au>Yamazaki, Hideki</au><au>Sakiyama, Kazutaka</au><au>Takatani, Tomohiro</au><au>Arakawa, Osamu</au><au>Hagiwara, Atsushi</au><au>Sakakura, Yoshitaka</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transcriptome analysis of tetrodotoxin sensing and tetrodotoxin action in the central nervous system of tiger puffer Takifugu rubripes juveniles</atitle><jtitle>Fisheries science</jtitle><stitle>Fish Sci</stitle><date>2017-05-01</date><risdate>2017</risdate><volume>83</volume><issue>3</issue><spage>401</spage><epage>412</epage><pages>401-412</pages><issn>0919-9268</issn><eissn>1444-2906</eissn><abstract>To reveal the sensing of tetrodotoxin (TTX) by tiger puffer Takifugu rubripes juveniles and its action in the central nervous system (CNS), we conducted transcriptome analysis using next-generation sequencing for the olfactory system and brain of non-toxic cultured juveniles administered TTX. Sixty-seven million reads from the nasal region (olfactory epithelium and skin) and the brain of each of three individuals of the control, TTX-sensing and TTX-administered juveniles were assembled into 153,958 contigs. Mapping raw reads from each sample onto the nucleotide sequences of predicted transcripts in the T. rubripes genome (FUGU version 4) and the de novo assembled contigs to investigate their frequency of expression revealed that the expression of 21 and 81 known genes significantly changed in TTX-sensing and TTX-administered juveniles in comparison with control juveniles, respectively. These genes included those related to feeding regulation and a reward system, and indicated that TTX ingestion of T. rubripes juveniles is controlled in the feeding center in the brain, that T. rubripes may sense TTX as a reward, and that accumulated TTX directly acts on the central nervous system to adjust TTX ingestion.</abstract><cop>Tokyo</cop><pub>Springer Japan</pub><doi>10.1007/s12562-017-1079-z</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0919-9268
ispartof Fisheries science, 2017-05, Vol.83 (3), p.401-412
issn 0919-9268
1444-2906
language eng
recordid cdi_proquest_journals_1899614325
source Springer Nature - Complete Springer Journals
subjects Biomedical and Life Sciences
Brain
Central nervous system
Detection
Epithelium
Feeding
Fish & Wildlife Biology & Management
Fish culture
Fish skin
Fisheries
Food Science
Freshwater & Marine Ecology
Gene expression
Gene mapping
Gene sequencing
Genes
Ingestion
Juveniles
Life Sciences
Mapping
Minors
Nervous system
Nucleotides
Odour
Olfaction
Olfactory epithelium
Olfactory system
Original Article
Reinforcement
Sampling
Smell
Takifugu rubripes
Tetrodotoxin
Toxins
title Transcriptome analysis of tetrodotoxin sensing and tetrodotoxin action in the central nervous system of tiger puffer Takifugu rubripes juveniles
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-16T21%3A43%3A41IST&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=Transcriptome%20analysis%20of%20tetrodotoxin%20sensing%20and%20tetrodotoxin%20action%20in%20the%20central%20nervous%20system%20of%20tiger%20puffer%20Takifugu%20rubripes%20juveniles&rft.jtitle=Fisheries%20science&rft.au=Okita,%20Kogen&rft.date=2017-05-01&rft.volume=83&rft.issue=3&rft.spage=401&rft.epage=412&rft.pages=401-412&rft.issn=0919-9268&rft.eissn=1444-2906&rft_id=info:doi/10.1007/s12562-017-1079-z&rft_dat=%3Cproquest_cross%3E1899614325%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=1899614325&rft_id=info:pmid/&rfr_iscdi=true