The Oxygen Sensor PHD2 Controls Dendritic Spines and Synapses via Modification of Filamin A
Identifieur interne : 000001 ( France/Analysis ); précédent : 000000; suivant : 000002The Oxygen Sensor PHD2 Controls Dendritic Spines and Synapses via Modification of Filamin A
Auteurs : Inmaculada Segura [Belgique] ; Christian Lange [Belgique] ; Ellen Knevels [Belgique] ; Anastasiya Moskalyuk [Belgique] ; Rocco Pulizzi [Belgique] ; Guy Eelen [Belgique] ; Thibault Chaze [France] ; Cicerone Tudor [Belgique] ; Cyril Boulegue [France] ; Matthew Holt [Belgique] ; Dirk Daelemans [Belgique] ; Mariette Matondo [France] ; Bart Ghesquière [Belgique] ; Michele Giugliano [Belgique, Suisse] ; Carmen Ruiz De Almodovar [Belgique] ; Mieke Dewerchin [Belgique] ; Peter Carmeliet [Belgique]Source :
- Cell Reports [ 2211-1247 ] ; 2016.
Abstract
Neuronal function is highly sensitive to changes in oxygen levels, but how hypoxia affects dendritic spine formation and synaptogenesis is unknown. Here we report that hypoxia, chemical inhibition of the oxygen-sensing prolyl hydroxylase domain proteins (PHDs), and silencing of
Url:
DOI: 10.1016/j.celrep.2016.02.047
PubMed: 26972007
PubMed Central: 4805856
Affiliations:
- Belgique, France, Suisse
- Canton de Vaud, Province d'Anvers, Province du Brabant flamand, Île-de-France
- Anvers, Heverlee, Lausanne, Louvain, Paris
- Université d'Anvers
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PMC:4805856Le document en format XML
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Oxygen Sensor PHD2 Controls Dendritic Spines and Synapses via Modification of Filamin A</title><author><name sortKey="Segura, Inmaculada" sort="Segura, Inmaculada" uniqKey="Segura I" first="Inmaculada" last="Segura">Inmaculada Segura</name><affiliation wicri:level="3"><nlm:aff id="aff1">Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, 3000 Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff2">Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, VIB, 3000 Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, VIB, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName></affiliation></author><author><name sortKey="Lange, Christian" sort="Lange, Christian" uniqKey="Lange C" first="Christian" last="Lange">Christian Lange</name><affiliation wicri:level="3"><nlm:aff id="aff1">Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, 3000 Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff2">Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, VIB, 3000 Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, VIB, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName></affiliation></author><author><name sortKey="Knevels, Ellen" sort="Knevels, Ellen" uniqKey="Knevels E" first="Ellen" last="Knevels">Ellen Knevels</name><affiliation wicri:level="3"><nlm:aff id="aff1">Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, 3000 Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff2">Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, VIB, 3000 Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, VIB, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName></affiliation></author><author><name sortKey="Moskalyuk, Anastasiya" sort="Moskalyuk, Anastasiya" uniqKey="Moskalyuk A" first="Anastasiya" last="Moskalyuk">Anastasiya Moskalyuk</name><affiliation wicri:level="4"><nlm:aff id="aff3">Laboratory of Theoretical Neurobiology and Neuroengineering, University of Antwerp, 2610 Wilrijk, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Theoretical Neurobiology and Neuroengineering, University of Antwerp, 2610 Wilrijk</wicri:regionArea><orgName type="university">Université d'Anvers</orgName><placeName><settlement type="city">Anvers</settlement><region type="district" nuts="2">Province d'Anvers</region></placeName></affiliation></author><author><name sortKey="Pulizzi, Rocco" sort="Pulizzi, Rocco" uniqKey="Pulizzi R" first="Rocco" last="Pulizzi">Rocco Pulizzi</name><affiliation wicri:level="4"><nlm:aff id="aff3">Laboratory of Theoretical Neurobiology and Neuroengineering, University of Antwerp, 2610 Wilrijk, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Theoretical Neurobiology and Neuroengineering, University of Antwerp, 2610 Wilrijk</wicri:regionArea><orgName type="university">Université d'Anvers</orgName><placeName><settlement type="city">Anvers</settlement><region type="district" nuts="2">Province d'Anvers</region></placeName></affiliation></author><author><name sortKey="Eelen, Guy" sort="Eelen, Guy" uniqKey="Eelen G" first="Guy" last="Eelen">Guy Eelen</name><affiliation wicri:level="3"><nlm:aff id="aff1">Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, 3000 Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff2">Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, VIB, 3000 Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, VIB, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName></affiliation></author><author><name sortKey="Chaze, Thibault" sort="Chaze, Thibault" uniqKey="Chaze T" first="Thibault" last="Chaze">Thibault Chaze</name><affiliation wicri:level="3"><nlm:aff id="aff4">Proteomics Platform, Institute Pasteur, 75015 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Proteomics Platform, Institute Pasteur, 75015 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Tudor, Cicerone" sort="Tudor, Cicerone" uniqKey="Tudor C" first="Cicerone" last="Tudor">Cicerone Tudor</name><affiliation wicri:level="3"><nlm:aff id="aff5">Laboratory of Glia Biology, VIB, 3000 Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Glia Biology, VIB, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName></affiliation></author><author><name sortKey="Boulegue, Cyril" sort="Boulegue, Cyril" uniqKey="Boulegue C" first="Cyril" last="Boulegue">Cyril Boulegue</name><affiliation wicri:level="3"><nlm:aff id="aff4">Proteomics Platform, Institute Pasteur, 75015 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Proteomics Platform, Institute Pasteur, 75015 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Holt, Matthew" sort="Holt, Matthew" uniqKey="Holt M" first="Matthew" last="Holt">Matthew Holt</name><affiliation wicri:level="3"><nlm:aff id="aff5">Laboratory of Glia Biology, VIB, 3000 Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Glia Biology, VIB, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName></affiliation></author><author><name sortKey="Daelemans, Dirk" sort="Daelemans, Dirk" uniqKey="Daelemans D" first="Dirk" last="Daelemans">Dirk Daelemans</name><affiliation wicri:level="3"><nlm:aff id="aff6">Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven, 3000 Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName></affiliation></author><author><name sortKey="Matondo, Mariette" sort="Matondo, Mariette" uniqKey="Matondo M" first="Mariette" last="Matondo">Mariette Matondo</name><affiliation wicri:level="3"><nlm:aff id="aff4">Proteomics Platform, Institute Pasteur, 75015 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Proteomics Platform, Institute Pasteur, 75015 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Ghesquiere, Bart" sort="Ghesquiere, Bart" uniqKey="Ghesquiere B" first="Bart" last="Ghesquière">Bart Ghesquière</name><affiliation wicri:level="3"><nlm:aff id="aff7">Metabolomics Core Facility, Vesalius Research Center, VIB, 3000 Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Metabolomics Core Facility, Vesalius Research Center, VIB, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName></affiliation></author><author><name sortKey="Giugliano, Michele" sort="Giugliano, Michele" uniqKey="Giugliano M" first="Michele" last="Giugliano">Michele Giugliano</name><affiliation wicri:level="4"><nlm:aff id="aff3">Laboratory of Theoretical Neurobiology and Neuroengineering, University of Antwerp, 2610 Wilrijk, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Theoretical Neurobiology and Neuroengineering, University of Antwerp, 2610 Wilrijk</wicri:regionArea><orgName type="university">Université d'Anvers</orgName><placeName><settlement type="city">Anvers</settlement><region type="district" nuts="2">Province d'Anvers</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff8">Neuro-Electronics Research Flanders, 3001 Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Neuro-Electronics Research Flanders, 3001 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="town">Heverlee</settlement><settlement type="city">Louvain</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff9">Brain Mind Institute, Swiss Federal Institute of Technology of Lausanne, 1015 Lausanne, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Brain Mind Institute, Swiss Federal Institute of Technology of Lausanne, 1015 Lausanne</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Ruiz De Almodovar, Carmen" sort="Ruiz De Almodovar, Carmen" uniqKey="Ruiz De Almodovar C" first="Carmen" last="Ruiz De Almodovar">Carmen Ruiz De Almodovar</name><affiliation wicri:level="3"><nlm:aff id="aff1">Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, 3000 Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff2">Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, VIB, 3000 Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, VIB, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName></affiliation></author><author><name sortKey="Dewerchin, Mieke" sort="Dewerchin, Mieke" uniqKey="Dewerchin M" first="Mieke" last="Dewerchin">Mieke Dewerchin</name><affiliation wicri:level="3"><nlm:aff id="aff1">Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, 3000 Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff2">Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, VIB, 3000 Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, VIB, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName></affiliation></author><author><name sortKey="Carmeliet, Peter" sort="Carmeliet, Peter" uniqKey="Carmeliet P" first="Peter" last="Carmeliet">Peter Carmeliet</name><affiliation wicri:level="3"><nlm:aff id="aff1">Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, 3000 Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff2">Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, VIB, 3000 Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, VIB, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName></affiliation></author></analytic><series><title level="j">Cell Reports</title><idno type="eISSN">2211-1247</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Summary</title><p>Neuronal function is highly sensitive to changes in oxygen levels, but how hypoxia affects dendritic spine formation and synaptogenesis is unknown. Here we report that hypoxia, chemical inhibition of the oxygen-sensing prolyl hydroxylase domain proteins (PHDs), and silencing of <italic>Phd2</italic> induce immature filopodium-like dendritic protrusions, promote spine regression, reduce synaptic density, and decrease the frequency of spontaneous action potentials independently of HIF signaling. We identified the actin cross-linker filamin A (FLNA) as a target of PHD2 mediating these effects. In normoxia, PHD2 hydroxylates the proline residues P2309 and P2316 in FLNA, leading to von Hippel-Lindau (VHL)-mediated ubiquitination and proteasomal degradation. In hypoxia, PHD2 inactivation rapidly upregulates FLNA protein levels because of blockage of its proteasomal degradation. 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Poellinger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhou, A X" uniqKey="Zhou A">A.X. Zhou</name></author><author><name sortKey="Hartwig, J H" uniqKey="Hartwig J">J.H. Hartwig</name></author><author><name sortKey="Akyurek, L M" uniqKey="Akyurek L">L.M. Akyürek</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Belgique</li><li>France</li><li>Suisse</li></country><region><li>Canton de Vaud</li><li>Province d'Anvers</li><li>Province du Brabant flamand</li><li>Île-de-France</li></region><settlement><li>Anvers</li><li>Heverlee</li><li>Lausanne</li><li>Louvain</li><li>Paris</li></settlement><orgName><li>Université d'Anvers</li></orgName></list><tree><country name="Belgique"><region name="Province du Brabant flamand"><name sortKey="Segura, Inmaculada" sort="Segura, Inmaculada" uniqKey="Segura I" first="Inmaculada" last="Segura">Inmaculada Segura</name></region><name sortKey="Carmeliet, Peter" sort="Carmeliet, Peter" uniqKey="Carmeliet P" first="Peter" last="Carmeliet">Peter Carmeliet</name><name sortKey="Carmeliet, Peter" sort="Carmeliet, Peter" uniqKey="Carmeliet P" first="Peter" last="Carmeliet">Peter Carmeliet</name><name sortKey="Daelemans, Dirk" sort="Daelemans, Dirk" uniqKey="Daelemans D" first="Dirk" last="Daelemans">Dirk Daelemans</name><name sortKey="Dewerchin, Mieke" sort="Dewerchin, Mieke" uniqKey="Dewerchin M" first="Mieke" last="Dewerchin">Mieke Dewerchin</name><name sortKey="Dewerchin, Mieke" sort="Dewerchin, Mieke" uniqKey="Dewerchin M" first="Mieke" last="Dewerchin">Mieke Dewerchin</name><name sortKey="Eelen, Guy" sort="Eelen, Guy" uniqKey="Eelen G" first="Guy" last="Eelen">Guy Eelen</name><name sortKey="Eelen, Guy" sort="Eelen, Guy" uniqKey="Eelen G" first="Guy" last="Eelen">Guy Eelen</name><name sortKey="Ghesquiere, Bart" sort="Ghesquiere, Bart" uniqKey="Ghesquiere B" first="Bart" last="Ghesquière">Bart Ghesquière</name><name sortKey="Giugliano, Michele" sort="Giugliano, Michele" uniqKey="Giugliano M" first="Michele" last="Giugliano">Michele Giugliano</name><name sortKey="Giugliano, Michele" sort="Giugliano, Michele" uniqKey="Giugliano M" first="Michele" last="Giugliano">Michele Giugliano</name><name sortKey="Holt, Matthew" sort="Holt, Matthew" uniqKey="Holt M" first="Matthew" last="Holt">Matthew Holt</name><name sortKey="Knevels, Ellen" sort="Knevels, Ellen" uniqKey="Knevels E" first="Ellen" last="Knevels">Ellen Knevels</name><name sortKey="Knevels, Ellen" sort="Knevels, Ellen" uniqKey="Knevels E" first="Ellen" last="Knevels">Ellen Knevels</name><name sortKey="Lange, Christian" sort="Lange, Christian" uniqKey="Lange C" first="Christian" last="Lange">Christian Lange</name><name sortKey="Lange, Christian" sort="Lange, Christian" uniqKey="Lange C" first="Christian" last="Lange">Christian Lange</name><name sortKey="Moskalyuk, Anastasiya" sort="Moskalyuk, Anastasiya" uniqKey="Moskalyuk A" first="Anastasiya" last="Moskalyuk">Anastasiya Moskalyuk</name><name sortKey="Pulizzi, Rocco" sort="Pulizzi, Rocco" uniqKey="Pulizzi R" first="Rocco" last="Pulizzi">Rocco Pulizzi</name><name sortKey="Ruiz De Almodovar, Carmen" sort="Ruiz De Almodovar, Carmen" uniqKey="Ruiz De Almodovar C" first="Carmen" last="Ruiz De Almodovar">Carmen Ruiz De Almodovar</name><name sortKey="Ruiz De Almodovar, Carmen" sort="Ruiz De Almodovar, Carmen" uniqKey="Ruiz De Almodovar C" first="Carmen" last="Ruiz De Almodovar">Carmen Ruiz De Almodovar</name><name sortKey="Segura, Inmaculada" sort="Segura, Inmaculada" uniqKey="Segura I" first="Inmaculada" last="Segura">Inmaculada Segura</name><name sortKey="Tudor, Cicerone" sort="Tudor, Cicerone" uniqKey="Tudor C" first="Cicerone" last="Tudor">Cicerone Tudor</name></country><country name="France"><region name="Île-de-France"><name sortKey="Chaze, Thibault" sort="Chaze, Thibault" uniqKey="Chaze T" first="Thibault" last="Chaze">Thibault Chaze</name></region><name sortKey="Boulegue, Cyril" sort="Boulegue, Cyril" uniqKey="Boulegue C" first="Cyril" last="Boulegue">Cyril Boulegue</name><name sortKey="Matondo, Mariette" sort="Matondo, Mariette" uniqKey="Matondo M" first="Mariette" last="Matondo">Mariette Matondo</name></country><country name="Suisse"><region name="Canton de Vaud"><name sortKey="Giugliano, Michele" sort="Giugliano, Michele" uniqKey="Giugliano M" first="Michele" last="Giugliano">Michele Giugliano</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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