AR-12 Inhibits Multiple Chaperones Concomitant With Stimulating Autophagosome Formation Collectively Preventing Virus Replication.
Identifieur interne : 000C04 ( Main/Exploration ); précédent : 000C03; suivant : 000C05AR-12 Inhibits Multiple Chaperones Concomitant With Stimulating Autophagosome Formation Collectively Preventing Virus Replication.
Auteurs : Laurence Booth [États-Unis] ; Jane L. Roberts [États-Unis] ; Heath Ecroyd [Australie] ; Sarah R. Tritsch [États-Unis] ; Sina Bavari [États-Unis] ; St Patrick Reid [États-Unis] ; Stefan Proniuk [États-Unis] ; Alexander Zukiwski [États-Unis] ; Abraham Jacob [États-Unis] ; Claudia S. Sepúlveda [Argentine] ; Federico Giovannoni [Argentine] ; Cybele C. García [Argentine] ; Elsa Damonte [Argentine] ; Javier González-Gallego [Espagne] ; María J. Tu N [Espagne] ; Paul Dent [États-Unis]Source :
- Journal of cellular physiology [ 1097-4652 ] ; 2016.
Descripteurs français
- KwdFr :
- Autophagie (), Autophagosomes (), Chaperons moléculaires (métabolisme), Humains, Lignée cellulaire, Pyrazoles (pharmacologie), Réplication virale (), Réplication virale (physiologie), Réticulum endoplasmique (), Réticulum endoplasmique (métabolisme), Stress du réticulum endoplasmique (), Stress du réticulum endoplasmique (physiologie), Sulfonamides (pharmacologie).
- MESH :
- métabolisme : Chaperons moléculaires, Réticulum endoplasmique.
- pharmacologie : Pyrazoles, Sulfonamides.
- physiologie : Réplication virale, Stress du réticulum endoplasmique.
- Autophagie, Autophagosomes, Humains, Lignée cellulaire, Réplication virale, Réticulum endoplasmique, Stress du réticulum endoplasmique.
English descriptors
- KwdEn :
- Autophagosomes (drug effects), Autophagy (drug effects), Cell Line, Endoplasmic Reticulum (drug effects), Endoplasmic Reticulum (metabolism), Endoplasmic Reticulum Stress (drug effects), Endoplasmic Reticulum Stress (physiology), Humans, Molecular Chaperones (metabolism), Pyrazoles (pharmacology), Sulfonamides (pharmacology), Virus Replication (drug effects), Virus Replication (physiology).
- MESH :
- chemical , metabolism : Molecular Chaperones.
- drug effects : Autophagosomes, Autophagy, Endoplasmic Reticulum, Endoplasmic Reticulum Stress, Virus Replication.
- metabolism : Endoplasmic Reticulum.
- chemical , pharmacology : Pyrazoles, Sulfonamides.
- physiology : Endoplasmic Reticulum Stress, Virus Replication.
- Cell Line, Humans.
Abstract
We have recently demonstrated that AR-12 (OSU-03012) reduces the function and ATPase activities of multiple HSP90 and HSP70 family chaperones. Combined knock down of chaperones or AR-12 treatment acted to reduce the expression of virus receptors and essential glucosidase proteins. Combined knock down of chaperones or AR-12 treatment inactivated mTOR and elevated ATG13 S318 phosphorylation concomitant with inducing an endoplasmic reticulum stress response that in an eIF2α-dependent fashion increased Beclin1 and LC3 expression and autophagosome formation. Over-expression of chaperones prevented the reduction in receptor/glucosidase expression, mTOR inactivation, the ER stress response, and autophagosome formation. AR-12 reduced the reproduction of viruses including Mumps, Influenza, Measles, Junín, Rubella, HIV (wild type and protease resistant), and Ebola, an effect replicated by knock down of multiple chaperone proteins. AR-12-stimulated the co-localization of Influenza, EBV and HIV virus proteins with LC3 in autophagosomes and reduced viral protein association with the chaperones HSP90, HSP70, and GRP78. Knock down of Beclin1 suppressed drug-induced autophagosome formation and reduced the anti-viral protection afforded by AR-12. In an animal model of hemorrhagic fever virus, a transient exposure of animals to low doses of AR-12 doubled animal survival from ∼30% to ∼60% and suppressed liver damage as measured by ATL, GGT and LDH release. Thus through inhibition of chaperone protein functions; reducing the production, stability and processing of viral proteins; and stimulating autophagosome formation/viral protein degradation, AR-12 acts as a broad-specificity anti-viral drug in vitro and in vivo. We argue future patient studies with AR-12 are warranted. J. Cell. Physiol. 231: 2286-2302, 2016. © 2016 Wiley Periodicals, Inc.
DOI: 10.1002/jcp.25431
PubMed: 27187154
Affiliations:
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Sepúlveda</name><affiliation wicri:level="1"><nlm:affiliation>FCEN-UBA, Ciudad Universitaria, Pabellón 2 Piso 4, lab QB-17, Buenos Aires, Argentina.</nlm:affiliation><country xml:lang="fr">Argentine</country><wicri:regionArea>FCEN-UBA, Ciudad Universitaria, Pabellón 2 Piso 4, lab QB-17, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Giovannoni, Federico" sort="Giovannoni, Federico" uniqKey="Giovannoni F" first="Federico" last="Giovannoni">Federico Giovannoni</name><affiliation wicri:level="1"><nlm:affiliation>FCEN-UBA, Ciudad Universitaria, Pabellón 2 Piso 4, lab QB-17, Buenos Aires, Argentina.</nlm:affiliation><country xml:lang="fr">Argentine</country><wicri:regionArea>FCEN-UBA, Ciudad Universitaria, Pabellón 2 Piso 4, lab QB-17, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Garcia, Cybele C" sort="Garcia, Cybele C" uniqKey="Garcia C" first="Cybele C" last="García">Cybele C. García</name><affiliation wicri:level="1"><nlm:affiliation>FCEN-UBA, Ciudad Universitaria, Pabellón 2 Piso 4, lab QB-17, Buenos Aires, Argentina.</nlm:affiliation><country xml:lang="fr">Argentine</country><wicri:regionArea>FCEN-UBA, Ciudad Universitaria, Pabellón 2 Piso 4, lab QB-17, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Damonte, Elsa" sort="Damonte, Elsa" uniqKey="Damonte E" first="Elsa" last="Damonte">Elsa Damonte</name><affiliation wicri:level="1"><nlm:affiliation>FCEN-UBA, Ciudad Universitaria, Pabellón 2 Piso 4, lab QB-17, Buenos Aires, Argentina.</nlm:affiliation><country xml:lang="fr">Argentine</country><wicri:regionArea>FCEN-UBA, Ciudad Universitaria, Pabellón 2 Piso 4, lab QB-17, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Gonzalez Gallego, Javier" sort="Gonzalez Gallego, Javier" uniqKey="Gonzalez Gallego J" first="Javier" last="González-Gallego">Javier González-Gallego</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Biomedicine and CIBEREhd, University of León, León, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Institute of Biomedicine and CIBEREhd, University of León, León</wicri:regionArea><wicri:noRegion>León</wicri:noRegion></affiliation></author><author><name sortKey="Tu N, Maria J" sort="Tu N, Maria J" uniqKey="Tu N M" first="María J" last="Tu N">María J. Tu N</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Biomedicine and CIBEREhd, University of León, León, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Institute of Biomedicine and CIBEREhd, University of León, León</wicri:regionArea><wicri:noRegion>León</wicri:noRegion></affiliation></author><author><name sortKey="Dent, Paul" sort="Dent, Paul" uniqKey="Dent P" first="Paul" last="Dent">Paul Dent</name><affiliation wicri:level="2"><nlm:affiliation>Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:27187154</idno><idno type="pmid">27187154</idno><idno type="doi">10.1002/jcp.25431</idno><idno type="wicri:Area/PubMed/Corpus">000362</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000362</idno><idno type="wicri:Area/PubMed/Curation">000361</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000361</idno><idno type="wicri:Area/PubMed/Checkpoint">000383</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000383</idno><idno type="wicri:Area/Ncbi/Merge">000794</idno><idno type="wicri:Area/Ncbi/Curation">000794</idno><idno type="wicri:Area/Ncbi/Checkpoint">000794</idno><idno type="wicri:Area/Main/Merge">000C04</idno><idno type="wicri:Area/Main/Curation">000C04</idno><idno type="wicri:Area/Main/Exploration">000C04</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">AR-12 Inhibits Multiple Chaperones Concomitant With Stimulating Autophagosome Formation Collectively Preventing Virus Replication.</title><author><name sortKey="Booth, Laurence" sort="Booth, Laurence" uniqKey="Booth L" first="Laurence" last="Booth">Laurence Booth</name><affiliation wicri:level="2"><nlm:affiliation>Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation></author><author><name sortKey="Roberts, Jane L" sort="Roberts, Jane L" uniqKey="Roberts J" first="Jane L" last="Roberts">Jane L. Roberts</name><affiliation wicri:level="2"><nlm:affiliation>Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation></author><author><name sortKey="Ecroyd, Heath" sort="Ecroyd, Heath" uniqKey="Ecroyd H" first="Heath" last="Ecroyd">Heath Ecroyd</name><affiliation wicri:level="1"><nlm:affiliation>School of Biological Sciences and Illawarra Health and Medical Research Institute, University of Wollongong, New South Wales, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Biological Sciences and Illawarra Health and Medical Research Institute, University of Wollongong, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author><author><name sortKey="Tritsch, Sarah R" sort="Tritsch, Sarah R" uniqKey="Tritsch S" first="Sarah R" last="Tritsch">Sarah R. Tritsch</name><affiliation wicri:level="2"><nlm:affiliation>Molecular and Translational Science, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Molecular and Translational Science, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick</wicri:cityArea></affiliation></author><author><name sortKey="Bavari, Sina" sort="Bavari, Sina" uniqKey="Bavari S" first="Sina" last="Bavari">Sina Bavari</name><affiliation wicri:level="2"><nlm:affiliation>Molecular and Translational Science, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Molecular and Translational Science, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick</wicri:cityArea></affiliation></author><author><name sortKey="Reid, St Patrick" sort="Reid, St Patrick" uniqKey="Reid S" first="St Patrick" last="Reid">St Patrick Reid</name><affiliation wicri:level="2"><nlm:affiliation>Molecular and Translational Science, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Molecular and Translational Science, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick</wicri:cityArea></affiliation></author><author><name sortKey="Proniuk, Stefan" sort="Proniuk, Stefan" uniqKey="Proniuk S" first="Stefan" last="Proniuk">Stefan Proniuk</name><affiliation wicri:level="2"><nlm:affiliation>Arno Therapeutics, Flemington, New Jersey.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">New Jersey</region></placeName><wicri:cityArea>Arno Therapeutics, Flemington</wicri:cityArea></affiliation></author><author><name sortKey="Zukiwski, Alexander" sort="Zukiwski, Alexander" uniqKey="Zukiwski A" first="Alexander" last="Zukiwski">Alexander Zukiwski</name><affiliation wicri:level="2"><nlm:affiliation>Arno Therapeutics, Flemington, New Jersey.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">New Jersey</region></placeName><wicri:cityArea>Arno Therapeutics, Flemington</wicri:cityArea></affiliation></author><author><name sortKey="Jacob, Abraham" sort="Jacob, Abraham" uniqKey="Jacob A" first="Abraham" last="Jacob">Abraham Jacob</name><affiliation wicri:level="2"><nlm:affiliation>Department of Otolaryngology, University of Arizona Ear Institute, Tucson, Arizona.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Arizona</region></placeName><wicri:cityArea>Department of Otolaryngology, University of Arizona Ear Institute, Tucson</wicri:cityArea></affiliation></author><author><name sortKey="Sepulveda, Claudia S" sort="Sepulveda, Claudia S" uniqKey="Sepulveda C" first="Claudia S" last="Sepúlveda">Claudia S. Sepúlveda</name><affiliation wicri:level="1"><nlm:affiliation>FCEN-UBA, Ciudad Universitaria, Pabellón 2 Piso 4, lab QB-17, Buenos Aires, Argentina.</nlm:affiliation><country xml:lang="fr">Argentine</country><wicri:regionArea>FCEN-UBA, Ciudad Universitaria, Pabellón 2 Piso 4, lab QB-17, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Giovannoni, Federico" sort="Giovannoni, Federico" uniqKey="Giovannoni F" first="Federico" last="Giovannoni">Federico Giovannoni</name><affiliation wicri:level="1"><nlm:affiliation>FCEN-UBA, Ciudad Universitaria, Pabellón 2 Piso 4, lab QB-17, Buenos Aires, Argentina.</nlm:affiliation><country xml:lang="fr">Argentine</country><wicri:regionArea>FCEN-UBA, Ciudad Universitaria, Pabellón 2 Piso 4, lab QB-17, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Garcia, Cybele C" sort="Garcia, Cybele C" uniqKey="Garcia C" first="Cybele C" last="García">Cybele C. García</name><affiliation wicri:level="1"><nlm:affiliation>FCEN-UBA, Ciudad Universitaria, Pabellón 2 Piso 4, lab QB-17, Buenos Aires, Argentina.</nlm:affiliation><country xml:lang="fr">Argentine</country><wicri:regionArea>FCEN-UBA, Ciudad Universitaria, Pabellón 2 Piso 4, lab QB-17, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Damonte, Elsa" sort="Damonte, Elsa" uniqKey="Damonte E" first="Elsa" last="Damonte">Elsa Damonte</name><affiliation wicri:level="1"><nlm:affiliation>FCEN-UBA, Ciudad Universitaria, Pabellón 2 Piso 4, lab QB-17, Buenos Aires, Argentina.</nlm:affiliation><country xml:lang="fr">Argentine</country><wicri:regionArea>FCEN-UBA, Ciudad Universitaria, Pabellón 2 Piso 4, lab QB-17, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Gonzalez Gallego, Javier" sort="Gonzalez Gallego, Javier" uniqKey="Gonzalez Gallego J" first="Javier" last="González-Gallego">Javier González-Gallego</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Biomedicine and CIBEREhd, University of León, León, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Institute of Biomedicine and CIBEREhd, University of León, León</wicri:regionArea><wicri:noRegion>León</wicri:noRegion></affiliation></author><author><name sortKey="Tu N, Maria J" sort="Tu N, Maria J" uniqKey="Tu N M" first="María J" last="Tu N">María J. Tu N</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Biomedicine and CIBEREhd, University of León, León, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Institute of Biomedicine and CIBEREhd, University of León, León</wicri:regionArea><wicri:noRegion>León</wicri:noRegion></affiliation></author><author><name sortKey="Dent, Paul" sort="Dent, Paul" uniqKey="Dent P" first="Paul" last="Dent">Paul Dent</name><affiliation wicri:level="2"><nlm:affiliation>Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation></author></analytic><series><title level="j">Journal of cellular physiology</title><idno type="eISSN">1097-4652</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Autophagosomes (drug effects)</term><term>Autophagy (drug effects)</term><term>Cell Line</term><term>Endoplasmic Reticulum (drug effects)</term><term>Endoplasmic Reticulum (metabolism)</term><term>Endoplasmic Reticulum Stress (drug effects)</term><term>Endoplasmic Reticulum Stress (physiology)</term><term>Humans</term><term>Molecular Chaperones (metabolism)</term><term>Pyrazoles (pharmacology)</term><term>Sulfonamides (pharmacology)</term><term>Virus Replication (drug effects)</term><term>Virus Replication (physiology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Autophagie ()</term><term>Autophagosomes ()</term><term>Chaperons moléculaires (métabolisme)</term><term>Humains</term><term>Lignée cellulaire</term><term>Pyrazoles (pharmacologie)</term><term>Réplication virale ()</term><term>Réplication virale (physiologie)</term><term>Réticulum endoplasmique ()</term><term>Réticulum endoplasmique (métabolisme)</term><term>Stress du réticulum endoplasmique ()</term><term>Stress du réticulum endoplasmique (physiologie)</term><term>Sulfonamides (pharmacologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Molecular Chaperones</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Autophagosomes</term><term>Autophagy</term><term>Endoplasmic Reticulum</term><term>Endoplasmic Reticulum Stress</term><term>Virus Replication</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Endoplasmic Reticulum</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Chaperons moléculaires</term><term>Réticulum endoplasmique</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Pyrazoles</term><term>Sulfonamides</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Pyrazoles</term><term>Sulfonamides</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Réplication virale</term><term>Stress du réticulum endoplasmique</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Endoplasmic Reticulum Stress</term><term>Virus Replication</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Line</term><term>Humans</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Autophagie</term><term>Autophagosomes</term><term>Humains</term><term>Lignée cellulaire</term><term>Réplication virale</term><term>Réticulum endoplasmique</term><term>Stress du réticulum endoplasmique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We have recently demonstrated that AR-12 (OSU-03012) reduces the function and ATPase activities of multiple HSP90 and HSP70 family chaperones. Combined knock down of chaperones or AR-12 treatment acted to reduce the expression of virus receptors and essential glucosidase proteins. Combined knock down of chaperones or AR-12 treatment inactivated mTOR and elevated ATG13 S318 phosphorylation concomitant with inducing an endoplasmic reticulum stress response that in an eIF2α-dependent fashion increased Beclin1 and LC3 expression and autophagosome formation. Over-expression of chaperones prevented the reduction in receptor/glucosidase expression, mTOR inactivation, the ER stress response, and autophagosome formation. AR-12 reduced the reproduction of viruses including Mumps, Influenza, Measles, Junín, Rubella, HIV (wild type and protease resistant), and Ebola, an effect replicated by knock down of multiple chaperone proteins. AR-12-stimulated the co-localization of Influenza, EBV and HIV virus proteins with LC3 in autophagosomes and reduced viral protein association with the chaperones HSP90, HSP70, and GRP78. Knock down of Beclin1 suppressed drug-induced autophagosome formation and reduced the anti-viral protection afforded by AR-12. In an animal model of hemorrhagic fever virus, a transient exposure of animals to low doses of AR-12 doubled animal survival from ∼30% to ∼60% and suppressed liver damage as measured by ATL, GGT and LDH release. Thus through inhibition of chaperone protein functions; reducing the production, stability and processing of viral proteins; and stimulating autophagosome formation/viral protein degradation, AR-12 acts as a broad-specificity anti-viral drug in vitro and in vivo. We argue future patient studies with AR-12 are warranted. J. Cell. Physiol. 231: 2286-2302, 2016. © 2016 Wiley Periodicals, Inc.</div></front></TEI><affiliations><list><country><li>Argentine</li><li>Australie</li><li>Espagne</li><li>États-Unis</li></country><region><li>Arizona</li><li>Maryland</li><li>New Jersey</li><li>Virginie</li></region></list><tree><country name="États-Unis"><region name="Virginie"><name sortKey="Booth, Laurence" sort="Booth, Laurence" uniqKey="Booth L" first="Laurence" last="Booth">Laurence Booth</name></region><name sortKey="Bavari, Sina" sort="Bavari, Sina" uniqKey="Bavari S" first="Sina" last="Bavari">Sina Bavari</name><name sortKey="Dent, Paul" sort="Dent, Paul" uniqKey="Dent P" first="Paul" last="Dent">Paul Dent</name><name sortKey="Jacob, Abraham" sort="Jacob, Abraham" uniqKey="Jacob A" first="Abraham" last="Jacob">Abraham Jacob</name><name sortKey="Proniuk, Stefan" sort="Proniuk, Stefan" uniqKey="Proniuk S" first="Stefan" last="Proniuk">Stefan Proniuk</name><name sortKey="Reid, St Patrick" sort="Reid, St Patrick" uniqKey="Reid S" first="St Patrick" last="Reid">St Patrick Reid</name><name sortKey="Roberts, Jane L" sort="Roberts, Jane L" uniqKey="Roberts J" first="Jane L" last="Roberts">Jane L. Roberts</name><name sortKey="Tritsch, Sarah R" sort="Tritsch, Sarah R" uniqKey="Tritsch S" first="Sarah R" last="Tritsch">Sarah R. Tritsch</name><name sortKey="Zukiwski, Alexander" sort="Zukiwski, Alexander" uniqKey="Zukiwski A" first="Alexander" last="Zukiwski">Alexander Zukiwski</name></country><country name="Australie"><noRegion><name sortKey="Ecroyd, Heath" sort="Ecroyd, Heath" uniqKey="Ecroyd H" first="Heath" last="Ecroyd">Heath Ecroyd</name></noRegion></country><country name="Argentine"><noRegion><name sortKey="Sepulveda, Claudia S" sort="Sepulveda, Claudia S" uniqKey="Sepulveda C" first="Claudia S" last="Sepúlveda">Claudia S. Sepúlveda</name></noRegion><name sortKey="Damonte, Elsa" sort="Damonte, Elsa" uniqKey="Damonte E" first="Elsa" last="Damonte">Elsa Damonte</name><name sortKey="Garcia, Cybele C" sort="Garcia, Cybele C" uniqKey="Garcia C" first="Cybele C" last="García">Cybele C. García</name><name sortKey="Giovannoni, Federico" sort="Giovannoni, Federico" uniqKey="Giovannoni F" first="Federico" last="Giovannoni">Federico Giovannoni</name></country><country name="Espagne"><noRegion><name sortKey="Gonzalez Gallego, Javier" sort="Gonzalez Gallego, Javier" uniqKey="Gonzalez Gallego J" first="Javier" last="González-Gallego">Javier González-Gallego</name></noRegion><name sortKey="Tu N, Maria J" sort="Tu N, Maria J" uniqKey="Tu N M" first="María J" last="Tu N">María J. Tu N</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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