A single dopamine pathway underlies progressive locomotor deficits in a Drosophila model of Parkinson disease.
Identifieur interne : 000663 ( PubMed/Corpus ); précédent : 000662; suivant : 000664A single dopamine pathway underlies progressive locomotor deficits in a Drosophila model of Parkinson disease.
Auteurs : Thomas Riemensperger ; Abdul-Raouf Issa ; Ulrike Pech ; Hélène Coulom ; M Vân Nguy ; Marlène Cassar ; Mélanie Jacquet ; André Fiala ; Serge BirmanSource :
- Cell reports [ 2211-1247 ] ; 2013.
English descriptors
- KwdEn :
- Animals, Animals, Genetically Modified, Brain (metabolism), Disease Models, Animal, Dopamine (metabolism), Dopaminergic Neurons (metabolism), Drosophila Proteins (metabolism), Drosophila melanogaster (metabolism), Female, Green Fluorescent Proteins (genetics), Humans, Locomotion (genetics), Locomotion (physiology), Mushroom Bodies (innervation), Oxidative Stress, Parkinson Disease (metabolism), Parkinson Disease (physiopathology), Reflex, Startle (genetics), Reflex, Startle (physiology), Signal Transduction, TRPC Cation Channels (metabolism), alpha-Synuclein (biosynthesis), alpha-Synuclein (genetics).
- MESH :
- chemical , biosynthesis : alpha-Synuclein.
- chemical , genetics : Green Fluorescent Proteins, alpha-Synuclein.
- chemical , metabolism : Dopamine, Drosophila Proteins, TRPC Cation Channels.
- genetics : Locomotion, Reflex, Startle.
- innervation : Mushroom Bodies.
- metabolism : Brain, Dopaminergic Neurons, Drosophila melanogaster, Parkinson Disease.
- physiology : Locomotion, Reflex, Startle.
- physiopathology : Parkinson Disease.
- Animals, Animals, Genetically Modified, Disease Models, Animal, Female, Humans, Oxidative Stress, Signal Transduction.
Abstract
Expression of the human Parkinson-disease-associated protein α-synuclein in all Drosophila neurons induces progressive locomotor deficits. Here, we identify a group of 15 dopaminergic neurons per hemisphere in the anterior medial region of the brain whose disruption correlates with climbing impairments in this model. These neurons selectively innervate the horizontal β and β' lobes of the mushroom bodies, and their connections to the Kenyon cells are markedly reduced when they express α-synuclein. Using selective mushroom body drivers, we show that blocking or overstimulating neuronal activity in the β' lobe, but not the β or γ lobes, significantly inhibits negative geotaxis behavior. This suggests that modulation of the mushroom body β' lobes by this dopaminergic pathway is specifically required for an efficient control of startle-induced locomotion in flies.
DOI: 10.1016/j.celrep.2013.10.032
PubMed: 24239353
Links to Exploration step
pubmed:24239353Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A single dopamine pathway underlies progressive locomotor deficits in a Drosophila model of Parkinson disease.</title>
<author><name sortKey="Riemensperger, Thomas" sort="Riemensperger, Thomas" uniqKey="Riemensperger T" first="Thomas" last="Riemensperger">Thomas Riemensperger</name>
<affiliation><nlm:affiliation>Genetics and Physiopathology of Neurotransmission, Neurobiology Unit, CNRS, ESPCI ParisTech, 10 rue Vauquelin, 75005 Paris, France; Molecular Neurobiology of Behaviour, Johann-Friedrich-Blumenbach Institute, Georg-August-University of Goettingen, Schwann-Schleiden Research Center, Julia-Lermontowa Weg 3, 37077 Goettingen, Germany. Electronic address: triemen@gwdg.de.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Issa, Abdul Raouf" sort="Issa, Abdul Raouf" uniqKey="Issa A" first="Abdul-Raouf" last="Issa">Abdul-Raouf Issa</name>
</author>
<author><name sortKey="Pech, Ulrike" sort="Pech, Ulrike" uniqKey="Pech U" first="Ulrike" last="Pech">Ulrike Pech</name>
</author>
<author><name sortKey="Coulom, Helene" sort="Coulom, Helene" uniqKey="Coulom H" first="Hélène" last="Coulom">Hélène Coulom</name>
</author>
<author><name sortKey="Nguy, M Van" sort="Nguy, M Van" uniqKey="Nguy M" first="M Vân" last="Nguy">M Vân Nguy</name>
</author>
<author><name sortKey="Cassar, Marlene" sort="Cassar, Marlene" uniqKey="Cassar M" first="Marlène" last="Cassar">Marlène Cassar</name>
</author>
<author><name sortKey="Jacquet, Melanie" sort="Jacquet, Melanie" uniqKey="Jacquet M" first="Mélanie" last="Jacquet">Mélanie Jacquet</name>
</author>
<author><name sortKey="Fiala, Andre" sort="Fiala, Andre" uniqKey="Fiala A" first="André" last="Fiala">André Fiala</name>
</author>
<author><name sortKey="Birman, Serge" sort="Birman, Serge" uniqKey="Birman S" first="Serge" last="Birman">Serge Birman</name>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2013">2013</date>
<idno type="RBID">pubmed:24239353</idno>
<idno type="pmid">24239353</idno>
<idno type="doi">10.1016/j.celrep.2013.10.032</idno>
<idno type="wicri:Area/PubMed/Corpus">000663</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000663</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">A single dopamine pathway underlies progressive locomotor deficits in a Drosophila model of Parkinson disease.</title>
<author><name sortKey="Riemensperger, Thomas" sort="Riemensperger, Thomas" uniqKey="Riemensperger T" first="Thomas" last="Riemensperger">Thomas Riemensperger</name>
<affiliation><nlm:affiliation>Genetics and Physiopathology of Neurotransmission, Neurobiology Unit, CNRS, ESPCI ParisTech, 10 rue Vauquelin, 75005 Paris, France; Molecular Neurobiology of Behaviour, Johann-Friedrich-Blumenbach Institute, Georg-August-University of Goettingen, Schwann-Schleiden Research Center, Julia-Lermontowa Weg 3, 37077 Goettingen, Germany. Electronic address: triemen@gwdg.de.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Issa, Abdul Raouf" sort="Issa, Abdul Raouf" uniqKey="Issa A" first="Abdul-Raouf" last="Issa">Abdul-Raouf Issa</name>
</author>
<author><name sortKey="Pech, Ulrike" sort="Pech, Ulrike" uniqKey="Pech U" first="Ulrike" last="Pech">Ulrike Pech</name>
</author>
<author><name sortKey="Coulom, Helene" sort="Coulom, Helene" uniqKey="Coulom H" first="Hélène" last="Coulom">Hélène Coulom</name>
</author>
<author><name sortKey="Nguy, M Van" sort="Nguy, M Van" uniqKey="Nguy M" first="M Vân" last="Nguy">M Vân Nguy</name>
</author>
<author><name sortKey="Cassar, Marlene" sort="Cassar, Marlene" uniqKey="Cassar M" first="Marlène" last="Cassar">Marlène Cassar</name>
</author>
<author><name sortKey="Jacquet, Melanie" sort="Jacquet, Melanie" uniqKey="Jacquet M" first="Mélanie" last="Jacquet">Mélanie Jacquet</name>
</author>
<author><name sortKey="Fiala, Andre" sort="Fiala, Andre" uniqKey="Fiala A" first="André" last="Fiala">André Fiala</name>
</author>
<author><name sortKey="Birman, Serge" sort="Birman, Serge" uniqKey="Birman S" first="Serge" last="Birman">Serge Birman</name>
</author>
</analytic>
<series><title level="j">Cell reports</title>
<idno type="eISSN">2211-1247</idno>
<imprint><date when="2013" type="published">2013</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Animals, Genetically Modified</term>
<term>Brain (metabolism)</term>
<term>Disease Models, Animal</term>
<term>Dopamine (metabolism)</term>
<term>Dopaminergic Neurons (metabolism)</term>
<term>Drosophila Proteins (metabolism)</term>
<term>Drosophila melanogaster (metabolism)</term>
<term>Female</term>
<term>Green Fluorescent Proteins (genetics)</term>
<term>Humans</term>
<term>Locomotion (genetics)</term>
<term>Locomotion (physiology)</term>
<term>Mushroom Bodies (innervation)</term>
<term>Oxidative Stress</term>
<term>Parkinson Disease (metabolism)</term>
<term>Parkinson Disease (physiopathology)</term>
<term>Reflex, Startle (genetics)</term>
<term>Reflex, Startle (physiology)</term>
<term>Signal Transduction</term>
<term>TRPC Cation Channels (metabolism)</term>
<term>alpha-Synuclein (biosynthesis)</term>
<term>alpha-Synuclein (genetics)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>alpha-Synuclein</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Green Fluorescent Proteins</term>
<term>alpha-Synuclein</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dopamine</term>
<term>Drosophila Proteins</term>
<term>TRPC Cation Channels</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Locomotion</term>
<term>Reflex, Startle</term>
</keywords>
<keywords scheme="MESH" qualifier="innervation" xml:lang="en"><term>Mushroom Bodies</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Brain</term>
<term>Dopaminergic Neurons</term>
<term>Drosophila melanogaster</term>
<term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Locomotion</term>
<term>Reflex, Startle</term>
</keywords>
<keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Animals, Genetically Modified</term>
<term>Disease Models, Animal</term>
<term>Female</term>
<term>Humans</term>
<term>Oxidative Stress</term>
<term>Signal Transduction</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Expression of the human Parkinson-disease-associated protein α-synuclein in all Drosophila neurons induces progressive locomotor deficits. Here, we identify a group of 15 dopaminergic neurons per hemisphere in the anterior medial region of the brain whose disruption correlates with climbing impairments in this model. These neurons selectively innervate the horizontal β and β' lobes of the mushroom bodies, and their connections to the Kenyon cells are markedly reduced when they express α-synuclein. Using selective mushroom body drivers, we show that blocking or overstimulating neuronal activity in the β' lobe, but not the β or γ lobes, significantly inhibits negative geotaxis behavior. This suggests that modulation of the mushroom body β' lobes by this dopaminergic pathway is specifically required for an efficient control of startle-induced locomotion in flies.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">24239353</PMID>
<DateCreated><Year>2013</Year>
<Month>12</Month>
<Day>02</Day>
</DateCreated>
<DateCompleted><Year>2014</Year>
<Month>08</Month>
<Day>19</Day>
</DateCompleted>
<DateRevised><Year>2014</Year>
<Month>11</Month>
<Day>20</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">2211-1247</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>5</Volume>
<Issue>4</Issue>
<PubDate><Year>2013</Year>
<Month>Nov</Month>
<Day>27</Day>
</PubDate>
</JournalIssue>
<Title>Cell reports</Title>
<ISOAbbreviation>Cell Rep</ISOAbbreviation>
</Journal>
<ArticleTitle>A single dopamine pathway underlies progressive locomotor deficits in a Drosophila model of Parkinson disease.</ArticleTitle>
<Pagination><MedlinePgn>952-60</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1016/j.celrep.2013.10.032</ELocationID>
<ELocationID EIdType="pii" ValidYN="Y">S2211-1247(13)00616-5</ELocationID>
<Abstract><AbstractText>Expression of the human Parkinson-disease-associated protein α-synuclein in all Drosophila neurons induces progressive locomotor deficits. Here, we identify a group of 15 dopaminergic neurons per hemisphere in the anterior medial region of the brain whose disruption correlates with climbing impairments in this model. These neurons selectively innervate the horizontal β and β' lobes of the mushroom bodies, and their connections to the Kenyon cells are markedly reduced when they express α-synuclein. Using selective mushroom body drivers, we show that blocking or overstimulating neuronal activity in the β' lobe, but not the β or γ lobes, significantly inhibits negative geotaxis behavior. This suggests that modulation of the mushroom body β' lobes by this dopaminergic pathway is specifically required for an efficient control of startle-induced locomotion in flies.</AbstractText>
<CopyrightInformation>Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Riemensperger</LastName>
<ForeName>Thomas</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>Genetics and Physiopathology of Neurotransmission, Neurobiology Unit, CNRS, ESPCI ParisTech, 10 rue Vauquelin, 75005 Paris, France; Molecular Neurobiology of Behaviour, Johann-Friedrich-Blumenbach Institute, Georg-August-University of Goettingen, Schwann-Schleiden Research Center, Julia-Lermontowa Weg 3, 37077 Goettingen, Germany. Electronic address: triemen@gwdg.de.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Issa</LastName>
<ForeName>Abdul-Raouf</ForeName>
<Initials>AR</Initials>
</Author>
<Author ValidYN="Y"><LastName>Pech</LastName>
<ForeName>Ulrike</ForeName>
<Initials>U</Initials>
</Author>
<Author ValidYN="Y"><LastName>Coulom</LastName>
<ForeName>Hélène</ForeName>
<Initials>H</Initials>
</Author>
<Author ValidYN="Y"><LastName>Nguyễn</LastName>
<ForeName>Mỹ-Vân</ForeName>
<Initials>MV</Initials>
</Author>
<Author ValidYN="Y"><LastName>Cassar</LastName>
<ForeName>Marlène</ForeName>
<Initials>M</Initials>
</Author>
<Author ValidYN="Y"><LastName>Jacquet</LastName>
<ForeName>Mélanie</ForeName>
<Initials>M</Initials>
</Author>
<Author ValidYN="Y"><LastName>Fiala</LastName>
<ForeName>André</ForeName>
<Initials>A</Initials>
</Author>
<Author ValidYN="Y"><LastName>Birman</LastName>
<ForeName>Serge</ForeName>
<Initials>S</Initials>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>R01-GM084947</GrantID>
<Acronym>GM</Acronym>
<Agency>NIGMS NIH HHS</Agency>
<Country>United States</Country>
</Grant>
</GrantList>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2013</Year>
<Month>11</Month>
<Day>14</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>Cell Rep</MedlineTA>
<NlmUniqueID>101573691</NlmUniqueID>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D029721">Drosophila Proteins</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D050052">TRPC Cation Channels</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C530642">TrpA1 protein, Drosophila</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D051844">alpha-Synuclein</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>147336-22-9</RegistryNumber>
<NameOfSubstance UI="D049452">Green Fluorescent Proteins</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>VTD58H1Z2X</RegistryNumber>
<NameOfSubstance UI="D004298">Dopamine</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D030801" MajorTopicYN="N">Animals, Genetically Modified</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D001921" MajorTopicYN="N">Brain</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004195" MajorTopicYN="Y">Disease Models, Animal</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004298" MajorTopicYN="N">Dopamine</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D059290" MajorTopicYN="N">Dopaminergic Neurons</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D029721" MajorTopicYN="N">Drosophila Proteins</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004331" MajorTopicYN="N">Drosophila melanogaster</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D049452" MajorTopicYN="N">Green Fluorescent Proteins</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008124" MajorTopicYN="N">Locomotion</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D024521" MajorTopicYN="N">Mushroom Bodies</DescriptorName>
<QualifierName UI="Q000294" MajorTopicYN="N">innervation</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018384" MajorTopicYN="N">Oxidative Stress</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D010300" MajorTopicYN="N">Parkinson Disease</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
<QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D013216" MajorTopicYN="N">Reflex, Startle</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D050052" MajorTopicYN="N">TRPC Cation Channels</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051844" MajorTopicYN="N">alpha-Synuclein</DescriptorName>
<QualifierName UI="Q000096" MajorTopicYN="N">biosynthesis</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
</MeshHeadingList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2012</Year>
<Month>12</Month>
<Day>29</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="revised"><Year>2013</Year>
<Month>09</Month>
<Day>18</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2013</Year>
<Month>10</Month>
<Day>21</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2013</Year>
<Month>11</Month>
<Day>19</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2013</Year>
<Month>11</Month>
<Day>19</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2014</Year>
<Month>8</Month>
<Day>20</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">24239353</ArticleId>
<ArticleId IdType="pii">S2211-1247(13)00616-5</ArticleId>
<ArticleId IdType="doi">10.1016/j.celrep.2013.10.032</ArticleId>
</ArticleIdList>
</PubmedData>
</pubmed>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonFranceV1/Data/PubMed/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000663 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PubMed/Corpus/biblio.hfd -nk 000663 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Sante |area= ParkinsonFranceV1 |flux= PubMed |étape= Corpus |type= RBID |clé= pubmed:24239353 |texte= A single dopamine pathway underlies progressive locomotor deficits in a Drosophila model of Parkinson disease. }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/PubMed/Corpus/RBID.i -Sk "pubmed:24239353" \ | HfdSelect -Kh $EXPLOR_AREA/Data/PubMed/Corpus/biblio.hfd \ | NlmPubMed2Wicri -a ParkinsonFranceV1
This area was generated with Dilib version V0.6.29. |