Massive excretion of calcium oxalate from late prepupal salivary glands of Drosophila melanogaster demonstrates active nephridial‐like anion transport

The Drosophila salivary glands (SGs) were well known for the puffing patterns of their polytene chromosomes and so became a tissue of choice to study sequential gene activation by the steroid hormone ecdysone. One well‐documented function of these glands is to produce a secretory glue, which is rele...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Development, growth & differentiation growth & differentiation, 2016-08, Vol.58 (6), p.562-574
Hauptverfasser: Farkaš, Robert, Pečeňová, Ludmila, Mentelová, Lucia, Beňo, Milan, Beňová‐Liszeková, Denisa, Mahmoodová, Silvia, Tejnecký, Václav, Raška, Otakar, Juda, Pavel, Svidenská, Silvie, Hornáček, Matúš, Chase, Bruce A., Raška, Ivan
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 574
container_issue 6
container_start_page 562
container_title Development, growth & differentiation
container_volume 58
creator Farkaš, Robert
Pečeňová, Ludmila
Mentelová, Lucia
Beňo, Milan
Beňová‐Liszeková, Denisa
Mahmoodová, Silvia
Tejnecký, Václav
Raška, Otakar
Juda, Pavel
Svidenská, Silvie
Hornáček, Matúš
Chase, Bruce A.
Raška, Ivan
description The Drosophila salivary glands (SGs) were well known for the puffing patterns of their polytene chromosomes and so became a tissue of choice to study sequential gene activation by the steroid hormone ecdysone. One well‐documented function of these glands is to produce a secretory glue, which is released during pupariation to fix the freshly formed puparia to the substrate. Over the past two decades SGs have been used to address specific aspects of developmentally‐regulated programmed cell death (PCD) as it was thought that they are doomed for histolysis and after pupariation are just awaiting their fate. More recently, however, we have shown that for the first 3–4 h after pupariation SGs undergo tremendous endocytosis and vacuolation followed by vacuole neutralization and membrane consolidation. Furthermore, from 8 to 10 h after puparium formation (APF) SGs display massive apocrine secretion of a diverse set of cellular proteins. Here, we show that during the period from 11 to 12 h APF, the prepupal glands are very active in calcium oxalate (CaOx) extrusion that resembles renal or nephridial excretory activity. We provide genetic evidence that Prestin, a Drosophila homologue of the mammalian electrogenic anion exchange carrier SLC26A5, is responsible for the instantaneous production of CaOx by the late prepupal SGs. Its positive regulation by the protein kinases encoded by fray and wnk lead to increased production of CaOx. The formation of CaOx appears to be dependent on the cooperation between Prestin and the vATPase complex as treatment with bafilomycin A1 or concanamycin A abolishes the production of detectable CaOx. These data demonstrate that prepupal SGs remain fully viable, physiologically active and engaged in various cellular activities at least until early pupal period, that is, until moments prior to the execution of PCD. Description of a new and unexpected function of late prepupal salivary glands of Drosophila melanogaster: production and release of calcium oxalate which strongly resembles renal or nephridial excretory activity.
doi_str_mv 10.1111/dgd.12300
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_1806078600</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1806078600</sourcerecordid><originalsourceid>FETCH-LOGICAL-j3380-e7926e3acedc42459d2f9fecd09495b0c8f74b1bc28fea6cb546bd7f36f423a63</originalsourceid><addsrcrecordid>eNpdkc9u1DAQxi0EokvhwAsgS1y4pB07zh8fURcKUhEXkLhFjj3eenHiYCelvfUReuT5eBKcbeHAXGZk_2a-0XyEvGRwwnKcmp05YbwEeEQ2TAgoWC2_PSYbAMYLVkl-RJ6ltAcAIRh_So54U8qmbWBDfn1SKbkrpHitI84ujDRYqpXXbhlouFZezUhtDAM9VFPEaZmUp0l5d6XiDd15NZq0dm1jSGG6dF7RAfNr2Kk0Y6QGhzCmOeb-RJWeV7kRp8vojFP-9-2dd9-RqnEVz9SYphDn5-SJVT7hi4d8TL6-f_fl7ENx8fn849nbi2Jfli0U2EheY6k0Gi24qKThVlrUBqSQVQ-6tY3oWa95a1HVuq9E3ZvGlrUVvFR1eUze3M-dYvixYJq7wSWNPu-PYUkda6GGpq0BMvr6P3Qfljjm7VaqyuKVkJl69UAt_YCmm6Ib8p26vzfPwOk98NN5vPn3z6Bbzeyymd3BzG57vj0U5R-IJpZP</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1805459549</pqid></control><display><type>article</type><title>Massive excretion of calcium oxalate from late prepupal salivary glands of Drosophila melanogaster demonstrates active nephridial‐like anion transport</title><source>MEDLINE</source><source>Wiley Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Wiley Free Content</source><source>Open Access Titles of Japan</source><creator>Farkaš, Robert ; Pečeňová, Ludmila ; Mentelová, Lucia ; Beňo, Milan ; Beňová‐Liszeková, Denisa ; Mahmoodová, Silvia ; Tejnecký, Václav ; Raška, Otakar ; Juda, Pavel ; Svidenská, Silvie ; Hornáček, Matúš ; Chase, Bruce A. ; Raška, Ivan</creator><creatorcontrib>Farkaš, Robert ; Pečeňová, Ludmila ; Mentelová, Lucia ; Beňo, Milan ; Beňová‐Liszeková, Denisa ; Mahmoodová, Silvia ; Tejnecký, Václav ; Raška, Otakar ; Juda, Pavel ; Svidenská, Silvie ; Hornáček, Matúš ; Chase, Bruce A. ; Raška, Ivan</creatorcontrib><description>The Drosophila salivary glands (SGs) were well known for the puffing patterns of their polytene chromosomes and so became a tissue of choice to study sequential gene activation by the steroid hormone ecdysone. One well‐documented function of these glands is to produce a secretory glue, which is released during pupariation to fix the freshly formed puparia to the substrate. Over the past two decades SGs have been used to address specific aspects of developmentally‐regulated programmed cell death (PCD) as it was thought that they are doomed for histolysis and after pupariation are just awaiting their fate. More recently, however, we have shown that for the first 3–4 h after pupariation SGs undergo tremendous endocytosis and vacuolation followed by vacuole neutralization and membrane consolidation. Furthermore, from 8 to 10 h after puparium formation (APF) SGs display massive apocrine secretion of a diverse set of cellular proteins. Here, we show that during the period from 11 to 12 h APF, the prepupal glands are very active in calcium oxalate (CaOx) extrusion that resembles renal or nephridial excretory activity. We provide genetic evidence that Prestin, a Drosophila homologue of the mammalian electrogenic anion exchange carrier SLC26A5, is responsible for the instantaneous production of CaOx by the late prepupal SGs. Its positive regulation by the protein kinases encoded by fray and wnk lead to increased production of CaOx. The formation of CaOx appears to be dependent on the cooperation between Prestin and the vATPase complex as treatment with bafilomycin A1 or concanamycin A abolishes the production of detectable CaOx. These data demonstrate that prepupal SGs remain fully viable, physiologically active and engaged in various cellular activities at least until early pupal period, that is, until moments prior to the execution of PCD. Description of a new and unexpected function of late prepupal salivary glands of Drosophila melanogaster: production and release of calcium oxalate which strongly resembles renal or nephridial excretory activity.</description><identifier>ISSN: 0012-1592</identifier><identifier>EISSN: 1440-169X</identifier><identifier>DOI: 10.1111/dgd.12300</identifier><identifier>PMID: 27397870</identifier><identifier>CODEN: DGDFA5</identifier><language>eng</language><publisher>Japan: Wiley Subscription Services, Inc</publisher><subject>Animals ; anion extrusion ; Anion Transport Proteins - biosynthesis ; Anion Transport Proteins - genetics ; Anion Transport Proteins - metabolism ; Biological Transport, Active - physiology ; calcium oxalate ; Calcium Oxalate - metabolism ; Drosophila ; Drosophila melanogaster ; Drosophila Proteins - genetics ; Drosophila Proteins - metabolism ; fruitfly salivary glands ; labial nephridia ; prestin ; Protein-Serine-Threonine Kinases - genetics ; Protein-Serine-Threonine Kinases - metabolism ; Salivary Glands - secretion</subject><ispartof>Development, growth &amp; differentiation, 2016-08, Vol.58 (6), p.562-574</ispartof><rights>2016 Japanese Society of Developmental Biologists</rights><rights>2016 Japanese Society of Developmental Biologists.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fdgd.12300$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fdgd.12300$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27397870$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Farkaš, Robert</creatorcontrib><creatorcontrib>Pečeňová, Ludmila</creatorcontrib><creatorcontrib>Mentelová, Lucia</creatorcontrib><creatorcontrib>Beňo, Milan</creatorcontrib><creatorcontrib>Beňová‐Liszeková, Denisa</creatorcontrib><creatorcontrib>Mahmoodová, Silvia</creatorcontrib><creatorcontrib>Tejnecký, Václav</creatorcontrib><creatorcontrib>Raška, Otakar</creatorcontrib><creatorcontrib>Juda, Pavel</creatorcontrib><creatorcontrib>Svidenská, Silvie</creatorcontrib><creatorcontrib>Hornáček, Matúš</creatorcontrib><creatorcontrib>Chase, Bruce A.</creatorcontrib><creatorcontrib>Raška, Ivan</creatorcontrib><title>Massive excretion of calcium oxalate from late prepupal salivary glands of Drosophila melanogaster demonstrates active nephridial‐like anion transport</title><title>Development, growth &amp; differentiation</title><addtitle>Dev Growth Differ</addtitle><description>The Drosophila salivary glands (SGs) were well known for the puffing patterns of their polytene chromosomes and so became a tissue of choice to study sequential gene activation by the steroid hormone ecdysone. One well‐documented function of these glands is to produce a secretory glue, which is released during pupariation to fix the freshly formed puparia to the substrate. Over the past two decades SGs have been used to address specific aspects of developmentally‐regulated programmed cell death (PCD) as it was thought that they are doomed for histolysis and after pupariation are just awaiting their fate. More recently, however, we have shown that for the first 3–4 h after pupariation SGs undergo tremendous endocytosis and vacuolation followed by vacuole neutralization and membrane consolidation. Furthermore, from 8 to 10 h after puparium formation (APF) SGs display massive apocrine secretion of a diverse set of cellular proteins. Here, we show that during the period from 11 to 12 h APF, the prepupal glands are very active in calcium oxalate (CaOx) extrusion that resembles renal or nephridial excretory activity. We provide genetic evidence that Prestin, a Drosophila homologue of the mammalian electrogenic anion exchange carrier SLC26A5, is responsible for the instantaneous production of CaOx by the late prepupal SGs. Its positive regulation by the protein kinases encoded by fray and wnk lead to increased production of CaOx. The formation of CaOx appears to be dependent on the cooperation between Prestin and the vATPase complex as treatment with bafilomycin A1 or concanamycin A abolishes the production of detectable CaOx. These data demonstrate that prepupal SGs remain fully viable, physiologically active and engaged in various cellular activities at least until early pupal period, that is, until moments prior to the execution of PCD. Description of a new and unexpected function of late prepupal salivary glands of Drosophila melanogaster: production and release of calcium oxalate which strongly resembles renal or nephridial excretory activity.</description><subject>Animals</subject><subject>anion extrusion</subject><subject>Anion Transport Proteins - biosynthesis</subject><subject>Anion Transport Proteins - genetics</subject><subject>Anion Transport Proteins - metabolism</subject><subject>Biological Transport, Active - physiology</subject><subject>calcium oxalate</subject><subject>Calcium Oxalate - metabolism</subject><subject>Drosophila</subject><subject>Drosophila melanogaster</subject><subject>Drosophila Proteins - genetics</subject><subject>Drosophila Proteins - metabolism</subject><subject>fruitfly salivary glands</subject><subject>labial nephridia</subject><subject>prestin</subject><subject>Protein-Serine-Threonine Kinases - genetics</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Salivary Glands - secretion</subject><issn>0012-1592</issn><issn>1440-169X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc9u1DAQxi0EokvhwAsgS1y4pB07zh8fURcKUhEXkLhFjj3eenHiYCelvfUReuT5eBKcbeHAXGZk_2a-0XyEvGRwwnKcmp05YbwEeEQ2TAgoWC2_PSYbAMYLVkl-RJ6ltAcAIRh_So54U8qmbWBDfn1SKbkrpHitI84ujDRYqpXXbhlouFZezUhtDAM9VFPEaZmUp0l5d6XiDd15NZq0dm1jSGG6dF7RAfNr2Kk0Y6QGhzCmOeb-RJWeV7kRp8vojFP-9-2dd9-RqnEVz9SYphDn5-SJVT7hi4d8TL6-f_fl7ENx8fn849nbi2Jfli0U2EheY6k0Gi24qKThVlrUBqSQVQ-6tY3oWa95a1HVuq9E3ZvGlrUVvFR1eUze3M-dYvixYJq7wSWNPu-PYUkda6GGpq0BMvr6P3Qfljjm7VaqyuKVkJl69UAt_YCmm6Ib8p26vzfPwOk98NN5vPn3z6Bbzeyymd3BzG57vj0U5R-IJpZP</recordid><startdate>201608</startdate><enddate>201608</enddate><creator>Farkaš, Robert</creator><creator>Pečeňová, Ludmila</creator><creator>Mentelová, Lucia</creator><creator>Beňo, Milan</creator><creator>Beňová‐Liszeková, Denisa</creator><creator>Mahmoodová, Silvia</creator><creator>Tejnecký, Václav</creator><creator>Raška, Otakar</creator><creator>Juda, Pavel</creator><creator>Svidenská, Silvie</creator><creator>Hornáček, Matúš</creator><creator>Chase, Bruce A.</creator><creator>Raška, Ivan</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7SS</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201608</creationdate><title>Massive excretion of calcium oxalate from late prepupal salivary glands of Drosophila melanogaster demonstrates active nephridial‐like anion transport</title><author>Farkaš, Robert ; Pečeňová, Ludmila ; Mentelová, Lucia ; Beňo, Milan ; Beňová‐Liszeková, Denisa ; Mahmoodová, Silvia ; Tejnecký, Václav ; Raška, Otakar ; Juda, Pavel ; Svidenská, Silvie ; Hornáček, Matúš ; Chase, Bruce A. ; Raška, Ivan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-j3380-e7926e3acedc42459d2f9fecd09495b0c8f74b1bc28fea6cb546bd7f36f423a63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>anion extrusion</topic><topic>Anion Transport Proteins - biosynthesis</topic><topic>Anion Transport Proteins - genetics</topic><topic>Anion Transport Proteins - metabolism</topic><topic>Biological Transport, Active - physiology</topic><topic>calcium oxalate</topic><topic>Calcium Oxalate - metabolism</topic><topic>Drosophila</topic><topic>Drosophila melanogaster</topic><topic>Drosophila Proteins - genetics</topic><topic>Drosophila Proteins - metabolism</topic><topic>fruitfly salivary glands</topic><topic>labial nephridia</topic><topic>prestin</topic><topic>Protein-Serine-Threonine Kinases - genetics</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>Salivary Glands - secretion</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Farkaš, Robert</creatorcontrib><creatorcontrib>Pečeňová, Ludmila</creatorcontrib><creatorcontrib>Mentelová, Lucia</creatorcontrib><creatorcontrib>Beňo, Milan</creatorcontrib><creatorcontrib>Beňová‐Liszeková, Denisa</creatorcontrib><creatorcontrib>Mahmoodová, Silvia</creatorcontrib><creatorcontrib>Tejnecký, Václav</creatorcontrib><creatorcontrib>Raška, Otakar</creatorcontrib><creatorcontrib>Juda, Pavel</creatorcontrib><creatorcontrib>Svidenská, Silvie</creatorcontrib><creatorcontrib>Hornáček, Matúš</creatorcontrib><creatorcontrib>Chase, Bruce A.</creatorcontrib><creatorcontrib>Raška, Ivan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Development, growth &amp; differentiation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Farkaš, Robert</au><au>Pečeňová, Ludmila</au><au>Mentelová, Lucia</au><au>Beňo, Milan</au><au>Beňová‐Liszeková, Denisa</au><au>Mahmoodová, Silvia</au><au>Tejnecký, Václav</au><au>Raška, Otakar</au><au>Juda, Pavel</au><au>Svidenská, Silvie</au><au>Hornáček, Matúš</au><au>Chase, Bruce A.</au><au>Raška, Ivan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Massive excretion of calcium oxalate from late prepupal salivary glands of Drosophila melanogaster demonstrates active nephridial‐like anion transport</atitle><jtitle>Development, growth &amp; differentiation</jtitle><addtitle>Dev Growth Differ</addtitle><date>2016-08</date><risdate>2016</risdate><volume>58</volume><issue>6</issue><spage>562</spage><epage>574</epage><pages>562-574</pages><issn>0012-1592</issn><eissn>1440-169X</eissn><coden>DGDFA5</coden><abstract>The Drosophila salivary glands (SGs) were well known for the puffing patterns of their polytene chromosomes and so became a tissue of choice to study sequential gene activation by the steroid hormone ecdysone. One well‐documented function of these glands is to produce a secretory glue, which is released during pupariation to fix the freshly formed puparia to the substrate. Over the past two decades SGs have been used to address specific aspects of developmentally‐regulated programmed cell death (PCD) as it was thought that they are doomed for histolysis and after pupariation are just awaiting their fate. More recently, however, we have shown that for the first 3–4 h after pupariation SGs undergo tremendous endocytosis and vacuolation followed by vacuole neutralization and membrane consolidation. Furthermore, from 8 to 10 h after puparium formation (APF) SGs display massive apocrine secretion of a diverse set of cellular proteins. Here, we show that during the period from 11 to 12 h APF, the prepupal glands are very active in calcium oxalate (CaOx) extrusion that resembles renal or nephridial excretory activity. We provide genetic evidence that Prestin, a Drosophila homologue of the mammalian electrogenic anion exchange carrier SLC26A5, is responsible for the instantaneous production of CaOx by the late prepupal SGs. Its positive regulation by the protein kinases encoded by fray and wnk lead to increased production of CaOx. The formation of CaOx appears to be dependent on the cooperation between Prestin and the vATPase complex as treatment with bafilomycin A1 or concanamycin A abolishes the production of detectable CaOx. These data demonstrate that prepupal SGs remain fully viable, physiologically active and engaged in various cellular activities at least until early pupal period, that is, until moments prior to the execution of PCD. Description of a new and unexpected function of late prepupal salivary glands of Drosophila melanogaster: production and release of calcium oxalate which strongly resembles renal or nephridial excretory activity.</abstract><cop>Japan</cop><pub>Wiley Subscription Services, Inc</pub><pmid>27397870</pmid><doi>10.1111/dgd.12300</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0012-1592
ispartof Development, growth & differentiation, 2016-08, Vol.58 (6), p.562-574
issn 0012-1592
1440-169X
language eng
recordid cdi_proquest_miscellaneous_1806078600
source MEDLINE; Wiley Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Wiley Free Content; Open Access Titles of Japan
subjects Animals
anion extrusion
Anion Transport Proteins - biosynthesis
Anion Transport Proteins - genetics
Anion Transport Proteins - metabolism
Biological Transport, Active - physiology
calcium oxalate
Calcium Oxalate - metabolism
Drosophila
Drosophila melanogaster
Drosophila Proteins - genetics
Drosophila Proteins - metabolism
fruitfly salivary glands
labial nephridia
prestin
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
Salivary Glands - secretion
title Massive excretion of calcium oxalate from late prepupal salivary glands of Drosophila melanogaster demonstrates active nephridial‐like anion transport
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T03%3A43%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Massive%20excretion%20of%20calcium%20oxalate%20from%20late%20prepupal%20salivary%20glands%20of%20Drosophila%20melanogaster%20demonstrates%20active%20nephridial%E2%80%90like%20anion%20transport&rft.jtitle=Development,%20growth%20&%20differentiation&rft.au=Farka%C5%A1,%20Robert&rft.date=2016-08&rft.volume=58&rft.issue=6&rft.spage=562&rft.epage=574&rft.pages=562-574&rft.issn=0012-1592&rft.eissn=1440-169X&rft.coden=DGDFA5&rft_id=info:doi/10.1111/dgd.12300&rft_dat=%3Cproquest_pubme%3E1806078600%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1805459549&rft_id=info:pmid/27397870&rfr_iscdi=true