Autophagy Activation in Asthma Airways Remodeling.
Identifieur interne : 000A48 ( Main/Exploration ); précédent : 000A47; suivant : 000A49Autophagy Activation in Asthma Airways Remodeling.
Auteurs : Kielan D. Mcalinden ; Deepak A. Deshpande [États-Unis] ; Saeid Ghavami [Canada] ; Dia Xenaki [Australie] ; Sukhwinder Singh Sohal [Australie] ; Brian G. Oliver [Australie] ; Mehra Haghi ; Pawan Sharma [Australie]Source :
- American journal of respiratory cell and molecular biology [ 1535-4989 ] ; 2019.
Descripteurs français
- KwdFr :
- Adolescent, Adulte, Adulte d'âge moyen, Animaux, Antiasthmatiques (pharmacologie), Asthme (anatomopathologie), Asthme (génétique), Asthme (métabolisme), Asthme (traitement médicamenteux), Autophagie (), Autophagie (génétique), Bécline-1 (antagonistes et inhibiteurs), Bécline-1 (génétique), Bécline-1 (métabolisme), Chloroquine (pharmacologie), Cils vibratiles (), Cils vibratiles (anatomopathologie), Cils vibratiles (métabolisme), Culture primaire de cellules, Femelle, Humains, Modèles animaux de maladie humaine, Muqueuse respiratoire (), Muqueuse respiratoire (anatomopathologie), Muqueuse respiratoire (métabolisme), Muscles lisses (), Muscles lisses (anatomopathologie), Muscles lisses (métabolisme), Myocytes du muscle lisse (), Myocytes du muscle lisse (anatomopathologie), Myocytes du muscle lisse (métabolisme), Mâle, Poumon (), Poumon (anatomopathologie), Poumon (métabolisme), Protéine-5 associée à l'autophagie (antagonistes et inhibiteurs), Protéine-5 associée à l'autophagie (génétique), Protéine-5 associée à l'autophagie (métabolisme), Remodelage des voies aériennes (), Régulation de l'expression des gènes, Souris, Souris de lignée BALB C, Sujet âgé, Sujet âgé de 80 ans ou plus, Séquestosome-1 (génétique), Séquestosome-1 (métabolisme), Transduction du signal, Études cas-témoins.
- MESH :
- anatomopathologie : Asthme, Cils vibratiles, Muqueuse respiratoire, Muscles lisses, Myocytes du muscle lisse, Poumon.
- antagonistes et inhibiteurs : Bécline-1, Protéine-5 associée à l'autophagie.
- génétique : Asthme, Autophagie, Bécline-1, Protéine-5 associée à l'autophagie, Séquestosome-1.
- métabolisme : Asthme, Bécline-1, Cils vibratiles, Muqueuse respiratoire, Muscles lisses, Myocytes du muscle lisse, Poumon, Protéine-5 associée à l'autophagie, Séquestosome-1.
- pharmacologie : Antiasthmatiques, Chloroquine.
- traitement médicamenteux : Asthme.
- Adolescent, Adulte, Adulte d'âge moyen, Animaux, Autophagie, Cils vibratiles, Culture primaire de cellules, Femelle, Humains, Modèles animaux de maladie humaine, Muqueuse respiratoire, Muscles lisses, Myocytes du muscle lisse, Mâle, Poumon, Remodelage des voies aériennes, Régulation de l'expression des gènes, Souris, Souris de lignée BALB C, Sujet âgé, Sujet âgé de 80 ans ou plus, Transduction du signal, Études cas-témoins.
English descriptors
- KwdEn :
- Adolescent, Adult, Aged, Aged, 80 and over, Airway Remodeling (drug effects), Animals, Anti-Asthmatic Agents (pharmacology), Asthma (drug therapy), Asthma (genetics), Asthma (metabolism), Asthma (pathology), Autophagy (drug effects), Autophagy (genetics), Autophagy-Related Protein 5 (antagonists & inhibitors), Autophagy-Related Protein 5 (genetics), Autophagy-Related Protein 5 (metabolism), Beclin-1 (antagonists & inhibitors), Beclin-1 (genetics), Beclin-1 (metabolism), Case-Control Studies, Chloroquine (pharmacology), Cilia (drug effects), Cilia (metabolism), Cilia (pathology), Disease Models, Animal, Female, Gene Expression Regulation, Humans, Lung (drug effects), Lung (metabolism), Lung (pathology), Male, Mice, Mice, Inbred BALB C, Middle Aged, Muscle, Smooth (drug effects), Muscle, Smooth (metabolism), Muscle, Smooth (pathology), Myocytes, Smooth Muscle (drug effects), Myocytes, Smooth Muscle (metabolism), Myocytes, Smooth Muscle (pathology), Primary Cell Culture, Respiratory Mucosa (drug effects), Respiratory Mucosa (metabolism), Respiratory Mucosa (pathology), Sequestosome-1 Protein (genetics), Sequestosome-1 Protein (metabolism), Signal Transduction.
- MESH :
- chemical , antagonists & inhibitors : Autophagy-Related Protein 5, Beclin-1.
- chemical , genetics : Autophagy-Related Protein 5, Beclin-1, Sequestosome-1 Protein.
- chemical , metabolism : Autophagy-Related Protein 5, Beclin-1, Sequestosome-1 Protein.
- chemical , pharmacology : Anti-Asthmatic Agents, Chloroquine.
- drug effects : Airway Remodeling, Autophagy, Cilia, Lung, Muscle, Smooth, Myocytes, Smooth Muscle, Respiratory Mucosa.
- drug therapy : Asthma.
- genetics : Asthma, Autophagy.
- metabolism : Asthma, Cilia, Lung, Muscle, Smooth, Myocytes, Smooth Muscle, Respiratory Mucosa.
- pathology : Asthma, Cilia, Lung, Muscle, Smooth, Myocytes, Smooth Muscle, Respiratory Mucosa.
- Adolescent, Adult, Aged, Aged, 80 and over, Animals, Case-Control Studies, Disease Models, Animal, Female, Gene Expression Regulation, Humans, Male, Mice, Mice, Inbred BALB C, Middle Aged, Primary Cell Culture, Signal Transduction.
Abstract
Current asthma therapies fail to target airway remodeling that correlates with asthma severity driving disease progression that ultimately leads to loss of lung function. Macroautophagy (hereinafter "autophagy") is a fundamental cell-recycling mechanism in all eukaryotic cells; emerging evidence suggests that it is dysregulated in asthma. We investigated the interrelationship between autophagy and airway remodeling and assessed preclinical efficacy of a known autophagy inhibitor in murine models of asthma. Human asthmatic and nonasthmatic lung tissues were histologically evaluated and were immunostained for key autophagy markers. The percentage area of positive staining was quantified in the epithelium and airway smooth muscle bundles using ImageJ software. Furthermore, the autophagy inhibitor chloroquine was tested intranasally in prophylactic (3 wk) and treatment (5 wk) models of allergic asthma in mice. Human asthmatic tissues showed greater tissue inflammation and demonstrated hallmark features of airway remodeling, displaying thickened epithelium (P < 0.001) and reticular basement membrane (P < 0.0001), greater lamina propria depth (P < 0.005), and increased airway smooth muscle bundles (P < 0.001) with higher expression of Beclin-1 (P < 0.01) and ATG5 (autophagy-related gene 5) (P < 0.05) together with reduced p62 (P < 0.05) compared with nonasthmatic control tissues. Beclin-1 expression was significantly higher in asthmatic epithelium and ciliated cells (P < 0.05), suggesting a potential role of ciliophagy in asthma. Murine asthma models demonstrated effective preclinical efficacy (reduced key features of allergic asthma: airway inflammation, airway hyperresponsiveness, and airway remodeling) of the autophagy inhibitor chloroquine. Our data demonstrate cell context-dependent and selective activation of autophagy in structural cells in asthma. Furthermore, this pathway can be effectively targeted to ameliorate airway remodeling in asthma.
DOI: 10.1165/rcmb.2018-0169OC
PubMed: 30383396
Affiliations:
- Australie, Canada, États-Unis
- Manitoba, Nouvelle-Galles du Sud, Pennsylvanie
- Sydney, Winnipeg
- Université de Sydney, Université du Manitoba
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Le document en format XML
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Mcalinden</name><affiliation><nlm:affiliation>1 Graduate School of Health and.</nlm:affiliation><wicri:noCountry code="no comma">1 Graduate School of Health and.</wicri:noCountry></affiliation></author><author><name sortKey="Deshpande, Deepak A" sort="Deshpande, Deepak A" uniqKey="Deshpande D" first="Deepak A" last="Deshpande">Deepak A. Deshpande</name><affiliation wicri:level="2"><nlm:affiliation>4 Center for Translational Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>4 Center for Translational Medicine, Thomas Jefferson University, Philadelphia</wicri:cityArea></affiliation></author><author><name sortKey="Ghavami, Saeid" sort="Ghavami, Saeid" uniqKey="Ghavami S" first="Saeid" last="Ghavami">Saeid Ghavami</name><affiliation wicri:level="4"><nlm:affiliation>5 Department of Anatomy & Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada; and.</nlm:affiliation><orgName type="university">Université du Manitoba</orgName><country>Canada</country><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Xenaki, Dia" sort="Xenaki, Dia" uniqKey="Xenaki D" first="Dia" last="Xenaki">Dia Xenaki</name><affiliation wicri:level="4"><nlm:affiliation>2 Woolcock Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>2 Woolcock Institute of Medical Research, University of Sydney, Sydney, New South Wales</wicri:regionArea><orgName type="university">Université de Sydney</orgName><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Sohal, Sukhwinder Singh" sort="Sohal, Sukhwinder Singh" uniqKey="Sohal S" first="Sukhwinder Singh" last="Sohal">Sukhwinder Singh Sohal</name><affiliation wicri:level="1"><nlm:affiliation>6 Respiratory Translational Research Group, Department of Laboratory Medicine, University of Tasmania, Launceston, Tasmania, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>6 Respiratory Translational Research Group, Department of Laboratory Medicine, University of Tasmania, Launceston, Tasmania</wicri:regionArea><wicri:noRegion>Tasmania</wicri:noRegion></affiliation></author><author><name sortKey="Oliver, Brian G" sort="Oliver, Brian G" uniqKey="Oliver B" first="Brian G" last="Oliver">Brian G. Oliver</name><affiliation wicri:level="1"><nlm:affiliation>3 School of Life Sciences, University of Technology Sydney, Sydney, New South Wales, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>3 School of Life Sciences, University of Technology Sydney, Sydney, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author><author><name sortKey="Haghi, Mehra" sort="Haghi, Mehra" uniqKey="Haghi M" first="Mehra" last="Haghi">Mehra Haghi</name><affiliation><nlm:affiliation>1 Graduate School of Health and.</nlm:affiliation><wicri:noCountry code="no comma">1 Graduate School of Health and.</wicri:noCountry></affiliation></author><author><name sortKey="Sharma, Pawan" sort="Sharma, Pawan" uniqKey="Sharma P" first="Pawan" last="Sharma">Pawan Sharma</name><affiliation wicri:level="1"><nlm:affiliation>3 School of Life Sciences, University of Technology Sydney, Sydney, New South Wales, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>3 School of Life Sciences, University of Technology Sydney, Sydney, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author></analytic><series><title level="j">American journal of respiratory cell and molecular biology</title><idno type="eISSN">1535-4989</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Airway Remodeling (drug effects)</term><term>Animals</term><term>Anti-Asthmatic Agents (pharmacology)</term><term>Asthma (drug therapy)</term><term>Asthma (genetics)</term><term>Asthma (metabolism)</term><term>Asthma (pathology)</term><term>Autophagy (drug effects)</term><term>Autophagy (genetics)</term><term>Autophagy-Related Protein 5 (antagonists & inhibitors)</term><term>Autophagy-Related Protein 5 (genetics)</term><term>Autophagy-Related Protein 5 (metabolism)</term><term>Beclin-1 (antagonists & inhibitors)</term><term>Beclin-1 (genetics)</term><term>Beclin-1 (metabolism)</term><term>Case-Control Studies</term><term>Chloroquine (pharmacology)</term><term>Cilia (drug effects)</term><term>Cilia (metabolism)</term><term>Cilia (pathology)</term><term>Disease Models, Animal</term><term>Female</term><term>Gene Expression Regulation</term><term>Humans</term><term>Lung (drug effects)</term><term>Lung (metabolism)</term><term>Lung (pathology)</term><term>Male</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Middle Aged</term><term>Muscle, Smooth (drug effects)</term><term>Muscle, Smooth (metabolism)</term><term>Muscle, Smooth (pathology)</term><term>Myocytes, Smooth Muscle (drug effects)</term><term>Myocytes, Smooth Muscle (metabolism)</term><term>Myocytes, Smooth Muscle (pathology)</term><term>Primary Cell Culture</term><term>Respiratory Mucosa (drug effects)</term><term>Respiratory Mucosa (metabolism)</term><term>Respiratory Mucosa (pathology)</term><term>Sequestosome-1 Protein (genetics)</term><term>Sequestosome-1 Protein (metabolism)</term><term>Signal Transduction</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adolescent</term><term>Adulte</term><term>Adulte d'âge moyen</term><term>Animaux</term><term>Antiasthmatiques (pharmacologie)</term><term>Asthme (anatomopathologie)</term><term>Asthme (génétique)</term><term>Asthme (métabolisme)</term><term>Asthme (traitement médicamenteux)</term><term>Autophagie ()</term><term>Autophagie (génétique)</term><term>Bécline-1 (antagonistes et inhibiteurs)</term><term>Bécline-1 (génétique)</term><term>Bécline-1 (métabolisme)</term><term>Chloroquine (pharmacologie)</term><term>Cils vibratiles ()</term><term>Cils vibratiles (anatomopathologie)</term><term>Cils vibratiles (métabolisme)</term><term>Culture primaire de cellules</term><term>Femelle</term><term>Humains</term><term>Modèles animaux de maladie humaine</term><term>Muqueuse respiratoire ()</term><term>Muqueuse respiratoire (anatomopathologie)</term><term>Muqueuse respiratoire (métabolisme)</term><term>Muscles lisses ()</term><term>Muscles lisses (anatomopathologie)</term><term>Muscles lisses (métabolisme)</term><term>Myocytes du muscle lisse ()</term><term>Myocytes du muscle lisse (anatomopathologie)</term><term>Myocytes du muscle lisse (métabolisme)</term><term>Mâle</term><term>Poumon ()</term><term>Poumon (anatomopathologie)</term><term>Poumon (métabolisme)</term><term>Protéine-5 associée à l'autophagie (antagonistes et inhibiteurs)</term><term>Protéine-5 associée à l'autophagie (génétique)</term><term>Protéine-5 associée à l'autophagie (métabolisme)</term><term>Remodelage des voies aériennes ()</term><term>Régulation de l'expression des gènes</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Sujet âgé</term><term>Sujet âgé de 80 ans ou plus</term><term>Séquestosome-1 (génétique)</term><term>Séquestosome-1 (métabolisme)</term><term>Transduction du signal</term><term>Études cas-témoins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Autophagy-Related Protein 5</term><term>Beclin-1</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Autophagy-Related Protein 5</term><term>Beclin-1</term><term>Sequestosome-1 Protein</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Autophagy-Related Protein 5</term><term>Beclin-1</term><term>Sequestosome-1 Protein</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Anti-Asthmatic Agents</term><term>Chloroquine</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Asthme</term><term>Cils vibratiles</term><term>Muqueuse respiratoire</term><term>Muscles lisses</term><term>Myocytes du muscle lisse</term><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Bécline-1</term><term>Protéine-5 associée à l'autophagie</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Airway Remodeling</term><term>Autophagy</term><term>Cilia</term><term>Lung</term><term>Muscle, Smooth</term><term>Myocytes, Smooth Muscle</term><term>Respiratory Mucosa</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Asthma</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Asthma</term><term>Autophagy</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Asthme</term><term>Autophagie</term><term>Bécline-1</term><term>Protéine-5 associée à l'autophagie</term><term>Séquestosome-1</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Asthma</term><term>Cilia</term><term>Lung</term><term>Muscle, Smooth</term><term>Myocytes, Smooth Muscle</term><term>Respiratory Mucosa</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Asthme</term><term>Bécline-1</term><term>Cils vibratiles</term><term>Muqueuse respiratoire</term><term>Muscles lisses</term><term>Myocytes du muscle lisse</term><term>Poumon</term><term>Protéine-5 associée à l'autophagie</term><term>Séquestosome-1</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Asthma</term><term>Cilia</term><term>Lung</term><term>Muscle, Smooth</term><term>Myocytes, Smooth Muscle</term><term>Respiratory Mucosa</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antiasthmatiques</term><term>Chloroquine</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Asthme</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Animals</term><term>Case-Control Studies</term><term>Disease Models, Animal</term><term>Female</term><term>Gene Expression Regulation</term><term>Humans</term><term>Male</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Middle Aged</term><term>Primary Cell Culture</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adolescent</term><term>Adulte</term><term>Adulte d'âge moyen</term><term>Animaux</term><term>Autophagie</term><term>Cils vibratiles</term><term>Culture primaire de cellules</term><term>Femelle</term><term>Humains</term><term>Modèles animaux de maladie humaine</term><term>Muqueuse respiratoire</term><term>Muscles lisses</term><term>Myocytes du muscle lisse</term><term>Mâle</term><term>Poumon</term><term>Remodelage des voies aériennes</term><term>Régulation de l'expression des gènes</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Sujet âgé</term><term>Sujet âgé de 80 ans ou plus</term><term>Transduction du signal</term><term>Études cas-témoins</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Current asthma therapies fail to target airway remodeling that correlates with asthma severity driving disease progression that ultimately leads to loss of lung function. Macroautophagy (hereinafter "autophagy") is a fundamental cell-recycling mechanism in all eukaryotic cells; emerging evidence suggests that it is dysregulated in asthma. We investigated the interrelationship between autophagy and airway remodeling and assessed preclinical efficacy of a known autophagy inhibitor in murine models of asthma. Human asthmatic and nonasthmatic lung tissues were histologically evaluated and were immunostained for key autophagy markers. The percentage area of positive staining was quantified in the epithelium and airway smooth muscle bundles using ImageJ software. Furthermore, the autophagy inhibitor chloroquine was tested intranasally in prophylactic (3 wk) and treatment (5 wk) models of allergic asthma in mice. Human asthmatic tissues showed greater tissue inflammation and demonstrated hallmark features of airway remodeling, displaying thickened epithelium (<i>P</i> < 0.001) and reticular basement membrane (<i>P</i> < 0.0001), greater lamina propria depth (<i>P</i> < 0.005), and increased airway smooth muscle bundles (<i>P</i> < 0.001) with higher expression of Beclin-1 (<i>P</i> < 0.01) and ATG5 (autophagy-related gene 5) (<i>P</i> < 0.05) together with reduced p62 (<i>P</i> < 0.05) compared with nonasthmatic control tissues. Beclin-1 expression was significantly higher in asthmatic epithelium and ciliated cells (<i>P</i> < 0.05), suggesting a potential role of ciliophagy in asthma. Murine asthma models demonstrated effective preclinical efficacy (reduced key features of allergic asthma: airway inflammation, airway hyperresponsiveness, and airway remodeling) of the autophagy inhibitor chloroquine. Our data demonstrate cell context-dependent and selective activation of autophagy in structural cells in asthma. Furthermore, this pathway can be effectively targeted to ameliorate airway remodeling in asthma.</div></front></TEI><affiliations><list><country><li>Australie</li><li>Canada</li><li>États-Unis</li></country><region><li>Manitoba</li><li>Nouvelle-Galles du Sud</li><li>Pennsylvanie</li></region><settlement><li>Sydney</li><li>Winnipeg</li></settlement><orgName><li>Université de Sydney</li><li>Université du Manitoba</li></orgName></list><tree><noCountry><name sortKey="Haghi, Mehra" sort="Haghi, Mehra" uniqKey="Haghi M" first="Mehra" last="Haghi">Mehra Haghi</name><name sortKey="Mcalinden, Kielan D" sort="Mcalinden, Kielan D" uniqKey="Mcalinden K" first="Kielan D" last="Mcalinden">Kielan D. Mcalinden</name></noCountry><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Deshpande, Deepak A" sort="Deshpande, Deepak A" uniqKey="Deshpande D" first="Deepak A" last="Deshpande">Deepak A. Deshpande</name></region></country><country name="Canada"><region name="Manitoba"><name sortKey="Ghavami, Saeid" sort="Ghavami, Saeid" uniqKey="Ghavami S" first="Saeid" last="Ghavami">Saeid Ghavami</name></region></country><country name="Australie"><region name="Nouvelle-Galles du Sud"><name sortKey="Xenaki, Dia" sort="Xenaki, Dia" uniqKey="Xenaki D" first="Dia" last="Xenaki">Dia Xenaki</name></region><name sortKey="Oliver, Brian G" sort="Oliver, Brian G" uniqKey="Oliver B" first="Brian G" last="Oliver">Brian G. Oliver</name><name sortKey="Sharma, Pawan" sort="Sharma, Pawan" uniqKey="Sharma P" first="Pawan" last="Sharma">Pawan Sharma</name><name sortKey="Sohal, Sukhwinder Singh" sort="Sohal, Sukhwinder Singh" uniqKey="Sohal S" first="Sukhwinder Singh" last="Sohal">Sukhwinder Singh Sohal</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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