miR-206 controls LXRα expression and promotes LXR-mediated cholesterol efflux in macrophages
Identifieur interne : 001845 ( Ncbi/Checkpoint ); précédent : 001844; suivant : 001846miR-206 controls LXRα expression and promotes LXR-mediated cholesterol efflux in macrophages
Auteurs : Manjula Vinod [Autriche] ; Indumathi Chennamsetty [États-Unis] ; Sophie Colin [France] ; Loic Belloy [France] ; Federica De Paoli [France] ; Helmut Schaider [Australie] ; Wolfgang F. Graier [Autriche] ; Saša Frank [Autriche] ; Dagmar Kratky [Autriche] ; Bart Staels [France] ; Giulia Chinetti-Gbaguidi [France] ; Gerhard M. Kostner [Autriche]Source :
- Biochimica et Biophysica Acta [ 0006-3002 ] ; 2014.
Descripteurs français
- KwdFr :
- Animaux, Athérosclérose (anatomopathologie), Athérosclérose (génétique), Cellules HepG2, Cholestérol (génétique), Cholestérol (métabolisme), Humains, Hépatocytes (anatomopathologie), Hépatocytes (métabolisme), Macrophages (métabolisme), Métabolisme des lipides (génétique), Récepteurs hépatiques X, Récepteurs nucléaires orphelins (génétique), Récepteurs nucléaires orphelins (métabolisme), Régulation de l'expression des gènes, Souris, Souris knockout, Transduction du signal, microARN (génétique).
- MESH :
- anatomopathologie : Athérosclérose, Hépatocytes.
- génétique : Athérosclérose, Cholestérol, Métabolisme des lipides, Récepteurs nucléaires orphelins, microARN.
- métabolisme : Cholestérol, Hépatocytes, Macrophages, Récepteurs nucléaires orphelins.
- Animaux, Cellules HepG2, Humains, Récepteurs hépatiques X, Régulation de l'expression des gènes, Souris, Souris knockout, Transduction du signal.
English descriptors
- KwdEn :
- Animals, Atherosclerosis (genetics), Atherosclerosis (pathology), Cholesterol (genetics), Cholesterol (metabolism), Gene Expression Regulation, Hep G2 Cells, Hepatocytes (metabolism), Hepatocytes (pathology), Humans, Lipid Metabolism (genetics), Liver X Receptors, Macrophages (metabolism), Mice, Mice, Knockout, MicroRNAs (genetics), Orphan Nuclear Receptors (genetics), Orphan Nuclear Receptors (metabolism), Signal Transduction.
- MESH :
- chemical , genetics : Cholesterol, MicroRNAs, Orphan Nuclear Receptors.
- genetics : Atherosclerosis, Lipid Metabolism.
- chemical , metabolism : Cholesterol, Hepatocytes, Macrophages, Orphan Nuclear Receptors.
- pathology : Atherosclerosis, Hepatocytes.
- Animals, Gene Expression Regulation, Hep G2 Cells, Humans, Liver X Receptors, Mice, Mice, Knockout, Signal Transduction.
Abstract
Liver X receptors (LXRα and LXRβ) are key transcription factors in cholesterol metabolism that regulate cholesterol biosynthesis/efflux and bile acid metabolism/excretion in the liver and numerous organs. In macrophages, LXR signaling modulates cholesterol handling and the inflammatory response, pathways involved in atherosclerosis. Since regulatory pathways of LXR transcription control are well understood, in the present study we aimed at identifying post-transcriptional regulators of LXR activity. MicroRNAs (miRs) are such post-transcriptional regulators of genes that in the canonical pathway mediate mRNA inactivation. In silico analysis identified miR-206 as a putative regulator of LXRα but not LXRβ. Indeed, as recently shown, we found that miR-206 represses LXRα activity and expression of LXRα and its target genes in hepatic cells. Interestingly, miR-206 regulates LXRα differently in macrophages. Stably overexpressing miR-206 in THP-1 human macrophages revealed an up-regulation and miR-206 knockdown led to a down-regulation of LXRα and its target genes. In support of these results, bone marrow-derived macrophages (BMDMs) from miR-206 KO mice also exhibited lower expression of LXRα target genes. The physiological relevance of these findings was proven by gain- and loss-of-function of miR-206; overexpression of miR-206 enhanced cholesterol efflux in human macrophages and knocking out miR-206 decreased cholesterol efflux from MPMs. Moreover, we show that miR-206 expression in macrophages is repressed by LXRα activation, while oxidized LDL and inflammatory stimuli profoundly induced miR-206 expression. We therefore propose a feed-back loop between miR-206 and LXRα that might be part of an LXR auto-regulatory mechanism to fine tune LXR activity.
Url:
DOI: 10.1016/j.bbalip.2014.02.006
PubMed: 24603323
PubMed Central: 3996726
Affiliations:
- Australie, Autriche, France, États-Unis
- Hauts-de-France, Nord-Pas-de-Calais
- Lille
- Université Lille 2
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PMC:3996726Le document en format XML
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<affiliation wicri:level="1"><nlm:aff id="af0030">European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France</nlm:aff>
<country xml:lang="fr">France</country>
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<author><name sortKey="De Paoli, Federica" sort="De Paoli, Federica" uniqKey="De Paoli F" first="Federica" last="De Paoli">Federica De Paoli</name>
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<country xml:lang="fr">France</country>
<wicri:regionArea>Université Lille 2, F-59000 Lille</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:aff id="af0020">Inserm, U1011, F-59000 Lille, France</nlm:aff>
<country xml:lang="fr">France</country>
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<affiliation wicri:level="1"><nlm:aff id="af0025">Institut Pasteur de Lille, F-59019 Lille, France</nlm:aff>
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<affiliation wicri:level="1"><nlm:aff id="af0030">European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France</nlm:aff>
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</affiliation>
</author>
<author><name sortKey="Schaider, Helmut" sort="Schaider, Helmut" uniqKey="Schaider H" first="Helmut" last="Schaider">Helmut Schaider</name>
<affiliation wicri:level="1"><nlm:aff id="af0035">Translation Research Institute, University of Queensland, Brisbane, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Translation Research Institute, University of Queensland, Brisbane</wicri:regionArea>
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<author><name sortKey="Graier, Wolfgang F" sort="Graier, Wolfgang F" uniqKey="Graier W" first="Wolfgang F." last="Graier">Wolfgang F. Graier</name>
<affiliation wicri:level="1"><nlm:aff id="af0005">Institute of Molecular Biology and Biochemistry, Medical University of Graz, Austria</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Institute of Molecular Biology and Biochemistry, Medical University of Graz</wicri:regionArea>
<wicri:noRegion>Medical University of Graz</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Frank, Sasa" sort="Frank, Sasa" uniqKey="Frank S" first="Saša" last="Frank">Saša Frank</name>
<affiliation wicri:level="1"><nlm:aff id="af0005">Institute of Molecular Biology and Biochemistry, Medical University of Graz, Austria</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Institute of Molecular Biology and Biochemistry, Medical University of Graz</wicri:regionArea>
<wicri:noRegion>Medical University of Graz</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kratky, Dagmar" sort="Kratky, Dagmar" uniqKey="Kratky D" first="Dagmar" last="Kratky">Dagmar Kratky</name>
<affiliation wicri:level="1"><nlm:aff id="af0005">Institute of Molecular Biology and Biochemistry, Medical University of Graz, Austria</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Institute of Molecular Biology and Biochemistry, Medical University of Graz</wicri:regionArea>
<wicri:noRegion>Medical University of Graz</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Staels, Bart" sort="Staels, Bart" uniqKey="Staels B" first="Bart" last="Staels">Bart Staels</name>
<affiliation wicri:level="4"><nlm:aff id="af0015">Université Lille 2, F-59000 Lille, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Lille 2, F-59000 Lille</wicri:regionArea>
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<placeName><settlement type="city">Lille</settlement>
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<region type="old region" nuts="2">Nord-Pas-de-Calais</region>
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</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af0020">Inserm, U1011, F-59000 Lille, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Inserm, U1011, F-59000 Lille</wicri:regionArea>
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<wicri:noRegion>59000 Lille</wicri:noRegion>
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<affiliation wicri:level="1"><nlm:aff id="af0025">Institut Pasteur de Lille, F-59019 Lille, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut Pasteur de Lille, F-59019 Lille</wicri:regionArea>
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</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af0030">European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille</wicri:regionArea>
<wicri:noRegion>59000 Lille</wicri:noRegion>
<wicri:noRegion>59000 Lille</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chinetti Gbaguidi, Giulia" sort="Chinetti Gbaguidi, Giulia" uniqKey="Chinetti Gbaguidi G" first="Giulia" last="Chinetti-Gbaguidi">Giulia Chinetti-Gbaguidi</name>
<affiliation wicri:level="4"><nlm:aff id="af0015">Université Lille 2, F-59000 Lille, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Lille 2, F-59000 Lille</wicri:regionArea>
<wicri:noRegion>59000 Lille</wicri:noRegion>
<orgName type="university">Université Lille 2</orgName>
<placeName><settlement type="city">Lille</settlement>
<region type="region" nuts="2">Hauts-de-France</region>
<region type="old region" nuts="2">Nord-Pas-de-Calais</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af0020">Inserm, U1011, F-59000 Lille, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Inserm, U1011, F-59000 Lille</wicri:regionArea>
<wicri:noRegion>59000 Lille</wicri:noRegion>
<wicri:noRegion>59000 Lille</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af0025">Institut Pasteur de Lille, F-59019 Lille, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut Pasteur de Lille, F-59019 Lille</wicri:regionArea>
<wicri:noRegion>59019 Lille</wicri:noRegion>
<wicri:noRegion>59019 Lille</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af0030">European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille</wicri:regionArea>
<wicri:noRegion>59000 Lille</wicri:noRegion>
<wicri:noRegion>59000 Lille</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kostner, Gerhard M" sort="Kostner, Gerhard M" uniqKey="Kostner G" first="Gerhard M." last="Kostner">Gerhard M. Kostner</name>
<affiliation wicri:level="1"><nlm:aff id="af0005">Institute of Molecular Biology and Biochemistry, Medical University of Graz, Austria</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Institute of Molecular Biology and Biochemistry, Medical University of Graz</wicri:regionArea>
<wicri:noRegion>Medical University of Graz</wicri:noRegion>
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</analytic>
<series><title level="j">Biochimica et Biophysica Acta</title>
<idno type="ISSN">0006-3002</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Atherosclerosis (genetics)</term>
<term>Atherosclerosis (pathology)</term>
<term>Cholesterol (genetics)</term>
<term>Cholesterol (metabolism)</term>
<term>Gene Expression Regulation</term>
<term>Hep G2 Cells</term>
<term>Hepatocytes (metabolism)</term>
<term>Hepatocytes (pathology)</term>
<term>Humans</term>
<term>Lipid Metabolism (genetics)</term>
<term>Liver X Receptors</term>
<term>Macrophages (metabolism)</term>
<term>Mice</term>
<term>Mice, Knockout</term>
<term>MicroRNAs (genetics)</term>
<term>Orphan Nuclear Receptors (genetics)</term>
<term>Orphan Nuclear Receptors (metabolism)</term>
<term>Signal Transduction</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Athérosclérose (anatomopathologie)</term>
<term>Athérosclérose (génétique)</term>
<term>Cellules HepG2</term>
<term>Cholestérol (génétique)</term>
<term>Cholestérol (métabolisme)</term>
<term>Humains</term>
<term>Hépatocytes (anatomopathologie)</term>
<term>Hépatocytes (métabolisme)</term>
<term>Macrophages (métabolisme)</term>
<term>Métabolisme des lipides (génétique)</term>
<term>Récepteurs hépatiques X</term>
<term>Récepteurs nucléaires orphelins (génétique)</term>
<term>Récepteurs nucléaires orphelins (métabolisme)</term>
<term>Régulation de l'expression des gènes</term>
<term>Souris</term>
<term>Souris knockout</term>
<term>Transduction du signal</term>
<term>microARN (génétique)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Cholesterol</term>
<term>MicroRNAs</term>
<term>Orphan Nuclear Receptors</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Athérosclérose</term>
<term>Hépatocytes</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Atherosclerosis</term>
<term>Lipid Metabolism</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Athérosclérose</term>
<term>Cholestérol</term>
<term>Métabolisme des lipides</term>
<term>Récepteurs nucléaires orphelins</term>
<term>microARN</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cholesterol</term>
<term>Hepatocytes</term>
<term>Macrophages</term>
<term>Orphan Nuclear Receptors</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cholestérol</term>
<term>Hépatocytes</term>
<term>Macrophages</term>
<term>Récepteurs nucléaires orphelins</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Atherosclerosis</term>
<term>Hepatocytes</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Gene Expression Regulation</term>
<term>Hep G2 Cells</term>
<term>Humans</term>
<term>Liver X Receptors</term>
<term>Mice</term>
<term>Mice, Knockout</term>
<term>Signal Transduction</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Cellules HepG2</term>
<term>Humains</term>
<term>Récepteurs hépatiques X</term>
<term>Régulation de l'expression des gènes</term>
<term>Souris</term>
<term>Souris knockout</term>
<term>Transduction du signal</term>
</keywords>
</textClass>
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<front><div type="abstract" xml:lang="en"><p>Liver X receptors (LXRα and LXRβ) are key transcription factors in cholesterol metabolism that regulate cholesterol biosynthesis/efflux and bile acid metabolism/excretion in the liver and numerous organs. In macrophages, LXR signaling modulates cholesterol handling and the inflammatory response, pathways involved in atherosclerosis. Since regulatory pathways of LXR transcription control are well understood, in the present study we aimed at identifying post-transcriptional regulators of LXR activity. MicroRNAs (miRs) are such post-transcriptional regulators of genes that in the canonical pathway mediate mRNA inactivation. In silico analysis identified miR-206 as a putative regulator of LXRα but not LXRβ. Indeed, as recently shown, we found that miR-206 represses LXRα activity and expression of LXRα and its target genes in hepatic cells. Interestingly, miR-206 regulates LXRα differently in macrophages. Stably overexpressing miR-206 in THP-1 human macrophages revealed an up-regulation and miR-206 knockdown led to a down-regulation of LXRα and its target genes. In support of these results, bone marrow-derived macrophages (BMDMs) from miR-206 KO mice also exhibited lower expression of LXRα target genes. The physiological relevance of these findings was proven by gain- and loss-of-function of miR-206; overexpression of miR-206 enhanced cholesterol efflux in human macrophages and knocking out miR-206 decreased cholesterol efflux from MPMs. Moreover, we show that miR-206 expression in macrophages is repressed by LXRα activation, while oxidized LDL and inflammatory stimuli profoundly induced miR-206 expression. We therefore propose a feed-back loop between miR-206 and LXRα that might be part of an LXR auto-regulatory mechanism to fine tune LXR activity.</p>
</div>
</front>
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</listBibl>
</div1>
</back>
</TEI>
<affiliations><list><country><li>Australie</li>
<li>Autriche</li>
<li>France</li>
<li>États-Unis</li>
</country>
<region><li>Hauts-de-France</li>
<li>Nord-Pas-de-Calais</li>
</region>
<settlement><li>Lille</li>
</settlement>
<orgName><li>Université Lille 2</li>
</orgName>
</list>
<tree><country name="Autriche"><noRegion><name sortKey="Vinod, Manjula" sort="Vinod, Manjula" uniqKey="Vinod M" first="Manjula" last="Vinod">Manjula Vinod</name>
</noRegion>
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<name sortKey="Kostner, Gerhard M" sort="Kostner, Gerhard M" uniqKey="Kostner G" first="Gerhard M." last="Kostner">Gerhard M. Kostner</name>
<name sortKey="Kratky, Dagmar" sort="Kratky, Dagmar" uniqKey="Kratky D" first="Dagmar" last="Kratky">Dagmar Kratky</name>
</country>
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</noRegion>
</country>
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</region>
<name sortKey="Belloy, Loic" sort="Belloy, Loic" uniqKey="Belloy L" first="Loic" last="Belloy">Loic Belloy</name>
<name sortKey="Belloy, Loic" sort="Belloy, Loic" uniqKey="Belloy L" first="Loic" last="Belloy">Loic Belloy</name>
<name sortKey="Belloy, Loic" sort="Belloy, Loic" uniqKey="Belloy L" first="Loic" last="Belloy">Loic Belloy</name>
<name sortKey="Belloy, Loic" sort="Belloy, Loic" uniqKey="Belloy L" first="Loic" last="Belloy">Loic Belloy</name>
<name sortKey="Chinetti Gbaguidi, Giulia" sort="Chinetti Gbaguidi, Giulia" uniqKey="Chinetti Gbaguidi G" first="Giulia" last="Chinetti-Gbaguidi">Giulia Chinetti-Gbaguidi</name>
<name sortKey="Chinetti Gbaguidi, Giulia" sort="Chinetti Gbaguidi, Giulia" uniqKey="Chinetti Gbaguidi G" first="Giulia" last="Chinetti-Gbaguidi">Giulia Chinetti-Gbaguidi</name>
<name sortKey="Chinetti Gbaguidi, Giulia" sort="Chinetti Gbaguidi, Giulia" uniqKey="Chinetti Gbaguidi G" first="Giulia" last="Chinetti-Gbaguidi">Giulia Chinetti-Gbaguidi</name>
<name sortKey="Chinetti Gbaguidi, Giulia" sort="Chinetti Gbaguidi, Giulia" uniqKey="Chinetti Gbaguidi G" first="Giulia" last="Chinetti-Gbaguidi">Giulia Chinetti-Gbaguidi</name>
<name sortKey="Colin, Sophie" sort="Colin, Sophie" uniqKey="Colin S" first="Sophie" last="Colin">Sophie Colin</name>
<name sortKey="Colin, Sophie" sort="Colin, Sophie" uniqKey="Colin S" first="Sophie" last="Colin">Sophie Colin</name>
<name sortKey="Colin, Sophie" sort="Colin, Sophie" uniqKey="Colin S" first="Sophie" last="Colin">Sophie Colin</name>
<name sortKey="De Paoli, Federica" sort="De Paoli, Federica" uniqKey="De Paoli F" first="Federica" last="De Paoli">Federica De Paoli</name>
<name sortKey="De Paoli, Federica" sort="De Paoli, Federica" uniqKey="De Paoli F" first="Federica" last="De Paoli">Federica De Paoli</name>
<name sortKey="De Paoli, Federica" sort="De Paoli, Federica" uniqKey="De Paoli F" first="Federica" last="De Paoli">Federica De Paoli</name>
<name sortKey="De Paoli, Federica" sort="De Paoli, Federica" uniqKey="De Paoli F" first="Federica" last="De Paoli">Federica De Paoli</name>
<name sortKey="Staels, Bart" sort="Staels, Bart" uniqKey="Staels B" first="Bart" last="Staels">Bart Staels</name>
<name sortKey="Staels, Bart" sort="Staels, Bart" uniqKey="Staels B" first="Bart" last="Staels">Bart Staels</name>
<name sortKey="Staels, Bart" sort="Staels, Bart" uniqKey="Staels B" first="Bart" last="Staels">Bart Staels</name>
<name sortKey="Staels, Bart" sort="Staels, Bart" uniqKey="Staels B" first="Bart" last="Staels">Bart Staels</name>
</country>
<country name="Australie"><noRegion><name sortKey="Schaider, Helmut" sort="Schaider, Helmut" uniqKey="Schaider H" first="Helmut" last="Schaider">Helmut Schaider</name>
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</tree>
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</record>
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