The amino acid metabolite homocysteine activates mTORC1 to inhibit autophagy and form abnormal proteins in human neurons and mice.
Identifieur interne : 000714 ( Main/Exploration ); précédent : 000713; suivant : 000715The amino acid metabolite homocysteine activates mTORC1 to inhibit autophagy and form abnormal proteins in human neurons and mice.
Auteurs : Khoosheh Khayati [États-Unis] ; Henri Antikainen [États-Unis] ; Edward M. Bonder [États-Unis] ; Gregory F. Weber [États-Unis] ; Warren D. Kruger [États-Unis] ; Hieronim Jakubowski [États-Unis, Pologne] ; Radek Dobrowolski [États-Unis]Source :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology [ 1530-6860 ] ; 2017.
Descripteurs français
- KwdFr :
- Animaux (MeSH), Autophagie (physiologie), Complexe-1 cible mécanistique de la rapamycine (MeSH), Complexes multiprotéiques (génétique), Complexes multiprotéiques (métabolisme), Homocystéine (métabolisme), Humains (MeSH), Lignée cellulaire (MeSH), Neurones (métabolisme), Régulation de l'expression des gènes (physiologie), Souris (MeSH), Sérine-thréonine kinases TOR (génétique), Sérine-thréonine kinases TOR (métabolisme).
- MESH :
- génétique : Complexes multiprotéiques, Sérine-thréonine kinases TOR.
- métabolisme : Complexes multiprotéiques, Homocystéine, Neurones, Sérine-thréonine kinases TOR.
- physiologie : Autophagie, Régulation de l'expression des gènes.
- Animaux, Complexe-1 cible mécanistique de la rapamycine, Humains, Lignée cellulaire, Souris.
English descriptors
- KwdEn :
- Animals (MeSH), Autophagy (physiology), Cell Line (MeSH), Gene Expression Regulation (physiology), Homocysteine (metabolism), Humans (MeSH), Mechanistic Target of Rapamycin Complex 1 (MeSH), Mice (MeSH), Multiprotein Complexes (genetics), Multiprotein Complexes (metabolism), Neurons (metabolism), TOR Serine-Threonine Kinases (genetics), TOR Serine-Threonine Kinases (metabolism).
- MESH :
- chemical , genetics : Multiprotein Complexes, TOR Serine-Threonine Kinases.
- chemical , metabolism : Homocysteine, Multiprotein Complexes, TOR Serine-Threonine Kinases.
- metabolism : Neurons.
- physiology : Autophagy, Gene Expression Regulation.
- Animals, Cell Line, Humans, Mechanistic Target of Rapamycin Complex 1, Mice.
Abstract
The molecular mechanisms leading to and responsible for age-related, sporadic Alzheimer's disease (AD) remain largely unknown. It is well documented that aging patients with elevated levels of the amino acid metabolite homocysteine (Hcy) are at high risk of developing AD. We investigated the impact of Hcy on molecular clearance pathways in mammalian cells, including in vitro cultured induced pluripotent stem cell-derived forebrain neurons and in vivo neurons in mouse brains. Exposure to Hcy resulted in up-regulation of the mechanistic target of rapamycin complex 1 (mTORC1) activity, one of the major kinases in cells that is tightly linked to anabolic and catabolic pathways. Hcy is sensed by a constitutive protein complex composed of leucyl-tRNA-synthetase and folliculin, which regulates mTOR tethering to lysosomal membranes. In hyperhomocysteinemic human cells and cystathionine β-synthase-deficient mouse brains, we find an acute and chronic inhibition of the molecular clearance of protein products resulting in a buildup of abnormal proteins, including β-amyloid and phospho-Tau. Formation of these protein aggregates leads to AD-like neurodegeneration. This pathology can be prevented by inhibition of mTORC1 or by induction of autophagy. We conclude that an increase of intracellular Hcy levels predisposes neurons to develop abnormal protein aggregates, which are hallmarks of AD and its associated onset and pathophysiology with age.-Khayati, K., Antikainen, H., Bonder, E. M., Weber, G. F., Kruger, W. D., Jakubowski, H., Dobrowolski, R. The amino acid metabolite homocysteine activates mTORC1 to inhibit autophagy and form abnormal proteins in human neurons and mice.
DOI: 10.1096/fj.201600915R
PubMed: 28148781
Affiliations:
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Le document en format XML
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Bonder</name><affiliation wicri:level="2"><nlm:affiliation>Federated Department of Biological Sciences, Rutgers University/New Jersey Institute of Technology, Newark, New Jersey, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Federated Department of Biological Sciences, Rutgers University/New Jersey Institute of Technology, Newark, New Jersey</wicri:regionArea><placeName><region type="state">New Jersey</region></placeName></affiliation></author><author><name sortKey="Weber, Gregory F" sort="Weber, Gregory F" uniqKey="Weber G" first="Gregory F" last="Weber">Gregory F. Weber</name><affiliation wicri:level="2"><nlm:affiliation>Federated Department of Biological Sciences, Rutgers University/New Jersey Institute of Technology, Newark, New Jersey, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Federated Department of Biological Sciences, Rutgers University/New Jersey Institute of Technology, Newark, New Jersey</wicri:regionArea><placeName><region type="state">New Jersey</region></placeName></affiliation></author><author><name sortKey="Kruger, Warren D" sort="Kruger, Warren D" uniqKey="Kruger W" first="Warren D" last="Kruger">Warren D. Kruger</name><affiliation wicri:level="2"><nlm:affiliation>Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Fox Chase Cancer Center, Philadelphia, Pennsylvania</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Jakubowski, Hieronim" sort="Jakubowski, Hieronim" uniqKey="Jakubowski H" first="Hieronim" last="Jakubowski">Hieronim Jakubowski</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology, Biochemistry, and Molecular Genetics, International Center for Public Health, Rutgers-New Jersey Medical School, Newark, New Jersey, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Biochemistry, and Molecular Genetics, International Center for Public Health, Rutgers-New Jersey Medical School, Newark, New Jersey</wicri:regionArea><placeName><region type="state">New Jersey</region></placeName></affiliation><affiliation><nlm:affiliation>Institute of Bioorganic Chemistry, Poznań, Poland; and.</nlm:affiliation><wicri:noCountry code="subField">Poland; and</wicri:noCountry></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry and Biotechnology, University of Life Sciences, Poznań, Poland.</nlm:affiliation><country xml:lang="fr">Pologne</country><wicri:regionArea>Department of Biochemistry and Biotechnology, University of Life Sciences, Poznań</wicri:regionArea><wicri:noRegion>Poznań</wicri:noRegion></affiliation></author><author><name sortKey="Dobrowolski, Radek" sort="Dobrowolski, Radek" uniqKey="Dobrowolski R" first="Radek" last="Dobrowolski">Radek Dobrowolski</name><affiliation wicri:level="2"><nlm:affiliation>Federated Department of Biological Sciences, Rutgers University/New Jersey Institute of Technology, Newark, New Jersey, USA; r.dobrowolski@rutgers.edu.</nlm:affiliation><country wicri:rule="url">États-Unis</country><wicri:regionArea>Federated Department of Biological Sciences, Rutgers University/New Jersey Institute of Technology, Newark, New Jersey</wicri:regionArea><placeName><region type="state">New Jersey</region></placeName></affiliation></author></analytic><series><title level="j">FASEB journal : official publication of the Federation of American Societies for Experimental Biology</title><idno type="eISSN">1530-6860</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term><term>Autophagy (physiology)</term><term>Cell Line (MeSH)</term><term>Gene Expression Regulation (physiology)</term><term>Homocysteine (metabolism)</term><term>Humans (MeSH)</term><term>Mechanistic Target of Rapamycin Complex 1 (MeSH)</term><term>Mice (MeSH)</term><term>Multiprotein Complexes (genetics)</term><term>Multiprotein Complexes (metabolism)</term><term>Neurons (metabolism)</term><term>TOR Serine-Threonine Kinases (genetics)</term><term>TOR Serine-Threonine Kinases (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux (MeSH)</term><term>Autophagie (physiologie)</term><term>Complexe-1 cible mécanistique de la rapamycine (MeSH)</term><term>Complexes multiprotéiques (génétique)</term><term>Complexes multiprotéiques (métabolisme)</term><term>Homocystéine (métabolisme)</term><term>Humains (MeSH)</term><term>Lignée cellulaire (MeSH)</term><term>Neurones (métabolisme)</term><term>Régulation de l'expression des gènes (physiologie)</term><term>Souris (MeSH)</term><term>Sérine-thréonine kinases TOR (génétique)</term><term>Sérine-thréonine kinases TOR (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Multiprotein Complexes</term><term>TOR Serine-Threonine Kinases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Homocysteine</term><term>Multiprotein Complexes</term><term>TOR Serine-Threonine Kinases</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Complexes multiprotéiques</term><term>Sérine-thréonine kinases TOR</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Neurons</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Complexes multiprotéiques</term><term>Homocystéine</term><term>Neurones</term><term>Sérine-thréonine kinases TOR</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Autophagie</term><term>Régulation de l'expression des gènes</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Autophagy</term><term>Gene Expression Regulation</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line</term><term>Humans</term><term>Mechanistic Target of Rapamycin Complex 1</term><term>Mice</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Complexe-1 cible mécanistique de la rapamycine</term><term>Humains</term><term>Lignée cellulaire</term><term>Souris</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The molecular mechanisms leading to and responsible for age-related, sporadic Alzheimer's disease (AD) remain largely unknown. It is well documented that aging patients with elevated levels of the amino acid metabolite homocysteine (Hcy) are at high risk of developing AD. We investigated the impact of Hcy on molecular clearance pathways in mammalian cells, including in vitro cultured induced pluripotent stem cell-derived forebrain neurons and in vivo neurons in mouse brains. Exposure to Hcy resulted in up-regulation of the mechanistic target of rapamycin complex 1 (mTORC1) activity, one of the major kinases in cells that is tightly linked to anabolic and catabolic pathways. Hcy is sensed by a constitutive protein complex composed of leucyl-tRNA-synthetase and folliculin, which regulates mTOR tethering to lysosomal membranes. In hyperhomocysteinemic human cells and cystathionine β-synthase-deficient mouse brains, we find an acute and chronic inhibition of the molecular clearance of protein products resulting in a buildup of abnormal proteins, including β-amyloid and phospho-Tau. Formation of these protein aggregates leads to AD-like neurodegeneration. This pathology can be prevented by inhibition of mTORC1 or by induction of autophagy. We conclude that an increase of intracellular Hcy levels predisposes neurons to develop abnormal protein aggregates, which are hallmarks of AD and its associated onset and pathophysiology with age.-Khayati, K., Antikainen, H., Bonder, E. M., Weber, G. F., Kruger, W. D., Jakubowski, H., Dobrowolski, R. The amino acid metabolite homocysteine activates mTORC1 to inhibit autophagy and form abnormal proteins in human neurons and mice.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">28148781</PMID><DateCompleted><Year>2017</Year><Month>09</Month><Day>01</Day></DateCompleted><DateRevised><Year>2017</Year><Month>12</Month><Day>20</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1530-6860</ISSN><JournalIssue CitedMedium="Internet"><Volume>31</Volume><Issue>2</Issue><PubDate><Year>2017</Year><Month>02</Month></PubDate></JournalIssue><Title>FASEB journal : official publication of the Federation of American Societies for Experimental Biology</Title><ISOAbbreviation>FASEB J</ISOAbbreviation></Journal><ArticleTitle>The amino acid metabolite homocysteine activates mTORC1 to inhibit autophagy and form abnormal proteins in human neurons and mice.</ArticleTitle><Pagination><MedlinePgn>598-609</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1096/fj.201600915R</ELocationID><Abstract><AbstractText>The molecular mechanisms leading to and responsible for age-related, sporadic Alzheimer's disease (AD) remain largely unknown. It is well documented that aging patients with elevated levels of the amino acid metabolite homocysteine (Hcy) are at high risk of developing AD. We investigated the impact of Hcy on molecular clearance pathways in mammalian cells, including in vitro cultured induced pluripotent stem cell-derived forebrain neurons and in vivo neurons in mouse brains. Exposure to Hcy resulted in up-regulation of the mechanistic target of rapamycin complex 1 (mTORC1) activity, one of the major kinases in cells that is tightly linked to anabolic and catabolic pathways. Hcy is sensed by a constitutive protein complex composed of leucyl-tRNA-synthetase and folliculin, which regulates mTOR tethering to lysosomal membranes. In hyperhomocysteinemic human cells and cystathionine β-synthase-deficient mouse brains, we find an acute and chronic inhibition of the molecular clearance of protein products resulting in a buildup of abnormal proteins, including β-amyloid and phospho-Tau. Formation of these protein aggregates leads to AD-like neurodegeneration. This pathology can be prevented by inhibition of mTORC1 or by induction of autophagy. We conclude that an increase of intracellular Hcy levels predisposes neurons to develop abnormal protein aggregates, which are hallmarks of AD and its associated onset and pathophysiology with age.-Khayati, K., Antikainen, H., Bonder, E. M., Weber, G. F., Kruger, W. D., Jakubowski, H., Dobrowolski, R. The amino acid metabolite homocysteine activates mTORC1 to inhibit autophagy and form abnormal proteins in human neurons and mice.</AbstractText><CopyrightInformation>© FASEB.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Khayati</LastName><ForeName>Khoosheh</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Federated Department of Biological Sciences, Rutgers University/New Jersey Institute of Technology, Newark, New Jersey, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Antikainen</LastName><ForeName>Henri</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Federated Department of Biological Sciences, Rutgers University/New Jersey Institute of Technology, Newark, New Jersey, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bonder</LastName><ForeName>Edward M</ForeName><Initials>EM</Initials><AffiliationInfo><Affiliation>Federated Department of Biological Sciences, Rutgers University/New Jersey Institute of Technology, Newark, New Jersey, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Weber</LastName><ForeName>Gregory F</ForeName><Initials>GF</Initials><AffiliationInfo><Affiliation>Federated Department of Biological Sciences, Rutgers University/New Jersey Institute of Technology, Newark, New Jersey, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kruger</LastName><ForeName>Warren D</ForeName><Initials>WD</Initials><AffiliationInfo><Affiliation>Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jakubowski</LastName><ForeName>Hieronim</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Microbiology, Biochemistry, and Molecular Genetics, International Center for Public Health, Rutgers-New Jersey Medical School, Newark, New Jersey, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Bioorganic Chemistry, Poznań, Poland; and.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biochemistry and Biotechnology, University of Life Sciences, Poznań, Poland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dobrowolski</LastName><ForeName>Radek</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Federated Department of Biological Sciences, Rutgers University/New Jersey Institute of Technology, Newark, New Jersey, USA; r.dobrowolski@rutgers.edu.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>10</Month><Day>25</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>FASEB J</MedlineTA><NlmUniqueID>8804484</NlmUniqueID><ISSNLinking>0892-6638</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D046912">Multiprotein Complexes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0LVT1QZ0BA</RegistryNumber><NameOfSubstance UI="D006710">Homocysteine</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber><NameOfSubstance UI="D058570">TOR Serine-Threonine Kinases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="D000076222">Mechanistic Target of Rapamycin Complex 1</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001343" MajorTopicYN="N">Autophagy</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002460" MajorTopicYN="N">Cell Line</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005786" MajorTopicYN="N">Gene Expression Regulation</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006710" MajorTopicYN="N">Homocysteine</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000076222" MajorTopicYN="N">Mechanistic Target of Rapamycin Complex 1</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D046912" MajorTopicYN="N">Multiprotein Complexes</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009474" MajorTopicYN="N">Neurons</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D058570" MajorTopicYN="N">TOR Serine-Threonine Kinases</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">Alzheimer’s disease</Keyword><Keyword MajorTopicYN="Y">lysosomal clearance</Keyword><Keyword MajorTopicYN="Y">metabolism</Keyword><Keyword MajorTopicYN="Y">signaling</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year><Month>08</Month><Day>23</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2016</Year><Month>10</Month><Day>11</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2017</Year><Month>2</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2017</Year><Month>2</Month><Day>6</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2017</Year><Month>9</Month><Day>2</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">28148781</ArticleId><ArticleId IdType="pii">fj.201600915R</ArticleId><ArticleId IdType="doi">10.1096/fj.201600915R</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Pologne</li><li>États-Unis</li></country><region><li>New Jersey</li><li>Pennsylvanie</li></region></list><tree><country name="États-Unis"><region name="New Jersey"><name sortKey="Khayati, Khoosheh" sort="Khayati, Khoosheh" uniqKey="Khayati K" first="Khoosheh" last="Khayati">Khoosheh Khayati</name></region><name sortKey="Antikainen, Henri" sort="Antikainen, Henri" uniqKey="Antikainen H" first="Henri" last="Antikainen">Henri Antikainen</name><name sortKey="Bonder, Edward M" sort="Bonder, Edward M" uniqKey="Bonder E" first="Edward M" last="Bonder">Edward M. Bonder</name><name sortKey="Dobrowolski, Radek" sort="Dobrowolski, Radek" uniqKey="Dobrowolski R" first="Radek" last="Dobrowolski">Radek Dobrowolski</name><name sortKey="Jakubowski, Hieronim" sort="Jakubowski, Hieronim" uniqKey="Jakubowski H" first="Hieronim" last="Jakubowski">Hieronim Jakubowski</name><name sortKey="Kruger, Warren D" sort="Kruger, Warren D" uniqKey="Kruger W" first="Warren D" last="Kruger">Warren D. Kruger</name><name sortKey="Weber, Gregory F" sort="Weber, Gregory F" uniqKey="Weber G" first="Gregory F" last="Weber">Gregory F. Weber</name></country><country name="Pologne"><noRegion><name sortKey="Jakubowski, Hieronim" sort="Jakubowski, Hieronim" uniqKey="Jakubowski H" first="Hieronim" last="Jakubowski">Hieronim Jakubowski</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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