Evidence for a divergence in function between two glucocorticoid receptors from a basal teleost.
Identifieur interne : 000302 ( PubMed/Curation ); précédent : 000301; suivant : 000303Evidence for a divergence in function between two glucocorticoid receptors from a basal teleost.
Auteurs : Yi Li [Royaume-Uni] ; Armin Sturm ; Phil Cunningham ; Nicolas R. BurySource :
- BMC evolutionary biology [ 1471-2148 ] ; 2012.
English descriptors
- KwdEn :
- MESH :
- chemical , chemistry : Fish Proteins, Receptors, Glucocorticoid.
- chemical , genetics : Fish Proteins, Receptors, Glucocorticoid.
- genetics : Fishes.
- Animals, Evolution, Molecular, Phylogeny, Protein Structure, Tertiary.
Abstract
Duplicated glucocorticoid receptors (GR) are present in most teleost fish. The evolutionary advantage of retaining two GRs is unclear, as no subtype specific functional traits or physiological roles have been defined. To identify factors driving the retention of duplicate GRs in teleosts, the current study examined GRs in representatives of two basal ray-finned fish taxa that emerged either side of the teleost lineage whole genome duplication event (WGD) event, the acipenseriform, Acipenser ruthenus, (pre-WGD) and the osteoglossimorph, Pantodon buchholzi, (post-WGD).
DOI: 10.1186/1471-2148-12-137
PubMed: 22862956
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: Pour aller vers cette notice dans l'étape Curation :000302
Links to Exploration step
pubmed:22862956Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Evidence for a divergence in function between two glucocorticoid receptors from a basal teleost.</title><author><name sortKey="Li, Yi" sort="Li, Yi" uniqKey="Li Y" first="Yi" last="Li">Yi Li</name><affiliation wicri:level="1"><nlm:affiliation>Nutritional Sciences Research Division, King's College London, Franklin Wilkins Building, 150 Stamford Street, London SE1 9NH, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Nutritional Sciences Research Division, King's College London, Franklin Wilkins Building, 150 Stamford Street, London SE1 9NH</wicri:regionArea></affiliation></author><author><name sortKey="Sturm, Armin" sort="Sturm, Armin" uniqKey="Sturm A" first="Armin" last="Sturm">Armin Sturm</name></author><author><name sortKey="Cunningham, Phil" sort="Cunningham, Phil" uniqKey="Cunningham P" first="Phil" last="Cunningham">Phil Cunningham</name></author><author><name sortKey="Bury, Nicolas R" sort="Bury, Nicolas R" uniqKey="Bury N" first="Nicolas R" last="Bury">Nicolas R. Bury</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2012">2012</date><idno type="RBID">pubmed:22862956</idno><idno type="pmid">22862956</idno><idno type="doi">10.1186/1471-2148-12-137</idno><idno type="wicri:Area/PubMed/Corpus">000302</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000302</idno><idno type="wicri:Area/PubMed/Curation">000302</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000302</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Evidence for a divergence in function between two glucocorticoid receptors from a basal teleost.</title><author><name sortKey="Li, Yi" sort="Li, Yi" uniqKey="Li Y" first="Yi" last="Li">Yi Li</name><affiliation wicri:level="1"><nlm:affiliation>Nutritional Sciences Research Division, King's College London, Franklin Wilkins Building, 150 Stamford Street, London SE1 9NH, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Nutritional Sciences Research Division, King's College London, Franklin Wilkins Building, 150 Stamford Street, London SE1 9NH</wicri:regionArea></affiliation></author><author><name sortKey="Sturm, Armin" sort="Sturm, Armin" uniqKey="Sturm A" first="Armin" last="Sturm">Armin Sturm</name></author><author><name sortKey="Cunningham, Phil" sort="Cunningham, Phil" uniqKey="Cunningham P" first="Phil" last="Cunningham">Phil Cunningham</name></author><author><name sortKey="Bury, Nicolas R" sort="Bury, Nicolas R" uniqKey="Bury N" first="Nicolas R" last="Bury">Nicolas R. Bury</name></author></analytic><series><title level="j">BMC evolutionary biology</title><idno type="eISSN">1471-2148</idno><imprint><date when="2012" type="published">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Evolution, Molecular</term><term>Fish Proteins (chemistry)</term><term>Fish Proteins (genetics)</term><term>Fishes (genetics)</term><term>Phylogeny</term><term>Protein Structure, Tertiary</term><term>Receptors, Glucocorticoid (chemistry)</term><term>Receptors, Glucocorticoid (genetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Fish Proteins</term><term>Receptors, Glucocorticoid</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Fish Proteins</term><term>Receptors, Glucocorticoid</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Fishes</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Evolution, Molecular</term><term>Phylogeny</term><term>Protein Structure, Tertiary</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Duplicated glucocorticoid receptors (GR) are present in most teleost fish. The evolutionary advantage of retaining two GRs is unclear, as no subtype specific functional traits or physiological roles have been defined. To identify factors driving the retention of duplicate GRs in teleosts, the current study examined GRs in representatives of two basal ray-finned fish taxa that emerged either side of the teleost lineage whole genome duplication event (WGD) event, the acipenseriform, Acipenser ruthenus, (pre-WGD) and the osteoglossimorph, Pantodon buchholzi, (post-WGD).</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">22862956</PMID><DateCreated><Year>2012</Year><Month>09</Month><Day>26</Day></DateCreated><DateCompleted><Year>2012</Year><Month>12</Month><Day>11</Day></DateCompleted><DateRevised><Year>2016</Year><Month>10</Month><Day>19</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1471-2148</ISSN><JournalIssue CitedMedium="Internet"><Volume>12</Volume><PubDate><Year>2012</Year><Month>Aug</Month><Day>03</Day></PubDate></JournalIssue><Title>BMC evolutionary biology</Title><ISOAbbreviation>BMC Evol. Biol.</ISOAbbreviation></Journal><ArticleTitle>Evidence for a divergence in function between two glucocorticoid receptors from a basal teleost.</ArticleTitle><Pagination><MedlinePgn>137</MedlinePgn></Pagination><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Duplicated glucocorticoid receptors (GR) are present in most teleost fish. The evolutionary advantage of retaining two GRs is unclear, as no subtype specific functional traits or physiological roles have been defined. To identify factors driving the retention of duplicate GRs in teleosts, the current study examined GRs in representatives of two basal ray-finned fish taxa that emerged either side of the teleost lineage whole genome duplication event (WGD) event, the acipenseriform, Acipenser ruthenus, (pre-WGD) and the osteoglossimorph, Pantodon buchholzi, (post-WGD).</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">The study identified a single GR in A. ruthenus (ArGR) and two GRs in P. buchholzi (PbGR1 and PbGR2). Phylogenetic analyses showed that ArGR formed a distinct branch separate from the teleosts GRs. The teleost GR lineage was subdivded into two sublineages, each of which contained one of the two P. buchholzi GRs. ArGR, PbGR1 and PbGR2 all possess the unique 9 amino acid insert between the zinc-fingers of the DNA-binding domain that is present in one of the teleost GR lineages (GR1), but not the other (GR2). A splice variant of PbGR2 produces an isoform that lacked these 9 amino acids (PbGR2b). Cortisol stimulated transactivation activity of ArGR, PbGR2b and PbGR1 in vitro; with PbGR2b and PbGR1, the glucocorticoid 11-deoxycortisol was a more potent agonist than cortisol. The hormone sensitivity of PbGR2b and PbGR1 differed in the transactivation assay, with PbGR2b having lower EC50 values and greater fold induction.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">The difference in transactivation activity sensitivity between duplicated GRs of P. buchholzi suggests potential functional differences between the paralogs emerged early in the teleost lineage. Given the pleiotropic nature of GR function in vertebrates, this finding is in accordance with the hypothesis that duplicated GRs were potentially retained through subfunctionalisation followed by gene sharing. A 9 amino acid insert in the DNA-binding domain emerged in basal ray-finned fish GRs. However, the presence of a PbGR2 splice variant that lacks this insert, as well as the loss of the exon encoding these amino acids in the genes encoding for other teleost GR2 suggests the selection of two receptors with different DNA-binding domain structures in teleosts.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Yi</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Nutritional Sciences Research Division, King's College London, Franklin Wilkins Building, 150 Stamford Street, London SE1 9NH, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sturm</LastName><ForeName>Armin</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Cunningham</LastName><ForeName>Phil</ForeName><Initials>P</Initials></Author><Author ValidYN="Y"><LastName>Bury</LastName><ForeName>Nicolas R</ForeName><Initials>NR</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>BB/E001637/1</GrantID><Agency>Biotechnology and Biological Sciences Research Council</Agency><Country>United Kingdom</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2012</Year><Month>08</Month><Day>03</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>BMC Evol Biol</MedlineTA><NlmUniqueID>100966975</NlmUniqueID><ISSNLinking>1471-2148</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D029941">Fish Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011965">Receptors, Glucocorticoid</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>BMC Evol Biol. 2011;11:14</RefSource><PMID Version="1">21232159</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Gen Comp Endocrinol. 2007 Aug-Sep;153(1-3):47-56</RefSource><PMID Version="1">17470371</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Mar 15;879(9-10):591-8</RefSource><PMID Version="1">21317049</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Gen Comp Endocrinol. 2011 May 1;171(3):341-9</RefSource><PMID Version="1">21362423</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Comp Biochem Physiol Part D Genomics Proteomics. 2011 Jun;6(2):126-32</RefSource><PMID Version="1">21220219</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>PLoS Biol. 2007 Apr;5(4):e101</RefSource><PMID Version="1">17407382</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Science. 2007 Sep 14;317(5844):1544-8</RefSource><PMID Version="1">17702911</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Rev Endocr Metab Disord. 2007 Dec;8(4):321-30</RefSource><PMID Version="1">18049904</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Endocrinology. 2008 Apr;149(4):1591-9</RefSource><PMID Version="1">18096659</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Genome Res. 2008 Jul;18(7):1100-11</RefSource><PMID Version="1">18562680</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Endocrinol. 2008 Aug;198(2):403-17</RefSource><PMID Version="1">18505847</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Endocrinology. 2008 Sep;149(9):4567-76</RefSource><PMID Version="1">18483153</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Endocrinology. 2009 Apr;150(4):1731-8</RefSource><PMID Version="1">19036877</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Science. 2009 Apr 17;324(5925):407-10</RefSource><PMID Version="1">19372434</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Hered. 2009 Sep-Oct;100(5):605-17</RefSource><PMID Version="1">19596713</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Endocrinology. 2009 Dec;150(12):5415-27</RefSource><PMID Version="1">19819965</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13942-7</RefSource><PMID Version="1">20643930</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Mol Endocrinol. 2010 Dec;45(6):391-404</RefSource><PMID Version="1">20921243</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nucleic Acids Res. 2011 Jul;39(Web Server issue):W13-7</RefSource><PMID Version="1">21558174</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Mol Biol Evol. 2011 Oct;28(10):2731-9</RefSource><PMID Version="1">21546353</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Gen Comp Endocrinol. 2012 Jan 15;175(2):244-50</RefSource><PMID Version="1">22137911</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Cell. 2002 Jul 12;110(1):93-105</RefSource><PMID Version="1">12151000</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Mol Cell Endocrinol. 2002 Aug 30;194(1-2):107-16</RefSource><PMID Version="1">12242033</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Mol Endocrinol. 2003 Aug;31(1):141-56</RefSource><PMID Version="1">12914532</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Endocrinology. 2003 Oct;144(10):4226-36</RefSource><PMID Version="1">12959971</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Science. 2003 Sep 19;301(5640):1714-7</RefSource><PMID Version="1">14500980</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Toxicol Appl Pharmacol. 2004 Mar 1;195(2):247-61</RefSource><PMID Version="1">14998689</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Trends Genet. 2004 Nov;20(11):544-9</RefSource><PMID Version="1">15475113</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Mol Evol. 2004 Aug;59(2):190-203</RefSource><PMID Version="1">15486693</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nature. 2004 Oct 21;431(7011):946-57</RefSource><PMID Version="1">15496914</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Gen Comp Endocrinol. 1976 May;29(1):14-20</RefSource><PMID Version="1">939413</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nature. 1985 Dec 19-1986 Jan 1;318(6047):635-41</RefSource><PMID Version="1">2867473</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Cell. 1986 Aug 1;46(3):389-99</RefSource><PMID Version="1">3755378</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Science. 1987 Jul 17;237(4812):268-75</RefSource><PMID Version="1">3037703</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Endocrinology. 1995 Sep;136(9):3774-83</RefSource><PMID Version="1">7649084</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Physiol Rev. 1997 Jul;77(3):591-625</RefSource><PMID Version="1">9234959</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Curr Opin Nephrol Hypertens. 1999 Jan;8(1):45-51</RefSource><PMID Version="1">9914860</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Genetics. 1999 Apr;151(4):1531-45</RefSource><PMID Version="1">10101175</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Endocrinology. 2005 Jan;146(1):47-55</RefSource><PMID Version="1">15486226</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Annu Rev Physiol. 2005;67:259-84</RefSource><PMID Version="1">15709959</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Science. 2006 Apr 7;312(5770):97-101</RefSource><PMID Version="1">16601189</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Am J Physiol Cell Physiol. 2006 Jun;290(6):C1560-71</RefSource><PMID Version="1">16421205</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Endocrinol. 2006 Jul;190(1):17-28</RefSource><PMID Version="1">16837607</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Endocrinology. 2006 Aug;147(8):3861-9</RefSource><PMID Version="1">16690796</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Mol Biol Evol. 2006 Sep;23(9):1808-16</RefSource><PMID Version="1">16809621</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Gen Comp Endocrinol. 2007 Jun-Jul;152(2-3):295-303</RefSource><PMID Version="1">17289045</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Endocrinology. 2007 Aug;148(8):3554-65</RefSource><PMID Version="1">17446181</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Mol Cell Endocrinol. 2011 Feb 20;333(2):181-9</RefSource><PMID Version="1">21215791</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019143" MajorTopicYN="Y">Evolution, Molecular</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D029941" MajorTopicYN="N">Fish Proteins</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005399" MajorTopicYN="N">Fishes</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010802" MajorTopicYN="N">Phylogeny</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017434" MajorTopicYN="N">Protein Structure, Tertiary</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011965" MajorTopicYN="N">Receptors, Glucocorticoid</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading></MeshHeadingList><OtherID Source="NLM">PMC3457903</OtherID></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2011</Year><Month>10</Month><Day>21</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2012</Year><Month>07</Month><Day>26</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2012</Year><Month>8</Month><Day>7</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2012</Year><Month>8</Month><Day>7</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2012</Year><Month>12</Month><Day>12</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">22862956</ArticleId><ArticleId IdType="pii">1471-2148-12-137</ArticleId><ArticleId IdType="doi">10.1186/1471-2148-12-137</ArticleId><ArticleId IdType="pmc">PMC3457903</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Eau/explor/EsturgeonV1/Data/PubMed/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000302 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PubMed/Curation/biblio.hfd -nk 000302 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Eau
|area= EsturgeonV1
|flux= PubMed
|étape= Curation
|type= RBID
|clé= pubmed:22862956
|texte= Evidence for a divergence in function between two glucocorticoid receptors from a basal teleost.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/PubMed/Curation/RBID.i -Sk "pubmed:22862956" \
| HfdSelect -Kh $EXPLOR_AREA/Data/PubMed/Curation/biblio.hfd \
| NlmPubMed2Wicri -a EsturgeonV1
| This area was generated with Dilib version V0.6.27. |  |