Author: "Yong Loo Lin School of Medicine" - Searchworks@Jio Institute Digital Library Search Results

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20,527 results on '"Yong Loo Lin School of Medicine"'

1. Mechanical Dilation of the Cervix in a Scarred Uterus (MEDICS)

Author: Department of Obstetrics and Gynaecology, National University Hospital, Yong Loo Lin School of Medicine, National University Hospital, Singapore, National University of Singapore, and Soe-na Choo, Medical Officer
Published: 2019

2. Covid-19 Chronicles, The: Singapore's Journey From Pandemia To Peri-pandemic Limbo

Author: Yong Loo Lin School Of Medicine, Nus and Yong Loo Lin School Of Medicine, Nus
Subjects: COVID-19 Pandemic, 2020---Singapore--Pictorial works, COVID-19 Pandemic, 2020---Singapore
Abstract: No one is safe until everyone is safe. Singapore's struggle against the coronavirus mirrors those being waged by countries everywhere against a relentless, invisible enemy. In times of crisis, confusion and pandemonium abound. Sensing a need for simple and concise public health education and information that could help people to make sense of a bewildering new abnormal, the NUS Yong Loo Lin School of Medicine launched a long-running series of illustrated stories on social media platforms. The COVID-19 Chronicles quickly took off, drawing the attention of the WHO's Global Outbreak Alert and Response Network, which arranged for the series to be shared with other countries.This book features every Chronicles story published, and tells the story of the work behind the scenes to bring each episode to life. Offering bite-sized explanations of issues and topics seeded by the pandemic's global march, the Chronicles prods readers to stay safe, while also providing a humorous take on Singaporean life in the time of COVID-19.
Published: 2022

3. Telomere-mediated genomic instability and the clinico-pathological parameters in breast cancer

Author: Department of Cancer Biology and Pharmacology, Genome Institute of Singapore, Genome, Singapore ; Michigan Center for Translation Pathology, University of Michigan Health System, Comprehensive Cancer Center, Ann Arbor, MI, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Department of Cancer Biology and Pharmacology, Genome Institute of Singapore, Genome, Singapore, Department of Pathology, Yong Loo Lin School of Medicine, National University Singapore, Singapore, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore ; Genome Stability Laboratory, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Block MD9, 2 Medical Drive, Singapore 117597, Poonepalli, Anuradha, Banerjee, Birendranath, Ramnarayanan, Kalpana, Palanisamy, Nallasivam, Putti, Thomas Choudary, Hande, M. Prakash, Department of Cancer Biology and Pharmacology, Genome Institute of Singapore, Genome, Singapore ; Michigan Center for Translation Pathology, University of Michigan Health System, Comprehensive Cancer Center, Ann Arbor, MI, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Department of Cancer Biology and Pharmacology, Genome Institute of Singapore, Genome, Singapore, Department of Pathology, Yong Loo Lin School of Medicine, National University Singapore, Singapore, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore ; Genome Stability Laboratory, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Block MD9, 2 Medical Drive, Singapore 117597, Poonepalli, Anuradha, Banerjee, Birendranath, Ramnarayanan, Kalpana, Palanisamy, Nallasivam, Putti, Thomas Choudary, and Hande, M. Prakash
Abstract: A study was undertaken to correlate telomere dysfunction and genomic instability with the histopathological grades and the estrogen and progesterone receptor status in breast cancer. Sixty-one archived breast tissues (38 cancer tissues and 23 paired normal tissues) were used in the study. The breast tumor tissues showed significantly shorter telomeres (7.7 kb) compared with the paired adjacent tissues (9.0 kb) by Southern blot analysis. Moreover, telomere shortening was more significant in Grade III tumors than in the Grade II tumors ( P = 0.05). Quantitative fluorescence in situ hybridization on paraffin tissue sections revealed a similar trend in telomere shortening. Telomere attrition was associated with telomere dysfunction as revealed by the presence of significantly higher anaphase bridges in tumor cells which was tumor grade dependent. Furthermore, estrogen receptive negative tumors displayed higher anaphase and internuclear bridges. Selected samples from each grade showed greater genomic imbalances in the higher grades than the lower grade tumors as detected by array-comparative genomic hybridization. Telomerase activity was found to be higher in the higher grades (Grade II and III) compared with the lower grade (Grade I). The average mRNA expression of TRF1 and POT1 was lower in the tumor tissues than in the normal tissues. Tankyrase 1 mRNA expression showed a grade-dependent increase in tumor tissues and its expression was also high in estrogen and progesterone negative tumors. The data support the notion that telomere dysfunction might be of value as a marker of aggressiveness of the tumors in breast cancer patients. ?? 2008 Wiley-Liss, Inc.
Published: 2008

4. Studying Phenotypes of Gestational Diabetes Mellitus in an Asian Pregnant Cohort (GDM-CARE)

Author: Lingjun Li, Assistant Director, Public Affairs, Global Centre for Asian Women's Health, Assistant Professor, Department of O&G, Yong Loo Lin School of Medicine, National University of Singapore
Published: 2024

5. Guidelines for the use and interpretation of assays for monitoring autophagy.

Author: Molecular and Cellular Biology ; University of Leuven, Laboratoire d'Epigénétique et Cancer ; CNRS - Université Paris XI - Paris Sud, Department of Pharmacology ; Department of Pharmacology, Immunobiologie des Cellules Dendritiques ; INSERM - Institut Pasteur de Paris, Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (FEMTO-ST) ; CNRS - Université de Franche-Comté - Université de Technologie de Belfort-Montbeliard - Ecole Nationale Supérieure de Mécanique et des Microtechniques, Telethon Institute for Genetics and Medicine ; Telethon Institute, Medical Genetics ; Federico II University, Department of Molecular and Human Genetics ; Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute ; Texas Children's Hospital, Signalisation et physiopathologie des cellules épithéliales ; INSERM - Université Paris XI - Paris Sud, Dynamique des interactions membranaires normales et pathologiques (DIMNP) ; CNRS - Université Montpellier I - Université Montpellier II - Sciences et techniques, Institut de biochimie et génétique cellulaires (IBGC) ; CNRS - Université Victor Segalen - Bordeaux II, Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS) ; CNRS - Université Montpellier I - Université Montpellier II - Sciences et techniques, Celullar and Molecular Medicine ; Celullar and Molecular Medicine, Estrogène, Expression génique et pathologies du Système Nerveux Central (E2SNC) ; Université de Franche-Comté - IFR133, Infection bactérienne, inflammation, et carcinogenèse digestive ; INSERM - IFR50 - Université Nice Sophia Antipolis (UNS), Université Nice Sophia Antipolis (UNS) ; Université Nice Sophia Antipolis (UNS) - PRES Euro-Méditerranéen, Department of Computer Science [Tsukuba] ; University of Tsukuba, Gunma University ; Institute for Molecular & Cellular Regulation, Cell Biology, Physiology and Immunology ; Cell Biology, Physiology and Immunology, Dulbecco Telethon Institute/Department of Biology ; Dulbecco Telethon Institute/Department of Biology, Department of Chemistry and HKU-CAS Joint Laboratory ; University of Hong-Kong, Laboratoire Bordelais de Recherche en Informatique (LaBRI) ; CNRS - Université Sciences et Technologies - Bordeaux I - Université Victor Segalen - Bordeaux II - École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Learning Sciences Lab ; National Institute of Education, Nanyang Technological University, University of California ; University of California, Physiopathologie du cancer du foie ; INSERM - Université Victor Segalen - Bordeaux II, Emory University School of Medicine ; Emory University School of Medicine, Cytokines et Immunologie des Tumeurs Humaines ; INSERM - Institut Gustave Roussy - Université Paris XI - Paris Sud, Biology ; University of Rome"Tor Vergata", Oxford University ; Oxford University, Strathclyde Institute of Pharmacy and Biomedical Sciences ; University of Strathclyde, Interactions Bactéries-Cellules (UIBC) ; Institut national de la recherche agronomique (INRA) - INSERM - Institut Pasteur de Paris, Department of Experimental Medicine and Oncology ; University of Turin, Institut de génomique fonctionnelle (IGF) ; CNRS - INSERM - Université Montpellier I - Université Montpellier II - Sciences et techniques, CNV ; University of Valparaiso, Section of Haemato-oncology ; Institute of cancer research, Régulation de l'expression génétique (REG) ; CNRS - École normale supérieure [ENS] - Paris, Brunel University ; Brunel University, University of New-Mexico ; University of New-Mexico, Facultad de Ciencias Químicas y Farmacéuticas ; Centro de Estudios Moleculares de la Célula, Biochemistry and Molecular Biology ; Biochemistry and Molecular Biology, Dpt. of Cancer & Cell Biology ; University of Cincinnati, Institut Jacques Monod (IJM) ; CNRS - Université Paris VII - Paris Diderot, Virologie humaine ; INSERM - IFR128 - École Normale Supérieure (ENS) - Lyon, Instituto de Investigaciones Biotecnológicas, (IIB-INTECH) ; Universidad Nacional de San Martin, MRC Centre for Developmental Neurobiology ; MRC Centre for Developmental Neurobiology, University of Brescia ; University of Brescia, Immunité infection vaccination ; INSERM - Université Claude Bernard - Lyon I (UCBL) - IFR128, Dept of City and Regional Planning ; Peiking University, Montreal Neurological Institute ; McGill University, Department of Developmental Biology and Neurosciences ; Tohoku University - Graduate School of Life Sciences, Biologie Cellulaire du Noyau (BCN) ; CNRS - Institut Pasteur de Paris, Faculty of Medicine ; University of Ottawa, Institut de recherche en cancérologie de Montpellier (IRCM) ; INSERM - CRLCC Val d'Aurelle - Paul Lamarque - Université Montpellier I, Immunologie et chimie thérapeutiques (ICT) ; CNRS - Cancéropôle du Grand Est, Université de Strasbourg (UNISTRA) ; Université de Strasbourg, Département Digestif ; CHU Nice - Hôpital de l'Archet, Centre méditérannéen de médecine moléculaire (C3M) ; INSERM - Université Nice Sophia Antipolis (UNS), National Institute of Advanced Industrial Science and Technology [Tsukuba] (AIST) ; National Institute for Advanced Industrial Science and Technology - AIST (JAPAN), Department of Oncology ; John Radcliffe Hospital, School of Biochemistry and Immunology ; School of Biochemistry and Immunology, Department of Cellular and Structural Biology, University of Texas Health Science Center ; University of Texas, Laboratoire de Pathologie Clinique et Expérimentale ; CHU Nice, Department of Biochemistry ; University of Hong Kong, Danish Cancer Society ; Institute of Cancer Biology, Institut de biologie et chimie des protéines [Lyon] (IBCP) ; CNRS - Université Claude Bernard - Lyon I (UCBL), Department of Gastroenterology, Hepatology and Endocrinology (MHH) ; Hannover medical school, Cancer Research UK London Research Institute ; Cancer Research UK London Research Institute, Cell Biology, section Radiation & Stress Cell Biology ; UMCG, Univ. of Groningen, Department of Molecular Genetics ; Weizmann Institute of Science, Institute of Immunology ; University Hospital Schleswig-Holstein, Institute for Immunology ; Institute for Immunology, Department of Neuroscience ; University of Texas Southwestern Medical Center at Dallas, Centre de génétique et de physiologie moléculaire et cellulaire (CGphiMC) ; CNRS - Université Claude Bernard - Lyon I (UCBL), Centre de Recherche des Cordeliers ; INSERM - Université Paris V - Paris Descartes - Université Pierre et Marie Curie (UPMC) - Paris VI, Apoptose, cancer et immunité ; INSERM - Institut Gustave Roussy - Université Paris XI - Paris Sud, metabolomics platform ; Institut Gustave Roussy, Pôle de biologie ; Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital européen Georges Pompidou, Université Paris Descartes - Faculté de Médecine (UP5) ; Université Paris V - Paris Descartes - PRES Sorbonne Paris Cité, Department of Molecular Neuroscience ; Department of Molecular Neuroscience, European Organization for Nuclear Research (CERN) ; CERN, Center for Visual Information Technology (CVIT) ; International Institute of Information Technology, Massachusetts Institute of technology [Cambridge] (MIT) ; Massachusetts Institute of Technology (MIT), Department of Biochemistry and Molecular Biology ; University of Washington, Centre for Cancer Biology ; Hanson Institute, Adelaide, Jeune Equipe JE 2526 ; Université d'Auvergne - Clermont-Ferrand I, Institut de Recherche Agronomique (Unité sous contrat USC-2018) ; Institut national de la recherche agronomique (INRA), Facultad de Medicina ; Universidad de Chile, Institut de génétique moléculaire de Montpellier (IGMM) ; CNRS - Université Montpellier II - Sciences et techniques, Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC) ; IFR140 - Université de Rennes 1 - IRSET, Centre de génétique moléculaire (CGM) ; CNRS - Université Paris XI - Paris Sud - Université Pierre et Marie Curie (UPMC) - Paris VI, National Cheng Kung University [Taiwan] (NCKU) ; Institute of Basic Medical Sciences, Microenvironnement et Physiopathologie de la Differenciation ; INSERM - Université Paris XI - Paris Sud, Howard Hughes Medical Institute ; Howard Hugues Medical Institute, Southwestern Medical Center ; University of Texas, School of Information science and engineering ; Lanzhou University, School of computer and information ; Hefei University, National Neuroscience Institute ; National Neuroscience Institute, National University of Singapore (NUS) ; NUS, Institut de Mécanique des Fluides et des Solides (IMFS) ; CNRS - Université de Strasbourg - ENGEES, Institut Armand Frappier (IAF) ; Réseau International des Instituts Pasteur - Institut National de la Recherche Scientifique, Central China Normal University ; Central China Normal University, Center for International Blood and Marrow Transplant Research (CIBMTR) ; Medical College Of Wisconsin - Emory University School of Medicine, Departamento de Bioquímica y Biología Molecular ; Universidad de Oviedo - Instituto Universitario de Oncología, Laboratoire d'analyse et d'architecture des systèmes [Toulouse] (LAAS) ; CNRS - Université Paul Sabatier (UPS) - Toulouse III - Institut National Polytechnique de Toulouse - INPT - Institut National des Sciences Appliquées [INSA] - Toulouse, Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Equipe Labellisée par la Ligue Nationale contre le Cancer ; LNCC, Johns Hopkins University (JHU) ; Johns Hopkins University, Institute of Molecular Biosciences, Karl-Franzens University Graz, (IMB) ; Karl-Franzens University Graz, Department of Pediatrics ; Università degli studi di Napoli Federico II, Department of Experimental Pharmacology ; Università degli Study di Napoli Federico II, Drug Research and Evaluation ; Istituto Superiore di Sanita‘, Albert Einstein College of Medicine (ALBERT EINSTEIN COLLEGE OF MEDICINE) ; Albert Einstein College of Medicine, Institute of Molecular Biology and Biotechnology ; Foundation for Research and Technology - Hellas, Institut des Sciences de l'Evolution - Montpellier (ISEM) ; CNRS - Institut de recherche pour le développement [IRD] - Université Montpellier II - Sciences et techniques, Institut de signalisation, biologie du développement et cancer (ISBDC) ; CNRS - Université Nice Sophia Antipolis (UNS), Departments of Neurology ; Departments of Neurology, Vanderbilt University [Nashville] ; Vanderbilt University of Nashville, Departments of Pharmacology ; Departments of Pharmacology, Department of Cell Biology [New Haven] ; Yale University School of Medicine - Howard Hugues Medical Institute, Anatomic Pathology Section, Department of Human Pathology and Oncology ; University of Siena, Harvard Medical School (HMS) ; Harvard University, Depts of Radiation Oncology and Pathology ; Wayne State University - Karmanos Cancer Institute, USC Neuromuscular Center, Department of Neurology ; University of Southern California, Department of Biology ; University of Copenhagen, Department of Cell Biology and Biophysics ; University of Athens, Department of Pathology ; Case Western Reserve University, University of Texas at San Antonio ; University of Texas at San Antonio, Institute of Translational Medicine ; Institute of Translational Medicine, Institute of Biochemistry (IBC) ; Swiss Federal Institute of Technology Zurich - Eidgenössische Technische Hochschule Zürich (ETH), Department of Biology ; University of Rome Tor Vergata, Génétique, physiopathologie et ingénierie du tissu osseux (GéPITOS) ; CNRS - Université Nice Sophia Antipolis (UNS), Innovation Thérapeutique : du Fondamental au Médicament ; CNRS - Institut national de la recherche agronomique (INRA) - INSERM - MEDICEN - Université Paris XI - Paris Sud, Hôpital Antoine Béclère ; Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris XI - Paris Sud, Señalización Celular 4 ; Señalización Celular 4, Department of Molecular Biology ; University of Tuebingen, Department of Neurology Columbia University 650 West 168th Street ; Department of Neurology Columbia University 650 West 168th Street, Department of Pathology and Cell Biology Columbia University 650 West 168th Street ; Department of Pathology and Cell Biology Columbia University 650 West 168th Street, Center for Motor Neuron Biology and Disease Columbia University 650 West 168th Street ; Center for Motor Neuron Biology and Disease Columbia University 650 West 168th Street, Department of Cell Biology and Morphology ; Université de Lausanne, CC 101 ; Université Montpellier II - Sciences et techniques, Department of Cell Biology, Institute of Biomembranes, University Medical Center Utrecht ; Institute of Biomembranes, University Medical Center Utrecht, Service de dermatologie ; CHU Nice, Vieillissement, stress, inflammation ; Université Pierre et Marie Curie (UPMC) - Paris VI, University of Cambridge (UK) (CAM) ; University of Cambridge (UK), The Department of Chemical and Environmental Sciences ; University of Limerick, Fondazione IRCCS Istituto Nazionale dei Tumori ; Fondazione IRCCS Istituto Nazionale dei Tumori, Neurogenetics laboratory ; Neurogenetics laboratory, Department of Pathology ; Otto-von-Guericke University, Experimental Tumor Pathology ; University of Erlangen, Unit of Oculogenomics ; Institute for Research in Ophthalmology", Swiss Federal Institute of Technology ; University of Lausanne, Eye Hospital, Department of Ophthalmology, Jules-Gonin , ; Eye Hospital", Division of regenerative Medicine ; San Raffaele Scientific Institute, ICBM ; Faculty of Medicine - University of Chile, Department of pathology ; Harvard Medical School, Department of Endocrine and Oncology Surgery ; Royal North Shore Hospital, Department of Surgery, Bankstown Hospital and South Western Sydney Clinical School ; University of New South Wales, Medical Research Council Human Immunology Unit ; John Radcliffe Hospital - Weatherall Institute of Molecular Medicine, Department of Pharmacology and Molecular Sciences ; University of Bern, Université de Genève ; Université de Genève, Kimmel Cancer Center, and the Stem Cell Biology and Regenerative Medicine Center ; Thomas Jefferson University, Muscular and Neurodegenerative Disease Unit ; University of Genoa and G. Gaslini Pediatric Institute, Department of Clinical and Experimental Medicine ; Division of Cell Biology; and Linköping Diabetes Research Centre, Cancer Institute ; University College London, Department of Biochemistry and Biophysics ; University of California, San Francisco, Department of Experimental and Diagnostic Medicine and Interdisciplinary Center for Study of inflammation and ER-GenTech ; University of Ferrara, Laboratory of Molecular and Cellular Parasitology - Department of Microbiology ; Yong Loo Lin School of Medicine, National University of Singapore, Center of Microbial and Plant Genetics (CMPG) ; Katholieke Universiteit Leuven, Abramson Cancer Institute and Department of Cancer Biology ; University of Pennsylvania, Instituto de Microbiologia Paulo de Goes ; Universidade Federal do Rio de Janeiro, Immunité Innée et Signalisation ; Institut Pasteur de Paris, Istituto CSS Mendel ; Istituto CSS Mendel, Department of Medical and Surgical Pediatrics ; University Hospital, Messina, Department of Intensive care Medicine ; Katholieke Universiteit Leuven, Department of Cell Biology ; Vrije Universiteit Brussel, Department for Molecular Biomedical Research ; Department for Molecular Biomedical Research, Department of Pediatrics ; University of Padova, Department of Chemistry ; Peking University, Department of Mathematics ; Shanghai University, Sch Mat Sci & Engn ; Aucune, Institut de Recherche Interdisciplinaire (IRI) ; CNRS - Université Lille II - Droit et santé - Université Lille I - Sciences et technologies, Institut d'électronique, de microélectronique et de nanotechnologie (IEMN) ; CNRS - Institut supérieur de l'électronique et du nunérique (ISEN) - Université de Valenciennes et du Hainaut-Cambresis - Université Lille I - Sciences et technologies, Nankai University ; Nankai University, Division of Endocrinology and Diabetes ; University of Oklahoma Health Science Center, Department of Pharmacology and Cancer Biology ; Duke University, Modélisation, Information & Systèmes (MIS) ; Université de Picardie Jules Verne, Department of Experimental Oncology and Molecular Medicine ; Fondazione IRCCS Istituto Nazionale dei Tumori, Institute of Modern Physics ; Chinese Academy of Science (CAS), Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province ; ganzu Province, Institute of Computing Technology [Biejing] (ICT) ; Chinese Academy of Science (CAS), European Synchrotron Radiation Facility (ESRF) ; ESRF, Plant Physiology Laboratory ; Chinese Academy of Sciences - Botanical Institute of South china, Division of Biopharmaceutics ; Leiden University, The Institute of Environmental Medicine [Stockholm] (IMM) ; Karolinska Institutet, Institut de biochimie et biophysique moléculaire et cellulaire (IBBMC) ; CNRS - Université Paris XI - Paris Sud, Center for Brain Repair and Rehabilitation ; University of Gothenburg - Institute of Neuroscience and Physiology, department of genetics - Institute of biochemistry and biophysics ; institute of biochemistry an biophysics - polish academic of sciences, Departament de Bioquímica i Biologia Molecular ; Universitat de Barcelona - Facultat de Biologia - Institute for Research in Biomedicine - CIBERDEM, Chaperones Research Group ; Chaperones Research Group, Klionsky, Daniel J, Abdalla, Fabio C, Abeliovich, Hagai, Abraham, Robert T, Acevedo-Arozena, Abraham, Adeli, Khosrow, Agholme, Lotta, Agnello, Maria, Agostinis, Patrizia, Aguirre-Ghiso, Julio A, Ahn, Hyung Jun, Ait-Mohamed, Ouardia, Ait-Si-Ali, Slimane, Akematsu, Takahiko, Akira, Shizuo, Al-Younes, Hesham M, Al-Zeer, Munir A, Albert, Matthew L, Albin, Roger L, Alegre-Abarrategui, Javier, Aleo, Maria Francesca, Alirezaei, Mehrdad, Almasan, Alexandru, Almonte-Becerril, Maylin, Amano, Atsuo, Amaravadi, Ravi, Amarnath, Shoba, Amer, Amal O, Andrieu-Abadie, Nathalie, Anantharam, Vellareddy, Ann, David K, Anoopkumar-Dukie, Shailendra, Aoki, Hiroshi, Apostolova, Nadezda, Auberger, Patrick, Baba, Misuzu, Backues, Steven K, Baehrecke, Eric H, Bahr, Ben A, Bai, Xue-Yuan, Bailly, Yannick, Baiocchi, Robert, Baldini, Giulia, Balduini, Walter, Ballabio, Andrea, Bamber, Bruce A, Bampton, Edward T W, Bánhegyi, Gábor, Bartholomew, Clinton R, Bassham, Diane C, Bast, Robert C, Batoko, Henri, Bay, Boon-Huat, Beau, Isabelle, Béchet, Daniel M, Begley, Thomas J, Behl, Christian, Behrends, Christian, Bekri, Soumeya, Bellaire, Bryan, Bendall, Linda J, Benetti, Luca, Berliocchi, Laura, Bernardi, Henri, Bernassola, Francesca, Besteiro, Sébastien, Bhatia-Kissova, Ingrid, Bi, Xiaoning, Biard-Piechaczyk, Martine, Blum, Janice S, Boise, Lawrence H, Bonaldo, Paolo, Boone, David L, Bornhauser, Beat C, Bortoluci, Karina R, Bossis, Ioannis, Bost, Frédéric, Bourquin, Jean-Pierre, Boya, Patricia, Boyer-Guittaut, Michaël, Bozhkov, Peter V, Brady, Nathan R, Brancolini, Claudio, Brech, Andreas, Brenman, Jay E, Brennand, Ana, Bresnick, Emery H, Brest, Patrick, Bridges, Dave, Bristol, Molly L, Brookes, Paul S, Brown, Eric J, Brumell, John H, Brunetti-Pierri, Nicola, Brunk, Ulf T, Bulman, Dennis E, Bultman, Scott J, Bultynck, Geert, Burbulla, Lena F, Bursch, Wilfried, Butchar, Jonathan P, Buzgariu, Wanda, Bydlowski, Sergio P, Cadwell, Ken, Cahová, Monika, Cai, Dongsheng, Cai, Jiyang, Cai, Qian, Calabretta, Bruno, Calvo-Garrido, Javier, Camougrand, Nadine, Campanella, Michelangelo, Campos-Salinas, Jenny, Candi, Eleonora, Cao, Lizhi, Caplan, Allan B, Carding, Simon R, Cardoso, Sandra M, Carew, Jennifer S, Carlin, Cathleen R, Carmignac, Virginie, Carneiro, Leticia A M, Carra, Serena, Caruso, Rosario A, Casari, Giorgio, Casas, Caty, Castino, Roberta, Cebollero, Eduardo, Cecconi, Francesco, Celli, Jean, Chaachouay, Hassan, Chae, Han-Jung, Chai, Chee-Yin, Chan, David C, Chan, Edmond Y, Chang, Raymond Chuen-Chung, Che, Chi-Ming, Chen, Ching-Chow, Chen, Guang-Chao, Chen, Guo-Qiang, Chen, Min, Chen, Quan, Chen, Steve S-L, Chen, Wenli, Chen, Xi, Chen, Xiangmei, Chen, Xiequn, Chen, Ye-Guang, Chen, Yingyu, Chen, Yongqiang, Chen, Yu-Jen, Chen, Zhixiang, Cheng, Alan, Cheng, Christopher H K, Cheng, Yan, Cheong, Heesun, Cheong, Jae-Ho, Cherry, Sara, Chess-Williams, Russ, Cheung, Zelda H, Chevet, Eric, Chiang, Hui-Ling, Chiarelli, Roberto, Chiba, Tomoki, Chin, Lih-Shen, Chiou, Shih-Hwa, Chisari, Francis V, Cho, Chi Hin, Cho, Dong-Hyung, Choi, Augustine M K, Choi, Dooseok, Choi, Kyeong Sook, Choi, Mary E, Chouaib, Salem, Choubey, Divaker, Choubey, Vinay, Chu, Charleen T, Chuang, Tsung-Hsien, Chueh, Sheau-Huei, Chun, Taehoon, Chwae, Yong-Joon, Chye, Mee-Len, Ciarcia, Roberto, Ciriolo, Maria R, Clague, Michael J, Clark, Robert S B, Clarke, Peter G H, Clarke, Robert, Codogno, Patrice, Coller, Hilary A, Colombo, María I, Comincini, Sergio, Condello, Maria, Condorelli, Fabrizio, Cookson, Mark R, Coombs, Graham H, Coppens, Isabelle, Corbalan, Ramon, Cossart, Pascale, Costelli, Paola, Costes, Safia, Coto-Montes, Ana, Couve, Eduardo, Coxon, Fraser P, Cregg, James M, Crespo, José L, Cronjé, Marianne J, Cuervo, Ana Maria, Cullen, Joseph J, Czaja, Mark J, D'Amelio, Marcello, Darfeuille-Michaud, Arlette, Davids, Lester M, Davies, Faith E, De Felici, Massimo, De Groot, John F, De Haan, Cornelis A M, De Martino, Luisa, De Milito, Angelo, De Tata, Vincenzo, Debnath, Jayanta, Degterev, Alexei, Dehay, Benjamin, Delbridge, Lea M D, Demarchi, Francesca, Deng, Yi Zhen, Dengjel, Jörn, Dent, Paul, Denton, Donna, Deretic, Vojo, Desai, Shyamal D, Devenish, Rodney J, Di Gioacchino, Mario, Di Paolo, Gilbert, Di Pietro, Chiara, Díaz-Araya, Guillermo, Díaz-Laviada, Inés, Diaz-Meco, Maria T, Diaz-Nido, Javier, Dikic, Ivan, Dinesh-Kumar, Savithramma P, Ding, Wen-Xing, Distelhorst, Clark W, Diwan, Abhinav, Djavaheri-Mergny, Mojgan, Dokudovskaya, Svetlana, Dong, Zheng, Dorsey, Frank C, Dosenko, Victor, Dowling, James J, Doxsey, Stephen, Dreux, Marlène, Drew, Mark E, Duan, Qiuhong, Duchosal, Michel A, Duff, Karen, Dugail, Isabelle, Durbeej, Madeleine, Duszenko, Michael, Edelstein, Charles L, Edinger, Aimee L, Egea, Gustavo, Eichinger, Ludwig, Eissa, N Tony, Ekmekcioglu, Suhendan, El-Deiry, Wafik S, Elazar, Zvulun, Elgendy, Mohamed, Ellerby, Lisa M, Eng, Kai Er, Engelbrecht, Anna-Mart, Engelender, Simone, Erenpreisa, Jekaterina, Escalante, Ricardo, Esclatine, Audrey, Eskelinen, Eeva-Liisa, Espert, Lucile, Espina, Virginia, Fan, Huizhou, Fan, Jia, Fan, Qi-Wen, Fan, Zhen, Fang, Shengyun, Fang, Yongqi, Fanto, Manolis, Fanzani, Alessandro, Farkas, Thomas, Farré, Jean-Claude, Faure, Mathias, Fechheimer, Marcus, Feng, Carl G, Feng, Jian, Feng, Qili, Feng, Youji, Fésüs, László, Feuer, Ralph, Figueiredo-Pereira, Maria E, Fimia, Gian Maria, Fingar, Diane C, Finkbeiner, Steven, Finkel, Toren, Finley, Kim D, Fiorito, Filomena, Fisher, Edward A, Fisher, Paul B, Flajolet, Marc, Florez-Mcclure, Maria L, Florio, Salvatore, Fon, Edward A, Fornai, Francesco, Fortunato, Franco, Fotedar, Rati, Fowler, Daniel H, Fox, Howard S, Franco, Rodrigo, Frankel, Lisa B, Fransen, Marc, Fuentes, José M, Fueyo, Juan, Fujii, Jun, Fujisaki, Kozo, Fujita, Eriko, Fukuda, Mitsunori, Furukawa, Ruth H, Gaestel, Matthias, Gailly, Philippe, Gajewska, Malgorzata, Galliot, Brigitte, Galy, Vincent, Ganesh, Subramaniam, Ganetzky, Barry, Ganley, Ian G, Gao, Fen-Biao, Gao, George F, Gao, Jinming, Garcia, Lorena, Garcia-Manero, Guillermo, Garcia-Marcos, Mikel, Garmyn, Marjan, Gartel, Andrei L, Gatti, Evelina, Gautel, Mathias, Gawriluk, Thomas R, Gegg, Matthew E, Geng, Jiefei, Germain, Marc, Gestwicki, Jason E, Gewirtz, David A, Ghavami, Saeid, Ghosh, Pradipta, Giammarioli, Anna M, Giatromanolaki, Alexandra N, Gibson, Spencer B, Gilkerson, Robert W, Ginger, Michael L, Goncu, Ebru, Gongora, Céline, Gonzalez, Claudio D, Gonzalez, Ramon, González-Estévez, Cristina, González-Polo, Rosa Ana, Gonzalez-Rey, Elena, Gorbunov, Nikolai V, Gorski, Sharon, Goruppi, Sandro, Gottlieb, Roberta A, Gozuacik, Devrim, Granato, Giovanna Elvira, Grant, Gary D, Green, Kim N, Gregorc, Aleš, Gros, Frédéric, Grose, Charles, Grunt, Thomas W, Gual, Philippe, Guan, Jun-Lin, Guan, Kun-Liang, Guichard, Sylvie M, Gukovskaya, Anna S, Gukovsky, Ilya, Gunst, Jan, Gustafsson, Asa B, Halayko, Andrew J, Hale, Amber N, Halonen, Sandra K, Hamasaki, Maho, Han, Feng, Han, Ting, Hancock, Michael K, Hansen, Malene, Harada, Hisashi, Harada, Masaru, Hardt, Stefan E, Harper, J Wade, Harris, Adrian L, Harris, James, Harris, Steven D, Hébert, Marie-Joseé, Heidenreich, Kim A, Helfrich, Miep H, Helgason, Gudmundur V, Henske, Elizabeth P, Herman, Brian, Herman, Paul K, Hetz, Claudio, Hilfiker, Sabine, Hill, Joseph A, Hocking, Lynne J, Hofman, Paul, Hofmann, Thomas G, Höhfeld, Jörg, Holyoake, Tessa L, Hong, Ming-Huang, Hood, David A, Hotamisligil, Gökhan S, Houwerzijl, Ewout J, Høyer-Hansen, Maria, Hu, Bingren, Hu, Chien-An A, Hu, Hong-Ming, Hua, Ya, Huang, Canhua, Huang, Ju, Huang, Shengbing, Huang, Wei-Pang, Huber, Tobias B, Huh, Won-Ki, Hung, Tai-Ho, Hupp, Ted R, Hur, Gang Min, Hurley, James B, Hussain, Sabah N A, Hussey, Patrick J, Hwang, Jung Jin, Hwang, Seungmin, Ichihara, Atsuhiro, Ilkhanizadeh, Shirin, Inoki, Ken, Into, Takeshi, Iovane, Valentina, Iovanna, Juan L, Ip, Nancy Y, Isaka, Yoshitaka, Ishida, Hiroyuki, Isidoro, Ciro, Isobe, Ken-Ichi, Iwasaki, Akiko, Izquierdo, Marta, Izumi, Yotaro, Jaakkola, Panu M, Jäättelä, Marja, Jackson, George R, Jackson, William T, Janji, Bassam, Jendrach, Marina, Jeon, Ju-Hong, Jeung, Eui-Bae, Jiang, Hong, Jiang, Hongchi, Jiang, Jean X, Jiang, Ming, Jiang, Qing, Jiang, Xuejun, Jiménez, Alberto, Jin, Meiyan, Jin, Shengkan, Joe, Cheol O, Johansen, Terje, Johnson, Daniel E, Johnson, Gail V W, Jones, Nicola L, Joseph, Bertrand, Joseph, Suresh K, Joubert, Annie M, Juhász, Gábor, Juillerat-Jeanneret, Lucienne, Jung, Chang Hwa, Jung, Yong-Keun, Kaarniranta, Kai, Kaasik, Allen, Kabuta, Tomohiro, Kadowaki, Motoni, Kagedal, Katarina, Kamada, Yoshiaki, Kaminskyy, Vitaliy O, Kampinga, Harm H, Kanamori, Hiromitsu, Kang, Chanhee, Kang, Khong Bee, Kang, Kwang Il, Kang, Rui, Kang, Yoon-A, Kanki, Tomotake, Kanneganti, Thirumala-Devi, Kanno, Haruo, Kanthasamy, Anumantha G, Kanthasamy, Arthi, Karantza, Vassiliki, Kaushal, Gur P, Kaushik, Susmita, Kawazoe, Yoshinori, Ke, Po-Yuan, Kehrl, John H, Kelekar, Ameeta, Kerkhoff, Claus, Kessel, David H, Khalil, Hany, Kiel, Jan A K W, Kiger, Amy A, Kihara, Akio, Kim, Deok Ryong, Kim, Do-Hyung, Kim, Dong-Hou, Kim, Eun-Kyoung, Kim, Hyung-Ryong, Kim, Jae-Sung, Kim, Jeong Hun, Kim, Jin Cheon, Kim, John K, Kim, Peter K, Kim, Seong Who, Kim, Yong-Sun, Kim, Yonghyun, Kimchi, Adi, Kimmelman, Alec C, King, Jason S, Kinsella, Timothy J, Kirkin, Vladimir, Kirshenbaum, Lorrie A, Kitamoto, Katsuhiko, Kitazato, Kaio, Klein, Ludger, Klimecki, Walter T, Klucken, Jochen, Knecht, Erwin, Ko, Ben C B, Koch, Jan C, Koga, Hiroshi, Koh, Jae-Young, Koh, Young Ho, Koike, Masato, Komatsu, Masaaki, Kominami, Eiki, Kong, Hee Jeong, Kong, Wei-Jia, Korolchuk, Viktor I, Kotake, Yaichiro, Koukourakis, Michael I, Kouri Flores, Juan B, Kovács, Attila L, Kraft, Claudine, Krainc, Dimitri, Krämer, Helmut, Kretz-Remy, Carole, Krichevsky, Anna M, Kroemer, Guido, Krüger, Rejko, Krut, Oleg, Ktistakis, Nicholas T, Kuan, Chia-Yi, Kucharczyk, Roza, Kumar, Ashok, Kumar, Raj, Kumar, Sharad, Kundu, Mondira, Kung, Hsing-Jien, Kurz, Tino, Kwon, Ho Jeong, La Spada, Albert R, Lafont, Frank, Lamark, Trond, Landry, Jacques, Lane, Jon D, Lapaquette, Pierre, Laporte, Jocelyn F, László, Lajos, Lavandero, Sergio, Lavoie, Josée N, Layfield, Robert, Lazo, Pedro A, Le, Weidong, Le Cam, Laurent, Ledbetter, Daniel J, Lee, Alvin J X, Lee, Byung-Wan, Lee, Gyun Min, Lee, Jongdae, Lee, Ju-Hyun, Lee, Michael, Lee, Myung-Shik, Lee, Sug Hyung, Leeuwenburgh, Christiaan, Legembre, Patrick, Legouis, Renaud, Lehmann, Michael, Lei, Huan-Yao, Lei, Qun-Ying, Leib, David A, Leiro, José, Lemasters, John J, Lemoine, Antoinette, Lesniak, Maciej S, Lev, Dina, Levenson, Victor V, Levine, Beth, Levy, Efrat, Li, Faqiang, Li, Jun-Lin, Li, Lian, Li, Sheng, 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Christopher J, Ritis, Konstantinos, Rizzo, Elizete, Robbins, Jeffrey, Roberge, Michel, Roca, Hernan, Roccheri, Maria C, Rocchi, Stephane, Rodemann, H Peter, Rodríguez De Córdoba, Santiago, Rohrer, Bärbel, Roninson, Igor B, Rosen, Kirill, Rost-Roszkowska, Magdalena M, Rouis, Mustapha, Rouschop, Kasper M A, Rovetta, Francesca, Rubin, Brian P, Rubinsztein, David C, Ruckdeschel, Klaus, Rucker, Edmund B, Rudich, Assaf, Rudolf, Emil, Ruiz-Opazo, Nelson, Russo, Rossella, Rusten, Tor Erik, Ryan, Kevin M, Ryter, Stefan W, Sabatini, David M, Sadoshima, Junichi, Saha, Tapas, Saitoh, Tatsuya, Sakagami, Hiroshi, Sakai, Yasuyoshi, Salekdeh, Ghasem Hoseini, Salomoni, Paolo, Salvaterra, Paul M, Salvesen, Guy, Salvioli, Rosa, Sanchez, Anthony M J, Sánchez-Alcázar, José A, Sánchez-Prieto, Ricardo, Sandri, Marco, Sankar, Uma, Sansanwal, Poonam, Santambrogio, Laura, Saran, Shweta, Sarkar, Sovan, Sarwal, Minnie, Sasakawa, Chihiro, Sasnauskiene, Ausra, Sass, Miklós, Sato, Ken, Sato, Miyuki, 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Dingzhong, Tanida, Isei, Tannous, Bakhos A, Tavernarakis, Nektarios, Taylor, Graham S, Taylor, Gregory A, Taylor, J Paul, Terada, Lance S, Terman, Alexei, Tettamanti, Gianluca, Thevissen, Karin, Thompson, Craig B, Thorburn, Andrew, Thumm, Michael, Tian, Fengfeng, Tian, Yuan, Tocchini-Valentini, Glauco, Tolkovsky, Aviva M, Tomino, Yasuhiko, Tönges, Lars, Tooze, Sharon A, Tournier, Cathy, Tower, John, Towns, Roberto, Trajkovic, Vladimir, Travassos, Leonardo H, Tsai, Ting-Fen, Tschan, Mario P, Tsubata, Takeshi, Tsung, Allan, Turk, Boris, Turner, Lorianne S, Tyagi, Suresh C, Uchiyama, Yasuo, Ueno, Takashi, Umekawa, Midori, Umemiya-Shirafuji, Rika, Unni, Vivek K, Vaccaro, Maria I, Valente, Enza Maria, Van Den Berghe, Greet, Van Der Klei, Ida J, Van Doorn, Wouter, Van Dyk, Linda F, Van Egmond, Marjolein, Van Grunsven, Leo A, Vandenabeele, Peter, Vandenberghe, Wim P, Vanhorebeek, Ilse, Vaquero, Eva C, Velasco, Guillermo, Vellai, Tibor, Vicencio, Jose Miguel, Vierstra, Richard D, Vila, 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Xie, Zhiping, Xie, Zhonglin, Xu, Da-Zhi, Xu, Jianzhen, Xu, Liang, Xu, Xiaolei, Yamamoto, Ai, Yamamoto, Akitsugu, Yamashina, Shunhei, Yamashita, Michiaki, Yan, Xianghua, Yanagida, Mitsuhiro, Yang, Dun-Sheng, Yang, Elizabeth, Yang, Jin-Ming, Yang, Shi Yu, Yang, Wannian, Yang, Wei Yuan, Yang, Zhifen, Yao, Meng-Chao, Yao, Tso-Pang, Yeganeh, Behzad, Yen, Wei-Lien, Yin, Jia-Jing, Yin, Xiao-Ming, Yoo, Ook-Joon, Yoon, Gyesoon, Yoon, Seung-Yong, Yorimitsu, Tomohiro, Yoshikawa, Yuko, Yoshimori, Tamotsu, Yoshimoto, Kohki, You, Ho Jin, Youle, Richard J, Younes, Anas, Yu, Li, Yu, Long, Yu, Seong-Woon, Yu, Wai Haung, Yuan, Zhi-Min, Yue, Zhenyu, Yun, Cheol-Heui, Yuzaki, Michisuke, Zabirnyk, Olga, Silva-Zacarin, Elaine, Zacks, David, Zacksenhaus, Eldad, Zaffaroni, Nadia, Zakeri, Zahra, Zeh, Herbert J, Zeitlin, Scott O, Zhang, Hong, Zhang, Hui-Ling, Zhang, Jianhua, Zhang, Jing-Pu, Zhang, Lin, Zhang, Long, Zhang, Ming-Yong, Zhang, Xu Dong, Zhao, Mantong, Zhao, Yi-Fang, Zhao, Ying, Zhao, Zhizhuang J, Zheng, Xiaoxiang, Zhivotovsky, Boris, Zhong, Qing, Zhou, Cong-Zhao, Zhu, Changlian, Zhu, Wei-Guo, Zhu, Xiao-Feng, Zhu, Xiongwei, Zhu, Yuangang, Zoladek, Teresa, Zong, Wei-Xing, Zorzano, Antonio, Zschocke, Jürgen, Zuckerbraun, Brian, Molecular and Cellular Biology ; University of Leuven, Laboratoire d'Epigénétique et Cancer ; CNRS - Université Paris XI - Paris Sud, Department of Pharmacology ; Department of Pharmacology, Immunobiologie des Cellules Dendritiques ; INSERM - Institut Pasteur de Paris, Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (FEMTO-ST) ; CNRS - Université de Franche-Comté - Université de Technologie de Belfort-Montbeliard - Ecole Nationale Supérieure de Mécanique et des Microtechniques, Telethon Institute for Genetics and Medicine ; Telethon Institute, Medical Genetics ; Federico II University, Department of Molecular and Human Genetics ; Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute ; Texas Children's Hospital, Signalisation et physiopathologie des cellules épithéliales ; INSERM - Université Paris XI - Paris Sud, Dynamique des interactions membranaires normales et pathologiques (DIMNP) ; CNRS - Université Montpellier I - Université Montpellier II - Sciences et techniques, Institut de biochimie et génétique cellulaires (IBGC) ; CNRS - Université Victor Segalen - Bordeaux II, Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS) ; CNRS - Université Montpellier I - Université Montpellier II - Sciences et techniques, Celullar and Molecular Medicine ; Celullar and Molecular Medicine, Estrogène, Expression génique et pathologies du Système Nerveux Central (E2SNC) ; Université de Franche-Comté - IFR133, Infection bactérienne, inflammation, et carcinogenèse digestive ; INSERM - IFR50 - Université Nice Sophia Antipolis (UNS), Université Nice Sophia Antipolis (UNS) ; Université Nice Sophia Antipolis (UNS) - PRES Euro-Méditerranéen, Department of Computer Science [Tsukuba] ; University of Tsukuba, Gunma University ; Institute for Molecular & Cellular Regulation, Cell Biology, Physiology and Immunology ; Cell Biology, Physiology and Immunology, Dulbecco Telethon Institute/Department of Biology ; Dulbecco Telethon Institute/Department of Biology, Department of Chemistry and HKU-CAS Joint Laboratory ; University of Hong-Kong, Laboratoire Bordelais de Recherche en Informatique (LaBRI) ; CNRS - Université Sciences et Technologies - Bordeaux I - Université Victor Segalen - Bordeaux II - École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Learning Sciences Lab ; National Institute of Education, Nanyang Technological University, University of California ; University of California, Physiopathologie du cancer du foie ; INSERM - Université Victor Segalen - Bordeaux II, Emory University School of Medicine ; Emory University School of Medicine, Cytokines et Immunologie des Tumeurs Humaines ; INSERM - Institut Gustave Roussy - Université Paris XI - Paris Sud, Biology ; University of Rome"Tor Vergata", Oxford University ; Oxford University, Strathclyde Institute of Pharmacy and Biomedical Sciences ; University of Strathclyde, Interactions Bactéries-Cellules (UIBC) ; Institut national de la recherche agronomique (INRA) - INSERM - Institut Pasteur de Paris, Department of Experimental Medicine and Oncology ; University of Turin, Institut de génomique fonctionnelle (IGF) ; CNRS - INSERM - Université Montpellier I - Université Montpellier II - Sciences et techniques, CNV ; University of Valparaiso, Section of Haemato-oncology ; Institute of cancer research, Régulation de l'expression génétique (REG) ; CNRS - École normale supérieure [ENS] - Paris, Brunel University ; Brunel University, University of New-Mexico ; University of New-Mexico, Facultad de Ciencias Químicas y Farmacéuticas ; Centro de Estudios Moleculares de la 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biologie et chimie des protéines [Lyon] (IBCP) ; CNRS - Université Claude Bernard - Lyon I (UCBL), Department of Gastroenterology, Hepatology and Endocrinology (MHH) ; Hannover medical school, Cancer Research UK London Research Institute ; Cancer Research UK London Research Institute, Cell Biology, section Radiation & Stress Cell Biology ; UMCG, Univ. of Groningen, Department of Molecular Genetics ; Weizmann Institute of Science, Institute of Immunology ; University Hospital Schleswig-Holstein, Institute for Immunology ; Institute for Immunology, Department of Neuroscience ; University of Texas Southwestern Medical Center at Dallas, Centre de génétique et de physiologie moléculaire et cellulaire (CGphiMC) ; CNRS - Université Claude Bernard - Lyon I (UCBL), Centre de Recherche des Cordeliers ; INSERM - Université Paris V - Paris Descartes - Université Pierre et Marie Curie (UPMC) - Paris VI, Apoptose, cancer et immunité ; INSERM - Institut Gustave Roussy - Université Paris XI 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Karl-Franzens University Graz, Department of Pediatrics ; Università degli studi di Napoli Federico II, Department of Experimental Pharmacology ; Università degli Study di Napoli Federico II, Drug Research and Evaluation ; Istituto Superiore di Sanita‘, Albert Einstein College of Medicine (ALBERT EINSTEIN COLLEGE OF MEDICINE) ; Albert Einstein College of Medicine, Institute of Molecular Biology and Biotechnology ; Foundation for Research and Technology - Hellas, Institut des Sciences de l'Evolution - Montpellier (ISEM) ; CNRS - Institut de recherche pour le développement [IRD] - Université Montpellier II - Sciences et techniques, Institut de signalisation, biologie du développement et cancer (ISBDC) ; CNRS - Université Nice Sophia Antipolis (UNS), Departments of Neurology ; Departments of Neurology, Vanderbilt University [Nashville] ; Vanderbilt University of Nashville, Departments of Pharmacology ; Departments of Pharmacology, Department of Cell Biology [New Haven] ; Yale 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Nice Sophia Antipolis (UNS), Innovation Thérapeutique : du Fondamental au Médicament ; CNRS - Institut national de la recherche agronomique (INRA) - INSERM - MEDICEN - Université Paris XI - Paris Sud, Hôpital Antoine Béclère ; Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris XI - Paris Sud, Señalización Celular 4 ; Señalización Celular 4, Department of Molecular Biology ; University of Tuebingen, Department of Neurology Columbia University 650 West 168th Street ; Department of Neurology Columbia University 650 West 168th Street, Department of Pathology and Cell Biology Columbia University 650 West 168th Street ; Department of Pathology and Cell Biology Columbia University 650 West 168th Street, Center for Motor Neuron Biology and Disease Columbia University 650 West 168th Street ; Center for Motor Neuron Biology and Disease Columbia University 650 West 168th Street, Department of Cell Biology and Morphology ; Université de Lausanne, CC 101 ; Université 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Modélisation, Information & Systèmes (MIS) ; Université de Picardie Jules Verne, Department of Experimental Oncology and Molecular Medicine ; Fondazione IRCCS Istituto Nazionale dei Tumori, Institute of Modern Physics ; Chinese Academy of Science (CAS), Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province ; ganzu Province, Institute of Computing Technology [Biejing] (ICT) ; Chinese Academy of Science (CAS), European Synchrotron Radiation Facility (ESRF) ; ESRF, Plant Physiology Laboratory ; Chinese Academy of Sciences - Botanical Institute of South china, Division of Biopharmaceutics ; Leiden University, The Institute of Environmental Medicine [Stockholm] (IMM) ; Karolinska Institutet, Institut de biochimie et biophysique moléculaire et cellulaire (IBBMC) ; CNRS - Université Paris XI - Paris Sud, Center for Brain Repair and Rehabilitation ; University of Gothenburg - Institute of Neuroscience and Physiology, department of genetics - Institute of biochemistry and biophysics ; institute of biochemistry an biophysics - polish academic of sciences, Departament de Bioquímica i Biologia Molecular ; Universitat de Barcelona - Facultat de Biologia - Institute for Research in Biomedicine - CIBERDEM, Chaperones Research Group ; Chaperones Research Group, Klionsky, Daniel J, Abdalla, Fabio C, Abeliovich, Hagai, Abraham, Robert T, Acevedo-Arozena, Abraham, Adeli, Khosrow, Agholme, Lotta, Agnello, Maria, Agostinis, Patrizia, Aguirre-Ghiso, Julio A, Ahn, Hyung Jun, Ait-Mohamed, Ouardia, Ait-Si-Ali, Slimane, Akematsu, Takahiko, Akira, Shizuo, Al-Younes, Hesham M, Al-Zeer, Munir A, Albert, Matthew L, Albin, Roger L, Alegre-Abarrategui, Javier, Aleo, Maria Francesca, Alirezaei, Mehrdad, Almasan, Alexandru, Almonte-Becerril, Maylin, Amano, Atsuo, Amaravadi, Ravi, Amarnath, Shoba, Amer, Amal O, Andrieu-Abadie, Nathalie, Anantharam, Vellareddy, Ann, David K, Anoopkumar-Dukie, Shailendra, Aoki, Hiroshi, Apostolova, Nadezda, Auberger, Patrick, Baba, Misuzu, Backues, Steven K, Baehrecke, Eric H, Bahr, Ben A, Bai, Xue-Yuan, Bailly, Yannick, Baiocchi, Robert, Baldini, Giulia, Balduini, Walter, Ballabio, Andrea, Bamber, Bruce A, Bampton, Edward T W, Bánhegyi, Gábor, Bartholomew, Clinton R, Bassham, Diane C, Bast, Robert C, Batoko, Henri, Bay, Boon-Huat, Beau, Isabelle, Béchet, Daniel M, Begley, Thomas J, Behl, Christian, Behrends, Christian, Bekri, Soumeya, Bellaire, Bryan, Bendall, Linda J, Benetti, Luca, Berliocchi, Laura, Bernardi, Henri, Bernassola, Francesca, Besteiro, Sébastien, Bhatia-Kissova, Ingrid, Bi, Xiaoning, Biard-Piechaczyk, Martine, Blum, Janice S, Boise, Lawrence H, Bonaldo, Paolo, Boone, David L, Bornhauser, Beat C, Bortoluci, Karina R, Bossis, Ioannis, Bost, Frédéric, Bourquin, Jean-Pierre, Boya, Patricia, Boyer-Guittaut, Michaël, Bozhkov, Peter V, Brady, Nathan R, Brancolini, Claudio, Brech, Andreas, Brenman, Jay E, Brennand, Ana, Bresnick, Emery H, Brest, Patrick, Bridges, Dave, Bristol, Molly L, Brookes, Paul S, Brown, Eric J, Brumell, John H, Brunetti-Pierri, Nicola, Brunk, Ulf T, Bulman, Dennis E, Bultman, Scott J, Bultynck, Geert, Burbulla, Lena F, Bursch, Wilfried, Butchar, Jonathan P, Buzgariu, Wanda, Bydlowski, Sergio P, Cadwell, Ken, Cahová, Monika, Cai, Dongsheng, Cai, Jiyang, Cai, Qian, Calabretta, Bruno, Calvo-Garrido, Javier, Camougrand, Nadine, Campanella, Michelangelo, Campos-Salinas, Jenny, Candi, Eleonora, Cao, Lizhi, Caplan, Allan B, Carding, Simon R, Cardoso, Sandra M, Carew, Jennifer S, Carlin, Cathleen R, Carmignac, Virginie, Carneiro, Leticia A M, Carra, Serena, Caruso, Rosario A, Casari, Giorgio, Casas, Caty, Castino, Roberta, Cebollero, Eduardo, Cecconi, Francesco, Celli, Jean, Chaachouay, Hassan, Chae, Han-Jung, Chai, Chee-Yin, Chan, David C, Chan, Edmond Y, Chang, Raymond Chuen-Chung, Che, Chi-Ming, Chen, Ching-Chow, Chen, Guang-Chao, Chen, Guo-Qiang, Chen, Min, Chen, Quan, Chen, Steve S-L, Chen, Wenli, Chen, Xi, Chen, Xiangmei, Chen, Xiequn, Chen, Ye-Guang, Chen, 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Marianne J, Cuervo, Ana Maria, Cullen, Joseph J, Czaja, Mark J, D'Amelio, Marcello, Darfeuille-Michaud, Arlette, Davids, Lester M, Davies, Faith E, De Felici, Massimo, De Groot, John F, De Haan, Cornelis A M, De Martino, Luisa, De Milito, Angelo, De Tata, Vincenzo, Debnath, Jayanta, Degterev, Alexei, Dehay, Benjamin, Delbridge, Lea M D, Demarchi, Francesca, Deng, Yi Zhen, Dengjel, Jörn, Dent, Paul, Denton, Donna, Deretic, Vojo, Desai, Shyamal D, Devenish, Rodney J, Di Gioacchino, Mario, Di Paolo, Gilbert, Di Pietro, Chiara, Díaz-Araya, Guillermo, Díaz-Laviada, Inés, Diaz-Meco, Maria T, Diaz-Nido, Javier, Dikic, Ivan, Dinesh-Kumar, Savithramma P, Ding, Wen-Xing, Distelhorst, Clark W, Diwan, Abhinav, Djavaheri-Mergny, Mojgan, Dokudovskaya, Svetlana, Dong, Zheng, Dorsey, Frank C, Dosenko, Victor, Dowling, James J, Doxsey, Stephen, Dreux, Marlène, Drew, Mark E, Duan, Qiuhong, Duchosal, Michel A, Duff, Karen, Dugail, Isabelle, Durbeej, Madeleine, Duszenko, Michael, Edelstein, Charles L, Edinger, Aimee L, Egea, Gustavo, Eichinger, Ludwig, Eissa, N Tony, Ekmekcioglu, Suhendan, El-Deiry, Wafik S, Elazar, Zvulun, Elgendy, Mohamed, Ellerby, Lisa M, Eng, Kai Er, Engelbrecht, Anna-Mart, Engelender, Simone, Erenpreisa, Jekaterina, Escalante, Ricardo, Esclatine, Audrey, Eskelinen, Eeva-Liisa, Espert, Lucile, Espina, Virginia, Fan, Huizhou, Fan, Jia, Fan, Qi-Wen, Fan, Zhen, Fang, Shengyun, Fang, Yongqi, Fanto, Manolis, Fanzani, Alessandro, Farkas, Thomas, Farré, Jean-Claude, Faure, Mathias, Fechheimer, Marcus, Feng, Carl G, Feng, Jian, Feng, Qili, Feng, Youji, Fésüs, László, Feuer, Ralph, Figueiredo-Pereira, Maria E, Fimia, Gian Maria, Fingar, Diane C, Finkbeiner, Steven, Finkel, Toren, Finley, Kim D, Fiorito, Filomena, Fisher, Edward A, Fisher, Paul B, Flajolet, Marc, Florez-Mcclure, Maria L, Florio, Salvatore, Fon, Edward A, Fornai, Francesco, Fortunato, Franco, Fotedar, Rati, Fowler, Daniel H, Fox, Howard S, Franco, Rodrigo, Frankel, Lisa B, Fransen, Marc, Fuentes, José M, Fueyo, Juan, Fujii, Jun, Fujisaki, Kozo, Fujita, Eriko, Fukuda, Mitsunori, Furukawa, Ruth H, Gaestel, Matthias, Gailly, Philippe, Gajewska, Malgorzata, Galliot, Brigitte, Galy, Vincent, Ganesh, Subramaniam, Ganetzky, Barry, Ganley, Ian G, Gao, Fen-Biao, Gao, George F, Gao, Jinming, Garcia, Lorena, Garcia-Manero, Guillermo, Garcia-Marcos, Mikel, Garmyn, Marjan, Gartel, Andrei L, Gatti, Evelina, Gautel, Mathias, Gawriluk, Thomas R, Gegg, Matthew E, Geng, Jiefei, Germain, Marc, Gestwicki, Jason E, Gewirtz, David A, Ghavami, Saeid, Ghosh, Pradipta, Giammarioli, Anna M, Giatromanolaki, Alexandra N, Gibson, Spencer B, Gilkerson, Robert W, Ginger, Michael L, Goncu, Ebru, Gongora, Céline, Gonzalez, Claudio D, Gonzalez, Ramon, González-Estévez, Cristina, González-Polo, Rosa Ana, Gonzalez-Rey, Elena, Gorbunov, Nikolai V, Gorski, Sharon, Goruppi, Sandro, Gottlieb, Roberta A, Gozuacik, Devrim, Granato, Giovanna Elvira, Grant, Gary D, Green, Kim N, Gregorc, Aleš, Gros, Frédéric, Grose, Charles, Grunt, Thomas W, Gual, Philippe, Guan, Jun-Lin, Guan, Kun-Liang, Guichard, Sylvie M, Gukovskaya, Anna S, Gukovsky, Ilya, Gunst, Jan, Gustafsson, Asa B, Halayko, Andrew J, Hale, Amber N, Halonen, Sandra K, Hamasaki, Maho, Han, Feng, Han, Ting, Hancock, Michael K, Hansen, Malene, Harada, Hisashi, Harada, Masaru, Hardt, Stefan E, Harper, J Wade, Harris, Adrian L, Harris, James, Harris, Steven D, Hébert, Marie-Joseé, Heidenreich, Kim A, Helfrich, Miep H, Helgason, Gudmundur V, Henske, Elizabeth P, Herman, Brian, Herman, Paul K, Hetz, Claudio, Hilfiker, Sabine, Hill, Joseph A, Hocking, Lynne J, Hofman, Paul, Hofmann, Thomas G, Höhfeld, Jörg, Holyoake, Tessa L, Hong, Ming-Huang, Hood, David A, Hotamisligil, Gökhan S, Houwerzijl, Ewout J, Høyer-Hansen, Maria, Hu, Bingren, Hu, Chien-An A, Hu, Hong-Ming, Hua, Ya, Huang, Canhua, Huang, Ju, Huang, Shengbing, Huang, Wei-Pang, Huber, Tobias B, Huh, Won-Ki, Hung, Tai-Ho, Hupp, Ted R, Hur, Gang Min, Hurley, James B, Hussain, Sabah N A, Hussey, Patrick J, Hwang, Jung Jin, Hwang, Seungmin, Ichihara, Atsuhiro, Ilkhanizadeh, Shirin, Inoki, Ken, Into, Takeshi, Iovane, Valentina, Iovanna, Juan L, Ip, Nancy Y, Isaka, Yoshitaka, Ishida, Hiroyuki, Isidoro, Ciro, Isobe, Ken-Ichi, Iwasaki, Akiko, Izquierdo, Marta, Izumi, Yotaro, Jaakkola, Panu M, Jäättelä, Marja, Jackson, George R, Jackson, William T, Janji, Bassam, Jendrach, Marina, Jeon, Ju-Hong, Jeung, Eui-Bae, Jiang, Hong, Jiang, Hongchi, Jiang, Jean X, Jiang, Ming, Jiang, Qing, Jiang, Xuejun, Jiménez, Alberto, Jin, Meiyan, Jin, Shengkan, Joe, Cheol O, Johansen, Terje, Johnson, Daniel E, Johnson, Gail V W, Jones, Nicola L, Joseph, Bertrand, Joseph, Suresh K, Joubert, Annie M, Juhász, Gábor, Juillerat-Jeanneret, Lucienne, Jung, Chang Hwa, Jung, Yong-Keun, Kaarniranta, Kai, Kaasik, Allen, Kabuta, Tomohiro, Kadowaki, Motoni, Kagedal, Katarina, Kamada, Yoshiaki, Kaminskyy, Vitaliy O, Kampinga, Harm H, Kanamori, Hiromitsu, Kang, Chanhee, Kang, Khong Bee, Kang, Kwang Il, Kang, Rui, Kang, Yoon-A, Kanki, Tomotake, Kanneganti, Thirumala-Devi, Kanno, Haruo, Kanthasamy, Anumantha G, Kanthasamy, Arthi, Karantza, Vassiliki, Kaushal, Gur P, Kaushik, Susmita, Kawazoe, Yoshinori, Ke, Po-Yuan, Kehrl, John H, Kelekar, Ameeta, Kerkhoff, Claus, Kessel, David H, Khalil, Hany, Kiel, Jan A K W, Kiger, Amy A, Kihara, Akio, Kim, Deok Ryong, Kim, Do-Hyung, Kim, Dong-Hou, Kim, Eun-Kyoung, Kim, Hyung-Ryong, Kim, Jae-Sung, Kim, Jeong Hun, Kim, Jin Cheon, Kim, John K, Kim, Peter K, Kim, Seong Who, Kim, Yong-Sun, Kim, Yonghyun, Kimchi, Adi, Kimmelman, Alec C, King, Jason S, Kinsella, Timothy J, Kirkin, Vladimir, Kirshenbaum, Lorrie A, Kitamoto, Katsuhiko, Kitazato, Kaio, Klein, Ludger, Klimecki, Walter T, Klucken, Jochen, Knecht, Erwin, Ko, Ben C B, Koch, Jan C, Koga, Hiroshi, Koh, Jae-Young, Koh, Young Ho, Koike, Masato, Komatsu, Masaaki, Kominami, Eiki, Kong, Hee Jeong, Kong, Wei-Jia, Korolchuk, Viktor I, Kotake, Yaichiro, Koukourakis, Michael I, Kouri Flores, Juan B, Kovács, Attila L, Kraft, Claudine, Krainc, Dimitri, Krämer, Helmut, Kretz-Remy, Carole, Krichevsky, Anna M, Kroemer, Guido, Krüger, Rejko, Krut, Oleg, Ktistakis, Nicholas T, Kuan, Chia-Yi, Kucharczyk, Roza, Kumar, Ashok, Kumar, Raj, Kumar, Sharad, Kundu, Mondira, Kung, Hsing-Jien, Kurz, Tino, Kwon, Ho Jeong, La Spada, Albert R, Lafont, Frank, Lamark, Trond, Landry, Jacques, Lane, Jon D, Lapaquette, Pierre, Laporte, Jocelyn F, László, Lajos, Lavandero, Sergio, Lavoie, Josée N, Layfield, Robert, Lazo, Pedro A, Le, Weidong, Le Cam, Laurent, Ledbetter, Daniel J, Lee, Alvin J X, Lee, Byung-Wan, Lee, Gyun Min, Lee, Jongdae, Lee, Ju-Hyun, Lee, Michael, Lee, Myung-Shik, Lee, Sug Hyung, Leeuwenburgh, Christiaan, Legembre, Patrick, Legouis, Renaud, Lehmann, Michael, Lei, Huan-Yao, Lei, Qun-Ying, Leib, David A, Leiro, José, Lemasters, John J, Lemoine, Antoinette, Lesniak, Maciej S, Lev, Dina, Levenson, Victor V, Levine, Beth, Levy, Efrat, Li, Faqiang, Li, Jun-Lin, Li, Lian, Li, Sheng, Li, Weijie, Li, Xue-Jun, Li, Yan-Bo, Li, Yi-Ping, Liang, Chengyu, Liang, Qiangrong, Liao, Yung-Feng, Liberski, Pawel P, Lieberman, Andrew, Lim, Hyunjung J, Lim, Kah-Leong, Lim, Kyu, Lin, Chiou-Feng, Lin, Fu-Cheng, Lin, Jian, Lin, Jiandie D, Lin, Kui, Lin, Wan-Wan, Lin, Weei-Chin, Lin, Yi-Ling, Linden, Rafael, Lingor, Paul, Lippincott-Schwartz, Jennifer, Lisanti, Michael P, Liton, Paloma B, Liu, Bo, Liu, Chun-Feng, Liu, Kaiyu, Liu, Leyuan, Liu, Qiong A, Liu, Wei, Liu, Young-Chau, Liu, Yule, Lockshin, Richard A, Lok, Chun-Nam, Lonial, Sagar, Loos, Benjamin, Lopez-Berestein, Gabriel, López-Otín, Carlos, Lossi, Laura, Lotze, Michael T, Lőw, Peter, Lu, Binfeng, Lu, Bingwei, Lu, Bo, Lu, Zhen, Luciano, Frédéric, Lukacs, Nicholas W, Lund, Anders H, Lynch-Day, Melinda A, Ma, Yong, Macian, Fernando, Mackeigan, Jeff P, Macleod, Kay F, Madeo, Frank, Maiuri, Luigi, Maiuri, Maria Chiara, Malagoli, Davide, Malicdan, May Christine V, Malorni, Walter, Man, Na, Mandelkow, Eva-Maria, Manon, Stéphen, Manov, Irena, Mao, Kai, Mao, Xiang, Mao, Zixu, Marambaud, Philippe, Marazziti, Daniela, Marcel, Yves L, Marchbank, Katie, Marchetti, Piero, Marciniak, Stefan J, Marcondes, Mateus, Mardi, Mohsen, Marfe, Gabriella, Mariño, Guillermo, Markaki, Maria, Marten, Mark R, Martin, Seamus J, Martinand-Mari, Camille, Martinet, Wim, Martinez-Vicente, Marta, Masini, Matilde, Matarrese, Paola, Matsuo, Saburo, Matteoni, Raffaele, Mayer, Andreas, Mazure, Nathalie M, Mcconkey, David J, Mcconnell, Melanie J, Mcdermott, Catherine, Mcdonald, Christine, Mcinerney, Gerald M, Mckenna, Sharon L, Mclaughlin, Bethann, Mclean, Pamela J, Mcmaster, Christopher R, Mcquibban, G Angus, Meijer, Alfred J, Meisler, Miriam H, Meléndez, Alicia, Melia, Thomas J, Melino, Gerry, Mena, Maria A, Menendez, Javier A, Menna-Barreto, Rubem F S, Menon, Manoj B, Menzies, Fiona M, Mercer, Carol A, Merighi, Adalberto, Merry, Diane E, Meschini, Stefania, Meyer, Christian G, Meyer, Thomas F, Miao, Chao-Yu, Miao, Jun-Ying, Michels, Paul A M, Michiels, Carine, Mijaljica, Dalibor, Milojkovic, Ana, Minucci, Saverio, Miracco, Clelia, Miranti, Cindy K, Mitroulis, Ioannis, Miyazawa, Keisuke, Mizushima, Noboru, Mograbi, Baharia, Mohseni, Simin, Molero, Xavier, Mollereau, Bertrand, Mollinedo, Faustino, Momoi, Takashi, Monastyrska, Iryna, Monick, Martha M, Monteiro, Mervyn J, Moore, Michael N, Mora, Rodrigo, Moreau, Kevin, Moreira, Paula I, Moriyasu, Yuji, Moscat, Jorge, Mostowy, Serge, Mottram, Jeremy C, Motyl, Tomasz, Moussa, Charbel E-H, Müller, Sylke, Muller, Sylviane, Münger, Karl, Münz, Christian, Murphy, Leon O, Murphy, Maureen E, Musarò, Antonio, Mysorekar, Indira, Nagata, Eiichiro, Nagata, Kazuhiro, Nahimana, Aimable, Nair, Usha, Nakagawa, Toshiyuki, Nakahira, Kiichi, Nakano, Hiroyasu, Nakatogawa, Hitoshi, Nanjundan, Meera, Naqvi, Naweed I, Narendra, Derek P, Narita, Masashi, Navarro, Miguel, Nawrocki, Steffan T, Nazarko, Taras Y, Nemchenko, Andriy, Netea, Mihai G, Neufeld, Thomas P, Ney, Paul A, Nezis, Ioannis P, Nguyen, Huu Phuc, Nie, Daotai, Nishino, Ichizo, Nislow, Corey, Nixon, Ralph A, Noda, Takeshi, Noegel, Angelika A, Nogalska, Anna, Noguchi, Satoru, Notterpek, Lucia, Novak, Ivana, Nozaki, Tomoyoshi, Nukina, Nobuyuki, Nürnberger, Thorsten, Nyfeler, Beat, Obara, Keisuke, Oberley, Terry D, Oddo, Salvatore, Ogawa, Michinaga, Ohashi, Toya, Okamoto, Koji, Oleinick, Nancy L, Oliver, F Javier, Olsen, Laura J, Olsson, Stefan, Opota, Onya, Osborne, Timothy F, Ostrander, Gary K, Otsu, Kinya, Ou, Jing-Hsiung James, Ouimet, Mireille, Overholtzer, Michael, Ozpolat, Bulent, Paganetti, Paolo, Pagnini, Ugo, Pallet, Nicolas, Palmer, Glen E, Palumbo, Camilla, Pan, Tianhong, Panaretakis, Theocharis, Pandey, Udai Bhan, Papackova, Zuzana, Papassideri, Issidora, Paris, Irmgard, Park, Junsoo, Park, Ohkmae K, Parys, Jan B, Parzych, Katherine R, Patschan, Susann, Patterson, Cam, Pattingre, Sophie, Pawelek, John M, Peng, Jianxin, Perlmutter, David H, Perrotta, Ida, Perry, George, Pervaiz, Shazib, Peter, Matthias, Peters, Godefridus J, Petersen, Morten, Petrovski, Goran, Phang, James M, Piacentini, Mauro, Pierre, Philippe, Pierrefite-Carle, Valérie, Pierron, Gérard, Pinkas-Kramarski, Ronit, Piras, Antonio, Piri, Natik, Platanias, Leonidas C, Pöggeler, Stefanie, Poirot, Marc, Poletti, Angelo, Poüs, Christian, Pozuelo-Rubio, Mercedes, Prætorius-Ibba, Mette, Prasad, Anil, Prescott, Mark, Priault, Muriel, Produit-Zengaffinen, Nathalie, Progulske-Fox, Ann, Proikas-Cezanne, Tassula, Przedborski, Serge, Przyklenk, Karin, Puertollano, Rosa, Puyal, Julien, Qian, Shu-Bing, Qin, Liang, Qin, Zheng-Hong, Quaggin, Susan E, Raben, Nina, Rabinowich, Hannah, Rabkin, Simon W, Rahman, Irfan, Rami, Abdelhaq, Ramm, Georg, Randall, Glenn, Randow, Felix, Rao, V Ashutosh, Rathmell, Jeffrey C, Ravikumar, Brinda, Ray, Swapan K, Reed, Bruce H, Reed, John C, Reggiori, Fulvio, Régnier-Vigouroux, Anne, Reichert, Andreas S, Reiners, John J, Reiter, Russel J, Ren, Jun, Revuelta, José L, Rhodes, Christopher J, Ritis, Konstantinos, Rizzo, Elizete, Robbins, Jeffrey, Roberge, Michel, Roca, Hernan, Roccheri, Maria C, Rocchi, Stephane, Rodemann, H Peter, Rodríguez De Córdoba, Santiago, Rohrer, Bärbel, Roninson, Igor B, Rosen, Kirill, Rost-Roszkowska, Magdalena M, Rouis, Mustapha, Rouschop, Kasper M A, Rovetta, Francesca, Rubin, Brian P, Rubinsztein, David C, Ruckdeschel, Klaus, Rucker, Edmund B, Rudich, Assaf, Rudolf, Emil, Ruiz-Opazo, Nelson, Russo, Rossella, Rusten, Tor Erik, Ryan, Kevin M, Ryter, Stefan W, Sabatini, David M, Sadoshima, Junichi, Saha, Tapas, Saitoh, Tatsuya, Sakagami, Hiroshi, Sakai, Yasuyoshi, Salekdeh, Ghasem Hoseini, Salomoni, Paolo, Salvaterra, Paul M, Salvesen, Guy, Salvioli, Rosa, Sanchez, Anthony M J, Sánchez-Alcázar, José A, Sánchez-Prieto, Ricardo, Sandri, Marco, Sankar, Uma, Sansanwal, Poonam, Santambrogio, Laura, Saran, Shweta, Sarkar, Sovan, Sarwal, Minnie, Sasakawa, Chihiro, Sasnauskiene, Ausra, Sass, Miklós, Sato, Ken, Sato, Miyuki, 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Abstract: International audience, In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused o

6. Guidelines for the use and interpretation of assays for monitoring autophagy.

Author: Molecular and Cellular Biology ; University of Leuven, Laboratoire d'Epigénétique et Cancer ; CNRS - Université Paris XI - Paris Sud, Department of Pharmacology ; Department of Pharmacology, Immunobiologie des Cellules Dendritiques ; INSERM - Institut Pasteur de Paris, Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (FEMTO-ST) ; CNRS - Université de Franche-Comté - Université de Technologie de Belfort-Montbeliard - Ecole Nationale Supérieure de Mécanique et des Microtechniques, Telethon Institute for Genetics and Medicine ; Telethon Institute, Medical Genetics ; Federico II University, Department of Molecular and Human Genetics ; Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute ; Texas Children's Hospital, Signalisation et physiopathologie des cellules épithéliales ; INSERM - Université Paris XI - Paris Sud, Dynamique des interactions membranaires normales et pathologiques (DIMNP) ; CNRS - Université Montpellier I - Université Montpellier II - Sciences et techniques, Institut de biochimie et génétique cellulaires (IBGC) ; CNRS - Université Victor Segalen - Bordeaux II, Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS) ; CNRS - Université Montpellier I - Université Montpellier II - Sciences et techniques, Celullar and Molecular Medicine ; Celullar and Molecular Medicine, Estrogène, Expression génique et pathologies du Système Nerveux Central (E2SNC) ; Université de Franche-Comté - IFR133, Infection bactérienne, inflammation, et carcinogenèse digestive ; INSERM - IFR50 - Université Nice Sophia Antipolis (UNS), Université Nice Sophia Antipolis (UNS) ; Université Nice Sophia Antipolis (UNS) - PRES Euro-Méditerranéen, Department of Computer Science [Tsukuba] ; University of Tsukuba, Gunma University ; Institute for Molecular & Cellular Regulation, Cell Biology, Physiology and Immunology ; Cell Biology, Physiology and Immunology, Dulbecco Telethon Institute/Department of Biology ; Dulbecco Telethon Institute/Department of Biology, Department of Chemistry and HKU-CAS Joint Laboratory ; University of Hong-Kong, Laboratoire Bordelais de Recherche en Informatique (LaBRI) ; CNRS - Université Sciences et Technologies - Bordeaux I - Université Victor Segalen - Bordeaux II - École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Learning Sciences Lab ; National Institute of Education, Nanyang Technological University, University of California ; University of California, Physiopathologie du cancer du foie ; INSERM - Université Victor Segalen - Bordeaux II, Emory University School of Medicine ; Emory University School of Medicine, Cytokines et Immunologie des Tumeurs Humaines ; INSERM - Institut Gustave Roussy - Université Paris XI - Paris Sud, Biology ; University of Rome"Tor Vergata", Oxford University ; Oxford University, Strathclyde Institute of Pharmacy and Biomedical Sciences ; University of Strathclyde, Interactions Bactéries-Cellules (UIBC) ; Institut national de la recherche agronomique (INRA) - INSERM - Institut Pasteur de Paris, Department of Experimental Medicine and Oncology ; University of Turin, Institut de génomique fonctionnelle (IGF) ; CNRS - INSERM - Université Montpellier I - Université Montpellier II - Sciences et techniques, CNV ; University of Valparaiso, Section of Haemato-oncology ; Institute of cancer research, Régulation de l'expression génétique (REG) ; CNRS - École normale supérieure [ENS] - Paris, Brunel University ; Brunel University, University of New-Mexico ; University of New-Mexico, Facultad de Ciencias Químicas y Farmacéuticas ; Centro de Estudios Moleculares de la Célula, Biochemistry and Molecular Biology ; Biochemistry and Molecular Biology, Dpt. of Cancer & Cell Biology ; University of Cincinnati, Institut Jacques Monod (IJM) ; CNRS - Université Paris VII - Paris Diderot, Virologie humaine ; INSERM - IFR128 - École Normale Supérieure (ENS) - Lyon, Instituto de Investigaciones Biotecnológicas, (IIB-INTECH) ; Universidad Nacional de San Martin, MRC Centre for Developmental Neurobiology ; MRC Centre for Developmental Neurobiology, University of Brescia ; University of Brescia, Immunité infection vaccination ; INSERM - Université Claude Bernard - Lyon I (UCBL) - IFR128, Dept of City and Regional Planning ; Peiking University, Montreal Neurological Institute ; McGill University, Department of Developmental Biology and Neurosciences ; Tohoku University - Graduate School of Life Sciences, Biologie Cellulaire du Noyau (BCN) ; CNRS - Institut Pasteur de Paris, Faculty of Medicine ; University of Ottawa, Institut de recherche en cancérologie de Montpellier (IRCM) ; INSERM - CRLCC Val d'Aurelle - Paul Lamarque - Université Montpellier I, Immunologie et chimie thérapeutiques (ICT) ; CNRS - Cancéropôle du Grand Est, Université de Strasbourg (UNISTRA) ; Université de Strasbourg, Département Digestif ; CHU Nice - Hôpital de l'Archet, Centre méditérannéen de médecine moléculaire (C3M) ; INSERM - Université Nice Sophia Antipolis (UNS), National Institute of Advanced Industrial Science and Technology [Tsukuba] (AIST) ; National Institute for Advanced Industrial Science and Technology - AIST (JAPAN), Department of Oncology ; John Radcliffe Hospital, School of Biochemistry and Immunology ; School of Biochemistry and Immunology, Department of Cellular and Structural Biology, University of Texas Health Science Center ; University of Texas, Laboratoire de Pathologie Clinique et Expérimentale ; CHU Nice, Department of Biochemistry ; University of Hong Kong, Danish Cancer Society ; Institute of Cancer Biology, Institut de biologie et chimie des protéines [Lyon] (IBCP) ; CNRS - Université Claude Bernard - Lyon I (UCBL), Department of Gastroenterology, Hepatology and Endocrinology (MHH) ; Hannover medical school, Cancer Research UK London Research Institute ; Cancer Research UK London Research Institute, Cell Biology, section Radiation & Stress Cell Biology ; UMCG, Univ. of Groningen, Department of Molecular Genetics ; Weizmann Institute of Science, Institute of Immunology ; University Hospital Schleswig-Holstein, Institute for Immunology ; Institute for Immunology, Department of Neuroscience ; University of Texas Southwestern Medical Center at Dallas, Centre de génétique et de physiologie moléculaire et cellulaire (CGphiMC) ; CNRS - Université Claude Bernard - Lyon I (UCBL), Centre de Recherche des Cordeliers ; INSERM - Université Paris V - Paris Descartes - Université Pierre et Marie Curie (UPMC) - Paris VI, Apoptose, cancer et immunité ; INSERM - Institut Gustave Roussy - Université Paris XI - Paris Sud, metabolomics platform ; Institut Gustave Roussy, Pôle de biologie ; Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital européen Georges Pompidou, Université Paris Descartes - Faculté de Médecine (UP5) ; Université Paris V - Paris Descartes - PRES Sorbonne Paris Cité, Department of Molecular Neuroscience ; Department of Molecular Neuroscience, European Organization for Nuclear Research (CERN) ; CERN, Center for Visual Information Technology (CVIT) ; International Institute of Information Technology, Massachusetts Institute of technology [Cambridge] (MIT) ; Massachusetts Institute of Technology (MIT), Department of Biochemistry and Molecular Biology ; University of Washington, Centre for Cancer Biology ; Hanson Institute, Adelaide, Jeune Equipe JE 2526 ; Université d'Auvergne - Clermont-Ferrand I, Institut de Recherche Agronomique (Unité sous contrat USC-2018) ; Institut national de la recherche agronomique (INRA), Facultad de Medicina ; Universidad de Chile, Institut de génétique moléculaire de Montpellier (IGMM) ; CNRS - Université Montpellier II - Sciences et techniques, Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC) ; IFR140 - Université de Rennes 1 - IRSET, Centre de génétique moléculaire (CGM) ; CNRS - Université Paris XI - Paris Sud - Université Pierre et Marie Curie (UPMC) - Paris VI, National Cheng Kung University [Taiwan] (NCKU) ; Institute of Basic Medical Sciences, Microenvironnement et Physiopathologie de la Differenciation ; INSERM - Université Paris XI - Paris Sud, Howard Hughes Medical Institute ; Howard Hugues Medical Institute, Southwestern Medical Center ; University of Texas, School of Information science and engineering ; Lanzhou University, School of computer and information ; Hefei University, National Neuroscience Institute ; National Neuroscience Institute, National University of Singapore (NUS) ; NUS, Institut de Mécanique des Fluides et des Solides (IMFS) ; CNRS - Université de Strasbourg - ENGEES, Institut Armand Frappier (IAF) ; Réseau International des Instituts Pasteur - Institut National de la Recherche Scientifique, Central China Normal University ; Central China Normal University, Center for International Blood and Marrow Transplant Research (CIBMTR) ; Medical College Of Wisconsin - Emory University School of Medicine, Departamento de Bioquímica y Biología Molecular ; Universidad de Oviedo - Instituto Universitario de Oncología, Laboratoire d'analyse et d'architecture des systèmes [Toulouse] (LAAS) ; CNRS - Université Paul Sabatier (UPS) - Toulouse III - Institut National Polytechnique de Toulouse - INPT - Institut National des Sciences Appliquées [INSA] - Toulouse, Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Equipe Labellisée par la Ligue Nationale contre le Cancer ; LNCC, Johns Hopkins University (JHU) ; Johns Hopkins University, Institute of Molecular Biosciences, Karl-Franzens University Graz, (IMB) ; Karl-Franzens University Graz, Department of Pediatrics ; Università degli studi di Napoli Federico II, Department of Experimental Pharmacology ; Università degli Study di Napoli Federico II, Drug Research and Evaluation ; Istituto Superiore di Sanita‘, Albert Einstein College of Medicine (ALBERT EINSTEIN COLLEGE OF MEDICINE) ; Albert Einstein College of Medicine, Institute of Molecular Biology and Biotechnology ; Foundation for Research and Technology - Hellas, Institut des Sciences de l'Evolution - Montpellier (ISEM) ; CNRS - Institut de recherche pour le développement [IRD] - Université Montpellier II - Sciences et techniques, Institut de signalisation, biologie du développement et cancer (ISBDC) ; CNRS - Université Nice Sophia Antipolis (UNS), Departments of Neurology ; Departments of Neurology, Vanderbilt University [Nashville] ; Vanderbilt University of Nashville, Departments of Pharmacology ; Departments of Pharmacology, Department of Cell Biology [New Haven] ; Yale University School of Medicine - Howard Hugues Medical Institute, Anatomic Pathology Section, Department of Human Pathology and Oncology ; University of Siena, Harvard Medical School (HMS) ; Harvard University, Depts of Radiation Oncology and Pathology ; Wayne State University - Karmanos Cancer Institute, USC Neuromuscular Center, Department of Neurology ; University of Southern California, Department of Biology ; University of Copenhagen, Department of Cell Biology and Biophysics ; University of Athens, Department of Pathology ; Case Western Reserve University, University of Texas at San Antonio ; University of Texas at San Antonio, Institute of Translational Medicine ; Institute of Translational Medicine, Institute of Biochemistry (IBC) ; Swiss Federal Institute of Technology Zurich - Eidgenössische Technische Hochschule Zürich (ETH), Department of Biology ; University of Rome Tor Vergata, Génétique, physiopathologie et ingénierie du tissu osseux (GéPITOS) ; CNRS - Université Nice Sophia Antipolis (UNS), Innovation Thérapeutique : du Fondamental au Médicament ; CNRS - Institut national de la recherche agronomique (INRA) - INSERM - MEDICEN - Université Paris XI - Paris Sud, Hôpital Antoine Béclère ; Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris XI - Paris Sud, Señalización Celular 4 ; Señalización Celular 4, Department of Molecular Biology ; University of Tuebingen, Department of Neurology Columbia University 650 West 168th Street ; Department of Neurology Columbia University 650 West 168th Street, Department of Pathology and Cell Biology Columbia University 650 West 168th Street ; Department of Pathology and Cell Biology Columbia University 650 West 168th Street, Center for Motor Neuron Biology and Disease Columbia University 650 West 168th Street ; Center for Motor Neuron Biology and Disease Columbia University 650 West 168th Street, Department of Cell Biology and Morphology ; Université de Lausanne, CC 101 ; Université Montpellier II - Sciences et techniques, Department of Cell Biology, Institute of Biomembranes, University Medical Center Utrecht ; Institute of Biomembranes, University Medical Center Utrecht, Service de dermatologie ; CHU Nice, Vieillissement, stress, inflammation ; Université Pierre et Marie Curie (UPMC) - Paris VI, University of Cambridge (UK) (CAM) ; University of Cambridge (UK), The Department of Chemical and Environmental Sciences ; University of Limerick, Fondazione IRCCS Istituto Nazionale dei Tumori ; Fondazione IRCCS Istituto Nazionale dei Tumori, Neurogenetics laboratory ; Neurogenetics laboratory, Department of Pathology ; Otto-von-Guericke University, Experimental Tumor Pathology ; University of Erlangen, Unit of Oculogenomics ; Institute for Research in Ophthalmology", Swiss Federal Institute of Technology ; University of Lausanne, Eye Hospital, Department of Ophthalmology, Jules-Gonin , ; Eye Hospital", Division of regenerative Medicine ; San Raffaele Scientific Institute, ICBM ; Faculty of Medicine - University of Chile, Department of pathology ; Harvard Medical School, Department of Endocrine and Oncology Surgery ; Royal North Shore Hospital, Department of Surgery, Bankstown Hospital and South Western Sydney Clinical School ; University of New South Wales, Medical Research Council Human Immunology Unit ; John Radcliffe Hospital - Weatherall Institute of Molecular Medicine, Department of Pharmacology and Molecular Sciences ; University of Bern, Université de Genève ; Université de Genève, Kimmel Cancer Center, and the Stem Cell Biology and Regenerative Medicine Center ; Thomas Jefferson University, Muscular and Neurodegenerative Disease Unit ; University of Genoa and G. Gaslini Pediatric Institute, Department of Clinical and Experimental Medicine ; Division of Cell Biology; and Linköping Diabetes Research Centre, Cancer Institute ; University College London, Department of Biochemistry and Biophysics ; University of California, San Francisco, Department of Experimental and Diagnostic Medicine and Interdisciplinary Center for Study of inflammation and ER-GenTech ; University of Ferrara, Laboratory of Molecular and Cellular Parasitology - Department of Microbiology ; Yong Loo Lin School of Medicine, National University of Singapore, Center of Microbial and Plant Genetics (CMPG) ; Katholieke Universiteit Leuven, Abramson Cancer Institute and Department of Cancer Biology ; University of Pennsylvania, Instituto de Microbiologia Paulo de Goes ; Universidade Federal do Rio de Janeiro, Immunité Innée et Signalisation ; Institut Pasteur de Paris, Istituto CSS Mendel ; Istituto CSS Mendel, Department of Medical and Surgical Pediatrics ; University Hospital, Messina, Department of Intensive care Medicine ; Katholieke Universiteit Leuven, Department of Cell Biology ; Vrije Universiteit Brussel, Department for Molecular Biomedical Research ; Department for Molecular Biomedical Research, Department of Pediatrics ; University of Padova, Department of Chemistry ; Peking University, Department of Mathematics ; Shanghai University, Sch Mat Sci & Engn ; Aucune, Institut de Recherche Interdisciplinaire (IRI) ; CNRS - Université Lille II - Droit et santé - Université Lille I - Sciences et technologies, Institut d'électronique, de microélectronique et de nanotechnologie (IEMN) ; CNRS - Institut supérieur de l'électronique et du nunérique (ISEN) - Université de Valenciennes et du Hainaut-Cambresis - Université Lille I - Sciences et technologies, Nankai University ; Nankai University, Division of Endocrinology and Diabetes ; University of Oklahoma Health Science Center, Department of Pharmacology and Cancer Biology ; Duke University, Modélisation, Information & Systèmes (MIS) ; Université de Picardie Jules Verne, Department of Experimental Oncology and Molecular Medicine ; Fondazione IRCCS Istituto Nazionale dei Tumori, Institute of Modern Physics ; Chinese Academy of Science (CAS), Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province ; ganzu Province, Institute of Computing Technology [Biejing] (ICT) ; Chinese Academy of Science (CAS), European Synchrotron Radiation Facility (ESRF) ; ESRF, Plant Physiology Laboratory ; Chinese Academy of Sciences - Botanical Institute of South china, Division of Biopharmaceutics ; Leiden University, The Institute of Environmental Medicine [Stockholm] (IMM) ; Karolinska Institutet, Institut de biochimie et biophysique moléculaire et cellulaire (IBBMC) ; CNRS - Université Paris XI - Paris Sud, Center for Brain Repair and Rehabilitation ; University of Gothenburg - Institute of Neuroscience and Physiology, department of genetics - Institute of biochemistry and biophysics ; institute of biochemistry an biophysics - polish academic of sciences, Departament de Bioquímica i Biologia Molecular ; Universitat de Barcelona - Facultat de Biologia - Institute for Research in Biomedicine - CIBERDEM, Chaperones Research Group ; Chaperones Research Group, Klionsky, Daniel J, Abdalla, Fabio C, Abeliovich, Hagai, Abraham, Robert T, Acevedo-Arozena, Abraham, Adeli, Khosrow, Agholme, Lotta, Agnello, Maria, Agostinis, Patrizia, Aguirre-Ghiso, Julio A, Ahn, Hyung Jun, Ait-Mohamed, Ouardia, Ait-Si-Ali, Slimane, Akematsu, Takahiko, Akira, Shizuo, Al-Younes, Hesham M, Al-Zeer, Munir A, Albert, Matthew L, Albin, Roger L, Alegre-Abarrategui, Javier, Aleo, Maria Francesca, Alirezaei, Mehrdad, Almasan, Alexandru, Almonte-Becerril, Maylin, Amano, Atsuo, Amaravadi, Ravi, Amarnath, Shoba, Amer, Amal O, Andrieu-Abadie, Nathalie, Anantharam, Vellareddy, Ann, David K, Anoopkumar-Dukie, Shailendra, Aoki, Hiroshi, Apostolova, Nadezda, Auberger, Patrick, Baba, Misuzu, Backues, Steven K, Baehrecke, Eric H, Bahr, Ben A, Bai, Xue-Yuan, Bailly, Yannick, Baiocchi, Robert, Baldini, Giulia, Balduini, Walter, Ballabio, Andrea, Bamber, Bruce A, Bampton, Edward T W, Bánhegyi, Gábor, Bartholomew, Clinton R, Bassham, Diane C, Bast, Robert C, Batoko, Henri, Bay, Boon-Huat, Beau, Isabelle, Béchet, Daniel M, Begley, Thomas J, Behl, Christian, Behrends, Christian, Bekri, Soumeya, Bellaire, Bryan, Bendall, Linda J, Benetti, Luca, Berliocchi, Laura, Bernardi, Henri, Bernassola, Francesca, Besteiro, Sébastien, Bhatia-Kissova, Ingrid, Bi, Xiaoning, Biard-Piechaczyk, Martine, Blum, Janice S, Boise, Lawrence H, Bonaldo, Paolo, Boone, David L, Bornhauser, Beat C, Bortoluci, Karina R, Bossis, Ioannis, Bost, Frédéric, Bourquin, Jean-Pierre, Boya, Patricia, Boyer-Guittaut, Michaël, Bozhkov, Peter V, Brady, Nathan R, Brancolini, Claudio, Brech, Andreas, Brenman, Jay E, Brennand, Ana, Bresnick, Emery H, Brest, Patrick, Bridges, Dave, Bristol, Molly L, Brookes, Paul S, Brown, Eric J, Brumell, John H, Brunetti-Pierri, Nicola, Brunk, Ulf T, Bulman, Dennis E, Bultman, Scott J, Bultynck, Geert, Burbulla, Lena F, Bursch, Wilfried, Butchar, Jonathan P, Buzgariu, Wanda, Bydlowski, Sergio P, Cadwell, Ken, Cahová, Monika, Cai, Dongsheng, Cai, Jiyang, Cai, Qian, Calabretta, Bruno, Calvo-Garrido, Javier, Camougrand, Nadine, Campanella, Michelangelo, Campos-Salinas, Jenny, Candi, Eleonora, Cao, Lizhi, Caplan, Allan B, Carding, Simon R, Cardoso, Sandra M, Carew, Jennifer S, Carlin, Cathleen R, Carmignac, Virginie, Carneiro, Leticia A M, Carra, Serena, Caruso, Rosario A, Casari, Giorgio, Casas, Caty, Castino, Roberta, Cebollero, Eduardo, Cecconi, Francesco, Celli, Jean, Chaachouay, Hassan, Chae, Han-Jung, Chai, Chee-Yin, Chan, David C, Chan, Edmond Y, Chang, Raymond Chuen-Chung, Che, Chi-Ming, Chen, Ching-Chow, Chen, Guang-Chao, Chen, Guo-Qiang, Chen, Min, Chen, Quan, Chen, Steve S-L, Chen, Wenli, Chen, Xi, Chen, Xiangmei, Chen, Xiequn, Chen, Ye-Guang, Chen, Yingyu, Chen, Yongqiang, Chen, Yu-Jen, Chen, Zhixiang, Cheng, Alan, Cheng, Christopher H K, Cheng, Yan, Cheong, Heesun, Cheong, Jae-Ho, Cherry, Sara, Chess-Williams, Russ, Cheung, Zelda H, Chevet, Eric, Chiang, Hui-Ling, Chiarelli, Roberto, Chiba, Tomoki, Chin, Lih-Shen, Chiou, Shih-Hwa, Chisari, Francis V, Cho, Chi Hin, Cho, Dong-Hyung, Choi, Augustine M K, Choi, Dooseok, Choi, Kyeong Sook, Choi, Mary E, Chouaib, Salem, Choubey, Divaker, Choubey, Vinay, Chu, Charleen T, Chuang, Tsung-Hsien, Chueh, Sheau-Huei, Chun, Taehoon, Chwae, Yong-Joon, Chye, Mee-Len, Ciarcia, Roberto, Ciriolo, Maria R, Clague, Michael J, Clark, Robert S B, Clarke, Peter G H, Clarke, Robert, Codogno, Patrice, Coller, Hilary A, Colombo, María I, Comincini, Sergio, Condello, Maria, Condorelli, Fabrizio, Cookson, Mark R, Coombs, Graham H, Coppens, Isabelle, Corbalan, Ramon, Cossart, Pascale, Costelli, Paola, Costes, Safia, Coto-Montes, Ana, Couve, Eduardo, Coxon, Fraser P, Cregg, James M, Crespo, José L, Cronjé, Marianne J, Cuervo, Ana Maria, Cullen, Joseph J, Czaja, Mark J, D'Amelio, Marcello, Darfeuille-Michaud, Arlette, Davids, Lester M, Davies, Faith E, De Felici, Massimo, De Groot, John F, De Haan, Cornelis A M, De Martino, Luisa, De Milito, Angelo, De Tata, Vincenzo, Debnath, Jayanta, Degterev, Alexei, Dehay, Benjamin, Delbridge, Lea M D, Demarchi, Francesca, Deng, Yi Zhen, Dengjel, Jörn, Dent, Paul, Denton, Donna, Deretic, Vojo, Desai, Shyamal D, Devenish, Rodney J, Di Gioacchino, Mario, Di Paolo, Gilbert, Di Pietro, Chiara, Díaz-Araya, Guillermo, Díaz-Laviada, Inés, Diaz-Meco, Maria T, Diaz-Nido, Javier, Dikic, Ivan, Dinesh-Kumar, Savithramma P, Ding, Wen-Xing, Distelhorst, Clark W, Diwan, Abhinav, Djavaheri-Mergny, Mojgan, Dokudovskaya, Svetlana, Dong, Zheng, Dorsey, Frank C, Dosenko, Victor, Dowling, James J, Doxsey, Stephen, Dreux, Marlène, Drew, Mark E, Duan, Qiuhong, Duchosal, Michel A, Duff, Karen, Dugail, Isabelle, Durbeej, Madeleine, Duszenko, Michael, Edelstein, Charles L, Edinger, Aimee L, Egea, Gustavo, Eichinger, Ludwig, Eissa, N Tony, Ekmekcioglu, Suhendan, El-Deiry, Wafik S, Elazar, Zvulun, Elgendy, Mohamed, Ellerby, Lisa M, Eng, Kai Er, Engelbrecht, Anna-Mart, Engelender, Simone, Erenpreisa, Jekaterina, Escalante, Ricardo, Esclatine, Audrey, Eskelinen, Eeva-Liisa, Espert, Lucile, Espina, Virginia, Fan, Huizhou, Fan, Jia, Fan, Qi-Wen, Fan, Zhen, Fang, Shengyun, Fang, Yongqi, Fanto, Manolis, Fanzani, Alessandro, Farkas, Thomas, Farré, Jean-Claude, Faure, Mathias, Fechheimer, Marcus, Feng, Carl G, Feng, Jian, Feng, Qili, Feng, Youji, Fésüs, László, Feuer, Ralph, Figueiredo-Pereira, Maria E, Fimia, Gian Maria, Fingar, Diane C, Finkbeiner, Steven, Finkel, Toren, Finley, Kim D, Fiorito, Filomena, Fisher, Edward A, Fisher, Paul B, Flajolet, Marc, Florez-Mcclure, Maria L, Florio, Salvatore, Fon, Edward A, Fornai, Francesco, Fortunato, Franco, Fotedar, Rati, Fowler, Daniel H, Fox, Howard S, Franco, Rodrigo, Frankel, Lisa B, Fransen, Marc, Fuentes, José M, Fueyo, Juan, Fujii, Jun, Fujisaki, Kozo, Fujita, Eriko, Fukuda, Mitsunori, Furukawa, Ruth H, Gaestel, Matthias, Gailly, Philippe, Gajewska, Malgorzata, Galliot, Brigitte, Galy, Vincent, Ganesh, Subramaniam, Ganetzky, Barry, Ganley, Ian G, Gao, Fen-Biao, Gao, George F, Gao, Jinming, Garcia, Lorena, Garcia-Manero, Guillermo, Garcia-Marcos, Mikel, Garmyn, Marjan, Gartel, Andrei L, Gatti, Evelina, Gautel, Mathias, Gawriluk, Thomas R, Gegg, Matthew E, Geng, Jiefei, Germain, Marc, Gestwicki, Jason E, Gewirtz, David A, Ghavami, Saeid, Ghosh, Pradipta, Giammarioli, Anna M, Giatromanolaki, Alexandra N, Gibson, Spencer B, Gilkerson, Robert W, Ginger, Michael L, Goncu, Ebru, Gongora, Céline, Gonzalez, Claudio D, Gonzalez, Ramon, González-Estévez, Cristina, González-Polo, Rosa Ana, Gonzalez-Rey, Elena, Gorbunov, Nikolai V, Gorski, Sharon, Goruppi, Sandro, Gottlieb, Roberta A, Gozuacik, Devrim, Granato, Giovanna Elvira, Grant, Gary D, Green, Kim N, Gregorc, Aleš, Gros, Frédéric, Grose, Charles, Grunt, Thomas W, Gual, Philippe, Guan, Jun-Lin, Guan, Kun-Liang, Guichard, Sylvie M, Gukovskaya, Anna S, Gukovsky, Ilya, Gunst, Jan, Gustafsson, Asa B, Halayko, Andrew J, Hale, Amber N, Halonen, Sandra K, Hamasaki, Maho, Han, Feng, Han, Ting, Hancock, Michael K, Hansen, Malene, Harada, Hisashi, Harada, Masaru, Hardt, Stefan E, Harper, J Wade, Harris, Adrian L, Harris, James, Harris, Steven D, Hébert, Marie-Joseé, Heidenreich, Kim A, Helfrich, Miep H, Helgason, Gudmundur V, Henske, Elizabeth P, Herman, Brian, Herman, Paul K, Hetz, Claudio, Hilfiker, Sabine, Hill, Joseph A, Hocking, Lynne J, Hofman, Paul, Hofmann, Thomas G, Höhfeld, Jörg, Holyoake, Tessa L, Hong, Ming-Huang, Hood, David A, Hotamisligil, Gökhan S, Houwerzijl, Ewout J, Høyer-Hansen, Maria, Hu, Bingren, Hu, Chien-An A, Hu, Hong-Ming, Hua, Ya, Huang, Canhua, Huang, Ju, Huang, Shengbing, Huang, Wei-Pang, Huber, Tobias B, Huh, Won-Ki, Hung, Tai-Ho, Hupp, Ted R, Hur, Gang Min, Hurley, James B, Hussain, Sabah N A, Hussey, Patrick J, Hwang, Jung Jin, Hwang, Seungmin, Ichihara, Atsuhiro, Ilkhanizadeh, Shirin, Inoki, Ken, Into, Takeshi, Iovane, Valentina, Iovanna, Juan L, Ip, Nancy Y, Isaka, Yoshitaka, Ishida, Hiroyuki, Isidoro, Ciro, Isobe, Ken-Ichi, Iwasaki, Akiko, Izquierdo, Marta, Izumi, Yotaro, Jaakkola, Panu M, Jäättelä, Marja, Jackson, George R, Jackson, William T, Janji, Bassam, Jendrach, Marina, Jeon, Ju-Hong, Jeung, Eui-Bae, Jiang, Hong, Jiang, Hongchi, Jiang, Jean X, Jiang, Ming, Jiang, Qing, Jiang, Xuejun, Jiménez, Alberto, Jin, Meiyan, Jin, Shengkan, Joe, Cheol O, Johansen, Terje, Johnson, Daniel E, Johnson, Gail V W, Jones, Nicola L, Joseph, Bertrand, Joseph, Suresh K, Joubert, Annie M, Juhász, Gábor, Juillerat-Jeanneret, Lucienne, Jung, Chang Hwa, Jung, Yong-Keun, Kaarniranta, Kai, Kaasik, Allen, Kabuta, Tomohiro, Kadowaki, Motoni, Kagedal, Katarina, Kamada, Yoshiaki, Kaminskyy, Vitaliy O, Kampinga, Harm H, Kanamori, Hiromitsu, Kang, Chanhee, Kang, Khong Bee, Kang, Kwang Il, Kang, Rui, Kang, Yoon-A, Kanki, Tomotake, Kanneganti, Thirumala-Devi, Kanno, Haruo, Kanthasamy, Anumantha G, Kanthasamy, Arthi, Karantza, Vassiliki, Kaushal, Gur P, Kaushik, Susmita, Kawazoe, Yoshinori, Ke, Po-Yuan, Kehrl, John H, Kelekar, Ameeta, Kerkhoff, Claus, Kessel, David H, Khalil, Hany, Kiel, Jan A K W, Kiger, Amy A, Kihara, Akio, Kim, Deok Ryong, Kim, Do-Hyung, Kim, Dong-Hou, Kim, Eun-Kyoung, Kim, Hyung-Ryong, Kim, Jae-Sung, Kim, Jeong Hun, Kim, Jin Cheon, Kim, John K, Kim, Peter K, Kim, Seong Who, Kim, Yong-Sun, Kim, Yonghyun, Kimchi, Adi, Kimmelman, Alec C, King, Jason S, Kinsella, Timothy J, Kirkin, Vladimir, Kirshenbaum, Lorrie A, Kitamoto, Katsuhiko, Kitazato, Kaio, Klein, Ludger, Klimecki, Walter T, Klucken, Jochen, Knecht, Erwin, Ko, Ben C B, Koch, Jan C, Koga, Hiroshi, Koh, Jae-Young, Koh, Young Ho, Koike, Masato, Komatsu, Masaaki, Kominami, Eiki, Kong, Hee Jeong, Kong, Wei-Jia, Korolchuk, Viktor I, Kotake, Yaichiro, Koukourakis, Michael I, Kouri Flores, Juan B, Kovács, Attila L, Kraft, Claudine, Krainc, Dimitri, Krämer, Helmut, Kretz-Remy, Carole, Krichevsky, Anna M, Kroemer, Guido, Krüger, Rejko, Krut, Oleg, Ktistakis, Nicholas T, Kuan, Chia-Yi, Kucharczyk, Roza, Kumar, Ashok, Kumar, Raj, Kumar, Sharad, Kundu, Mondira, Kung, Hsing-Jien, Kurz, Tino, Kwon, Ho Jeong, La Spada, Albert R, Lafont, Frank, Lamark, Trond, Landry, Jacques, Lane, Jon D, Lapaquette, Pierre, Laporte, Jocelyn F, László, Lajos, Lavandero, Sergio, Lavoie, Josée N, Layfield, Robert, Lazo, Pedro A, Le, Weidong, Le Cam, Laurent, Ledbetter, Daniel J, Lee, Alvin J X, Lee, Byung-Wan, Lee, Gyun Min, Lee, Jongdae, Lee, Ju-Hyun, Lee, Michael, Lee, Myung-Shik, Lee, Sug Hyung, Leeuwenburgh, Christiaan, Legembre, Patrick, Legouis, Renaud, Lehmann, Michael, Lei, Huan-Yao, Lei, Qun-Ying, Leib, David A, Leiro, José, Lemasters, John J, Lemoine, Antoinette, Lesniak, Maciej S, Lev, Dina, Levenson, Victor V, Levine, Beth, Levy, Efrat, Li, Faqiang, Li, Jun-Lin, Li, Lian, Li, Sheng, Li, Weijie, Li, Xue-Jun, Li, Yan-Bo, Li, Yi-Ping, Liang, Chengyu, Liang, Qiangrong, Liao, Yung-Feng, Liberski, Pawel P, Lieberman, Andrew, Lim, Hyunjung J, Lim, Kah-Leong, Lim, Kyu, Lin, Chiou-Feng, Lin, Fu-Cheng, Lin, Jian, Lin, Jiandie D, Lin, Kui, Lin, Wan-Wan, Lin, Weei-Chin, Lin, Yi-Ling, Linden, Rafael, Lingor, Paul, Lippincott-Schwartz, Jennifer, Lisanti, Michael P, Liton, Paloma B, Liu, Bo, Liu, Chun-Feng, Liu, Kaiyu, Liu, Leyuan, Liu, Qiong A, Liu, Wei, Liu, Young-Chau, Liu, Yule, Lockshin, Richard A, Lok, Chun-Nam, Lonial, Sagar, Loos, Benjamin, Lopez-Berestein, Gabriel, López-Otín, Carlos, Lossi, Laura, Lotze, Michael T, Lőw, Peter, Lu, Binfeng, Lu, Bingwei, Lu, Bo, Lu, Zhen, Luciano, Frédéric, Lukacs, Nicholas W, Lund, Anders H, Lynch-Day, Melinda A, Ma, Yong, Macian, Fernando, Mackeigan, Jeff P, Macleod, Kay F, Madeo, Frank, Maiuri, Luigi, Maiuri, Maria Chiara, Malagoli, Davide, Malicdan, May Christine V, Malorni, Walter, Man, Na, Mandelkow, Eva-Maria, Manon, Stéphen, Manov, Irena, Mao, Kai, Mao, Xiang, Mao, Zixu, Marambaud, Philippe, Marazziti, Daniela, Marcel, Yves L, Marchbank, Katie, Marchetti, Piero, Marciniak, Stefan J, Marcondes, Mateus, Mardi, Mohsen, Marfe, Gabriella, Mariño, Guillermo, Markaki, Maria, Marten, Mark R, Martin, Seamus J, Martinand-Mari, Camille, Martinet, Wim, Martinez-Vicente, Marta, Masini, Matilde, Matarrese, Paola, Matsuo, Saburo, Matteoni, Raffaele, Mayer, Andreas, Mazure, Nathalie M, Mcconkey, David J, Mcconnell, Melanie J, Mcdermott, Catherine, Mcdonald, Christine, Mcinerney, Gerald M, Mckenna, Sharon L, Mclaughlin, Bethann, Mclean, Pamela J, Mcmaster, Christopher R, Mcquibban, G Angus, Meijer, Alfred J, Meisler, Miriam H, Meléndez, Alicia, Melia, Thomas J, Melino, Gerry, Mena, Maria A, Menendez, Javier A, Menna-Barreto, Rubem F S, Menon, Manoj B, Menzies, Fiona M, Mercer, Carol A, Merighi, Adalberto, Merry, Diane E, Meschini, Stefania, Meyer, Christian G, Meyer, Thomas F, Miao, Chao-Yu, Miao, Jun-Ying, 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Montpellier II - Sciences et techniques, Department of Cell Biology, Institute of Biomembranes, University Medical Center Utrecht ; Institute of Biomembranes, University Medical Center Utrecht, Service de dermatologie ; CHU Nice, Vieillissement, stress, inflammation ; Université Pierre et Marie Curie (UPMC) - Paris VI, University of Cambridge (UK) (CAM) ; University of Cambridge (UK), The Department of Chemical and Environmental Sciences ; University of Limerick, Fondazione IRCCS Istituto Nazionale dei Tumori ; Fondazione IRCCS Istituto Nazionale dei Tumori, Neurogenetics laboratory ; Neurogenetics laboratory, Department of Pathology ; Otto-von-Guericke University, Experimental Tumor Pathology ; University of Erlangen, Unit of Oculogenomics ; Institute for Research in Ophthalmology", Swiss Federal Institute of Technology ; University of Lausanne, Eye Hospital, Department of Ophthalmology, Jules-Gonin , ; Eye Hospital", Division of regenerative Medicine ; San Raffaele Scientific Institute, ICBM ; Faculty of Medicine - University of Chile, Department of pathology ; Harvard Medical School, Department of Endocrine and Oncology Surgery ; Royal North Shore Hospital, Department of Surgery, Bankstown Hospital and South Western Sydney Clinical School ; University of New South Wales, Medical Research Council Human Immunology Unit ; John Radcliffe Hospital - Weatherall Institute of Molecular Medicine, Department of Pharmacology and Molecular Sciences ; University of Bern, Université de Genève ; Université de Genève, Kimmel Cancer Center, and the Stem Cell Biology and Regenerative Medicine Center ; Thomas Jefferson University, Muscular and Neurodegenerative Disease Unit ; University of Genoa and G. Gaslini Pediatric Institute, Department of Clinical and Experimental Medicine ; Division of Cell Biology; and Linköping Diabetes Research Centre, Cancer Institute ; University College London, Department of Biochemistry and Biophysics ; University of California, San Francisco, Department of Experimental and Diagnostic Medicine and Interdisciplinary Center for Study of inflammation and ER-GenTech ; University of Ferrara, Laboratory of Molecular and Cellular Parasitology - Department of Microbiology ; Yong Loo Lin School of Medicine, National University of Singapore, Center of Microbial and Plant Genetics (CMPG) ; Katholieke Universiteit Leuven, Abramson Cancer Institute and Department of Cancer Biology ; University of Pennsylvania, Instituto de Microbiologia Paulo de Goes ; Universidade Federal do Rio de Janeiro, Immunité Innée et Signalisation ; Institut Pasteur de Paris, Istituto CSS Mendel ; Istituto CSS Mendel, Department of Medical and Surgical Pediatrics ; University Hospital, Messina, Department of Intensive care Medicine ; Katholieke Universiteit Leuven, Department of Cell Biology ; Vrije Universiteit Brussel, Department for Molecular Biomedical Research ; Department for Molecular Biomedical Research, Department of Pediatrics ; University of Padova, Department of Chemistry ; Peking University, Department of Mathematics ; Shanghai University, Sch Mat Sci & Engn ; Aucune, Institut de Recherche Interdisciplinaire (IRI) ; CNRS - Université Lille II - Droit et santé - Université Lille I - Sciences et technologies, Institut d'électronique, de microélectronique et de nanotechnologie (IEMN) ; CNRS - Institut supérieur de l'électronique et du nunérique (ISEN) - Université de Valenciennes et du Hainaut-Cambresis - Université Lille I - Sciences et technologies, Nankai University ; Nankai University, Division of Endocrinology and Diabetes ; University of Oklahoma Health Science Center, Department of Pharmacology and Cancer Biology ; Duke University, Modélisation, Information & Systèmes (MIS) ; Université de Picardie Jules Verne, Department of Experimental Oncology and Molecular Medicine ; Fondazione IRCCS Istituto Nazionale dei Tumori, Institute of Modern Physics ; Chinese Academy of Science (CAS), Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province ; ganzu Province, Institute of Computing Technology [Biejing] (ICT) ; Chinese Academy of Science (CAS), European Synchrotron Radiation Facility (ESRF) ; ESRF, Plant Physiology Laboratory ; Chinese Academy of Sciences - Botanical Institute of South china, Division of Biopharmaceutics ; Leiden University, The Institute of Environmental Medicine [Stockholm] (IMM) ; Karolinska Institutet, Institut de biochimie et biophysique moléculaire et cellulaire (IBBMC) ; CNRS - Université Paris XI - Paris Sud, Center for Brain Repair and Rehabilitation ; University of Gothenburg - Institute of Neuroscience and Physiology, department of genetics - Institute of biochemistry and biophysics ; institute of biochemistry an biophysics - polish academic of sciences, Departament de Bioquímica i Biologia Molecular ; Universitat de Barcelona - Facultat de Biologia - Institute for Research in Biomedicine - CIBERDEM, Chaperones Research Group ; Chaperones Research Group, Klionsky, Daniel J, Abdalla, Fabio C, Abeliovich, Hagai, Abraham, Robert T, Acevedo-Arozena, Abraham, Adeli, Khosrow, Agholme, Lotta, Agnello, Maria, Agostinis, Patrizia, Aguirre-Ghiso, Julio A, Ahn, Hyung Jun, Ait-Mohamed, Ouardia, Ait-Si-Ali, Slimane, Akematsu, Takahiko, Akira, Shizuo, Al-Younes, Hesham M, Al-Zeer, Munir A, Albert, Matthew L, Albin, Roger L, Alegre-Abarrategui, Javier, Aleo, Maria Francesca, Alirezaei, Mehrdad, Almasan, Alexandru, Almonte-Becerril, Maylin, Amano, Atsuo, Amaravadi, Ravi, Amarnath, Shoba, Amer, Amal O, Andrieu-Abadie, Nathalie, Anantharam, Vellareddy, Ann, David K, Anoopkumar-Dukie, Shailendra, Aoki, Hiroshi, Apostolova, Nadezda, Auberger, Patrick, Baba, Misuzu, Backues, Steven K, Baehrecke, Eric H, Bahr, Ben A, Bai, Xue-Yuan, Bailly, Yannick, Baiocchi, Robert, Baldini, Giulia, Balduini, Walter, Ballabio, Andrea, Bamber, Bruce A, Bampton, Edward T W, Bánhegyi, Gábor, Bartholomew, Clinton R, Bassham, Diane C, Bast, Robert C, Batoko, Henri, Bay, Boon-Huat, Beau, Isabelle, Béchet, Daniel M, Begley, Thomas J, Behl, Christian, Behrends, Christian, Bekri, Soumeya, Bellaire, Bryan, Bendall, Linda J, Benetti, Luca, Berliocchi, Laura, Bernardi, Henri, Bernassola, Francesca, Besteiro, Sébastien, Bhatia-Kissova, Ingrid, Bi, Xiaoning, Biard-Piechaczyk, Martine, Blum, Janice S, Boise, Lawrence H, Bonaldo, Paolo, Boone, David L, Bornhauser, Beat C, Bortoluci, Karina R, Bossis, Ioannis, Bost, Frédéric, Bourquin, Jean-Pierre, Boya, Patricia, Boyer-Guittaut, Michaël, Bozhkov, Peter V, Brady, Nathan R, Brancolini, Claudio, Brech, Andreas, Brenman, Jay E, Brennand, Ana, Bresnick, Emery H, Brest, Patrick, Bridges, Dave, Bristol, Molly L, Brookes, Paul S, Brown, Eric J, Brumell, John H, Brunetti-Pierri, Nicola, Brunk, Ulf T, Bulman, Dennis E, Bultman, Scott J, Bultynck, Geert, Burbulla, Lena F, Bursch, Wilfried, Butchar, Jonathan P, Buzgariu, Wanda, Bydlowski, Sergio P, Cadwell, Ken, Cahová, Monika, Cai, Dongsheng, Cai, Jiyang, Cai, Qian, Calabretta, Bruno, Calvo-Garrido, Javier, Camougrand, Nadine, Campanella, Michelangelo, Campos-Salinas, Jenny, Candi, Eleonora, Cao, Lizhi, Caplan, Allan B, Carding, Simon R, Cardoso, Sandra M, Carew, Jennifer S, Carlin, Cathleen R, Carmignac, Virginie, Carneiro, Leticia A M, Carra, Serena, Caruso, Rosario A, Casari, Giorgio, Casas, Caty, Castino, Roberta, Cebollero, Eduardo, Cecconi, Francesco, Celli, Jean, Chaachouay, Hassan, Chae, Han-Jung, Chai, Chee-Yin, Chan, David C, Chan, Edmond Y, Chang, Raymond Chuen-Chung, Che, Chi-Ming, Chen, Ching-Chow, Chen, Guang-Chao, Chen, Guo-Qiang, Chen, Min, Chen, Quan, Chen, Steve S-L, Chen, Wenli, Chen, Xi, Chen, Xiangmei, Chen, Xiequn, Chen, Ye-Guang, Chen, Yingyu, Chen, Yongqiang, Chen, Yu-Jen, Chen, Zhixiang, Cheng, Alan, Cheng, Christopher H K, Cheng, Yan, Cheong, Heesun, Cheong, Jae-Ho, Cherry, Sara, Chess-Williams, Russ, Cheung, Zelda H, Chevet, Eric, Chiang, Hui-Ling, Chiarelli, Roberto, Chiba, Tomoki, Chin, Lih-Shen, Chiou, Shih-Hwa, Chisari, Francis V, Cho, Chi Hin, Cho, Dong-Hyung, Choi, Augustine M K, Choi, Dooseok, Choi, Kyeong Sook, Choi, Mary E, Chouaib, Salem, Choubey, Divaker, Choubey, Vinay, Chu, Charleen T, Chuang, Tsung-Hsien, Chueh, Sheau-Huei, Chun, Taehoon, Chwae, Yong-Joon, Chye, Mee-Len, Ciarcia, Roberto, Ciriolo, Maria R, Clague, Michael J, Clark, Robert S B, Clarke, Peter G H, Clarke, Robert, Codogno, Patrice, Coller, Hilary A, Colombo, María I, Comincini, Sergio, Condello, Maria, Condorelli, Fabrizio, Cookson, Mark R, Coombs, Graham H, Coppens, Isabelle, Corbalan, Ramon, Cossart, Pascale, Costelli, Paola, Costes, Safia, Coto-Montes, Ana, Couve, Eduardo, Coxon, Fraser P, Cregg, James M, Crespo, José L, Cronjé, Marianne J, Cuervo, Ana Maria, Cullen, Joseph J, Czaja, Mark J, D'Amelio, Marcello, Darfeuille-Michaud, Arlette, Davids, Lester M, Davies, Faith E, De Felici, Massimo, De Groot, John F, De Haan, Cornelis A M, De Martino, Luisa, De Milito, Angelo, De Tata, Vincenzo, Debnath, Jayanta, Degterev, Alexei, Dehay, Benjamin, Delbridge, Lea M D, Demarchi, Francesca, Deng, Yi Zhen, Dengjel, Jörn, Dent, Paul, Denton, Donna, Deretic, Vojo, Desai, Shyamal D, Devenish, Rodney J, Di Gioacchino, Mario, Di Paolo, Gilbert, Di Pietro, Chiara, Díaz-Araya, Guillermo, Díaz-Laviada, Inés, Diaz-Meco, Maria T, Diaz-Nido, Javier, Dikic, Ivan, Dinesh-Kumar, Savithramma P, Ding, Wen-Xing, Distelhorst, Clark W, Diwan, Abhinav, Djavaheri-Mergny, Mojgan, Dokudovskaya, Svetlana, Dong, Zheng, Dorsey, Frank C, Dosenko, Victor, Dowling, James J, Doxsey, Stephen, Dreux, Marlène, Drew, Mark E, Duan, Qiuhong, Duchosal, Michel A, Duff, Karen, Dugail, Isabelle, Durbeej, Madeleine, Duszenko, Michael, Edelstein, Charles L, Edinger, Aimee L, Egea, Gustavo, Eichinger, Ludwig, Eissa, N Tony, Ekmekcioglu, Suhendan, El-Deiry, Wafik S, Elazar, Zvulun, Elgendy, Mohamed, Ellerby, Lisa M, Eng, Kai Er, Engelbrecht, Anna-Mart, Engelender, Simone, Erenpreisa, Jekaterina, Escalante, Ricardo, Esclatine, Audrey, Eskelinen, Eeva-Liisa, Espert, Lucile, Espina, Virginia, Fan, Huizhou, Fan, Jia, Fan, Qi-Wen, Fan, Zhen, Fang, Shengyun, Fang, Yongqi, Fanto, Manolis, Fanzani, Alessandro, Farkas, Thomas, Farré, Jean-Claude, Faure, Mathias, Fechheimer, Marcus, Feng, Carl G, Feng, Jian, Feng, Qili, Feng, Youji, Fésüs, László, Feuer, Ralph, Figueiredo-Pereira, Maria E, Fimia, Gian Maria, Fingar, Diane C, Finkbeiner, Steven, Finkel, Toren, Finley, Kim D, Fiorito, Filomena, Fisher, Edward A, Fisher, Paul B, Flajolet, Marc, Florez-Mcclure, Maria L, Florio, Salvatore, Fon, Edward A, Fornai, Francesco, Fortunato, Franco, Fotedar, Rati, Fowler, Daniel H, Fox, Howard S, Franco, Rodrigo, Frankel, Lisa B, Fransen, Marc, Fuentes, José M, Fueyo, Juan, Fujii, Jun, Fujisaki, Kozo, Fujita, Eriko, Fukuda, Mitsunori, Furukawa, Ruth H, Gaestel, Matthias, Gailly, Philippe, Gajewska, Malgorzata, Galliot, Brigitte, Galy, Vincent, Ganesh, Subramaniam, Ganetzky, Barry, Ganley, Ian G, Gao, Fen-Biao, Gao, George F, Gao, Jinming, Garcia, Lorena, Garcia-Manero, Guillermo, Garcia-Marcos, Mikel, Garmyn, Marjan, Gartel, Andrei L, Gatti, Evelina, Gautel, Mathias, Gawriluk, Thomas R, Gegg, Matthew E, Geng, Jiefei, Germain, Marc, Gestwicki, Jason E, Gewirtz, David A, Ghavami, Saeid, Ghosh, Pradipta, Giammarioli, Anna M, Giatromanolaki, Alexandra N, Gibson, Spencer B, Gilkerson, Robert W, Ginger, Michael L, Goncu, Ebru, Gongora, Céline, Gonzalez, Claudio D, Gonzalez, Ramon, González-Estévez, Cristina, González-Polo, Rosa Ana, Gonzalez-Rey, Elena, Gorbunov, Nikolai V, Gorski, Sharon, Goruppi, Sandro, Gottlieb, Roberta A, Gozuacik, Devrim, Granato, Giovanna Elvira, Grant, Gary D, Green, Kim N, Gregorc, Aleš, Gros, Frédéric, Grose, Charles, Grunt, Thomas W, Gual, Philippe, Guan, Jun-Lin, Guan, Kun-Liang, Guichard, Sylvie M, Gukovskaya, Anna S, Gukovsky, Ilya, Gunst, Jan, Gustafsson, Asa B, Halayko, Andrew J, Hale, Amber N, Halonen, Sandra K, Hamasaki, Maho, Han, Feng, Han, Ting, Hancock, Michael K, Hansen, Malene, Harada, Hisashi, Harada, Masaru, Hardt, Stefan E, Harper, J Wade, Harris, Adrian L, Harris, James, Harris, Steven D, Hébert, Marie-Joseé, Heidenreich, Kim A, Helfrich, Miep H, Helgason, Gudmundur V, Henske, Elizabeth P, Herman, Brian, Herman, Paul K, Hetz, Claudio, Hilfiker, Sabine, Hill, Joseph A, Hocking, Lynne J, Hofman, Paul, Hofmann, Thomas G, Höhfeld, Jörg, Holyoake, Tessa L, Hong, Ming-Huang, Hood, David A, Hotamisligil, Gökhan S, Houwerzijl, Ewout J, Høyer-Hansen, Maria, Hu, Bingren, Hu, Chien-An A, Hu, Hong-Ming, Hua, Ya, Huang, Canhua, Huang, Ju, Huang, Shengbing, Huang, Wei-Pang, Huber, Tobias B, Huh, Won-Ki, Hung, Tai-Ho, Hupp, Ted R, Hur, Gang Min, Hurley, James B, Hussain, Sabah N A, Hussey, Patrick J, Hwang, Jung Jin, Hwang, Seungmin, Ichihara, Atsuhiro, Ilkhanizadeh, Shirin, Inoki, Ken, Into, Takeshi, Iovane, Valentina, Iovanna, Juan L, Ip, Nancy Y, Isaka, Yoshitaka, Ishida, Hiroyuki, Isidoro, Ciro, Isobe, Ken-Ichi, Iwasaki, Akiko, Izquierdo, Marta, Izumi, Yotaro, Jaakkola, Panu M, Jäättelä, Marja, Jackson, George R, Jackson, William T, Janji, Bassam, Jendrach, Marina, Jeon, Ju-Hong, Jeung, Eui-Bae, Jiang, Hong, Jiang, Hongchi, Jiang, Jean X, Jiang, Ming, Jiang, Qing, Jiang, Xuejun, Jiménez, Alberto, Jin, Meiyan, Jin, Shengkan, Joe, Cheol O, Johansen, Terje, Johnson, Daniel E, Johnson, Gail V W, Jones, Nicola L, Joseph, Bertrand, Joseph, Suresh K, Joubert, Annie M, Juhász, Gábor, Juillerat-Jeanneret, Lucienne, Jung, Chang Hwa, Jung, Yong-Keun, Kaarniranta, Kai, Kaasik, Allen, Kabuta, Tomohiro, Kadowaki, Motoni, Kagedal, Katarina, Kamada, Yoshiaki, Kaminskyy, Vitaliy O, Kampinga, Harm H, Kanamori, Hiromitsu, Kang, Chanhee, Kang, Khong Bee, Kang, Kwang Il, Kang, Rui, Kang, Yoon-A, Kanki, Tomotake, Kanneganti, Thirumala-Devi, Kanno, Haruo, Kanthasamy, Anumantha G, Kanthasamy, Arthi, Karantza, Vassiliki, Kaushal, Gur P, Kaushik, Susmita, Kawazoe, Yoshinori, Ke, Po-Yuan, Kehrl, John H, Kelekar, Ameeta, Kerkhoff, Claus, Kessel, David H, Khalil, Hany, Kiel, Jan A K W, Kiger, Amy A, Kihara, Akio, Kim, Deok Ryong, Kim, Do-Hyung, Kim, Dong-Hou, Kim, Eun-Kyoung, Kim, Hyung-Ryong, Kim, Jae-Sung, Kim, Jeong Hun, Kim, Jin Cheon, Kim, John K, Kim, Peter K, Kim, Seong Who, Kim, Yong-Sun, Kim, Yonghyun, Kimchi, Adi, Kimmelman, Alec C, King, Jason S, Kinsella, Timothy J, Kirkin, Vladimir, Kirshenbaum, Lorrie A, Kitamoto, Katsuhiko, Kitazato, Kaio, Klein, Ludger, Klimecki, Walter T, Klucken, Jochen, Knecht, Erwin, Ko, Ben C B, Koch, Jan C, Koga, Hiroshi, Koh, Jae-Young, Koh, Young Ho, Koike, Masato, Komatsu, Masaaki, Kominami, Eiki, Kong, Hee Jeong, Kong, Wei-Jia, Korolchuk, Viktor I, Kotake, Yaichiro, Koukourakis, Michael I, Kouri Flores, Juan B, Kovács, Attila L, Kraft, Claudine, Krainc, Dimitri, Krämer, Helmut, Kretz-Remy, Carole, Krichevsky, Anna M, Kroemer, Guido, Krüger, Rejko, Krut, Oleg, Ktistakis, Nicholas T, Kuan, Chia-Yi, Kucharczyk, Roza, Kumar, Ashok, Kumar, Raj, Kumar, Sharad, Kundu, Mondira, Kung, Hsing-Jien, Kurz, Tino, Kwon, Ho Jeong, La Spada, Albert R, Lafont, Frank, Lamark, Trond, Landry, Jacques, Lane, Jon D, Lapaquette, Pierre, Laporte, Jocelyn F, László, Lajos, Lavandero, Sergio, Lavoie, Josée N, Layfield, Robert, Lazo, Pedro A, Le, Weidong, Le Cam, Laurent, Ledbetter, Daniel J, Lee, Alvin J X, Lee, Byung-Wan, Lee, Gyun Min, Lee, Jongdae, Lee, Ju-Hyun, Lee, Michael, Lee, Myung-Shik, Lee, Sug Hyung, Leeuwenburgh, Christiaan, Legembre, Patrick, Legouis, Renaud, Lehmann, Michael, Lei, Huan-Yao, Lei, Qun-Ying, Leib, David A, Leiro, José, Lemasters, John J, Lemoine, Antoinette, Lesniak, Maciej S, Lev, Dina, Levenson, Victor V, Levine, Beth, Levy, Efrat, Li, Faqiang, Li, Jun-Lin, Li, Lian, Li, Sheng, Li, Weijie, Li, Xue-Jun, Li, Yan-Bo, Li, Yi-Ping, Liang, Chengyu, Liang, Qiangrong, Liao, Yung-Feng, Liberski, Pawel P, Lieberman, Andrew, Lim, Hyunjung J, Lim, Kah-Leong, Lim, Kyu, Lin, Chiou-Feng, Lin, Fu-Cheng, Lin, Jian, Lin, Jiandie D, Lin, Kui, Lin, Wan-Wan, Lin, Weei-Chin, Lin, Yi-Ling, Linden, Rafael, Lingor, Paul, Lippincott-Schwartz, Jennifer, Lisanti, Michael P, Liton, Paloma B, Liu, Bo, Liu, Chun-Feng, Liu, Kaiyu, Liu, Leyuan, Liu, Qiong A, Liu, Wei, Liu, Young-Chau, Liu, Yule, Lockshin, Richard A, Lok, Chun-Nam, Lonial, Sagar, Loos, Benjamin, Lopez-Berestein, Gabriel, López-Otín, Carlos, Lossi, Laura, Lotze, Michael T, Lőw, Peter, Lu, Binfeng, Lu, Bingwei, Lu, Bo, Lu, Zhen, Luciano, Frédéric, Lukacs, Nicholas W, Lund, Anders H, Lynch-Day, Melinda A, Ma, Yong, Macian, Fernando, Mackeigan, Jeff P, Macleod, Kay F, Madeo, Frank, Maiuri, Luigi, Maiuri, Maria Chiara, Malagoli, Davide, Malicdan, May Christine V, Malorni, Walter, Man, Na, Mandelkow, Eva-Maria, Manon, Stéphen, Manov, Irena, Mao, Kai, Mao, Xiang, Mao, Zixu, Marambaud, Philippe, Marazziti, Daniela, Marcel, Yves L, Marchbank, Katie, Marchetti, Piero, Marciniak, Stefan J, Marcondes, Mateus, Mardi, Mohsen, Marfe, Gabriella, Mariño, Guillermo, Markaki, Maria, Marten, Mark R, Martin, Seamus J, Martinand-Mari, Camille, Martinet, Wim, Martinez-Vicente, Marta, Masini, Matilde, Matarrese, Paola, Matsuo, Saburo, Matteoni, Raffaele, Mayer, Andreas, Mazure, Nathalie M, Mcconkey, David J, Mcconnell, Melanie J, Mcdermott, Catherine, Mcdonald, Christine, Mcinerney, Gerald M, Mckenna, Sharon L, Mclaughlin, Bethann, Mclean, Pamela J, Mcmaster, Christopher R, Mcquibban, G Angus, Meijer, Alfred J, Meisler, Miriam H, Meléndez, Alicia, Melia, Thomas J, Melino, Gerry, Mena, Maria A, Menendez, Javier A, Menna-Barreto, Rubem F S, Menon, Manoj B, Menzies, Fiona M, Mercer, Carol A, Merighi, Adalberto, Merry, Diane E, Meschini, Stefania, Meyer, Christian G, Meyer, Thomas F, Miao, Chao-Yu, Miao, Jun-Ying, Michels, Paul A M, Michiels, Carine, Mijaljica, Dalibor, Milojkovic, Ana, Minucci, Saverio, Miracco, Clelia, Miranti, Cindy K, Mitroulis, Ioannis, Miyazawa, Keisuke, Mizushima, Noboru, Mograbi, Baharia, Mohseni, Simin, Molero, Xavier, Mollereau, Bertrand, Mollinedo, Faustino, Momoi, Takashi, Monastyrska, Iryna, Monick, Martha M, Monteiro, Mervyn J, Moore, Michael N, Mora, Rodrigo, Moreau, Kevin, Moreira, Paula I, Moriyasu, Yuji, Moscat, Jorge, Mostowy, Serge, Mottram, Jeremy C, Motyl, Tomasz, Moussa, Charbel E-H, Müller, Sylke, Muller, Sylviane, Münger, Karl, Münz, Christian, Murphy, Leon O, Murphy, Maureen E, Musarò, Antonio, Mysorekar, Indira, Nagata, Eiichiro, Nagata, Kazuhiro, Nahimana, Aimable, Nair, Usha, Nakagawa, Toshiyuki, Nakahira, Kiichi, Nakano, Hiroyasu, Nakatogawa, Hitoshi, Nanjundan, Meera, Naqvi, Naweed I, Narendra, Derek P, Narita, Masashi, Navarro, Miguel, Nawrocki, Steffan T, Nazarko, Taras Y, Nemchenko, Andriy, Netea, Mihai G, Neufeld, Thomas P, Ney, Paul A, Nezis, Ioannis P, Nguyen, Huu Phuc, Nie, Daotai, Nishino, Ichizo, Nislow, Corey, Nixon, Ralph A, Noda, Takeshi, Noegel, Angelika A, Nogalska, Anna, Noguchi, Satoru, Notterpek, Lucia, Novak, Ivana, Nozaki, Tomoyoshi, Nukina, Nobuyuki, Nürnberger, Thorsten, Nyfeler, Beat, Obara, Keisuke, Oberley, Terry D, Oddo, Salvatore, Ogawa, Michinaga, Ohashi, Toya, Okamoto, Koji, Oleinick, Nancy L, Oliver, F Javier, Olsen, Laura J, Olsson, Stefan, Opota, Onya, Osborne, Timothy F, Ostrander, Gary K, Otsu, Kinya, Ou, Jing-Hsiung James, Ouimet, Mireille, Overholtzer, Michael, Ozpolat, Bulent, Paganetti, Paolo, Pagnini, Ugo, Pallet, Nicolas, Palmer, Glen E, Palumbo, Camilla, Pan, Tianhong, Panaretakis, Theocharis, Pandey, Udai Bhan, Papackova, Zuzana, Papassideri, Issidora, Paris, Irmgard, Park, Junsoo, Park, Ohkmae K, Parys, Jan B, Parzych, Katherine R, Patschan, Susann, Patterson, Cam, Pattingre, Sophie, Pawelek, John M, Peng, Jianxin, Perlmutter, David H, Perrotta, Ida, Perry, George, Pervaiz, Shazib, Peter, Matthias, Peters, Godefridus J, Petersen, Morten, Petrovski, Goran, Phang, James M, Piacentini, Mauro, Pierre, Philippe, Pierrefite-Carle, Valérie, Pierron, Gérard, Pinkas-Kramarski, Ronit, Piras, Antonio, Piri, Natik, Platanias, Leonidas C, Pöggeler, Stefanie, Poirot, Marc, Poletti, Angelo, Poüs, Christian, Pozuelo-Rubio, Mercedes, Prætorius-Ibba, Mette, Prasad, Anil, Prescott, Mark, Priault, Muriel, Produit-Zengaffinen, Nathalie, Progulske-Fox, Ann, Proikas-Cezanne, Tassula, Przedborski, Serge, Przyklenk, Karin, Puertollano, Rosa, Puyal, Julien, Qian, Shu-Bing, Qin, Liang, Qin, Zheng-Hong, Quaggin, Susan E, Raben, Nina, Rabinowich, Hannah, Rabkin, Simon W, Rahman, Irfan, Rami, Abdelhaq, Ramm, Georg, Randall, Glenn, Randow, Felix, Rao, V Ashutosh, Rathmell, Jeffrey C, Ravikumar, Brinda, Ray, Swapan K, Reed, Bruce H, Reed, John C, Reggiori, Fulvio, Régnier-Vigouroux, Anne, Reichert, Andreas S, Reiners, John J, Reiter, Russel J, Ren, Jun, Revuelta, José L, Rhodes, Christopher J, Ritis, Konstantinos, Rizzo, Elizete, Robbins, Jeffrey, Roberge, Michel, Roca, Hernan, Roccheri, Maria C, Rocchi, Stephane, Rodemann, H Peter, Rodríguez De Córdoba, Santiago, Rohrer, Bärbel, Roninson, Igor B, Rosen, Kirill, Rost-Roszkowska, Magdalena M, Rouis, Mustapha, Rouschop, Kasper M A, Rovetta, Francesca, Rubin, Brian P, Rubinsztein, David C, Ruckdeschel, Klaus, Rucker, Edmund B, Rudich, Assaf, Rudolf, Emil, Ruiz-Opazo, Nelson, Russo, Rossella, Rusten, Tor Erik, Ryan, Kevin M, Ryter, Stefan W, Sabatini, David M, Sadoshima, Junichi, Saha, Tapas, Saitoh, Tatsuya, Sakagami, Hiroshi, Sakai, Yasuyoshi, Salekdeh, Ghasem Hoseini, Salomoni, Paolo, Salvaterra, Paul M, Salvesen, Guy, Salvioli, Rosa, Sanchez, Anthony M J, Sánchez-Alcázar, José A, Sánchez-Prieto, Ricardo, Sandri, Marco, Sankar, Uma, Sansanwal, Poonam, Santambrogio, Laura, Saran, Shweta, Sarkar, Sovan, Sarwal, Minnie, Sasakawa, Chihiro, Sasnauskiene, Ausra, Sass, Miklós, Sato, Ken, Sato, Miyuki, Schapira, Anthony H V, Scharl, Michael, Schätzl, Hermann M, Scheper, Wiep, Schiaffino, Stefano, Schneider, Claudio, Schneider, Marion E, Schneider-Stock, Regine, Schoenlein, Patricia V, Schorderet, Daniel F, Schüller, Christoph, Schwartz, Gary K, Scorrano, Luca, Sealy, Linda, Seglen, Per O, Segura-Aguilar, Juan, Seiliez, Iban, Seleverstov, Oleksandr, Sell, Christian, Seo, Jong Bok, Separovic, Duska, Setaluri, Vijayasaradhi, Setoguchi, Takao, Settembre, Carmine, Shacka, John J, Shanmugam, Mala, Shapiro, Irving M, Shaulian, Eitan, Shaw, Reuben J, Shelhamer, James H, Shen, Han-Ming, Shen, Wei-Chiang, Sheng, Zu-Hang, Shi, Yang, Shibuya, Kenichi, Shidoji, Yoshihiro, Shieh, Jeng-Jer, Shih, Chwen-Ming, Shimada, Yohta, Shimizu, Shigeomi, Shintani, Takahiro, Shirihai, Orian S, Shore, Gordon C, Sibirny, Andriy A, Sidhu, Stan B, Sikorska, Beata, Silva-Zacarin, Elaine C M, Simmons, Alison, Simon, Anna Katharina, Simon, Hans-Uwe, Simone, Cristiano, Simonsen, Anne, Sinclair, David A, Singh, Rajat, Sinha, Debasish, Sinicrope, Frank A, Sirko, Agnieszka, Siu, Parco M, Sivridis, Efthimios, Skop, Vojtech, Skulachev, Vladimir P, Slack, Ruth S, Smaili, Soraya S, Smith, Duncan R, Soengas, Maria S, Soldati, Thierry, Song, Xueqin, Sood, Anil K, Soong, Tuck Wah, Sotgia, Federica, Spector, Stephen A, Spies, Claudia D, Springer, Wolfdieter, Srinivasula, Srinivasa M, Stefanis, Leonidas, Steffan, Joan S, Stendel, Ruediger, Stenmark, Harald, Stephanou, Anastasis, Stern, Stephan T, Sternberg, Cinthya, Stork, Björn, Strålfors, Peter, Subauste, Carlos S, Sui, Xinbing, Sulzer, David, Sun, Jiaren, Sun, Shi-Yong, Sun, Zhi-Jun, Sung, Joseph J Y, Suzuki, Kuninori, Suzuki, Toshihiko, Swanson, Michele S, Swanton, Charles, Sweeney, Sean T, Sy, Lai-King, Szabadkai, Gyorgy, Tabas, Ira, Taegtmeyer, Heinrich, Tafani, Marco, Takács-Vellai, Krisztina, Takano, Yoshitaka, Takegawa, Kaoru, Takemura, Genzou, Takeshita, Fumihiko, Talbot, Nicholas J, Tan, Kevin S W, Tanaka, Keiji, Tanaka, Kozo, Tang, Daolin, Tang, Dingzhong, Tanida, Isei, Tannous, Bakhos A, Tavernarakis, Nektarios, Taylor, Graham S, Taylor, Gregory A, Taylor, J Paul, Terada, Lance S, Terman, Alexei, Tettamanti, Gianluca, Thevissen, Karin, Thompson, Craig B, Thorburn, Andrew, Thumm, Michael, Tian, Fengfeng, Tian, Yuan, Tocchini-Valentini, Glauco, Tolkovsky, Aviva M, Tomino, Yasuhiko, Tönges, Lars, Tooze, Sharon A, Tournier, Cathy, Tower, John, Towns, Roberto, Trajkovic, Vladimir, Travassos, Leonardo H, Tsai, Ting-Fen, Tschan, Mario P, Tsubata, Takeshi, Tsung, Allan, Turk, Boris, Turner, Lorianne S, Tyagi, Suresh C, Uchiyama, Yasuo, Ueno, Takashi, Umekawa, Midori, Umemiya-Shirafuji, Rika, Unni, Vivek K, Vaccaro, Maria I, Valente, Enza Maria, Van Den Berghe, Greet, Van Der Klei, Ida J, Van Doorn, Wouter, Van Dyk, Linda F, Van Egmond, Marjolein, Van Grunsven, Leo A, Vandenabeele, Peter, Vandenberghe, Wim P, Vanhorebeek, Ilse, Vaquero, Eva C, Velasco, Guillermo, Vellai, Tibor, Vicencio, Jose Miguel, Vierstra, Richard D, Vila, 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Abstract: International audience, In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused o

7. Guidelines for the use and interpretation of assays for monitoring autophagy.

Author: Molecular and Cellular Biology ; University of Leuven, Laboratoire d'Epigénétique et Cancer ; CNRS - Université Paris XI - Paris Sud, Department of Pharmacology ; Department of Pharmacology, Immunobiologie des Cellules Dendritiques ; INSERM - Institut Pasteur de Paris, Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (FEMTO-ST) ; CNRS - Université de Franche-Comté - Université de Technologie de Belfort-Montbeliard - Ecole Nationale Supérieure de Mécanique et des Microtechniques, Telethon Institute for Genetics and Medicine ; Telethon Institute, Medical Genetics ; Federico II University, Department of Molecular and Human Genetics ; Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute ; Texas Children's Hospital, Signalisation et physiopathologie des cellules épithéliales ; INSERM - Université Paris XI - Paris Sud, Dynamique des interactions membranaires normales et pathologiques (DIMNP) ; CNRS - Université Montpellier I - Université Montpellier II - Sciences et techniques, Institut de biochimie et génétique cellulaires (IBGC) ; CNRS - Université Victor Segalen - Bordeaux II, Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS) ; CNRS - Université Montpellier I - Université Montpellier II - Sciences et techniques, Celullar and Molecular Medicine ; Celullar and Molecular Medicine, Estrogène, Expression génique et pathologies du Système Nerveux Central (E2SNC) ; Université de Franche-Comté - IFR133, Infection bactérienne, inflammation, et carcinogenèse digestive ; INSERM - IFR50 - Université Nice Sophia Antipolis (UNS), Université Nice Sophia Antipolis (UNS) ; Université Nice Sophia Antipolis (UNS) - PRES Euro-Méditerranéen, Department of Computer Science [Tsukuba] ; University of Tsukuba, Gunma University ; Institute for Molecular & Cellular Regulation, Cell Biology, Physiology and Immunology ; Cell Biology, Physiology and Immunology, Dulbecco Telethon Institute/Department of Biology ; Dulbecco Telethon Institute/Department of Biology, Department of Chemistry and HKU-CAS Joint Laboratory ; 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University of Brescia, Immunité infection vaccination ; INSERM - Université Claude Bernard - Lyon I (UCBL) - IFR128, Dept of City and Regional Planning ; Peiking University, Montreal Neurological Institute ; McGill University, Department of Developmental Biology and Neurosciences ; Tohoku University - Graduate School of Life Sciences, Biologie Cellulaire du Noyau (BCN) ; CNRS - Institut Pasteur de Paris, Faculty of Medicine ; University of Ottawa, Institut de recherche en cancérologie de Montpellier (IRCM) ; INSERM - CRLCC Val d'Aurelle - Paul Lamarque - Université Montpellier I, Immunologie et chimie thérapeutiques (ICT) ; CNRS - Cancéropôle du Grand Est, Université de Strasbourg (UNISTRA) ; Université de Strasbourg, Département Digestif ; CHU Nice - Hôpital de l'Archet, Centre méditérannéen de médecine moléculaire (C3M) ; INSERM - Université Nice Sophia Antipolis (UNS), National Institute of Advanced Industrial Science and Technology [Tsukuba] (AIST) ; National Institute for Advanced Industrial Science and Technology - AIST (JAPAN), Department of Oncology ; John Radcliffe Hospital, School of Biochemistry and Immunology ; School of Biochemistry and Immunology, Department of Cellular and Structural Biology, University of Texas Health Science Center ; University of Texas, Laboratoire de Pathologie Clinique et Expérimentale ; CHU Nice, Department of Biochemistry ; University of Hong Kong, Danish Cancer Society ; Institute of Cancer Biology, Institut de biologie et chimie des protéines [Lyon] (IBCP) ; CNRS - Université Claude Bernard - Lyon I (UCBL), Department of Gastroenterology, Hepatology and Endocrinology (MHH) ; Hannover medical school, Cancer Research UK London Research Institute ; Cancer Research UK London Research Institute, Cell Biology, section Radiation & Stress Cell Biology ; UMCG, Univ. of Groningen, Department of Molecular Genetics ; Weizmann Institute of Science, Institute of Immunology ; University Hospital Schleswig-Holstein, Institute for Immunology ; Institute for Immunology, Department of Neuroscience ; University of Texas Southwestern Medical Center at Dallas, Centre de génétique et de physiologie moléculaire et cellulaire (CGphiMC) ; CNRS - Université Claude Bernard - Lyon I (UCBL), Centre de Recherche des Cordeliers ; INSERM - Université Paris V - Paris Descartes - Université Pierre et Marie Curie (UPMC) - Paris VI, Apoptose, cancer et immunité ; INSERM - Institut Gustave Roussy - Université Paris XI - Paris Sud, metabolomics platform ; Institut Gustave Roussy, Pôle de biologie ; Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital européen Georges Pompidou, Université Paris Descartes - Faculté de Médecine (UP5) ; Université Paris V - Paris Descartes - PRES Sorbonne Paris Cité, Department of Molecular Neuroscience ; Department of Molecular Neuroscience, European Organization for Nuclear Research (CERN) ; CERN, Center for Visual Information Technology (CVIT) ; International Institute of Information Technology, Massachusetts Institute of technology [Cambridge] (MIT) ; Massachusetts Institute of Technology (MIT), Department of Biochemistry and Molecular Biology ; University of Washington, Centre for Cancer Biology ; 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biophysics ; institute of biochemistry an biophysics - polish academic of sciences, Departament de Bioquímica i Biologia Molecular ; Universitat de Barcelona - Facultat de Biologia - Institute for Research in Biomedicine - CIBERDEM, Chaperones Research Group ; Chaperones Research Group, Klionsky, Daniel J, Abdalla, Fabio C, Abeliovich, Hagai, Abraham, Robert T, Acevedo-Arozena, Abraham, Adeli, Khosrow, Agholme, Lotta, Agnello, Maria, Agostinis, Patrizia, Aguirre-Ghiso, Julio A, Ahn, Hyung Jun, Ait-Mohamed, Ouardia, Ait-Si-Ali, Slimane, Akematsu, Takahiko, Akira, Shizuo, Al-Younes, Hesham M, Al-Zeer, Munir A, Albert, Matthew L, Albin, Roger L, Alegre-Abarrategui, Javier, Aleo, Maria Francesca, Alirezaei, Mehrdad, Almasan, Alexandru, Almonte-Becerril, Maylin, Amano, Atsuo, Amaravadi, Ravi, Amarnath, Shoba, Amer, Amal O, Andrieu-Abadie, Nathalie, Anantharam, Vellareddy, Ann, David K, Anoopkumar-Dukie, Shailendra, Aoki, Hiroshi, Apostolova, Nadezda, Auberger, Patrick, Baba, Misuzu, Backues, Steven K, Baehrecke, Eric H, Bahr, Ben A, Bai, Xue-Yuan, Bailly, Yannick, Baiocchi, Robert, Baldini, Giulia, Balduini, Walter, Ballabio, Andrea, Bamber, Bruce A, Bampton, Edward T W, Bánhegyi, Gábor, Bartholomew, Clinton R, Bassham, Diane C, Bast, Robert C, Batoko, Henri, Bay, Boon-Huat, Beau, Isabelle, Béchet, Daniel M, Begley, Thomas J, Behl, Christian, Behrends, Christian, Bekri, Soumeya, Bellaire, Bryan, Bendall, Linda J, Benetti, Luca, Berliocchi, Laura, Bernardi, Henri, Bernassola, Francesca, Besteiro, Sébastien, Bhatia-Kissova, Ingrid, Bi, Xiaoning, Biard-Piechaczyk, Martine, Blum, Janice S, Boise, Lawrence H, Bonaldo, Paolo, Boone, David L, Bornhauser, Beat C, Bortoluci, Karina R, Bossis, Ioannis, Bost, Frédéric, Bourquin, Jean-Pierre, Boya, Patricia, Boyer-Guittaut, Michaël, Bozhkov, Peter V, Brady, Nathan R, Brancolini, Claudio, Brech, Andreas, Brenman, Jay E, Brennand, Ana, Bresnick, Emery H, Brest, Patrick, Bridges, Dave, Bristol, Molly L, Brookes, Paul S, Brown, Eric J, Brumell, John H, Brunetti-Pierri, Nicola, Brunk, Ulf T, Bulman, Dennis E, Bultman, Scott J, Bultynck, Geert, Burbulla, Lena F, Bursch, Wilfried, Butchar, Jonathan P, Buzgariu, Wanda, Bydlowski, Sergio P, Cadwell, Ken, Cahová, Monika, Cai, Dongsheng, Cai, Jiyang, Cai, Qian, Calabretta, Bruno, Calvo-Garrido, Javier, Camougrand, Nadine, Campanella, Michelangelo, Campos-Salinas, Jenny, Candi, Eleonora, Cao, Lizhi, Caplan, Allan B, Carding, Simon R, Cardoso, Sandra M, Carew, Jennifer S, Carlin, Cathleen R, Carmignac, Virginie, Carneiro, Leticia A M, Carra, Serena, Caruso, Rosario A, Casari, Giorgio, Casas, Caty, Castino, Roberta, Cebollero, Eduardo, Cecconi, Francesco, Celli, Jean, Chaachouay, Hassan, Chae, Han-Jung, Chai, Chee-Yin, Chan, David C, Chan, Edmond Y, Chang, Raymond Chuen-Chung, Che, Chi-Ming, Chen, Ching-Chow, Chen, Guang-Chao, Chen, Guo-Qiang, Chen, Min, Chen, Quan, Chen, Steve S-L, Chen, Wenli, Chen, Xi, Chen, Xiangmei, Chen, Xiequn, Chen, Ye-Guang, Chen, Yingyu, Chen, Yongqiang, Chen, Yu-Jen, Chen, Zhixiang, Cheng, Alan, Cheng, Christopher H K, Cheng, Yan, Cheong, Heesun, Cheong, Jae-Ho, Cherry, Sara, Chess-Williams, Russ, Cheung, Zelda H, Chevet, Eric, Chiang, Hui-Ling, Chiarelli, Roberto, Chiba, Tomoki, Chin, Lih-Shen, Chiou, Shih-Hwa, Chisari, Francis V, Cho, Chi Hin, Cho, Dong-Hyung, Choi, Augustine M K, Choi, Dooseok, Choi, Kyeong Sook, Choi, Mary E, Chouaib, Salem, Choubey, Divaker, Choubey, Vinay, Chu, Charleen T, Chuang, Tsung-Hsien, Chueh, Sheau-Huei, Chun, Taehoon, Chwae, Yong-Joon, Chye, Mee-Len, Ciarcia, Roberto, Ciriolo, Maria R, Clague, Michael J, Clark, Robert S B, Clarke, Peter G H, Clarke, Robert, Codogno, Patrice, Coller, Hilary A, Colombo, María I, Comincini, Sergio, Condello, Maria, Condorelli, Fabrizio, Cookson, Mark R, Coombs, Graham H, Coppens, Isabelle, Corbalan, Ramon, Cossart, Pascale, Costelli, Paola, Costes, Safia, Coto-Montes, Ana, Couve, Eduardo, Coxon, Fraser P, Cregg, James M, Crespo, José L, Cronjé, Marianne J, Cuervo, Ana Maria, Cullen, Joseph J, Czaja, Mark J, D'Amelio, Marcello, Darfeuille-Michaud, Arlette, Davids, Lester M, Davies, Faith E, De Felici, Massimo, De Groot, John F, De Haan, Cornelis A M, De Martino, Luisa, De Milito, Angelo, De Tata, Vincenzo, Debnath, Jayanta, Degterev, Alexei, Dehay, Benjamin, Delbridge, Lea M D, Demarchi, Francesca, Deng, Yi Zhen, Dengjel, Jörn, Dent, Paul, Denton, Donna, Deretic, Vojo, Desai, Shyamal D, Devenish, Rodney J, Di Gioacchino, Mario, Di Paolo, Gilbert, Di Pietro, Chiara, Díaz-Araya, Guillermo, Díaz-Laviada, Inés, Diaz-Meco, Maria T, Diaz-Nido, Javier, Dikic, Ivan, Dinesh-Kumar, Savithramma P, Ding, Wen-Xing, Distelhorst, Clark W, Diwan, Abhinav, Djavaheri-Mergny, Mojgan, Dokudovskaya, Svetlana, Dong, Zheng, Dorsey, Frank C, Dosenko, Victor, Dowling, James J, Doxsey, Stephen, Dreux, Marlène, Drew, Mark E, Duan, Qiuhong, Duchosal, Michel A, Duff, Karen, Dugail, Isabelle, Durbeej, Madeleine, Duszenko, Michael, Edelstein, Charles L, Edinger, Aimee L, Egea, Gustavo, Eichinger, Ludwig, Eissa, N Tony, Ekmekcioglu, Suhendan, El-Deiry, Wafik S, Elazar, Zvulun, Elgendy, Mohamed, Ellerby, Lisa M, Eng, Kai Er, Engelbrecht, Anna-Mart, Engelender, Simone, Erenpreisa, Jekaterina, Escalante, Ricardo, Esclatine, Audrey, Eskelinen, Eeva-Liisa, Espert, Lucile, Espina, Virginia, Fan, Huizhou, Fan, Jia, Fan, Qi-Wen, Fan, Zhen, Fang, Shengyun, Fang, Yongqi, Fanto, Manolis, Fanzani, Alessandro, Farkas, Thomas, Farré, Jean-Claude, Faure, Mathias, Fechheimer, Marcus, Feng, Carl G, Feng, Jian, Feng, Qili, Feng, Youji, Fésüs, László, Feuer, Ralph, Figueiredo-Pereira, Maria E, Fimia, Gian Maria, Fingar, Diane C, Finkbeiner, Steven, Finkel, Toren, Finley, Kim D, Fiorito, Filomena, Fisher, Edward A, Fisher, Paul B, Flajolet, Marc, Florez-Mcclure, Maria L, Florio, Salvatore, Fon, Edward A, Fornai, Francesco, Fortunato, Franco, Fotedar, Rati, Fowler, Daniel H, Fox, Howard S, Franco, Rodrigo, Frankel, Lisa B, Fransen, Marc, Fuentes, José M, Fueyo, Juan, Fujii, Jun, Fujisaki, Kozo, Fujita, Eriko, Fukuda, Mitsunori, Furukawa, Ruth H, Gaestel, Matthias, Gailly, Philippe, Gajewska, Malgorzata, Galliot, Brigitte, Galy, Vincent, Ganesh, Subramaniam, Ganetzky, Barry, Ganley, Ian G, Gao, Fen-Biao, Gao, George F, Gao, Jinming, Garcia, Lorena, Garcia-Manero, Guillermo, Garcia-Marcos, Mikel, Garmyn, Marjan, Gartel, Andrei L, Gatti, Evelina, Gautel, Mathias, Gawriluk, Thomas R, Gegg, Matthew E, Geng, Jiefei, Germain, Marc, Gestwicki, Jason E, Gewirtz, David A, Ghavami, Saeid, Ghosh, Pradipta, Giammarioli, Anna M, Giatromanolaki, Alexandra N, Gibson, Spencer B, Gilkerson, Robert W, Ginger, Michael L, Goncu, Ebru, Gongora, Céline, Gonzalez, Claudio D, Gonzalez, Ramon, González-Estévez, Cristina, González-Polo, Rosa Ana, Gonzalez-Rey, Elena, Gorbunov, Nikolai V, Gorski, Sharon, Goruppi, Sandro, Gottlieb, Roberta A, Gozuacik, Devrim, Granato, Giovanna Elvira, Grant, Gary D, Green, Kim N, Gregorc, Aleš, Gros, Frédéric, Grose, Charles, Grunt, Thomas W, Gual, Philippe, Guan, Jun-Lin, Guan, Kun-Liang, Guichard, Sylvie M, Gukovskaya, Anna S, Gukovsky, Ilya, Gunst, Jan, Gustafsson, Asa B, Halayko, Andrew J, Hale, Amber N, Halonen, Sandra K, Hamasaki, Maho, Han, Feng, Han, Ting, Hancock, Michael K, Hansen, Malene, Harada, Hisashi, Harada, Masaru, Hardt, Stefan E, Harper, J Wade, Harris, Adrian L, Harris, James, Harris, Steven D, Hébert, Marie-Joseé, Heidenreich, Kim A, Helfrich, Miep H, Helgason, Gudmundur V, Henske, Elizabeth P, Herman, Brian, Herman, Paul K, Hetz, Claudio, Hilfiker, Sabine, Hill, Joseph A, Hocking, Lynne J, Hofman, Paul, Hofmann, Thomas G, Höhfeld, Jörg, Holyoake, Tessa L, Hong, Ming-Huang, Hood, David A, Hotamisligil, Gökhan S, Houwerzijl, Ewout J, Høyer-Hansen, Maria, Hu, Bingren, Hu, Chien-An A, Hu, Hong-Ming, Hua, Ya, Huang, Canhua, Huang, Ju, Huang, Shengbing, Huang, Wei-Pang, Huber, Tobias B, Huh, Won-Ki, Hung, Tai-Ho, Hupp, Ted R, Hur, Gang Min, Hurley, James B, Hussain, Sabah N A, Hussey, Patrick J, Hwang, Jung Jin, Hwang, Seungmin, Ichihara, Atsuhiro, Ilkhanizadeh, Shirin, Inoki, Ken, Into, Takeshi, Iovane, Valentina, Iovanna, Juan L, Ip, Nancy Y, Isaka, Yoshitaka, Ishida, Hiroyuki, Isidoro, Ciro, Isobe, Ken-Ichi, Iwasaki, Akiko, Izquierdo, Marta, Izumi, Yotaro, Jaakkola, Panu M, Jäättelä, Marja, Jackson, George R, Jackson, William T, Janji, Bassam, Jendrach, Marina, Jeon, Ju-Hong, Jeung, Eui-Bae, Jiang, Hong, Jiang, Hongchi, Jiang, Jean X, Jiang, Ming, Jiang, Qing, Jiang, Xuejun, Jiménez, Alberto, Jin, Meiyan, Jin, Shengkan, Joe, Cheol O, Johansen, Terje, Johnson, Daniel E, Johnson, Gail V W, Jones, Nicola L, Joseph, Bertrand, Joseph, Suresh K, Joubert, Annie M, Juhász, Gábor, Juillerat-Jeanneret, Lucienne, Jung, Chang Hwa, Jung, Yong-Keun, Kaarniranta, Kai, Kaasik, Allen, Kabuta, Tomohiro, Kadowaki, Motoni, Kagedal, Katarina, Kamada, Yoshiaki, Kaminskyy, Vitaliy O, Kampinga, Harm H, Kanamori, Hiromitsu, Kang, Chanhee, Kang, Khong Bee, Kang, Kwang Il, Kang, Rui, Kang, Yoon-A, Kanki, Tomotake, Kanneganti, Thirumala-Devi, Kanno, Haruo, Kanthasamy, Anumantha G, Kanthasamy, Arthi, Karantza, Vassiliki, Kaushal, Gur P, Kaushik, Susmita, Kawazoe, Yoshinori, Ke, Po-Yuan, Kehrl, John H, Kelekar, Ameeta, Kerkhoff, Claus, Kessel, David H, Khalil, Hany, Kiel, Jan A K W, Kiger, Amy A, Kihara, Akio, Kim, Deok Ryong, Kim, Do-Hyung, Kim, Dong-Hou, Kim, Eun-Kyoung, Kim, Hyung-Ryong, Kim, Jae-Sung, Kim, Jeong Hun, Kim, Jin Cheon, Kim, John K, Kim, Peter K, Kim, Seong Who, Kim, Yong-Sun, Kim, Yonghyun, Kimchi, Adi, Kimmelman, Alec C, King, Jason S, Kinsella, Timothy J, Kirkin, Vladimir, Kirshenbaum, Lorrie A, Kitamoto, Katsuhiko, Kitazato, Kaio, Klein, Ludger, Klimecki, Walter T, Klucken, Jochen, Knecht, Erwin, Ko, Ben C B, Koch, Jan C, Koga, Hiroshi, Koh, Jae-Young, Koh, Young Ho, Koike, Masato, Komatsu, Masaaki, Kominami, Eiki, Kong, Hee Jeong, Kong, Wei-Jia, Korolchuk, Viktor I, Kotake, Yaichiro, Koukourakis, Michael I, Kouri Flores, Juan B, Kovács, Attila L, Kraft, Claudine, Krainc, Dimitri, Krämer, Helmut, Kretz-Remy, Carole, Krichevsky, Anna M, Kroemer, Guido, Krüger, Rejko, Krut, Oleg, Ktistakis, Nicholas T, Kuan, Chia-Yi, Kucharczyk, Roza, Kumar, Ashok, Kumar, Raj, Kumar, Sharad, Kundu, Mondira, Kung, Hsing-Jien, Kurz, Tino, Kwon, Ho Jeong, La Spada, Albert R, Lafont, Frank, Lamark, Trond, Landry, Jacques, Lane, Jon D, Lapaquette, Pierre, Laporte, Jocelyn F, László, Lajos, Lavandero, Sergio, Lavoie, Josée N, Layfield, Robert, Lazo, Pedro A, Le, Weidong, Le Cam, Laurent, Ledbetter, Daniel J, Lee, Alvin J X, Lee, Byung-Wan, Lee, Gyun Min, Lee, Jongdae, Lee, Ju-Hyun, Lee, Michael, Lee, Myung-Shik, Lee, Sug Hyung, Leeuwenburgh, Christiaan, Legembre, Patrick, Legouis, Renaud, Lehmann, Michael, Lei, Huan-Yao, Lei, Qun-Ying, Leib, David A, Leiro, José, Lemasters, John J, Lemoine, Antoinette, Lesniak, Maciej S, Lev, Dina, Levenson, Victor V, Levine, Beth, Levy, Efrat, Li, Faqiang, Li, Jun-Lin, Li, Lian, Li, Sheng, Li, Weijie, Li, Xue-Jun, Li, Yan-Bo, Li, Yi-Ping, Liang, Chengyu, Liang, Qiangrong, Liao, Yung-Feng, Liberski, Pawel P, Lieberman, Andrew, Lim, Hyunjung J, Lim, Kah-Leong, Lim, Kyu, Lin, Chiou-Feng, Lin, Fu-Cheng, Lin, Jian, Lin, Jiandie D, Lin, Kui, Lin, Wan-Wan, Lin, Weei-Chin, Lin, Yi-Ling, Linden, Rafael, Lingor, Paul, Lippincott-Schwartz, Jennifer, Lisanti, Michael P, Liton, Paloma B, Liu, Bo, Liu, Chun-Feng, Liu, Kaiyu, Liu, Leyuan, Liu, Qiong A, Liu, Wei, Liu, Young-Chau, Liu, Yule, Lockshin, Richard A, Lok, Chun-Nam, Lonial, Sagar, Loos, Benjamin, Lopez-Berestein, Gabriel, López-Otín, Carlos, Lossi, Laura, Lotze, Michael T, Lőw, Peter, Lu, Binfeng, Lu, Bingwei, Lu, Bo, Lu, Zhen, Luciano, Frédéric, Lukacs, Nicholas W, Lund, Anders H, Lynch-Day, Melinda A, Ma, Yong, Macian, Fernando, Mackeigan, Jeff P, Macleod, Kay F, Madeo, Frank, Maiuri, Luigi, Maiuri, Maria Chiara, Malagoli, Davide, Malicdan, May Christine V, Malorni, Walter, Man, Na, Mandelkow, Eva-Maria, Manon, Stéphen, Manov, Irena, Mao, Kai, Mao, Xiang, Mao, Zixu, Marambaud, Philippe, Marazziti, Daniela, Marcel, Yves L, Marchbank, Katie, Marchetti, Piero, Marciniak, Stefan J, Marcondes, Mateus, Mardi, Mohsen, Marfe, Gabriella, Mariño, Guillermo, Markaki, Maria, Marten, Mark R, Martin, Seamus J, Martinand-Mari, Camille, Martinet, Wim, Martinez-Vicente, Marta, Masini, Matilde, Matarrese, Paola, Matsuo, Saburo, Matteoni, Raffaele, Mayer, Andreas, Mazure, Nathalie M, Mcconkey, David J, Mcconnell, Melanie J, Mcdermott, Catherine, Mcdonald, Christine, Mcinerney, Gerald M, Mckenna, Sharon L, Mclaughlin, Bethann, Mclean, Pamela J, Mcmaster, Christopher R, Mcquibban, G Angus, Meijer, Alfred J, Meisler, Miriam H, Meléndez, Alicia, Melia, Thomas J, Melino, Gerry, Mena, Maria A, Menendez, Javier A, Menna-Barreto, Rubem F S, Menon, Manoj B, Menzies, Fiona M, Mercer, Carol A, Merighi, Adalberto, Merry, Diane E, Meschini, Stefania, Meyer, Christian G, Meyer, Thomas F, Miao, Chao-Yu, Miao, Jun-Ying, Michels, Paul A M, Michiels, Carine, Mijaljica, Dalibor, Milojkovic, Ana, Minucci, Saverio, Miracco, Clelia, Miranti, Cindy K, Mitroulis, Ioannis, Miyazawa, Keisuke, Mizushima, Noboru, Mograbi, Baharia, Mohseni, Simin, Molero, Xavier, Mollereau, Bertrand, Mollinedo, Faustino, Momoi, Takashi, Monastyrska, Iryna, Monick, Martha M, Monteiro, Mervyn J, Moore, Michael N, Mora, Rodrigo, Moreau, Kevin, Moreira, Paula I, Moriyasu, Yuji, Moscat, Jorge, Mostowy, Serge, Mottram, Jeremy C, Motyl, Tomasz, Moussa, Charbel E-H, Müller, Sylke, Muller, Sylviane, Münger, Karl, Münz, Christian, Murphy, Leon O, Murphy, Maureen E, Musarò, Antonio, Mysorekar, Indira, Nagata, Eiichiro, Nagata, Kazuhiro, Nahimana, Aimable, Nair, Usha, Nakagawa, Toshiyuki, Nakahira, Kiichi, Nakano, Hiroyasu, Nakatogawa, Hitoshi, Nanjundan, Meera, Naqvi, Naweed I, Narendra, Derek P, Narita, Masashi, Navarro, Miguel, Nawrocki, Steffan T, Nazarko, Taras Y, Nemchenko, Andriy, Netea, Mihai G, Neufeld, Thomas P, Ney, Paul A, Nezis, Ioannis P, Nguyen, Huu Phuc, Nie, Daotai, Nishino, Ichizo, Nislow, Corey, Nixon, Ralph A, Noda, Takeshi, Noegel, Angelika A, Nogalska, Anna, Noguchi, Satoru, Notterpek, Lucia, Novak, Ivana, Nozaki, Tomoyoshi, Nukina, Nobuyuki, Nürnberger, Thorsten, Nyfeler, Beat, Obara, Keisuke, Oberley, Terry D, Oddo, Salvatore, Ogawa, Michinaga, Ohashi, Toya, Okamoto, Koji, Oleinick, Nancy L, Oliver, F Javier, Olsen, Laura J, Olsson, Stefan, Opota, Onya, Osborne, Timothy F, Ostrander, Gary K, Otsu, Kinya, Ou, Jing-Hsiung James, Ouimet, Mireille, Overholtzer, Michael, Ozpolat, Bulent, Paganetti, Paolo, Pagnini, Ugo, Pallet, Nicolas, Palmer, Glen E, Palumbo, Camilla, Pan, Tianhong, Panaretakis, Theocharis, Pandey, Udai Bhan, Papackova, Zuzana, Papassideri, Issidora, Paris, Irmgard, Park, Junsoo, Park, Ohkmae K, Parys, Jan B, Parzych, Katherine R, Patschan, Susann, Patterson, Cam, Pattingre, Sophie, Pawelek, John M, Peng, Jianxin, Perlmutter, David H, Perrotta, Ida, Perry, George, Pervaiz, Shazib, Peter, Matthias, Peters, Godefridus J, Petersen, Morten, Petrovski, Goran, Phang, James M, Piacentini, Mauro, Pierre, Philippe, Pierrefite-Carle, Valérie, Pierron, Gérard, Pinkas-Kramarski, Ronit, Piras, Antonio, Piri, Natik, Platanias, Leonidas C, Pöggeler, Stefanie, Poirot, Marc, Poletti, Angelo, Poüs, Christian, Pozuelo-Rubio, Mercedes, Prætorius-Ibba, Mette, Prasad, Anil, Prescott, Mark, Priault, Muriel, Produit-Zengaffinen, Nathalie, Progulske-Fox, Ann, Proikas-Cezanne, Tassula, Przedborski, Serge, Przyklenk, Karin, Puertollano, Rosa, Puyal, Julien, Qian, Shu-Bing, Qin, Liang, Qin, Zheng-Hong, Quaggin, Susan E, Raben, Nina, Rabinowich, Hannah, Rabkin, Simon W, Rahman, Irfan, Rami, Abdelhaq, Ramm, Georg, Randall, Glenn, Randow, Felix, Rao, V Ashutosh, Rathmell, Jeffrey C, Ravikumar, Brinda, Ray, Swapan K, Reed, Bruce H, Reed, John C, Reggiori, Fulvio, Régnier-Vigouroux, Anne, Reichert, Andreas S, Reiners, John J, Reiter, Russel J, Ren, Jun, Revuelta, José L, Rhodes, Christopher J, Ritis, Konstantinos, Rizzo, Elizete, Robbins, Jeffrey, Roberge, Michel, Roca, Hernan, Roccheri, Maria C, Rocchi, Stephane, Rodemann, H Peter, Rodríguez De Córdoba, Santiago, Rohrer, Bärbel, Roninson, Igor B, Rosen, Kirill, Rost-Roszkowska, Magdalena M, Rouis, Mustapha, Rouschop, Kasper M A, Rovetta, Francesca, Rubin, Brian P, Rubinsztein, David C, Ruckdeschel, Klaus, Rucker, Edmund B, Rudich, Assaf, Rudolf, Emil, Ruiz-Opazo, Nelson, Russo, Rossella, Rusten, Tor Erik, Ryan, Kevin M, Ryter, Stefan W, Sabatini, David M, Sadoshima, Junichi, Saha, Tapas, Saitoh, Tatsuya, Sakagami, Hiroshi, Sakai, Yasuyoshi, Salekdeh, Ghasem Hoseini, Salomoni, Paolo, Salvaterra, Paul M, Salvesen, Guy, Salvioli, Rosa, Sanchez, Anthony M J, Sánchez-Alcázar, José A, Sánchez-Prieto, Ricardo, Sandri, Marco, Sankar, Uma, Sansanwal, Poonam, Santambrogio, Laura, Saran, Shweta, Sarkar, Sovan, Sarwal, Minnie, Sasakawa, Chihiro, Sasnauskiene, Ausra, Sass, Miklós, Sato, Ken, Sato, Miyuki, Schapira, Anthony H V, Scharl, Michael, Schätzl, Hermann M, Scheper, Wiep, Schiaffino, Stefano, Schneider, Claudio, Schneider, Marion E, Schneider-Stock, Regine, Schoenlein, Patricia V, Schorderet, Daniel F, Schüller, Christoph, Schwartz, Gary K, Scorrano, Luca, Sealy, Linda, Seglen, Per O, Segura-Aguilar, Juan, Seiliez, Iban, Seleverstov, Oleksandr, Sell, Christian, Seo, Jong Bok, Separovic, Duska, Setaluri, Vijayasaradhi, Setoguchi, Takao, Settembre, Carmine, Shacka, John J, Shanmugam, Mala, Shapiro, Irving M, Shaulian, Eitan, Shaw, Reuben J, Shelhamer, James H, Shen, Han-Ming, Shen, Wei-Chiang, Sheng, Zu-Hang, Shi, Yang, Shibuya, Kenichi, Shidoji, Yoshihiro, Shieh, Jeng-Jer, Shih, Chwen-Ming, Shimada, Yohta, Shimizu, Shigeomi, Shintani, Takahiro, Shirihai, Orian S, Shore, Gordon C, Sibirny, Andriy A, Sidhu, Stan B, Sikorska, Beata, Silva-Zacarin, Elaine C M, Simmons, Alison, Simon, Anna Katharina, Simon, Hans-Uwe, Simone, Cristiano, Simonsen, Anne, Sinclair, David A, Singh, Rajat, Sinha, Debasish, Sinicrope, Frank A, Sirko, Agnieszka, Siu, Parco M, Sivridis, Efthimios, Skop, Vojtech, Skulachev, Vladimir P, Slack, Ruth S, Smaili, Soraya S, Smith, Duncan R, Soengas, Maria S, Soldati, Thierry, Song, Xueqin, Sood, Anil K, Soong, Tuck Wah, Sotgia, Federica, Spector, Stephen A, Spies, Claudia D, Springer, Wolfdieter, Srinivasula, Srinivasa M, Stefanis, Leonidas, Steffan, Joan S, Stendel, Ruediger, Stenmark, Harald, Stephanou, Anastasis, Stern, Stephan T, Sternberg, Cinthya, Stork, Björn, Strålfors, Peter, Subauste, Carlos S, Sui, Xinbing, Sulzer, David, Sun, Jiaren, Sun, Shi-Yong, Sun, Zhi-Jun, Sung, Joseph J Y, Suzuki, Kuninori, Suzuki, Toshihiko, Swanson, Michele S, Swanton, Charles, Sweeney, Sean T, Sy, Lai-King, Szabadkai, Gyorgy, Tabas, Ira, Taegtmeyer, Heinrich, Tafani, Marco, Takács-Vellai, Krisztina, Takano, Yoshitaka, Takegawa, Kaoru, Takemura, Genzou, Takeshita, Fumihiko, Talbot, Nicholas J, Tan, Kevin S W, Tanaka, Keiji, Tanaka, Kozo, Tang, Daolin, Tang, Dingzhong, Tanida, Isei, Tannous, Bakhos A, Tavernarakis, Nektarios, Taylor, Graham S, Taylor, Gregory A, Taylor, J Paul, Terada, Lance S, Terman, Alexei, Tettamanti, Gianluca, Thevissen, Karin, Thompson, Craig B, Thorburn, Andrew, Thumm, Michael, Tian, Fengfeng, Tian, Yuan, Tocchini-Valentini, Glauco, Tolkovsky, Aviva M, Tomino, Yasuhiko, Tönges, Lars, Tooze, Sharon A, Tournier, Cathy, Tower, John, Towns, Roberto, Trajkovic, Vladimir, Travassos, Leonardo H, Tsai, Ting-Fen, Tschan, Mario P, Tsubata, Takeshi, Tsung, Allan, Turk, Boris, Turner, Lorianne S, Tyagi, Suresh C, Uchiyama, Yasuo, Ueno, Takashi, Umekawa, Midori, Umemiya-Shirafuji, Rika, Unni, Vivek K, Vaccaro, Maria I, Valente, Enza Maria, Van Den Berghe, Greet, Van Der Klei, Ida J, Van Doorn, Wouter, Van Dyk, Linda F, Van Egmond, Marjolein, Van Grunsven, Leo A, Vandenabeele, Peter, Vandenberghe, Wim P, Vanhorebeek, Ilse, Vaquero, Eva C, Velasco, Guillermo, Vellai, Tibor, Vicencio, Jose Miguel, Vierstra, Richard D, Vila, 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Yingyu, Chen, Yongqiang, Chen, Yu-Jen, Chen, Zhixiang, Cheng, Alan, Cheng, Christopher H K, Cheng, Yan, Cheong, Heesun, Cheong, Jae-Ho, Cherry, Sara, Chess-Williams, Russ, Cheung, Zelda H, Chevet, Eric, Chiang, Hui-Ling, Chiarelli, Roberto, Chiba, Tomoki, Chin, Lih-Shen, Chiou, Shih-Hwa, Chisari, Francis V, Cho, Chi Hin, Cho, Dong-Hyung, Choi, Augustine M K, Choi, Dooseok, Choi, Kyeong Sook, Choi, Mary E, Chouaib, Salem, Choubey, Divaker, Choubey, Vinay, Chu, Charleen T, Chuang, Tsung-Hsien, Chueh, Sheau-Huei, Chun, Taehoon, Chwae, Yong-Joon, Chye, Mee-Len, Ciarcia, Roberto, Ciriolo, Maria R, Clague, Michael J, Clark, Robert S B, Clarke, Peter G H, Clarke, Robert, Codogno, Patrice, Coller, Hilary A, Colombo, María I, Comincini, Sergio, Condello, Maria, Condorelli, Fabrizio, Cookson, Mark R, Coombs, Graham H, Coppens, Isabelle, Corbalan, Ramon, Cossart, Pascale, Costelli, Paola, Costes, Safia, Coto-Montes, Ana, Couve, Eduardo, Coxon, Fraser P, Cregg, James M, Crespo, José L, Cronjé, Marianne J, Cuervo, Ana Maria, Cullen, Joseph J, Czaja, Mark J, D'Amelio, Marcello, Darfeuille-Michaud, Arlette, Davids, Lester M, Davies, Faith E, De Felici, Massimo, De Groot, John F, De Haan, Cornelis A M, De Martino, Luisa, De Milito, Angelo, De Tata, Vincenzo, Debnath, Jayanta, Degterev, Alexei, Dehay, Benjamin, Delbridge, Lea M D, Demarchi, Francesca, Deng, Yi Zhen, Dengjel, Jörn, Dent, Paul, Denton, Donna, Deretic, Vojo, Desai, Shyamal D, Devenish, Rodney J, Di Gioacchino, Mario, Di Paolo, Gilbert, Di Pietro, Chiara, Díaz-Araya, Guillermo, Díaz-Laviada, Inés, Diaz-Meco, Maria T, Diaz-Nido, Javier, Dikic, Ivan, Dinesh-Kumar, Savithramma P, Ding, Wen-Xing, Distelhorst, Clark W, Diwan, Abhinav, Djavaheri-Mergny, Mojgan, Dokudovskaya, Svetlana, Dong, Zheng, Dorsey, Frank C, Dosenko, Victor, Dowling, James J, Doxsey, Stephen, Dreux, Marlène, Drew, Mark E, Duan, Qiuhong, Duchosal, Michel A, Duff, Karen, Dugail, Isabelle, Durbeej, Madeleine, Duszenko, Michael, Edelstein, Charles 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Abstract: International audience, In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused o

8. Insights into the evolution of regulated actin dynamics via characterization of primitive gelsolin/cofilin proteins from Asgard archaea

Author: Edward Manser, Robert Robinson, Linh T. Tran, Yohendran Baskaran, Laurent Blanchoin, Magali Orhant-Prioux, Caner Akıl, Agency for science, technology and research [Singapore] (A*STAR), Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Research Institute for Interdisciplinary Science, Okayama University, CytoMorphoLab, Physiologie cellulaire et végétale (LPCV), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Vidyasirimedhi Institute of Science and Technology, Agency for Science, Technology and Research, Singapore National Medical Research Council (NMRC Grant OFIRG/0067/2018), Vidyasirimedhi Institute of Science and Technology, Research Institute for Interdisciplinary Science, Japan Society for the Promotion of Science (KAKENHI Grant JP20H00476), European Project: 741773,AAA, Department of Pharmacology, Yong Loo Lin School of Medicine [Singapour], National University of Singapore (NUS), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), and Vidyasirimedhi Institute of Science and Technology [Thaïlande] (VISTEC)
Subjects: Protein Conformation, alpha-Helical, gelsolin, Archaeal Proteins, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, macromolecular substances, Biochemistry, Polymerization, Evolution, Molecular, 03 medical and health sciences, 0302 clinical medicine, Genome, Archaeal, Lokiarchaeota, Amino Acid Sequence, Cytoskeleton, Actin, X-ray crystallography, 030304 developmental biology, 0303 health sciences, Multidisciplinary, biology, Chemistry, Actin filament severing, Biological Sciences, eukaryogenesis, Cofilin, musculoskeletal system, Actin cytoskeleton, Archaea, Actins, Cell biology, Actin Depolymerizing Factors, Asgard archaea, Profilin, biology.protein, Sequence Alignment, actin, Filopodia, Gelsolin, 030217 neurology & neurosurgery
Abstract: Significance Eukaryotic gelsolin superfamily proteins generally comprise three or more related domains. Here we characterize single- and double-domain gelsolins from Thorarchaeota (Thor). Similar domain architectures are present in Heimdall-, Loki-, and Odinarchaeota. Thor gelsolins are functional in regulating rabbit actin in in vitro assays, showing a range of activities including actin filament severing and bundling. These gelsolins bind to the eukaryotic gelsolin/cofilin-binding site on actin. Two-domain, but not one-domain, gelsolins are calcium regulated. Thor gelsolins appear to have the characteristics and structure consistent with primitive gelsolins/cofilins, suggesting that these single- and double-domain gelsolins are a record of a nascent preeukaryotic actin-regulation machinery., Asgard archaea genomes contain potential eukaryotic-like genes that provide intriguing insight for the evolution of eukaryotes. The eukaryotic actin polymerization/depolymerization cycle is critical for providing force and structure in many processes, including membrane remodeling. In general, Asgard genomes encode two classes of actin-regulating proteins from sequence analysis, profilins and gelsolins. Asgard profilins were demonstrated to regulate actin filament nucleation. Here, we identify actin filament severing, capping, annealing and bundling, and monomer sequestration activities by gelsolin proteins from Thorarchaeota (Thor), which complete a eukaryotic-like actin depolymerization cycle, and indicate complex actin cytoskeleton regulation in Asgard organisms. Thor gelsolins have homologs in other Asgard archaea and comprise one or two copies of the prototypical gelsolin domain. This appears to be a record of an initial preeukaryotic gene duplication event, since eukaryotic gelsolins are generally comprise three to six domains. X-ray structures of these proteins in complex with mammalian actin revealed similar interactions to the first domain of human gelsolin or cofilin with actin. Asgard two-domain, but not one-domain, gelsolins contain calcium-binding sites, which is manifested in calcium-controlled activities. Expression of two-domain gelsolins in mammalian cells enhanced actin filament disassembly on ionomycin-triggered calcium release. This functional demonstration, at the cellular level, provides evidence for a calcium-controlled Asgard actin cytoskeleton, indicating that the calcium-regulated actin cytoskeleton predates eukaryotes. In eukaryotes, dynamic bundled actin filaments are responsible for shaping filopodia and microvilli. By correlation, we hypothesize that the formation of the protrusions observed from Lokiarchaeota cell bodies may involve the gelsolin-regulated actin structures.
Published: 2020
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9. Immunological history governs human stem cell memory CD4 heterogeneity via the Wnt signaling pathway

Author: Ezequiel Ruiz-Mateos, Naomi Mc Govern, Bernett Lee, Tamas Fulop, Karolina Pilipow, Tze Pin Ng, Crystal Tze Ying Tan, Shu Wen Tan, Reena Rajasuriar, Hartmut Geiger, Wilson How, Mai Chan Lau, Benoit Malleret, Amanda Amoah, Florent Ginhoux, Marie Strickland, Jin Miao Chen, Maria Carolina Florian, Glenn Wong, Enrico Lugli, Adeeba Kamarulzaman, Marion Chevrier, Veronica Zanon, Hassen Kared, Anis Larbi, Josephine Lum, [Kared,H, Tan,SW, Lau,MC, Chevrier,M, Tan,C, How,W, Wong,G, Strickland,M, Malleret,B, Govern,NM, Lum,J, Chen,JM, Lee,B, Ginhoux,F, Larbi,A] Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), Immunos Building, Biopolis, Republic of Singapore. [Strickland,M] Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK. [Malleret,B, Larbi,A] Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore. [Amoah,A, Florian,MC, Geiger,H] Institute of Molecular Medicine, University of Ulm, Ulm, Germany. [Pilipow,K, Zanon,V, Lugli,E] Humanitas Clinical and Research Center, Laboratory of Translational Immunology (LTI), Rozzano, Italy. [Geiger,H] Experimental Hematology and Cancer Biology, CCHMC, Cincinnati, OH, USA. [Ruiz-Mateos,E] Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, CSIC, University of Seville, Seville, Spain. [Fulop.T, Larbi,A] Department of Medicine, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Quebec, Canada. [Rajasuriar,R, Kamarulzaman,A] Centre of Excellence for Research in AIDS (CERiA), University of Malaya, Kuala Lumpur, Malaysia. [Rajasuriar,R] The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia. [Rajasuriar,R, Kamarulzaman,A] Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [Ng,TP] Gerontology Research Programme and Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., The study is supported by a research grant from the Agency for Science, Technology and Research (No. 10-036), by the Singapore Immunology Network and by a Starting Grant from the European Research Council (ERC-StG-2014 PERSYST 640511 to E.L.). A.L. is a scholar of International Society for Advancement of Cytometry (ISAC). R.R. and A.K. are funded by the High Impact Research/Ministry of Higher Education Research Grant, Malaysia (HIR/ MOHE, H-20001-E000001) and the RU grant (UMRG RP029-14HTM). E.R-M was supported by Consejería de Salud y Bienestar Social of Junta de Andalucía through the Nicolás Monardes Program (C-0032/17) and Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Fondos Europeos para el Desarrollo Regional, FEDER, grants PI16/ 00684, PI19/01127, RETICS, Red de Investigación en SIDA (RD16/0025/0020)., Agency for Science, Technology and Research A*STAR (Singapore), Singapore Immunology Network, European Research Council, International Society for Advancement of Cytometry, Ministry of Higher Education (Malaysia), Junta de Andalucía, Instituto de Salud Carlos III, European Commission, and Red Española de Investigación en SIDA
Subjects: 0301 basic medicine, CD4-Positive T-Lymphocytes, Aging, animal diseases, General Physics and Astronomy, HIV Infections, Signal transduction, Immunological memory, Memory T cells, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Mice, 0302 clinical medicine, Organisms::Eukaryota::Animals [Medical Subject Headings], Cytotoxic T cell, Flow cytometry, lcsh:Science, Wnt Signaling Pathway, beta Catenin, Phenomena and Processes::Chemical Phenomena::Chemical Processes::Biochemical Processes::Signal Transduction::Wnt Signaling Pathway [Medical Subject Headings], Multidisciplinary, Wnt signaling pathway, Catenins, Chemicals and Drugs::Biological Factors::Intercellular Signaling Peptides and Proteins [Medical Subject Headings], 3. Good health, Cell biology, Intercellular Signaling Peptides and Proteins, Diseases::Immune System Diseases::Immunologic Deficiency Syndromes::HIV Infections [Medical Subject Headings], Stem cell, Naive T cell, Science, T cells, Context (language use), chemical and pharmacologic phenomena, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Gene Expression Profiling [Medical Subject Headings], Thymus Gland, Biology, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Immune system, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::beta Catenin [Medical Subject Headings], Antigen, Antigens, CD, Phenomena and Processes::Physiological Phenomena::Physiological Processes::Growth and Development::Aging [Medical Subject Headings], Anatomy::Tissues::Lymphoid Tissue::Thymus Gland [Medical Subject Headings], Cateninas, Animals, Humans, Anatomy::Hemic and Immune Systems::Immune System::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::CD4-Positive T-Lymphocytes [Medical Subject Headings], Chemicals and Drugs::Biological Factors::Antigens [Medical Subject Headings], Anatomy::Cells::Stem Cells::Hematopoietic Stem Cells::Lymphoid Progenitor Cells::Precursor Cells, T-Lymphoid [Medical Subject Headings], Vía de señalización wnt, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings], Precursor Cells, T-Lymphoid, Células T de memoria, Gene Expression Profiling, General Chemistry, biochemical phenomena, metabolism, and nutrition, 030104 developmental biology, Sistema inmunológico, Phenomena and Processes::Immune System Phenomena::Immunity::Adaptive Immunity::Immunologic Memory [Medical Subject Headings], bacteria, lcsh:Q, Citometría de flujo, Immunologic Memory, 030215 immunology
Abstract: The diversity of the naïve T cell repertoire drives the replenishment potential and capacity of memory T cells to respond to immune challenges. Attrition of the immune system is associated with an increased prevalence of pathologies in aged individuals, but whether stem cell memory T lymphocytes (TSCM) contribute to such attrition is still unclear. Using single cells RNA sequencing and high-dimensional flow cytometry, we demonstrate that TSCM heterogeneity results from differential engagement of Wnt signaling. In humans, aging is associated with the coupled loss of Wnt/β-catenin signature in CD4 TSCM and systemic increase in the levels of Dickkopf-related protein 1, a natural inhibitor of the Wnt/β-catenin pathway. Functional assays support recent thymic emigrants as the precursors of CD4 TSCM. Our data thus hint that reversing TSCM defects by metabolic targeting of the Wnt/β-catenin pathway may be a viable approach to restore and preserve immune homeostasis in the context of immunological history., Aging is associated with immune attrition that may impact the effectiveness of the immune system to protect the host from pathogens. Here the authors show that immune aging is associated with alterations in the Wnt/β-catenin signaling and reduced stem cell memory T lymphocytes, hinting the Wnt/β-catenin pathway as a potential therapy target.
Published: 2020

10. Antibody Treatment against Angiopoietin-Like 4 Reduces Pulmonary Edema and Injury in Secondary Pneumococcal Pneumonia

Author: Koichi Izumikawa, Vincent T. K. Chow, Ka Wai Kwok, Jean-Pierre Quenot, Noriho Sakamoto, Nguan Soon Tan, Liang Li, Wooi Keong Teh, Benjamin Jie Wei Foo, Stéphane Mandard, Laurent Lagrost, Hiroshi Mukae, Ju Ee Seet, Pengcheng Zhu, Fang He, Gurjeet S. Kohli, Liang Yang, Hyungwon Choi, Martin L. Buist, Institute of Biomedicine and Biotechnology [Shenzhen, China], Institut Pasteur de Shanghai, Académie des Sciences de Chine - Chinese Academy of Sciences (IPS-CAS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Shenzhen Institutes of Advanced Technology [Shenzhen, China], School of Biological Sciences [Singapore, Singapore], Nanyang Technological University [Singapour], Department of Respiratory Medicine [Nagasaki, Japan] (Unit of Translational Medicine), Nagasaki University Graduate School of Biomedical Sciences [Japan], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Montpellier (UM), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Singapore Centre for Environmental Life Sciences Engineering [Singapore] (SCELSE), Saw Swee Hock School of Public Health [Singapore, Singapore], National University of Singapore (NUS), Department of Biomedical Engineering [Singapore], Department of Pathology [Singapour], School of Medicine [Shenzhen, China], Southern University of Science and Technology of China (SUSTech), Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine [Hangzhou, China], Huzhou University [Zhejiang]-Institute of Preventive Veterinary Medicine [Hangzhou, China]-College of Animal Sciences [Hangzhou, China], Host and Pathogen Interactivity Laboratory [Singapore, Singapore] (Department of Microbiology and Immunology), National University of Singapore (NUS)-Yong Loo Lin School of Medicine [Singapore], Lee Kong Chian School of Medicine, Nanyang Technological University (NTU), Cooperative Basic Research Grant NMRC/CBRG/ 0030/2013 and National Health Innovation Centre Grant NHIC-I2D-1509081 from the National Medical Research Council, SingaporeNational Natural Science Foundation of China (81771617)French National Research Agency (ANR-11-LABX-0021-01-LipSTIC LabEx)Start-Up Grant Y01416206 from Southern University of Science and Technology (China), ANR-11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du(2011), Pirofski, Liise-anne, Lee Kong Chian School of Medicine (LKCMedicine), School of Biological Sciences, Interdisciplinary Graduate School (IGS), Singapore Centre for Environmental Life Sciences and Engineering, Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Southern University of Science and Technology (SUSTech), ANR-11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du cancer(2011), Mandard, Stéphane, Laboratoires d'excellence - Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du cancer - - Lipstic2011 - ANR-11-LABX-0021 - LABX - VALID, Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université de Montpellier (UM), Unité de soins intensifs [CHU Dijon], Singapore Centre for Environmental Life Sciences Engineering [Singapore, Singapore] (SCELSE), Nanyang Technological University [Singapour]-Interdisciplinary Graduate School [Singapore, Singapore], National University of Singapore (NUS)-Yong Loo Lin School of Medicine, Lee Kong Chian School of Medicine [Singapore, Singapore], and ANR: 11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du(2011)
Subjects: antibiotic resistance, Antibiotics, medicine.disease_cause, Mice, 0302 clinical medicine, ANGPTL4, Medicine, Lung, Mice, Inbred BALB C, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Coinfection, Biological sciences [Science], Pulmonary edema, QR1-502, Anti-Bacterial Agents, 3. Good health, Streptococcus pneumoniae, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, 030220 oncology & carcinogenesis, Pneumococcal pneumonia, Female, Research Article, medicine.drug_class, Secondary infection, Secondary Bacterial Pneumonia, Pulmonary Edema, host-directed immunotherapeutics, Lung injury, Microbiology, Antibodies, Host-Microbe Biology, 03 medical and health sciences, Immune system, Antibiotic resistance, Virology, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Angiopoietin-Like Protein 4, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, vascular permeability, 030304 developmental biology, secondary bacterial pneumonia, Inflammation, business.industry, Pneumonia, Pneumococcal, medicine.disease, Disease Models, Animal, Immunology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Despite extensive global efforts, secondary bacterial pneumonia still represents a major cause of death in developing countries and is an important cause of long-term functional disability arising from lung tissue damage. Newer approaches to improving treatment outcomes are needed to reduce the significant morbidity and mortality caused by infectious diseases. Our study, using an experimental mouse model of secondary S. pneumoniae infection, shows that a multimodal treatment that concurrently targets host and pathogen factors improved lung tissue integrity and extended the median survival time of infected mice. The immunoneutralization of host protein cANGPTL4 reduced the severity of pulmonary edema and damage. We show that host-directed therapeutic strategies as well as neutralizing antibodies against pathogen virulence factors are viable adjuncts to standard antimicrobial treatments such as antibiotics. In view of their different modes of action compared to antibiotics, concurrent immunotherapies using antibodies are potentially efficacious against secondary pneumococcal pneumonia caused by antibiotic-resistant pathogens., Secondary bacterial lung infection by Streptococcus pneumoniae (S. pneumoniae) poses a serious health concern, especially in developing countries. We posit that the emergence of multiantibiotic-resistant strains will jeopardize current treatments in these regions. Deaths arising from secondary infections are more often associated with acute lung injury, a common consequence of hypercytokinemia, than with the infection per se. Given that secondary bacterial pneumonia often has a poor prognosis, newer approaches to improve treatment outcomes are urgently needed to reduce the high levels of morbidity and mortality. Using a sequential dual-infection mouse model of secondary bacterial lung infection, we show that host-directed therapy via immunoneutralization of the angiopoietin-like 4 c-isoform (cANGPTL4) reduced pulmonary edema and damage in infected mice. RNA sequencing analysis revealed that anti-cANGPTL4 treatment improved immune and coagulation functions and reduced internal bleeding and edema. Importantly, anti-cANGPTL4 antibody, when used concurrently with either conventional antibiotics or antipneumolysin antibody, prolonged the median survival of mice compared to monotherapy. Anti-cANGPTL4 treatment enhanced immune cell phagocytosis of bacteria while restricting excessive inflammation. This modification of immune responses improved the disease outcomes of secondary pneumococcal pneumonia. Taken together, our study emphasizes that host-directed therapeutic strategies are viable adjuncts to standard antimicrobial treatments.
Published: 2019
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11. Maternal religion and breastfeeding intention and practice in the US Project Viva cohort

Author: Michael S. Kramer, Blandine de Lauzon-Guillain, Emily Oken, Sandrine Lioret, Sheryl L. Rifas-Shiman, Emmanuel Cohen, Jonathan Y. Bernard, Marie-Aline Charles, Equipe 6 : ORCHAD - Origines précoces de la santé du développement de l'enfant (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Singapore Institute for Clinical Sciences, Agency for science, technology and research [Singapore] (A*STAR), Harvard Medical School [Boston] (HMS), University of the Witwatersrand [Johannesburg] (WITS), Eco-Anthropologie et Ethnobiologie (EAE), Centre National de la Recherche Scientifique (CNRS)-Muséum national d'Histoire naturelle (MNHN)-Université Paris Diderot - Paris 7 (UPD7), Etude longitudinale française depuis l'enfance (UMS : Ined-Inserm-EFS) (ELFE), Institut national d'études démographiques (INED)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), McGill University = Université McGill [Montréal, Canada], Yong Loo Lin School of Medicine [Singapore], Harvard T.H. Chan School of Public Health, Bernard, Jonathan, Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Muséum national d'Histoire naturelle (MNHN)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Muséum National d’Histoire Naturelle (MNHN), EFS-Institut national d'études démographiques (INED)-Institut National de la Santé et de la Recherche Médicale (INSERM), McGill University, and Yong Loo Lin School of Medicine
Subjects: Adult, Breastfeeding, Mothers, Choice Behavior, Article, Christianity, [SHS]Humanities and Social Sciences, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Pregnancy, 030225 pediatrics, Surveys and Questionnaires, Medicine, Humans, 030212 general & internal medicine, Poisson regression, Longitudinal Studies, Maternal Behavior, ComputingMilieux_MISCELLANEOUS, Multinomial logistic regression, 2. Zero hunger, Breastfeeding promotion, [SHS.ANTHRO-SE] Humanities and Social Sciences/Social Anthropology and ethnology, business.industry, Infant, Newborn, Obstetrics and Gynecology, Infant, Odds ratio, [SHS.ANTHRO-SE]Humanities and Social Sciences/Social Anthropology and ethnology, [SDE.ES]Environmental Sciences/Environmental and Society, Infant Formula, 3. Good health, Religion, Breast Feeding, Logistic Models, Infant formula, Relative risk, Cohort, symbols, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SHS] Humanities and Social Sciences, business, Demography, Boston
Abstract: BACKGROUND Religion has rarely been studied as a determinant of infant feeding practices. We examined whether religious affiliation is associated with formula feeding vs breastfeeding intention and practice in women from the United States Project Viva cohort. METHODS Between 1999 and 2002, 2128 pregnant women were recruited in the area of Boston, Massachusetts. They reported by questionnaire their religious affiliation, and their intended and practiced infant feeding mode (exclusive formula feeding vs partial vs exclusive breastfeeding) at different time points. We examined associations of religious affiliation with infant feeding intention and practice by modified Poisson regression and multinomial logistic regression adjusted for known sociodemographic confounders. RESULTS Of 1637 women with complete data, 52% reported being Catholic, 29% Protestant, 11% unaffiliated, 4% Jewish, and 4% other religion. Overall, 8.5% and 15.9% women intended and initiated exclusive formula feeding, respectively. Compared with unaffiliated women, Catholics were more at risk to intend to exclusively formula-feed their infant at birth (risk ratio [95% CI]: 6.4 [1.6-26.0]) and to exclusively formula-feed after delivery (2.4 [1.3-4.2]) and 3 months postpartum (1.3 [0.98-1.8]). The odds ratio for intending and practicing partial (vs exclusive) breastfeeding did not differ by religious affiliation at most examined time points. Associations of Protestant women with infant feeding exhibited estimates closer to unaffiliated than to Catholic women. CONCLUSIONS Catholic women are more at risk to intend and practice exclusive formula feeding than women of other religious affiliations. Our findings may help health care practitioners adapt their breastfeeding promotion to the mother's religious affiliation.
Published: 2019
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12. Antibody-mediated enhancement aggravates chikungunya virus infection and disease severity

Author: Yee Sin Leo, Marc Lecuit, Thérèse Couderc, Angela Chow, Zhisheng Her, Yiu-Wing Kam, Bing Shao Chia, Ruo-Yan Ong, Fok-Moon Lum, Laurent Rénia, Lisa F. P. Ng, Yong Loo Lin School of Medicine, Agency for science, technology and research [Singapore] (A*STAR), Biologie des Infections - Biology of Infection, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute of Infectious Diseases and Epidemiology [Singapore, Singapore], Tan Tock Seng Hospital [Singapore, Singapore], Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Institut des Maladies Génétiques Imagine [Paris], University of Liverpool, This project was funded in part by the EU project FP7-ICRES (grant no. 261202), and LabEx IBEID, Institut Pasteur and Inserm. Lastly, we are grateful to Kai-Er Eng for editing of the manuscript, We acknowledge the study participants and healthy volunteers for providing the plasma and blood samples. We would also like to express our gratitude to the research staffs and clinical staffs from CDC/TTSH for patient enrolment, study coordination, and collection of patient samples. We would also want to thank Martial Jaume (Hong Kong University Pasteur Research Center) for providing the transformed ST486 cell lines. We would also like to thank Andres Merits for providing the Zs-Green tagged CHIKV infectious clone and the rabbit anti-CHIKV nsP2 polyclonal antibodies. In addition, we express our gratitude to the SIgN Flow Cytometry core and to Kenneth Low and Adeline Lin for their technical assistance. We thank P. Bergeat, Director of the Laboratoire Français du Fractionnement et des Biotechnologies, for his support., ANR-10-LABX-62-IBEID,IBEID,Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases'(2010), European Project: 261202,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,ICRES(2010), Yong Loo Lin School of Medicine [Singapore], Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Tan Tock Seng Hospital, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)
Subjects: 0301 basic medicine, viruses, lcsh:Medicine, medicine.disease_cause, Antibodies, Viral, Virus Replication, Severity of Illness Index, Zika virus, Pathogenesis, Mice, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, Chikungunya, lcsh:Science, Cells, Cultured, Mice, Knockout, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Multidisciplinary, biology, virus diseases, Viral Load, Arthralgia, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Antibody, medicine.symptom, Viral load, Chikungunya virus, 030106 microbiology, Inflammation, Virus, Article, 03 medical and health sciences, Interferon-gamma, Animals, Humans, business.industry, Macrophages, lcsh:R, Receptors, IgG, biology.organism_classification, Virology, Antibodies, Neutralizing, Mice, Inbred C57BL, 030104 developmental biology, Viral replication, biology.protein, Chikungunya Fever, lcsh:Q, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: The arthropod-transmitted chikungunya virus (CHIKV) causes a flu-like disease that is characterized by incapacitating arthralgia. The re-emergence of CHIKV and the continual risk of new epidemics have reignited research in CHIKV pathogenesis. Virus-specific antibodies have been shown to control virus clearance, but antibodies present at sub-neutralizing concentrations can also augment virus infection that exacerbates disease severity. To explore this occurrence, CHIKV infection was investigated in the presence of CHIKV-specific antibodies in both primary human cells and a murine macrophage cell line, RAW264.7. Enhanced attachment of CHIKV to the primary human monocytes and B cells was observed while increased viral replication was detected in RAW264.7 cells. Blocking of specific Fc receptors (FcγRs) led to the abrogation of these observations. Furthermore, experimental infection in adult mice showed that animals had higher viral RNA loads and endured more severe joint inflammation in the presence of sub-neutralizing concentrations of CHIKV-specific antibodies. In addition, CHIKV infection in 11 days old mice under enhancing condition resulted in higher muscles viral RNA load detected and death. These observations provide the first evidence of antibody-mediated enhancement in CHIKV infection and pathogenesis and could also be relevant for other important arboviruses such as Zika virus.
Published: 2018
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13. Protrusive waves guide 3D cell migration along nanofibers

Author: Lakshmi Venkatraman, Jie Zhu, Sing Yian Chew, Benoit Ladoux, Nils C. Gauthier, Alex Mogilner, Charlotte Guetta-Terrier, Hong-Yan Long, Yue Zhou, Peipei Wang, Pascale Monzo, Mechanobiology Institute [Singapore] (MBI), National University of Singapore (NUS), Department of Cellular and Molecular Physiology, Yale University School of Medicine, School of Chemical & Biomedical Engineering, Nanyang Technological University [Singapour], Cardiovascular Research Institute, National University Health System [Singapore] (NUHS), Department of Medicine, National University of Singapore (NUS)-Yong Loo Lin School of Medicine [Singapore], Lee Kong Chian School of Medicine, Nanyang Technological University (NTU), Courant Institute and Department of Biology, New York University [New York] (NYU), NYU System (NYU)-NYU System (NYU), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Agence Nationale pour la Recherche (Program Nanotechnologies et Nanosystèmes 2013, Institut Universitaire de France, National Institutes of Health, MOE (RG75/10), National Medical Research Council (NMRC/CBRG/0002/2012), Mechanobiology Institute, European Project: 617233,EC:FP7:ERC,ERC-2013-CoG,DURACELL(2014), National University Health System, National University of Singapore (NUS)-Yong Loo Lin School of Medicine, and Yale School of Medicine [New Haven, Connecticut] (YSM)
Subjects: Leading edge, Cell type, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, macromolecular substances, PC12 Cells, Article, Cell Line, Madin Darby Canine Kidney Cells, Extracellular matrix, Mice, Dogs, Cell Movement, Cell Line, Tumor, Cell Adhesion, Human Umbilical Vein Endothelial Cells, Animals, Humans, Cell adhesion, Research Articles, Actin, biology, Cell migration, 3T3 Cells, Actomyosin, Cell Biology, Anatomy, Adhesion, Actins, Extracellular Matrix, Fibronectins, Rats, HEK293 Cells, Formins, NIH 3T3 Cells, biology.protein, Biophysics, HeLa Cells, Signal Transduction
Abstract: Reductionist approaches based on 3D fibers reveal that single-cell migration along fibers is driven by lateral actin-based waves for various cell types., In vivo, cells migrate on complex three-dimensional (3D) fibrous matrices, which has made investigation of the key molecular and physical mechanisms that drive cell migration difficult. Using reductionist approaches based on 3D electrospun fibers, we report for various cell types that single-cell migration along fibronectin-coated nanofibers is associated with lateral actin-based waves. These cyclical waves have a fin-like shape and propagate up to several hundred micrometers from the cell body, extending the leading edge and promoting highly persistent directional movement. Cells generate these waves through balanced activation of the Rac1/N-WASP/Arp2/3 and Rho/formins pathways. The waves originate from one major adhesion site at leading end of the cell body, which is linked through actomyosin contractility to another site at the back of the cell, allowing force generation, matrix deformation and cell translocation. By combining experimental and modeling data, we demonstrate that cell migration in a fibrous environment requires the formation and propagation of dynamic, actin based fin-like protrusions.
Published: 2015
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14. Loss of TLR3 aggravates CHIKV replication and pathology due to an altered virus-specific neutralizing antibody response

Author: Lisa F. P. Ng, Yee Sin Leo, Jeslin J. L. Tan, Teck-Hui Teo, Angela Chow, Zhisheng Her, Valeria Lulla, Subhra K. Biswas, Aleksei Lulla, Terk-Shin Teng, Rossella Melchiotti, Wendy W. L. Lee, Mar Kyaw Win, Anand Kumar Andiappan, Marc Lecuit, Laurent Rénia, Fok-Moon Lum, Andres Merits, Christelle Gabriel, Yiu-Wing Kam, Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Yong Loo Lin School of Medicine [Singapore], National University of Singapore (NUS), Dipartimento di Informatica, Matematica, Elettronica e Trasporti [Reggio Calabria] (DIMET), Universita Mediterranea of Reggio Calabria [Reggio Calabria], University of Tartu, Tan Tock Seng Hospital, Biologie des Infections - Biology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des Maladies infectieuses et tropicales [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institute of Infection and Global Health [University of Liverpool, UK], University of Liverpool, This research was funded by SIgN, A*STAR and supported by the Biomedical Research Council, A*STAR, and European Union FP7 project ‘Integrated Chikungunya Research’ (ICRES, Grant no. 261202). Zhisheng Her and Fok‐Moon Lum are supported by the President's Graduate Fellowship from the Yong Loo Lin School of Medicine, National University of Singapore. Teck‐Hui Teo is supported by the A*STAR postgraduate scholarship. Wendy W.L. Lee is supported by the postgraduate scholarship from the NUS Graduate School for Integrative Science and Engineering., We thank Jean‐Laurent Casanova and his team (Shen‐Ying Zhang, Vanessa Sancho‐Shimizu, Michael J. Ciancanelli) from Rockefeller University for providing the human primary TRIF−/− fibroblasts. We thank Anis Larbi and the SIgN Flow Cytometry core for assistance with cytometry analysis. We are grateful to Michael Poidinger for assistance with genotyping analysis and to Ruo‐Yan Ong, Irina Shalova and Hong‐Rong Loh from SIgN for technical assistance. We also thank the Advanced Molecular Pathology Laboratory (IMCB, A*STAR) for performing the histology work. We acknowledge Kai‐Er Eng from SIgN and Lucy Robinson of Insight Editing London for assistance with manuscript editing., European Project: 261202,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,ICRES(2010), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Yong Loo Lin School of Medicine, Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP]-Institut des Maladies Génétiques Imagine [Paris], and Institut des Maladies Génétiques Imagine [Paris]
Subjects: Male, Pathology, viruses, [SDV]Life Sciences [q-bio], MESH: Chikungunya Fever, Antibodies, Viral, Virus Replication, medicine.disease_cause, MESH: Mice, Knockout, MESH: Antibodies, Neutralizing, Mice, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, TLR3 Subject Categories Immunology, MESH: Animals, Chikungunya, TLR3, Neutralizing antibody, innate immunity, Research Articles, Mice, Knockout, MESH: Aged, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Middle Aged, biology, MESH: Polymorphism, Single Nucleotide, virus diseases, hemic and immune systems, Middle Aged, MESH: Toll-Like Receptor 3, 3. Good health, medicine.anatomical_structure, MESH: Young Adult, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Molecular Medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Antibody, Chikungunya virus, Adult, medicine.medical_specialty, chemical and pharmacologic phenomena, Polymorphism, Single Nucleotide, Microbiology, Virus, Young Adult, 03 medical and health sciences, Species Specificity, MESH: Mice, Inbred C57BL, medicine, Animals, Humans, MESH: Species Specificity, neutralizing antibodies, MESH: Mice, Aged, 030304 developmental biology, Innate immune system, MESH: Humans, MESH: Virus Replication, MESH: Adult, MESH: Chikungunya virus, Antibodies, Neutralizing, Virology, MESH: Male, Toll-Like Receptor 3, Mice, Inbred C57BL, Virology & Host Pathogen Interaction, joint inflammation, Viral replication, Immunology, biology.protein, Chikungunya Fever, Bone marrow, MESH: Female, MESH: Antibodies, Viral, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract: International audience; RNA-sensing toll-like receptors (TLRs) mediate innate immunity and regulate anti-viral response. We show here that TLR3 regulates host immunity and the loss of TLR3 aggravates pathology in Chikungunya virus (CHIKV) infection. Susceptibility to CHIKV infection is markedly increased in human and mouse fibroblasts with defective TLR3 signaling. Up to 100-fold increase in CHIKV load was observed in Tlr3 À/À mice, alongside increased virus dissemination and pro-inflammatory myeloid cells infiltration. Infection in bone marrow chimeric mice showed that TLR3-expressing hemato-poietic cells are required for effective CHIKV clearance. CHIKV-specific antibodies from Tlr3 À/À mice exhibited significantly lower in vitro neutralization capacity, due to altered virus-neutralizing epitope specificity. Finally, SNP genotyping analysis of CHIKF patients on TLR3 identified SNP rs6552950 to be associated with disease severity and CHIKV-specific neutralizing antibody response. These results demonstrate a key role for TLR3-mediated antibody response to CHIKV infection, virus replication and pathology, providing a basis for future development of immunotherapeutics in vaccine development.
Published: 2014
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15. Mechanical confinement triggers glioma linear migration dependent on formin FHOD3

Author: Yuk Kien Chong, Anitha Krishnasamy, Carol Tang, Benoit Ladoux, Evelyn K.F. Yim, Nils C. Gauthier, Wai Hoe Ng, Beng Ti Ang, Sharvari R. Sathe, Charlotte Guetta-Terrier, Pascale Monzo, Michael P. Sheetz, Mechanobiology Institute [Singapore] (MBI), National University of Singapore (NUS), National Neuroscience Institute, National University Health System, Department of Surgery [Singapore], National University of Singapore (NUS)-Yong Loo Lin School of Medicine [Singapore], Department of Biomedical Engineering Singapore, National Neuroscience Institute of Singapore, Duke-NUS Medical School [Singapore], Yong Loo Lin School of Medicine, National University of Singapore, Singapore Institute for Clinical Sciences, Agency for science, technology and research [Singapore] (A*STAR), Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Columbia University [New York], Mechanobiology Institute, National University of Singapore, National Institutes of Health through Columbia University, and Duke-NUS Graduate Medical School Singapore
Subjects: 0301 basic medicine, Formins, Muscle Proteins, Motility, Cell Count, macromolecular substances, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Actin-Related Protein 2-3 Complex, 03 medical and health sciences, Cell Movement, Laminin, Glioma, Cell Adhesion, Tumor Cells, Cultured, medicine, Animals, Humans, Cell adhesion, Molecular Biology, Actin, Paxillin, ComputingMilieux_MISCELLANEOUS, Brain Neoplasms, fungi, Microfilament Proteins, Articles, Cell Biology, Anatomy, medicine.disease, Biomechanical Phenomena, Rats, Cell Motility, 030104 developmental biology, biology.protein, Biophysics, MDia1, Cell Migration Assays, Glioblastoma
Abstract: Glioma linear migration on brain blood vessels is recapitulated in vitro. This migration is characterized by a two-phase process activated by laminin, confinement, and linear topology. It requires a unique balance of actin polymerization systems emphasizing formins and not Arp2/3 and is a powerful tool for identifying new targets such as the formin FHOD3., Glioblastomas are extremely aggressive brain tumors with highly invasive properties. Brain linear tracks such as blood vessel walls constitute their main invasive routes. Here we analyze rat C6 and patient-derived glioma cell motility in vitro using micropatterned linear tracks to mimic blood vessels. On laminin-coated tracks (3–10 μm), these cells used an efficient saltatory mode of migration similar to their in vivo migration. This saltatory migration was also observed on larger tracks (50–400 μm in width) at high cell densities. In these cases, the mechanical constraints imposed by neighboring cells triggered this efficient mode of migration, resulting in the formation of remarkable antiparallel streams of cells along the tracks. This motility involved microtubule-dependent polarization, contractile actin bundles and dynamic paxillin-containing adhesions in the leading process and in the tail. Glioma linear migration was dramatically reduced by inhibiting formins but, surprisingly, accelerated by inhibiting Arp2/3. Protein expression and phenotypic analysis indicated that the formin FHOD3 played a role in this motility but not mDia1 or mDia2. We propose that glioma migration under confinement on laminin relies on formins, including FHOD3, but not Arp2/3 and that the low level of adhesion allows rapid antiparallel migration.
Published: 2016
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16. Brown adipose tissue influences adiponectin and thyroid hormone changes during Graves’ disease therapy

Author: Wei-En, Ho, Lijuan, Sun, Hui Jen, Goh, Mya Thway, Tint, Lei, Sun, Melvin Khee Shing, Leow, Lee Kong Chian School of Medicine (LKCMedicine), Singapore Institute for Clinical Sciences, A*STAR, Yong Loo Lin School of Medicine, NUS, and Tan Tock Seng Hospital
Subjects: Thyroid Hormones, Histology, Adipose Tissue, Adipose Tissue, Brown, Fluorodeoxyglucose F18, Humans, Medicine [Science], Adiponectin, Cell Biology, Hyperthyroidism, Graves Disease
Abstract: Thyroid hormones (TH), adiponectin and brown adipose tissue (BAT) are regulators of energy homoeostasis. Influence of BAT activity on the relationship between TH and adiponectin remains unexplored. The aim of the study was to identify the relationship between TH and adiponectin and to clarify the impact of active BAT on the metabolic effects of adiponectin before and after the correction of thyrotoxicosis. Twenty-one patients with newly diagnosed hyperthyroidism from Graves' disease were recruited. A titration dosing regimen of thionamide anti-thyroid drug (ATD) was used to establish euthyroidism over 12-24 weeks. Anthropometric, biochemical and adipocytokine parameters were measured before and after control of hyperthyroidism. BAT activity was quantified by fusion 18 F-fluorodeoxyglucose (18 F-FDG) PET/MR imaging, and patients were grouped based on BAT status. Plasma adiponectin level was significantly increased following correction of hyperthyroidism in the overall sample. Free thyroxine (FT4) was also identified as a predictor of adiponectin level in thyroid dysfunction. However, significant changes in adiponectin level and correlations involving adiponectin were absent in BAT-positive patients but maintained in BAT-negative patients. BAT activity diminishes the correlative relationship with body composition and abolishes TH and adiponectin relationships when transitioning from a hyperthyroid to euthyroid state. Agency for Science, Technology and Research (A*STAR) Published version The study was supported by the Singapore Ministry of Health’s National Medical Research Council (NMRC) Clinician Scientist Award. (grant ID NMRC/CSA-INV /0003/2015) and the Agency for Science, Technology and Research (A *STAR) awarded to A/Prof. Melvin Leow.
Published: 2022
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17. A comparative study of disorders of gut–brain interaction in Western Europe and Asia based on the Rome foundation global epidemiology study

Author: Johann P. Hreinsson, Reuben K. M. Wong, Jan Tack, Peter Whorwell, Marc A. Benninga, Viola Andresen, Bruno Bonaz, Suck Chei Choi, Enrico S. Corazziari, Javier Santos, Shin Fukudo, Motoyori Kanazawa, Xuicai Fang, Shrikant I. Bangdiwala, Ami D. Sperber, Olafur S. Palsson, Magnus Simrén, Institut Català de la Salut, [Hreinsson JP] Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. [Wong RKM] Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. [Tack J] Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium. [Whorwell P] University of Manchester, Neurogastroenterology Unit, Wythenshawe Hospital, Manchester, UK. [Benninga MA] Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Pediatric Gastroenterology, Hepatology and Nutrition, Amsterdam, The Netherlands. [Andresen V] Department of Medicine, Israelitic Hospital, Hamburg, Germany. [Santos J] Laboratori de Fisiologia i Fisiopatologia Digestiva, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei d’Aparell Digestiu, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERHED), Instituto de Salud Carlos III, Madrid, Spain, Vall d'Hebron Barcelona Hospital Campus, Pediatrics, Paediatric Gastroenterology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, and ARD - Amsterdam Reproduction and Development
Subjects: Investigative Techniques::Epidemiologic Methods::Data Collection::Surveys and Questionnaires [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], IRRITABLE-BOWEL-SYNDROME, Physiology, Clinical Neurology, QUESTIONNAIRE, cross-sectional studies, Qüestionaris, Nervous System::Central Nervous System::Brain [ANATOMY], Aparell digestiu - Malalties - Epidemiologia, sistema nervioso::sistema nervioso central::encéfalo::prosencéfalo::telencéfalo::cerebro [ANATOMÍA], CRITERIA, functional gastrointestinal disorders, Cervell, SCALE, irritable bowel syndrome, Science & Technology, Gastroenterology & Hepatology, Còlon irritable - Epidemiologia, Endocrine and Autonomic Systems, enfermedades del sistema digestivo::enfermedades gastrointestinales::enfermedades intestinales::enfermedades del colon::enfermedades funcionales del colon::síndrome del colon irritable [ENFERMEDADES], Neurosciences, Gastroenterology, técnicas de investigación::métodos epidemiológicos::recopilación de datos::encuestas y cuestionarios [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], functional constipation, functional dyspepsia, PREVALENCE, SEVERITY, Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Colonic Diseases::Colonic Diseases, Functional::Irritable Bowel Syndrome [DISEASES], RISK-FACTORS, Neurosciences & Neurology, Life Sciences & Biomedicine
Abstract: Functional constipation; Functional dyspepsia; Functional gastrointestinal disorders Estreñimiento funcional; Dispepsia funcional; Trastornos gastrointestinales funcionales Restrenyiment funcional; Dispèpsia funcional; Trastorns gastrointestinals funcionals Objective Many studies have been published on disorders of the gut–brain interaction (DGBI) in Asia and Western Europe, but no previous study has directly assessed the difference between the two regions. The aim was to compare the prevalence of DGBI in Asia and Western Europe. Methods We used data collected in a population-based Internet survey, the Rome Foundation Global Epidemiology Study, from countries in Western Europe (Belgium, France, Germany, Netherlands, Italy, Spain, Sweden, and the United Kingdom) and Asia (China, Japan, South Korea, and Singapore). We assessed DGBI diagnoses (Rome IV Adult Diagnostic Questionnaire), anxiety/depression (Patient Health Questionnaire-4, PHQ-4), non-GI somatic symptoms (PHQ-12), and access to and personal costs of doctor visits. Results The study included 9487 subjects in Asia and 16,314 in Western Europe. Overall, 38.0% had at least one DGBI; younger age, female sex, and higher scores on PHQ4 and PHQ12 were all associated with DGBI. The prevalence of having at least one DGBI was higher in Western Europe than in Asia (39.1% vs 36.1%, OR 1.14 [95% CI 1.08–1.20]). This difference was also observed for DGBI by anatomical regions, most prominently esophageal DGBI (OR 1.67 [1.48–1.88]). After adjustment, the difference in DGBI prevalence diminished and psychological (PHQ-4) and non-GI somatic symptoms (PHQ-12) had the greatest effect on the odds ratio estimates. Conclusion The prevalence of DGBI is generally higher in Western Europe compared to Asia. A considerable portion of the observed difference in prevalence rates seems to be explained by more severe psychological and non-GI somatic symptoms in Western Europe.
Published: 2023
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18. Scar prevention through topical delivery of gelatin-tyramine-siSPARC nanoplex loaded in dissolvable hyaluronic acid microneedle patch across skin barrier

Author: Yong Yao Chun, William Wei Ren Tan, Marcus Ivan Gerard Vos, Wen Kiat Chan, Hong Liang Tey, Nguan Soon Tan, Timothy Thatt Yang Tan, School of Chemical and Biomedical Engineering, School of Biological Sciences, Lee Kong Chian School of Medicine (LKCMedicine), National Skin Centre, and Yong Loo Lin School of Medicine, NUS
Subjects: Biomedical Engineering, Tyramine, Fibrosis, Cicatrix, Microneedle Patches, Scar Formation, Gelatin, Humans, Medicine [Science], General Materials Science, Collagen, Hyaluronic Acid, RNA, Small Interfering, Skin
Abstract: Currently, there is no effective method to prevent the formation of hypertrophic scars and keloids, which can cause severe physical and psychological burdens to patients. Secreted protein acidic and cysteine-rich (SPARC) is involved in wound fibrosis by modulating fibroblast functions, causing excessive collagen deposition during wound healing. Thus, the reduction in SPARC gene expression after wounding can contribute to the downstream reduction in collagen production at the wound site and prevent scar formation. In this study, a dissolvable and biocompatible hyaluronic acid (HA) microneedle patch loaded with nanoplexes containing tyramine-modified gelatin and siRNA for SPARC (siSPARC/Gtn-Tyr) was investigated for topical scar prevention. Tyramine-modified gelatin (Gtn-Tyr) provides electrostatic protection and enhances cell internalization for siSPARC. In vitro studies using human dermal fibroblasts showed that both siSPARC/Gtn-Tyr nanoplexes and siSPARC/Gtn-Tyr-loaded microneedle patches can significantly reduce SPARC gene expression (P < 0.05) and do not cause discernable cytotoxic effects. Further studies using a mouse wound model demonstrate that the siSPARC/Gtn-Tyr-loaded microneedle patch can reduce collagen production during wound healing without triggering an immune response. When Gtn-Tyr-siSPARC is administered transdermally at the wound site, effective collagen reduction is achieved through silencing of the matricellular SPARC protein, thus promising the reduction of scar formation. Overall, the siSPARC/Gtn-Tyr loaded microneedle patch can potentially provide an effective transdermal anti-fibrotic treatment. Ministry of Education (MOE) Ministry of Health (MOH) National Medical Research Council (NMRC) The authors gratefully acknowledge the support by Singapore Ministry of Education under its NTUitive Gap Fund grant scheme (NGF-2019-07-004) and Singapore Ministry of Health’s National Medical Research Council under its Clinician Scientist Award (CSAINV20nov-0003).
Published: 2022
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19. Human IRF1 governs macrophagic IFN-γ immunity to mycobacteria

Author: Jérémie Rosain, Anna-Lena Neehus, Jérémy Manry, Rui Yang, Jérémie Le Pen, Wassim Daher, Zhiyong Liu, Yi-Hao Chan, Natalia Tahuil, Özden Türel, Mathieu Bourgey, Masato Ogishi, Jean-Marc Doisne, Helena M. Izquierdo, Takayoshi Shirasaki, Tom Le Voyer, Antoine Guérin, Paul Bastard, Marcela Moncada-Vélez, Ji Eun Han, Taushif Khan, Franck Rapaport, Seon-Hui Hong, Andrew Cheung, Kathrin Haake, Barbara C. Mindt, Laura Pérez, Quentin Philippot, Danyel Lee, Peng Zhang, Darawan Rinchai, Fatima Al Ali, Manar Mahmoud Ahmad Ata, Mahbuba Rahman, Jessica N. Peel, Søren Heissel, Henrik Molina, Yasemin Kendir-Demirkol, Rasheed Bailey, Shuxiang Zhao, Jonathan Bohlen, Mathieu Mancini, Yoann Seeleuthner, Marie Roelens, Lazaro Lorenzo, Camille Soudée, María Elvira Josefina Paz, María Laura González, Mohamed Jeljeli, Jean Soulier, Serge Romana, Anne-Sophie L’Honneur, Marie Materna, Rubén Martínez-Barricarte, Mathieu Pochon, Carmen Oleaga-Quintas, Alexandre Michev, Mélanie Migaud, Romain Lévy, Marie-Alexandra Alyanakian, Flore Rozenberg, Carys A. Croft, Guillaume Vogt, Jean-François Emile, Laurent Kremer, Cindy S. Ma, Jörg H. Fritz, Stanley M. Lemon, András N. Spaan, Nicolas Manel, Laurent Abel, Margaret R. MacDonald, Stéphanie Boisson-Dupuis, Nico Marr, Stuart G. Tangye, James P. Di Santo, Qian Zhang, Shen-Ying Zhang, Charles M. Rice, Vivien Béziat, Nico Lachmann, David Langlais, Jean-Laurent Casanova, Philippe Gros, Jacinta Bustamante, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hannover Medical School [Hannover] (MHH), St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University [New York], Institut de Recherche en Infectiologie de Montpellier (IRIM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Yong Loo Lin School of Medicine [Singapore], Hospital del Niño Jesus, San Miguel de Tucumán, Bezmiâlem Vakıf Üniversitesi, McGill University = Université McGill [Montréal, Canada], Immunité Innée - Innate Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Curie [Paris], University of North Carolina System (UNC), Garvan Institute of medical research, The University of Sydney, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Universidad de Antioquia = University of Antioquia [Medellín, Colombia], East China Normal University [Shangaï] (ECNU), Sidra Medicine [Doha, Qatar], 'Juan Pedro Garrahan' National Hospital of Pediatrics, Buenos Aires, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Cochin [AP-HP], Hopital Saint-Louis [AP-HP] (AP-HP), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Hôpital Ambroise Paré [AP-HP], Université de Montpellier (UM), Howard Hughes Medical Institute (HHMI), The Laboratory of Human Genetics of Infectious Diseases is supported in part by grants from Inserm, Paris Cité University, the St. Giles Foundation, The Rockefeller University, the Center for Clinical and Translational Science (UL1TR001866), the National Center for Research Resources and the National Center for Advancing Sciences, the National Institutes of Health (NIH), (R01AI095983, R01AI088364, R01AI163029, and U19AI162568), the National Institute of Allergy and Infectious Diseases, the French National Research Agency (ANR) under the 'Investments for the future' program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the ANRS Nord-Sud (ANRS-COV05), ANRS (ECTZ170784-ANRS0073), GENVIR (ANR-20-CE93-003), GENMSMD (ANR-16-CE17-0005-01), AABIFNCOV (ANR-20-CO11-0001), GenMIS-C (ANR-21-COVR-0039), SUNLIVE (ANR-19-CE15-0012-01), MAFMACRO (ANR-22-CE92-0008) grants, Ecos-NORD (ECOS N°C19S01), the Fisher Center for Alzheimer's Research Foundation, the Meyer Foundation, the JPB Foundation, the European Union’s Horizon 2020 research and innovation program (824110, EASI-Genomics), the Square Foundation, Grandir–Fonds de solidarité pour l’Enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), and REACTing-INSERM. The Laboratory of Virology and Infectious Disease was supported in part by the NIH (R01AI091707-10 to C.M.R.). J.L.P. was supported by the Francois Wallace Monahan Postdoctoral Fellowship at The Rockefeller University and the European Molecular Biology Organization Long-Term Fellowship (ALTF 380-2018). N. Marr was supported by Sidra Medicine and the Qatar National Research Fund (NPRP9-251-3-045). The Yale Center for Mendelian Genomics (UM1HG006504) was funded by the National Human Genome Research Institute, the Yale GSP Coordinating Center (U24 HG008956), and the Yale High-Performance Computing Center (S10OD018521). This research was partly supported by Calcul Québec, Compute Canada Canadian Institutes of Health Research (CIHR) Project Grant to D. Langlais. (#168959) and a CIHR Foundation Grant (to P.G.). D. Langlais was also supported by an FRQS Chercheur-Boursier Junior 1 Award and the Calgary Foundation for Innovation John R. Evans Leaders Fund. P.G. is supported by a Distinguished James McGill Professorship award from McGill University. S.M.L is supported by the NIH: R01-AI103083 and R01-AI150095. J.R. was supported by poste d’accueil Inserm'. J.R., P.B., and T.L.V were supported by the MD-PhD program of the Imagine Institute by the Bettencourt Schueller Foundation. N.L received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (852178 grant), German Research Foundation,(DFG) under Germany’s Excellence Strategy—EXC 2155—project number 390874280 and REBIRTH 'Förderung aus Mitteln des Niedersächsischen Vorab'. A.-L.N. was supported by the international PhD program of the Imagine Institute, by the Bettencourt Schueller Foundation and the fin de thèse FRM program (FDT202204015102). R.Y. was supported by the Sackler Center for Biomedicine and Nutrition, the Shapiro-Silverberg Fund for the Advancement of Translational Research at the Center for Clinical and Translational Science of the Rockefeller University, and the Research Grant Program from the Immune Deficiency Foundation. D. Lee. was supported by FRMfellowship (FDM202006011282). C.S.M was supported by an Early-Mid Career Research Fellowship from the Department of Health of the New South Wales Government of Australia. S.G.T was supported by an NHMRC Leadership 3 Investigator Grant (1176665) and NHMRC grant (1113904). M.O. was supported by the David Rockefeller Graduate Program, the Funai Foundation for Information Technology, the Honjo International Scholarship Foundation, and the New York Hideyo Noguchi Memorial Society. This work was supported by grants from ANRS (ECTZ118797), Sidaction (20-2-AEQ-12822-2), and FRM (EQU202103012774) to N. Manel, and H.I. was supported by fellowships from Institut Curie, Seneca Foundation (20941/PD/18), and ANRS (ECTZ171453). A.N.S. was supported in part by the European Union’s Horizon 2020 research and innovation program (789645 Marie Sklodowska-Curie grant). Y.-H.C. is supported by an A∗STAR International Fellowship. J. Bohlen is an EMBO postdoctoral fellow. We thank the NIH Tetramer Core Facility (NTCF) for providing the 5-OP-RU-loaded MR1 tetramer, which was developed jointly with Dr. James McCluskey, Dr. Jamie Rossjohn, and Dr. David Fairlie., ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-16-CE17-0005,GENMSMD,Dissection génétique de la Susceptibilité Mendélienne aux infections mycobactériennes chez l'homme(2016), ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), ANR-21-COVR-0039,GenMIS-C,Recherche des Déficits immunitaires innées monogéniques prédisposant au syndrome inflammatoire multisystémique chez l'enfant.(2021), ANR-19-CE15-0012,SUNLIVE,Variabilité structurale et fonctionnelle des lipides complexes chez les mycobactéries : de l'assemblage de la paroi à la physiopathologie et virulence(2019), ANR-22-CE92-0008,MAFMACRO,Genetic predisposition and the role of myeloid cells in the susceptibility to mycobacterial infection(2022), European Project: 824110,H2020-INFRAIA-2018-1,EASI-Genomics(2019), and TÜREL, ÖZDEN
Subjects: inborn errors of immunity, Temel Bilimler, [SDV]Life Sciences [q-bio], interferon-stimulated gene, Life Sciences, Molecular Biology and Genetics, Genel Biyokimya, Genetik ve Moleküler Biyoloji, IRF1, General Biochemistry, Genetics and Molecular Biology, Mycobacterium, macrophages, interferon-γ, Yaşam Bilimleri, viruses, Cytogenetic, Natural Sciences, Moleküler Biyoloji ve Genetik, Sitogenetik
Abstract: Inborn errors of human IFN-γ-dependent macrophagic immunity underlie mycobacterial diseases, whereas inborn errors of IFN-α/β-dependent intrinsic immunity underlie viral diseases. Both types of IFNs induce the transcription factor IRF1. We describe unrelated children with inherited complete IRF1 deficiency and early-onset, multiple, life-threatening diseases caused by weakly virulent mycobacteria and related intramacrophagic pathogens. These children have no history of severe viral disease, despite exposure to many viruses, including SARS-CoV-2, which is life-threatening in individuals with impaired IFN-α/β immunity. In leukocytes or fibroblasts stimulated in vitro, IRF1-dependent responses to IFN-γ are, both quantitatively and qualitatively, much stronger than those to IFN-α/β. Moreover, IRF1-deficient mononuclear phagocytes do not control mycobacteria and related pathogens normally when stimulated with IFN-γ. By contrast, IFN-α/β-dependent intrinsic immunity to nine viruses, including SARS-CoV-2, is almost normal in IRF1-deficient fibroblasts. Human IRF1 is essential for IFN-γ-dependent macrophagic immunity to mycobacteria, but largely redundant for IFN-α/β-dependent antiviral immunity.
Published: 2023
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20. Melanoma-initiating cells exploit M2 macrophage TGFβ and arginase pathway for survival and proliferation

Author: Jean-Pierre Abastado, Veronique Angeli, Sandra Hubert, Luke Barron, Masashi Kato, Muly Tham, Jo Keeble, Xiaojie Wang, Armelle Prévost-Blondel, Kar Wai Tan, Nguan Soon Tan, Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Department of Clinical Research, Singapore General Hospital, National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Nanyang Technological University [Singapour], Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Microbiology, National University of Singapore (NUS)-Yong Loo Lin School of Medicine, Institut de Recherches Internationales Servier [Suresnes] (IRIS), This research was funded by government funding to SIgN, A*STAR, Singapore, and supported by the NIH/NIAID., Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Singapore Immunology Network, BMSI, A-STAR, National Institute of Allergy and Infectious Diseases [Bethesda], National Institutes of Health ( NIH ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), National University of Singapore ( NUS ) -Yong Loo Lin School of Medicine, Institut de Recherches Internationales Servier [Suresnes] ( IRIS ), School of Biological Sciences, and Bos, Mireille
Subjects: Male, Cell Survival, Population, Tumor-initiating cell, Metastasis, Mice, 03 medical and health sciences, TGFβ, 0302 clinical medicine, Transforming Growth Factor beta, mental disorders, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, General hospital, education, Melanoma, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Cell Proliferation, 030304 developmental biology, 0303 health sciences, education.field_of_study, biology, Arginase, Macrophages, Transforming growth factor beta, M2 Macrophage, medicine.disease, Mice, Mutant Strains, 3. Good health, Science::Biological sciences [DRNTU], Disease Models, Animal, Oncology, 030220 oncology & carcinogenesis, Immunology, Neoplastic Stem Cells, Cancer research, biology.protein, Female, Signal Transduction, Research Paper, Transforming growth factor
Abstract: // Muly Tham 1 , Kar Wai Tan 1,7 , Jo Keeble 1 , Xiaojie Wang 1 , Sandra Hubert 1 , Luke Barron 2 , Nguan Soon Tan 3 , Masashi Kato 4 , Armelle Prevost-Blondel 5 , Veronique Angeli 6 and Jean-Pierre Abastado 1,8 1 Singapore Immunology Network, BMSI, A-STAR, Singapore 2 Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA 3 School of Biological Sciences, Nanyang Technological University, Singapore 4 Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Japan 5 Institut Cochin, Universite Paris Descartes, CNRS UMR, Paris, France 6 Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 7 Department of Clinical Research, Singapore General Hospital, Singapore 8 Institut de Recherche Internationales Servier, 50 rue Carnot, Suresnes cedex, France Correspondence: Muly Tham, email: // Keywords : Arginase, Macrophages, TGFβ, Tumor-initiating cell Received : July 13, 2014 Accepted : September 15, 2014 Published : September 16, 2014 Abstract M2 macrophages promote tumor growth and metastasis, but their interactions with specific tumor cell populations are poorly characterized. Using a mouse model of spontaneous melanoma, we showed that CD34 - but not CD34 + tumor-initiating cells (TICs) depend on M2 macrophages for survival and proliferation. Tumor-associated macrophages (TAMs) and macrophage-conditioned media protected CD34 - TICs from chemotherapy in vitro . In vivo , while inhibition of CD115 suppressed the macrophage-dependent CD34 - TIC population, chemotherapy accelerated its development. The ability of TICs to respond to TAMs was acquired during melanoma progression and immediately preceded a surge in metastatic outgrowth. TAM-derived transforming growth factor-β (TGFβ) and polyamines produced via the Arginase pathway were critical for stimulation of TICs and synergized to promote their growth.
Published: 2014

21. Clostridium and Bacillus Binary Enterotoxins: Bad for the Bowels, and Eukaryotic Being

Author: Ramar Perumal Samy, Michel R. Popoff, Kisha Pradhan, Jodie M. Fleming, Holger Barth, Bradley G. Stiles, Wilson College, North Carolina Central University [Durham], University of North Carolina System (UNC), Yong Loo Lin School of Medicine [Singapore], National University of Singapore (NUS), Universität Ulm - Ulm University [Ulm, Allemagne], Bactéries anaérobies et Toxines, Institut Pasteur [Paris], Kisha Pradhan and Bradley G. Stiles thank Wilson College for generous use of facilities that include computers, copiers, and library services., Yong Loo Lin School of Medicine, National University of Singapore ( NUS ), University of Ulm, and Institut Pasteur [Paris] (IP)
Subjects: Clostridium spiroforme, Gastrointestinal Diseases, Protein Conformation, Health, Toxicology and Mutagenesis, receptor, Bacterial Toxins, [ SDV.TOX ] Life Sciences [q-bio]/Toxicology, lcsh:Medicine, Clostridium difficile toxin A, Clostridium difficile toxin B, Bacillus, Enterotoxin, Review, Biology, Toxicology, medicine.disease_cause, Microbiology, 03 medical and health sciences, Clostridium, Bacterial Proteins, medicine, Animals, Humans, 030304 developmental biology, 0303 health sciences, 030306 microbiology, lcsh:R, Bacterial Infections, binary enterotoxin, Clostridium perfringens, Clostridium difficile, biology.organism_classification, 3. Good health, Biochemistry, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Clostridium botulinum, protein, actin
Abstract: International audience; Some pathogenic spore-forming bacilli employ a binary protein mechanism for intoxicating the intestinal tracts of insects, animals, and humans. These Gram-positive bacteria and their toxins include Clostridium botulinum (C2 toxin), Clostridium difficile (C. difficile toxin or CDT), Clostridium perfringens (ι-toxin and binary enterotoxin, or BEC), Clostridium spiroforme (C. spiroforme toxin or CST), as well as Bacillus cereus (vegetative insecticidal protein or VIP). These gut-acting proteins form an AB complex composed of ADP-ribosyl transferase (A) and cell-binding (B) components that intoxicate cells via receptor-mediated endocytosis and endosomal trafficking. Once inside the cytosol, the A components inhibit normal cell functions by mono-ADP-ribosylation of globular actin, which induces cytoskeletal disarray and death. Important aspects of each bacterium and binary enterotoxin will be highlighted in this review, with particular focus upon the disease process involving the biochemistry and modes of action for each toxin.
Published: 2014
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22. The Management of Ocular Surface Squamous Neoplasia (OSSN)

Author: Clarice H. Y. Yeoh, Jerome J. R. Lee, Blanche X. H. Lim, Gangadhara Sundar, Jodhbir S. Mehta, Anita S. Y. Chan, Dawn K. A. Lim, Stephanie L. Watson, Santosh G. Honavar, Ray Manotosh, Chris H. L. Lim, Lee Kong Chian School of Medicine (LKCMedicine), Yong Loo Lin School of Medicine, NUS, and National University Health System
Subjects: Inorganic Chemistry, Organic Chemistry, Medicine [Science], General Medicine, Physical and Theoretical Chemistry, Molecular Biology, Ocular Surface Squamous Neoplasia, Spectroscopy, Catalysis, Topical Chemotherapy, Computer Science Applications
Abstract: The rise of primary topical monotherapy with chemotherapeutic drugs and immunomodulatory agents represents an increasing recognition of the medical management of ocular surface squamous neoplasia (OSSN), which may replace surgery as the standard of care in the future. Currently, there is no consensus regarding the best way to manage OSSN with no existing guidelines to date. This paper seeks to evaluate evidence surrounding available treatment modalities and proposes an approach to management. The approach will guide ophthalmologists in selecting the most appropriate treatment regime based on patient and disease factors to minimize treatment related morbidity and improve OSSN control. Further work can be done to validate this algorithm and to develop formal guidelines to direct the management of OSSN. Published version Publication fees associated with this article have been funded through the ExxonmobileNUS grant awarded to Chris Lim.
Published: 2022

23. Severe Chronic Allergic (and related) Diseases: a uniform approach- a MeDALL- GA(2)LEN-ARIA Position Paper

Author: WHO Collaborating Center for Asthma, Rhinitis, Bousquet, J, Anto, Jm, Demoly, P, Schünemann, Hj, Togias, A, Akdis, M, Auffray, C, Bachert, C, Bieber, T, Bousquet, Pj, Carlsen, Kh, Casale, Tb, Cruz, Aa, Keil, T, Lodrup Carlsen KC, Maurer, M, Ohta, K, Papadopoulos, Ng, Roman Rodriguez, M, Samolinski, B, Agache, I, Andrianarisoa, A, Ang, Cs, Annesi Maesano, I, Ballester, F, Baena Cagnani CE, Basagaña, X, Bateman, Ed, Bel, Eh, Bedbrook, A, Beghe', Bianca, Beji, M, Ben Kheder, A, Benet, M, Bennoor, Ks, Bergmann, Kc, Berrissoul, F, Bindslev Jensen, C, Bleecker, Er, Bonini, S, Boner, Al, Boulet, Lp, Brightling, Ce, Brozek, Jl, Bush, A, Busse, Ww, Camargos, Pa, Canonica, Gw, Carr, W, Cesario, A, Chen, Yz, Chiriac, Am, Costa, Dj, Cox, L, Custovic, A, Dahl, R, Darsow, U, Didi, T, Dolen, Wk, Douagui, H, Dubakiene, R, El Meziane, A, Fonseca, Ja, Fokkens, Wj, Fthenou, E, Gamkrelidze, A, Garcia Aymerich, J, Gerth van Wijk, R, Gimeno Santos, E, Guerra, S, Haahtela, T, Haddad, H, Hellings, Pw, Hellquist Dahl, B, Hohmann, C, Howarth, P, Hourihane, Jo, Humbert, M, Jacquemin, B, Just, J, Kalayci, O, Kaliner, Ma, Kauffmann, F, Kerkhof, M, Khayat, G, Koffi N'Goran, B, Kogevinas, M, Koppelman, Gh, Kowalski, Ml, Kull, I, Kuna, P, Larenas, D, Lavi, I, Le, Lt, Lieberman, P, Lipworth, B, Mahboub, B, Makela, Mj, Martin, F, Martinez, Fd, Marshall, Gd, Mazon, A, Melen, E, Meltzer, Eo, Mihaltan, F, Mohammad, Y, Mohammadi, A, Momas, I, Morais Almeida, M, Mullol, J, Muraro, A, Naclerio, R, Nafti, S, Namazova Baranova, L, Nawijn, Mc, Nyembue, Td, Oddie, S, O'Hehir, Re, Okamoto, Y, Orru, Mp, Ozdemir, C, Ouedraogo, Gs, Palkonen, S, Panzner, P, Passalacqua, G, Pawankar, R, Pigearias, B, Pin, I, Pinart, M, Pison, C, Popov, Ta, Porta, D, Postma, Ds, Price, D, Rabe, Kf, Ratomaharo, J, Reitamo, S, Rezagui, D, Ring, J, Roberts, R, Roca, J, Rogala, B, Romano, A, Rosado Pinto, J, Ryan, D, Sanchez Borges, M, Scadding, Gk, Sheikh, A, Simons, Fe, Siroux, V, Schmid Grendelmeier PD, Smit, Ha, Sooronbaev, T, Stein, Rt, Sterk, Pj, Sunyer, J, Terreehorst, I, Toskala, E, Tremblay, Y, Valenta, R, Valeyre, D, Vandenplas, O, van Weel, C, Vassilaki, M, Varraso, R, Viegi, G, Wang, Dy, Wickman, M, Williams, D, Wöhrl, S, Wright, J, Yorgancioglu, A, Yusuf, Om, Zar, Hj, Zernotti, Me, Zidarn, M, Zhong, N, Zuberbier, T., Beghe', B., Fthenou, E., Boudier, Anne, Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), IMIM-Hospital del Mar, Generalitat de Catalunya, Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, CIBER Epidemiologia y Salud Publica, CIBER de Epidemiología y Salud Pública (CIBERESP), Universitat Pompeu Fabra [Barcelona] (UPF), WHO Collaborating Center for Asthma and Rhinitis, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Pharmacoepidemiologie et évaluation de l'impact des produits de santé sur les populations, Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Clinical Epidemiology and Biostatistics and Medicine, McMaster University [Hamilton, Ontario], National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Génomique fonctionnelle et biologie systémique pour la santé, Institut des Sciences Biologiques du CNRS, Upper Airway Research Laboratory (URL), Ghent University Hospital, Department of Dermatology and Allergy, VU University Medical Center [Amsterdam], Department of Paediatrics, University of Oslo (UiO)-Oslo University Hospital [Oslo], Division of Allergy and Immunology, Department of Medicine, Creighton University, ProAR - FMB, Federal University of Bahia School of Medicine, Epidemiology and Health Economics, Instittute of Social Health-Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Dermatology, Medical School-Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Division of Respiratory Medicine and Allergology, Teikyo University School of Medicine, Allergy Department, 2nd Pediatric Clinic, Son Pisa Primary Care Centre, IB-Salut Balearic Health Service, Department of Prevention of Environmental Hazards and Allergology, Medical University of Warsaw - Poland-Faculté de Pharmacie de Paris, Department of Allergy and Clinical Immunology, Faculty of Medicine-Transylvania University, Public Hospital Medical Service, Ministry of Health [Mozambique], Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Public Health Research (CSISP), University of Valencia, Respiratory Medicine, Università degli studi di Genova = University of Genoa (UniGe)-School of Specialization, Faculty of Medicine, Catholic University, Health Sciences Faculty, University of Cape Town, Department of Pulmonology, University of Amsterdam [Amsterdam] (UvA)-Academic Medical Centre, Divisions of Human Genetics Infection, Inflammation and Repair, University of Southampton-School of Medicine, Service de Pneumologie Allergologie, Hôpital La Rabta [Tunis], Service de Pneumologie, Hôpital Abderrahmen Mami, National Asthma Centre, National Institute of Diseases of the Chest and Hospital (NIDCH), Pneumologie / Anesthésie - réanimation / Oxygénothérapie, Hôpital AKS Phnom Penh-Hôpital Provincial de Siemreap, Department of Dermatology and Allergy Center, Odense University Hospital, Center for Genomics and Personalized Medicine, Wake Forest University, Institute of Neurobiology and Molecular Medicine, CNR, Rome, Italy and Department of Medicine-University of Naples Federico II = Università degli studi di Napoli Federico II, Università degli studi di Verona = University of Verona (UNIVR), Institut de cardiologie et de pneumologie, Université Laval [Québec] (ULaval)-Centre Hospitalier de Laval (CH Laval), Department of Respiratory Medicine and Thoracic Surgery, University of Leicester-Institute for Lung Health, Department of Paediatric Respiratory Medicine, Imperial College London-Royal Brompton Hospital-National Heart and Lung Institute [UK], Department of Medicine, University of Wisconsin School of Medicine and Public Health, Department of Pediatrics, Universidade Federal de Minas Gerais [Belo Horizonte] (UFMG)-Medical School, Allergy & Respiratory Diseases, Università degli studi di Genova = University of Genoa (UniGe)-Department of Internal Medicine (DIMI), Allergy & Asthma Associates, University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), Deputy Scientific Director, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Pisana, Department of Thoracic Surgery, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), National Cooperative Group of Pediatric Research on Asthma, Asthma Clinic and Education Center of the Capital Institute of Pediatrics, Service des Premiers Soins, Université Montpellier 1 (UM1), Osteopathic College of Medicine, Nova Southeastern University (NSU), Respiratory Research Group, University of Manchester [Manchester]-School of Translational Medicine, Department of Respiratory Diseases, Aarhus University Hospital, Department of Dermatology and Allergy Biederstein, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Service de pneumologie, Centre hospitalier de la région d'Annecy, Service de pneumo-allergologie, Centre Hospitalo-Universitaire de Béni-Messous, Allergy Centre, Vilnius University Antakalnis Hospital, Société Marocaine des Maladies Respiratoires, Centre of Respiratory Diseases and Allergy-Centre commercial Nadia, Allergy Division, Hospital S. João-Centre for Research in Health Technologies and Information Systems (CINTESIS)-Biostatistics and Medical Informatics Department-Porto University Medical School, Department of Otorhinolaryngology, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Department of Social Medicine, University of Crete [Heraklion] (UOC)-Faculty of Medicine, Health Care, Minister Of Labour-Ministry of Labor, Health and Social Affairs, Section of Allergology, Erasmus Medical Centre, Epidemiology and Biostatistics Division, University of Arizona-Associate Research Scientist, Respiratory Sciences-Arizona Respiratory Center, Helsinki University Hospital-Skin and Allergy Hospital, Centre Hospitalier de Bigorre [Tarbes]-Association Franco-Libanaise de Pneumologie (AFLP), Department of Otorhinolaryngology, Head, and Neck Surgery, University Hospital Leuven, Engineering and the Environment, University of Southampton, Paediatrics and Child Health, University College Cork (UCC), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de l'Asthme et des Allergies [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Pediatric Allergy and Asthma Unit, Ihsan Dogramaci Children's Hospital-Hacettepe University School of Medicine, Institute for Asthma and Allergy, George Washington University Medical School, Department of Epidemiology, University of Groningen [Groningen]-University Medical Center Groningen [Groningen] (UMCG)-Groningen Research Institute for Asthma and COPD (GRIAC), Université Saint-Joseph de Beyrouth (USJ)-Faculté de Médecine-Hôtel-Dieu de France, Service des Maladies Respiratoires, CHU de Cocody-UFR des Sciences Médicales, Pediatric Pulmonology, Allergology & Epidemiology, University of Groningen [Groningen]-University Medical Center Groningen [Groningen] (UMCG)-Beatrix Children's Hospital-Groningen Research Institute for Asthma and COPD, Department of Clinical Immunology and Allergy, Medical University of Łódź (MUL)-Faculty ot Medicine, Centre for Allergy Research, Karolinska Institutet [Stockholm], Department of Clinical Science and Education, Division of Internal Medicine, Asthma and Allergy, Medical University of Łódź (MUL)-Barlicki University Hospital, Hospital Medica Sur, Physiology Department, University of Medicine and Pharmacy, Division of Allergy Immunology, Department of Medicine-The University of Tennessee Health Science Center [Memphis] (UTHSC), university of dundee asthma - allergic rhinitis - COPD - beta-2-adrenoceptor, University of Dundee, Pulmonary and allergy unit, American University of Sharjah-Rashid Hospital-Dubai Health Authority (DHA), Association Franco-Vietnamienne de Pneumologie (AFVP), Centre Hospitalier de Compiègne (CHC), Arizona Respiratory Center, Department of Medicine, Clinical Immunology and Allergy, University of Mississippi Medical Center (UMMC), Institute of Environmental Medicine, Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm]-Astrid Lindgren Children's Hospital, Allergy & Asthma Medical Group & Research Center, University of California [San Diego] (UC San Diego), Pneumology Department, Marius Nasta Institute of Pneumology, Department of Internal Medicine, Tishreen University School of Medicine, Association Franco-Marocaine de Pathologie Thoracique (AFMAPATH), Collège National des Pneumologues Marocains, Epidémiologie Environnementale : Impact Sanitaire des Pollutions (EA 4064), Université Paris Descartes - Paris 5 (UPD5), Immunoallergy Department, Hospital CUF Descobertas, Rhinology Unit & Smell Clinic, Universitat de Barcelona (UB)-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-Department of Medicine-Hospital Clinic-ENT Department, Allergy Unit, Università degli Studi di Padova = University of Padua (Unipd)-Department of Paediatrics, Section of Otolaryngology-Head & Neck Surgery (OHNS), University of Chicago, Clinique des maladies respiratoires, centre hospitalo-universitaire Mustapha Pacha d'Alger (CHUMA), Scientific Center for Children's Health, Russian Academy of Medical Sciences (RAMS), Laboratory of Allergology and Pulmonary Diseases, University of Groningen [Groningen]-University Medical Center Groningen [Groningen] (UMCG)-Department of Pathology and Medical Biology-GRIAC Research Institute, ENT Department, University of Kinshasa (UNIKIN), Bradford Neonatology, Bradford Teaching Hospitals NHS Foundation Trust-Bradford Institute for Health Research, Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital-Monash University Building, AMREP, Chiba University Hospital, Asthme Rhinite allergique, Pharmacie, Division of Pediatric Allergy and Immunology, marmara university, Pédiatrie, Centre Hospitalier National Pédiatrique Charles de Gaulle (CHNP-CDG), European Federation of Allergy (EFA), Airways Diseases Patients' Associations, Department of Allergology and Clinical Immunology, Charles University [Prague] (CU)-Medical Faculty in Pilsen, Immunopharmacology, Nippon Medical School-Medical Research Council Clinical, Laboratoire du Sommeil et de l'Effort, Société de Pneumologie de Langue Française (SPLF)-Clinique St George, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinic of Allergy and Asthma, Medical University Sofia-Alexander's University Hospital, Regional Health Service - Lazio, Primary Care Respiratory Medicine, University of Aberdeen-Department of General Practice and Primary Care-General Practice Airways Group (GPIAG), Department of Pulmonary Medicine, Leiden University Medical Center (LUMC), Pneumalgia, Centre Hospitalier Regional-Espace Francophone de Pneumologie (EFP)-Société de Pneumologie de l'Océan Indien (SPOI), Association Franco-Algérienne de Pneumologie (AFAP), Espace Francophone de pneumologie de la SPLF, Department of Pneumology, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-Hospital Clínic de Barcelona-Institut Clínic del Tórax (ICT)-CIBER de Enfermedades Respiratorias (CIBERES)-University of Barcelona, Allergology and Clinical Immunology, Medical University of Silesia (SUM)-Chair and Clinical Department of Internal Diseases, UCSC-Allergy Unit, Complesso Integrato Columbus-Department of Internal Medicine and Geriatrics, Hospital da Luz, Medical Centre, Woodbrook Medical Centre, Research Fellow, University of Aberdeen-Department of General Practice, Centro Médico Docente La Trinidad, Department of Pharmacology, University College of London [London] (UCL)-The Royal National Throat, Nose and Ear Hospital, Primary Care Research & Development, University of Edinburgh-Centre for Population Health Sciences, Section of Allergy & Clinical Immunology, University of Manitoba [Winnipeg]-Department of Pediatrics & Child Health, Allergy Unit - Department of Dermatology, Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], National Centre of Cardiology and Internal Medicine, Ministry of Health Kyrgyz Republic, School of Medicine, Pontifícia Universidade Católica, Department of ENT and Pediatrics, Finnish Institute of Occupational Health, Department of Obstetrics and Gynaecology, Université Laval [Québec] (ULaval)-Faculty of Medicine, Christian Doppler Laboratory for Allergy Research, Medizinische Universität Wien = Medical University of Vienna-Division of Immunopathology-Department of Pathophysiology and Allergy Research-Center for Pathophysiology, Infectiology and Immunology, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Department of Chest Medicine, Mont-Godinne Hospital-Catholic University of Louvain de Mont-Godinne, Department of Primary and Community Care, Radboud University Medical Center [Nijmegen], Epidemiology Unit, National Research Council (CNR)-Institute of Biomedicine and Molecular Immunology (IBIM), Pulmonary Environmental Epidemiology Unit, CNR Institute of Clinical Physiology, Department of Otolaryngology, National University of Singapore (NUS)-Yong Loo Lin School of Medicine, Karolinska Institutet [Stockholm]-Sachs' Children's Hospital, GLP Analytical Facility, School of Pharmacy, Department of Dermatology Division of Immunology, Allergy and Infectious Diseases (DIAID), Medical University of Vienna (MUW), Celal Bayar University School of Medicine, Allergy and Asthma Clinics, The Allergy and Asthma Institute, Department of Paediatrics and Child Health, Respiratory and Allergic Diseases, University Clinic of Respiratory and Allergic Diseases Golnik, State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Diseases-Guangzhou Medical College, Secretary General of the Global Allergy and Asthma European Network (GA2LEN), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], In collaboration with the WHO Collaborating Center for Asthma and Rhinitis, University of Genoa (UNIGE)-School of Specialization, CNR, Rome, Italy and Department of Medicine-University of Naples Federico II, University of Verona (UNIVR), Medical School-Federal University of Minas Gerais, University of Genoa (UNIGE)-Department of Internal Medicine (DIMI), University of California [Irvine] (UCI), University of California-University of California, Catholic University Rome, University of Amsterdam [Amsterdam] (UvA)-Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Centre Hospitalier de Bigorre (Tarbes)-Association Franco-Libanaise de Pneumologie (AFLP), CUF-Descobertas Hospital, Universita degli Studi di Padova-Department of Paediatrics, Medical Faculty in Pilsen-Charles University in Prague - the First Faculty of Medicine, Centro Medico-Docente La Trinidad, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]-Instittute of Social Health, Department of Internal Medicine (DIMI)-University of Genoa (UNIGE), Medical University of Silesia-Chair and Clinical Department of Internal Diseases, Dermatology, Internal Medicine, Immunology, Hôpital Arnaud de Villeneuve, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Center for Research in Environmental Epidemiology ( CREAL ), Universitat Pompeu Fabra [Barcelona]-Catalunya ministerio de salud, Universitat Pompeu Fabra [Barcelona], WHO(OMS), Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), National Institute of Allergy and Infectious Diseases [Bethesda], National Institutes of Health ( NIH ), Swiss Institute of Allergy and Asthma Research ( SIAF ), University of Zürich [Zürich] ( UZH ), Upper Airway Research Laboratory ( URL ), University Medical Center, University of Oslo ( UiO ) -Oslo University Hospital, Charite-Universitatsmedizin Berlin [Berlin]-Instittute of Social Health, Medical School-Charité - University Medicine Berlin, Medical University of Warsaw-Faculté de Pharmacie de Paris, Ministry of Health, Epidémiologie des maladies infectieuses et modélisation ( ESIM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Center for Public Health Research ( CSISP ), University of Genoa ( UNIGE ) -School of Specialization, University of Amsterdam [Amsterdam] ( UvA ) -Academic Medical Centre, University of Southampton [Southampton]-School of Medicine, Hôpital La Rabta [Tunis), Wake Forest University Health Sciences, CNR, Rome, Italy and Department of Medicine-Second University of Naples, Università degli Studi di Verona, Université Laval-l'Hôpital Laval, Imperial College London-Royal Brompton Hospital-National Heart and Lung Institute, University of Genoa ( UNIGE ) -Department of Internal Medicine (DIMI), Southern California Research, Université Montpellier 1 ( UM1 ), Nova Southeastern University, Technische Universität München [München] ( TUM ), Academic Medical Center [Amsterdam] ( AMC ), University of Amsterdam [Amsterdam] ( UvA ) -University of Amsterdam [Amsterdam] ( UvA ), University of Crete ( UOC ) -Faculty of Medicine, University of Southampton [Southampton], UUniversity College Cork - National University of Ireland, Cork (UCC), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Antoine Béclère, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], University of Groningen [Groningen]-University Medical Center Groningen-Groningen Research Institute for Asthma and COPD (GRIAC), Université Saint-Joseph de Beyrouth ( USJ ) -Faculté de Médecine-Hôtel-Dieu de France, University of Groningen [Groningen]-University Medical Center Groningen-Beatrix Children's Hospital-Groningen Research Institute for Asthma and COPD, Medical University of Łódź ( MUL ) -Faculty ot Medicine, Medical University of Łódź ( MUL ) -Barlicki University Hospital, Department of Medicine-University of Tennessee College for Medicine, Association Franco-Vietnamienne de Pneumologie ( AFVP ), University of Mississippi Medical Center, University of California [San Diego] ( UC San Diego ), Association Franco-Marocaine de Pathologie Thoracique ( AFMAPATH ), Epidémiologie Environnementale : Impact Sanitaire des Pollutions ( EA 4064 ), Université Paris Descartes - Paris 5 ( UPD5 ), Universitat de Barcelona ( UB ) -Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-Department of Medicine-Hospital Clinic-ENT Department, Section of Otolaryngology-Head & Neck Surgery ( OHNS ), University of Groningen [Groningen]-University Medical Center Groningen-Department of Pathology and Medical Biology-GRIAC Research Institute, University Hospital of Kinshasa, European Federation of Allergy ( EFA ), Institut d'oncologie/développement Albert Bonniot de Grenoble ( INSERM U823 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Bioenergétique fondamentale et appliquée ( LBFA ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Department of General Practice and Primary Care-General Practice Airways Group (GPIAG)-University of Aberdeen, Association Franco-Algérienne de Pneumologie ( AFAP ), Department of General Practice-University of Aberdeen, University College of London [London] ( UCL ) -The Royal National Throat, Nose and Ear Hospital, University Medical Center Utrecht, Faculty of Medicine-Laval University [Québec], Medical University of Vienna-Division of Immunopathology-Department of Pathophysiology and Allergy Research-Center for Pathophysiology, Infectiology and Immunology, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, National University of Singapore ( NUS ) -Yong Loo Lin School of Medicine, Department of Dermatology Division of Immunology, Allergy and Infectious Diseases ( DIAID ), Secretary General of the Global Allergy and Asthma European Network ( GA2LEN ), Network of Excellence, Charité - Universitätsmedizin Berlin, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK (BIHR), Universiteit Leiden-Universiteit Leiden, and Medizinische Universität Wien = Medical University of Vienna
Subjects: MESH: Asthma, severity, MESH: Comorbidity, Comorbidity, Severity of Illness Index, urticaria, MESH : Chronic Disease, MESH: Practice Guidelines as Topic, MESH : Dermatitis, Atopic, MESH: Urticaria, risk, 216-31 [Rhinitis, atopy, allergen Int Arch Allergy Immunol. 2012,158(3)], atopic dermatitis, MESH : Rhinitis, MESH: Rhinitis, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Effective primary care and public health [NCEBP 7], Immunoglobulin E - Asthma - Rhinitis - Rhinosinusitis - Urticaria - Atopic dermatitis, MESH : Practice Guidelines as Topic, Practice Guidelines as Topic, MESH : Comorbidity, MESH : Severity of Illness Index, IgE, MESH: Sinusitis, MESH : Urticaria, MESH: Hypersensitivity, macromolecular substances, MESH : Asthma, Dermatitis, Atopic, rhinitis, SDG 3 - Good Health and Well-being, MESH: Dermatitis, Atopic, MESH: Severity of Illness Index, Hypersensitivity, Humans, Sinusitis, rhinosinusitis, MESH : Hypersensitivity, MESH: Humans, MESH: Chronic Disease, MESH : Humans, Asthma, Atopic dermatitis, Immunoglobulin E, Rhinitis, Rhinosinusitis, Urticaria, asthma, allergy, MESH : Sinusitis, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Chronic Disease, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, control
Abstract: Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies. Copyright (C) 2012 S. Karger AG, Basel
Published: 2012
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24. The Impact of Stroke Subtype on Recovery and Functional Outcome after Inpatient Rehabilitation: A Retrospective Analysis of Factors

Author: Rathi Ratha Krishnan, Edgar Quan Yi Yeo, Chien Joo Lim, Karen Sui Geok Chua, Lee Kong Chian School of Medicine (LKCMedicine), Tan Tock Seng Hospital, Yong Loo Lin School of Medicine, NUS, and MOH Holdings, Singapore
Subjects: cerebral infarction, cerebral hemorrhage, rehabilitation, stroke, functional outcome, Space and Planetary Science, Paleontology, Medicine [Science], Cerebral Infarction, General Biochemistry, Genetics and Molecular Biology, Ecology, Evolution, Behavior and Systematics, Cerebral Hemorrhage
Abstract: The aims of this study were to compare inpatient rehabilitation outcomes between acute stroke subtypes of Cerebral Infarction (CI) and Intracerebral Hemorrhage (ICH), and to determine the predictors of discharge outcomes. A retrospective study of stroke inpatients was carried out using the discharge Functional Independence Measure (FIM) as the primary outcome measure. Relationships between stroke subtype, rehabilitation impairments, and medical complications on FIM -gain were analyzed. Altogether, 280 datasets including 211 (75.4%) CI and 69 (24.6%) ICH were analyzed. ICH patients were significantly younger than CI patients (55 years ICH vs. 64.0 years CI years, p < 0.001), had a 10-fold higher proportion needing ICU admission (ICH 82.6% vs. CI 7.6%, p < 0.001), and had significantly lower total admission FIM scores (67 points ICH vs. 74 CI points, p = 0.006), with lower motor-FIM scores in particular (38 points ICH vs. 48 points CI, p = 0.003). Significant functional improvements after inpatient rehabilitation, i.e., FIM gain, occurred regardless of stroke subtype (FIM-ICH Δ 27 vs. FIM-CI Δ 21, p = 0.05). Despite significantly worse initial stroke severity, ICH patients achieved similar functional gains, independence levels, and return-home rates compared with their CI counterparts after inpatient rehabilitation.
Published: 2022
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25. Characteristics of Patients with Unrecognized Sleep Apnea Requiring Postoperative Oxygen Therapy

Author: Edwin Seet, Rida Waseem, Matthew T. V. Chan, Chew Yin Wang, Vanessa Liao, Colin Suen, Frances Chung, Lee Kong Chian School of Medicine (LKCMedicine), Yong Loo Lin School of Medicine, NUS, and Khoo Teck Puat Hospital
Subjects: Obstructive Sleep Apnea, oxygen therapy, obstructive sleep apnea, personalized medicine, hypoxemia, postoperative care, oximetry parameters, phenotypes, Medicine (miscellaneous), Medicine [Science], Oxygen Therapy
Abstract: Surgical patients with obstructive sleep apnea (OSA) have increased risk of perioperative complications. The primary objective is to determine the characteristics of surgical patients with unrecognized OSA requiring oxygen therapy for postoperative hypoxemia. The secondary objective is to investigate the characteristics of patients who were responsive to oxygen therapy. This was a post-hoc multicenter study involving patients with cardiovascular risk factors undergoing major non-cardiac surgery. Patients ≥45 years old underwent Type 3 sleep apnea testing and nocturnal oximetry preoperatively. Responders to oxygen therapy were defined as individuals with ≥50% reduction in oxygen desaturation index (ODI) on postoperative night 1 versus preoperative ODI. In total, 624 out of 823 patients with unrecognized OSA required oxygen therapy. These were mostly males, had larger neck circumferences, higher Revised Cardiac Risk Indices, higher STOP-Bang scores, and higher ASA physical status, undergoing intraperitoneal or vascular surgery. Multivariable regression analysis showed that the preoperative longer cumulative time SpO2 < 90% or CT90% (adjusted p = 0.03), and lower average overnight SpO2 (adjusted p < 0.001), were independently associated with patients requiring oxygen therapy. Seventy percent of patients were responders to oxygen therapy with ≥50% ODI reduction. Preoperative ODI (19.0 ± 12.9 vs. 14.1 ± 11.4 events/h, p < 0.001), CT90% (42.3 ± 66.2 vs. 31.1 ± 57.0 min, p = 0.038), and CT80% (7.1 ± 22.6 vs. 3.6 ± 8.7 min, p = 0.007) were significantly higher in the responder than the non-responder. Patients with unrecognized OSA requiring postoperative oxygen therapy were males with larger neck circumferences and higher STOP-Bang scores. Those responding to oxygen therapy were likely to have severe OSA and worse preoperative nocturnal hypoxemia. Preoperative overnight oximetry parameters may help in stratifying patients. Published version This research was funded by University Health Network Foundation; ResMed Foundation; Health and Medical Research Fund (09100351), Hong Kong; National Healthcare Group Small Innovative Grant (12019, 15201); University of Malaya, High Impact Research Grant (UM.C/625/1/HIR/067).
Published: 2022

26. Long-Term Outcomes of Patients with Primary Brain Tumors after Acute Rehabilitation: A Retrospective Analyses of Factors

Author: Matthew Rong Jie Tay, Justin Desheng Seah, Karen Sui Geok Chua, Lee Kong Chian School of Medicine (LKCMedicine), Tan Tock Seng Hospital, and Yong Loo Lin School of Medicine, NUS
Subjects: brain tumors, neuro-oncology, brain cancer, central nervous system tumors, neurological rehabilitation, Space and Planetary Science, Neurological Rehabilitation, Brain Tumors, Paleontology, Medicine [Science], General Biochemistry, Genetics and Molecular Biology, Ecology, Evolution, Behavior and Systematics
Abstract: Although primary brain tumors are relatively rare, they cause significant morbidity and mortality due to the high rates of neurological impairment. The purpose of this study was to examine the physical and functional outcomes of patients with primary brain tumors who had undergone inpatient rehabilitation. This was a retrospective study which recruited 163 patients who had been admitted for inpatient rehabilitation. Rehabilitation outcomes, including the Functional Independence Measure (FIM) and Glasgow Outcome Scale (GOS), were recorded up to 1 year post-discharge. The majority of patients (79.1%) had low-grade (WHO Class I-II) tumors, 35 (21.5%) were diagnosed with GBM and 52 (31.9%) had recurrent brain tumors. Rehabilitation outcomes were sustained, with 125 (76.7%) and 113 (69.3%) patients having a GOS of ≥4 at 6 months and 1 year after discharge, respectively. A GOS of ≥4 at 1 year was negatively associated with high-grade tumors (p < 0.001) and radiotherapy (p = 0.028), and positively associated with a higher discharge FIM motor score (p < 0.001) and the presence of a caregiver after discharge (p = 0.034). Our study demonstrates significant positive functional benefits from 4 weeks of inpatient neuro-oncological rehabilitation for patients with primary brain tumors, as well as the importance of supportive care from caregivers.
Published: 2022

27. The EU Child Cohort Network's core data

Author: Rachel E. Foong, Marie Pedersen, Johan G. Eriksson, Barbara Heude, Faryal Zariouh, Johan Lerbech Vinther, Theano Roumeliotaki, John Wright, Veit Grote, Kathrin Guerlich, Anne-Marie Nybo Andersen, Tiffany Yang, Anne Cathrine Jørgensen, Martine Vrijheid, Ellis Voerman, Liesbeth Duijts, Marjo-Riitta Järvelin, Sido Haakma, Ahmed Elhakeem, Hazel Inskip, Angela Pinot de Moira, Maja Popovic, Sílvia Fernández-Barrés, Eva Corpeleijn, Anne Forhan, Tuija M. Mikkola, Sylvain Sebert, Morris A. Swertz, Rae-Chi Huang, Theodosia Salika, Justiina Ronkainen, Esther van Enckevort, Vincent W. V. Jaddoe, Lorenzo Richiardi, Tim Cadman, Marloes Cardol, Katrine Strandberg-Larsen, Marjolein N. Kooijman, Janine F. Felix, Marie-Aline Charles, Johanna L. Nader, Sarah Crozier, Nina Rautio, Department of Public Health [Copenhagen], Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), University Medical Center Groningen [Groningen] (UMCG), Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Bristol [Bristol], University of Southampton, University of Helsinki, Yong Loo Lin School of Medicine [Singapore], Folkhälsan Research Center, Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Universitat Pompeu Fabra [Barcelona] (UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Curtin University [Perth], Planning and Transport Research Centre (PATREC), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Oulu, Imperial College London, Norwegian Institute of Public Health [Oslo] (NIPH), University of Turin, University of Crete [Heraklion] (UOC), Etude longitudinale française depuis l'enfance (UMS : Ined-Inserm-EFS) (ELFE), EFS-Institut national d'études démographiques (INED)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Project: 733206,H2020,H2020-SC1-2016-RTD,LIFECYCLE(2017), Pediatrics, Clinicum, Research Programs Unit, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, HUS Helsinki and Uusimaa Hospital District, Faculty of Medicine, Reproductive Origins of Adult Health and Disease (ROAHD), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Università degli studi di Torino = University of Turin (UNITO), and Institut national d'études démographiques (INED)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Databases, Factual, Epidemiology, [SDV]Life Sciences [q-bio], Interoperability, Cohort Studies, Data harmonisation, 0302 clinical medicine, Resource (project management), Medicine, 030212 general & internal medicine, Child, DNA METHYLATION, Lifecourse epidemiology, 3142 Public health care science, environmental and occupational health, Europe, PREGNANCY, Child, Preschool, Cohort, GROWTH, HEALTH, Public Health, Birth cohort, Cohort study, Cross-cohort collaboration, FAIR (findable, accessible, interoperable and reusable) principles, Humans, Information Dissemination, DATA HARMONIZATION, PRETERM BIRTH, FAIR (findable, PROFILE, accessible, 03 medical and health sciences, Databases, interoperable and reusable) principles, Product (category theory), Preschool, Factual, Protocol (science), business.industry, NORWEGIAN MOTHER, AIR-POLLUTION, Data science, BIRTH-WEIGHT, Replication (computing), 030104 developmental biology, business, Data Resource
Abstract: The Horizon2020 LifeCycle Project is a cross-cohort collaboration which brings together data from multiple birth cohorts from across Europe and Australia to facilitate studies on the influence of early-life exposures on later health outcomes. A major product of this collaboration has been the establishment of a FAIR (findable, accessible, interoperable and reusable) data resource known as the EU Child Cohort Network. Here we focus on the EU Child Cohort Network's core variables. These are a set of basic variables, derivable by the majority of participating cohorts and frequently used as covariates or exposures in lifecourse research. First, we describe the process by which the list of core variables was established. Second, we explain the protocol according to which these variables were harmonised in order to make them interoperable. Third, we describe the catalogue developed to ensure that the network's data are findable and reusable. Finally, we describe the core data, including the proportion of variables harmonised by each cohort and the number of children for whom harmonised core data are available. EU Child Cohort Network data will be analysed using a federated analysis platform, removing the need to physically transfer data and thus making the data more accessible to researchers. The network will add value to participating cohorts by increasing statistical power and exposure heterogeneity, as well as facilitating cross-cohort comparisons, cross-validation and replication. Our aim is to motivate other cohorts to join the network and encourage the use of the EU Child Cohort Network by the wider research community. The LifeCycle project received funding from the European Union’s Horizon 2020 research and innovation programme (Grant Agreement No. 733206 LifeCycle). All study specific acknowledgements and funding are presented in the supplementary material. This manuscript reflects only the author’s view and the Commission is not responsible for any use that may be made of the information it contains.
Published: 2021
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28. Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes

Author: Aaron Ciechanover, Eric H. Baehrecke, Josef M. Penninger, Moshe Oren, Marja Jäättelä, Cecília M. P. Rodrigues, Seamus J. Martin, Lorenzo Galluzzi, Dale E. Bredesen, Stuart A. Aaronson, Donald W. Nicholson, Frank Madeo, Mikhail V. Blagosklonny, Gabriel Núñez, Hans-Uwe Simon, Adi Kimchi, Karen H. Vousden, Yoshihide Tsujimoto, David W. Andrews, Simone Fulda, J. Tschopp, John M. Abrams, Hinrich Gronemeyer, Nicolas G. Bazan, Michael O. Hengartner, Richard A. Flavell, Beth Levine, Thomas Rudel, Ilio Vitale, Eugenia Morselli, Rosario Rizzuto, Boris Zhivotovsky, Douglas R. Green, J. M. Hardwick, Maria Castedo, Guido Kroemer, Pierluigi Nicotera, Christoph Borner, David C. Rubinsztein, Junying Yuan, Jan Paul Medema, Oliver Kepp, Carmen Garrido, V De Laurenzi, Jean-Christophe Marine, Richard J. Youle, Hidenori Ichijo, Daniel J. Klionsky, Hamsa Puthalakath, Ute M. Moll, Shigekazu Nagata, R De Maria, Pierre Golstein, Marie-Lise Gougeon, Mohanish Deshmukh, Enrico Lugli, Brian David Dynlacht, Emad S. Alnemri, John A. Cidlowski, Luca Scorrano, Stuart A. Lipton, Hermann Steller, Sally Kornbluth, Gerry Melino, György Hajnóczky, Gabriel A. Rabinovich, Peter Vandenabeele, Gerald M. Cohen, Shazib Pervaiz, Marcus E. Peter, Richard A. Knight, Jochen H. M. Prehn, Sharad Kumar, Klas Blomgren, Walter Malorni, Wafik S. El-Deiry, Patrick Mehlen, Mauro Piacentini, Catherine Brenner, Apoptose, cancer et immunité (U848), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Department of Cell Biology, University of Texas Southwestern Medical Center [Dallas], Department of Biochemistry and Molecular Biology, Thomas Jefferson University-Sidney Kimmel Cancer Center, Jefferson (Philadelphia University + Thomas Jefferson University)-Jefferson (Philadelphia University + Thomas Jefferson University), Department of Biochemistry and Biomedical Sciences, McMaster University [Hamilton, Ontario], Department of Cancer Biology, University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS)-University of Massachusetts System (UMASS), Neuroscience Center of Excellence, LSU Health Sciences Center, Roswell Park Cancer Institute [Buffalo] (RPCI), Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology [Göteborg]-University of Gothenburg (GU), Department of Pediatric Oncology, The Queen Silvia Children's Hospital, Institute of Molecular Medicine and Cell Research (ZBMZ), University of Freiburg [Freiburg], Buck Institute for Age Research, Laboratoire de génétique et biologie cellulaire (LGBC), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), National Institutes of Environmental Health Sciences, National Institutes of Health [Bethesda] (NIH), Vascular and Tumor Biology Research Center, Israel Institute of Technology, Toxicology Unit, University of Leicester, Dipartimento di Scienze Biomediche, Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] (Ud'A), Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità (ISS), Mediterranean Institute of Oncology, Department of Cell and Developmental Biology, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Department of Pathology, New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Hematology-Oncology Division, Perelman School of Medicine, University of Pennsylvania-University of Pennsylvania, Section of Immunobiology, Yale School of Medicine [New Haven, Connecticut] (YSM), Howard Hughes Medical Institute [Chevy Chase] (HHMI), Howard Hughes Medical Institute (HHMI), University Children's Hospital, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunité Antivirale, Biothérapie et Vaccins, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Immunology, St Jude Children's Research Hospital, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Department of Pharmacology and Molecular Sciences, Johns Hopkins University (JHU), Institute of Molecular Biology, Universität Zürich [Zürich] = University of Zurich (UZH), Graduate School of Medecine, The University of Tokyo (UTokyo), Danish Cancer Society, Institute of Cancer Biology, Department of Molecular Genetics, Weizmann Institute of Science [Rehovot, Israël], Life Sciences Institute and Department of Molecular, Cellular, and Developmental Biology and Biological Chemistry, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Institute of Child Health [London], University College of London [London] (UCL), Duke University School of Medicine, Centre for Cancer Biology, Hanson Institute, Adelaide, Burnham Institute for Medical Research, The Salk Institute for Biological Studies, The Scripps Research Institute [La Jolla, San Diego], University of California [San Diego] (UC San Diego), University of California (UC), Immunotechnology Section, Vaccine Research Center, National Institutes of Health [Bethesda] (NIH)-National Institute of Allergy and Infectious Diseases, Institute of Molecular Biosciences, Karl-Franzens-Universität Graz, Department of Therapeutic Research and Medicines Evaluation, Laboratory for Molecular Cancer Biology, VIB-UGent, Department for Molecular Biology, Universiteit Gent = Ghent University (UGENT), Department of Genetics, Trinity College Dublin, Center for Experimental and Molecular Medicine, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), University of Amsterdam [Amsterdam] (UvA), Apoptosis, Cancer, and Development Laboratory, Centre Léon Bérard [Lyon], Apoptose Cancer et Développement, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Department of Experimental Medicine and Biochemical Sciences, Università degli Studi di Roma Tor Vergata [Roma], Stony Brook University [SUNY] (SBU), State University of New York (SUNY)-State University of New York (SUNY), Department of Molecular Oncology, Göttingen Center of Molecular Biosciences, Faculty of Medicine, Georg-August-University = Georg-August-Universität Göttingen, Fujitsu Laboratories LTD., Fujitsu Laboratories Ltd., Department of Medical Chemistry, Kyoto University-Graduate School of Medicine, Merck & Co. Inc, University of Michigan Medical School [Ann Arbor], Department of Molecular Cell Biology [Rehovot], Institute of Molecular Biotechnology, Austrian Academy of Sciences (OeAW), Department of Physiology, National University of Singapore (NUS)-Yong Loo Lin School of Medicine-Graduate School for Integrative Sciences and Engineering, Singapore-MIT Alliance for Research and Technology (SMART), Massachusetts Institute of Technology (MIT), Duke-NUS Medical School [Singapore], Ben May Department for Cancer Research, University of Chicago-Ben May Department for Cancer Research, Laboratory of Cell Biology, National Institute for Infectious Diseases IRCCS 'L. Spallanzani', Department of Biology, Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland (RCSI), Department of Biochemistry, La Trobe University [Melbourne], Laboratorie de Inmunopatologia, Instituto de Biología y Medicina Experimental [Buenos Aires] (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Department of Biomedical Sciences, Università degli Studi di Padova = University of Padua (Unipd), iMed.UL, Universidade de Lisboa = University of Lisbon (ULISBOA), Cambridge Institute for Medical Research (CIMR), University of Cambridge [UK] (CAM), Biocenter, Julius-Maximilians-Universität Würzburg (JMU), Department of Cell Physiology and Metabolism, University of Geneva Medical School, Dulbecco-Telethon Institute, Venetian Institute Molecular Medicine (VIMM), University of Bern, Laboratory of Apoptosis and Cancer Biology, Rockefeller University [New York], Department of Biochemistry [Lausanne], Université de Lausanne = University of Lausanne (UNIL), Department of Medical Genetics, Osaka University Medical School, Department for Molecular Biomedical Research, The Beatson Institute for Cancer Research, University of Glasgow, Biochemistry Section, Surgical Neurology Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Neurological Disorders and Stroke, Department of cell biology, Harvard Medical School [Boston] (HMS), Division of Toxicology, karolinska institute-Institute of Environmental Medicine, Scorrano, Luca, Tschopp, Jean-Marie, Apoptose, cancer et immunité ( U848 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Mount Sinai School of Medicine, Thomas Jefferson University-Kimmel Cancer Institute, University of Massachusetts Medical School [Worcester] ( UMASS ), Roswell Park Cancer Institute [Buffalo], Institute of Neuroscience and Physiology [Göteborg]-University of Gothenburg ( GU ), Institute of Molecular Medicine and Cell Research ( ZBMZ ), Albert-Ludwigs University, Laboratoire de génétique et biologie cellulaire ( LGBC ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -École pratique des hautes études ( EPHE ) -Centre National de la Recherche Scientifique ( CNRS ), National Institutes of Health ( NIH ), Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] ( Ud'A ), Istituto Superiore di Sanita [Rome], The University of North Carolina at Chapel Hill, University of Pennsylvania School of Medicine, Yale School of Medicine, Howard Hughes Medical Institute, Howard Hugues Medical Institute, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre d'Immunologie de Marseille - Luminy ( CIML ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), St. Jude Children's Research Hospital, Institut de Génétique et de Biologie Moléculaire et Cellulaire ( IGBMC ), Université de Strasbourg ( UNISTRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Johns Hopkins University ( JHU ), University of Zürich [Zürich] ( UZH ), The University of Tokyo, Weizmann Institute of Science, University College of London [London] ( UCL ), The Scripps Research Institute, University of California [San Diego] ( UC San Diego ), National Institutes of Health ( NIH ) -National Institute of Allergy and Infectious Diseases, University of Graz, Ghent University [Belgium] ( UGENT ), Academic Medical Center [Amsterdam] ( AMC ), University of Amsterdam [Amsterdam] ( UvA ) -University of Amsterdam [Amsterdam] ( UvA ), University of Amsterdam [Amsterdam] ( UvA ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Stony Brook University [The State University of New York] ( SBU ), University of Göttingen, Kyoto University [Kyoto]-Graduate School of Medicine, Merck and Co [Rahway], University of Michigan Medical School, Austrian Academy of Sciences ( OeAW ), National University of Singapore ( NUS ) -Yong Loo Lin School of Medicine-Graduate School for Integrative Sciences and Engineering, Singapore-MIT Alliance, National University of Singapore ( NUS ), Duke-NUS Graduate Medical School, Royal College of Surgeons in Ireland, Instituto de Biología y Medicina Experimental (IBYME- CONICET), Universita degli Studi di Padova = University of Padua = Université de Padoue, University of Lisbon, Cambridge Institute for Medical Research, University of Würzburg, Venetian Institute of Molecular Medicine, The Rockefeller University, Université de Lausanne ( UNIL ), Vib Ghent University, National Institutes of Health ( NIH ) -National Institute of Neurological Disorders and Stroke, Harvard Medical School [Boston] ( HMS ), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Yale University School of Medicine, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), University of California, Karl-Franzens-Universität [Graz, Autriche], Universiteit Gent = Ghent University [Belgium] (UGENT), Georg-August-University [Göttingen], Universita degli Studi di Padova, Universidade de Lisboa (ULISBOA), Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Université de Lausanne (UNIL), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-École pratique des hautes études (EPHE), Peney, Maité, Galluzzi, L, Aaronson, SA, Abrams, J, Alnemri, ES, Kumar, Sharad, and Kroemer, Guido
Subjects: MESH: Cell Death, cytofluorometry, MESH : Microscopy, Fluorescence, ved/biology.organism_classification_rank.species, Cell, MESH: Flow Cytometry, MESH: Microscopy, Fluorescence, Apoptosis, fluorescence microscopy, MESH: Eukaryotic Cells, Annexin V, necrosis, 0302 clinical medicine, Eukaryotic Cells/cytology, Mitochondrial membrane permeabilization, Scanning, MESH : Immunoblotting, Genetics, Cell Death, Flow Cytometry, Guidelines as Topic, Humans, Immunoblotting, Microscopy, Electron, Scanning, Microscopy, Fluorescence, Spectrometry, Fluorescence, 0303 health sciences, Microscopy, MESH : Spectrometry, Fluorescence, MESH: Immunoblotting, MESH: Guidelines as Topic, purl.org/becyt/ford/3.1 [https], Bioquímica y Biología Molecular, 3. Good health, Tunel, Medicina Básica, medicine.anatomical_structure, Eukaryotic Cells, caspases, 030220 oncology & carcinogenesis, purl.org/becyt/ford/3 [https], MESH: Spectrometry, Fluorescence, MESH : Microscopy, Electron, Scanning, Programmed cell death, autophagy, CIENCIAS MÉDICAS Y DE LA SALUD, MESH: Microscopy, Electron, Scanning, MESH : Flow Cytometry, caspase, Computational biology, Biology, Electron, Fluorescence, Article, 03 medical and health sciences, Settore MED/04 - PATOLOGIA GENERALE, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Model organism, ddc:612, mitotic catastrophe, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Guidelines as Topic, 030304 developmental biology, cell death, Oxidative stress, MESH: Humans, ved/biology, Spectrometry, Interpretation (philosophy), MESH: Apoptosis, MESH : Eukaryotic Cells, MESH : Humans, Cell Biology, immunofluorescence microscopy, MESH : Cell Death, Cancer cell, MESH : Apoptosis
Abstract: Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases. Thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies. It is, therefore, of utmost importance to standardize the experimental procedures that identify dying and dead cells in cell cultures and/or in tissues, from model organisms and/or humans, in healthy and/or pathological scenarios. Thus far, dozens of methods have been proposed to quantify cell death-related parameters. However, no guidelines exist regarding their use and interpretation, and nobody has thoroughly annotated the experimental settings for which each of these techniques is most appropriate. Here, we provide a nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls. These guidelines are intended for investigators who study cell death, as well as for reviewers who need to constructively critique scientific reports that deal with cellular demise. Given the difficulties in determining the exact number of cells that have passed the point-of-no-return of the signaling cascades leading to cell death, we emphasize the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells. Fil: Galluzzi, L.. Inserm; Francia. Universite Paris Sud; Francia. Institut Gustave Roussy; Francia Fil: Aaronson, S. A.. Mount Sinai School of Medicine; Estados Unidos Fil: Abrams, J.. University of Texas. Southwestern Medical Center; Estados Unidos Fil: Alnemri, E. S.. Thomas Jefferson University; Estados Unidos Fil: Andrews, D. W.. McMaster University; Canadá Fil: Baehrecke, E. H.. University of Massachussets; Estados Unidos Fil: Bazan, N. G.. Louisiana State University Health Sciences Center; Estados Unidos Fil: Blagosklonny, M. V.. Roswell Park Cancer Institute; Estados Unidos Fil: Blomgren, K.. Universityt of Gothenburg; Suecia. The Queen Silvia Children; Suecia Fil: Borner, C.. Albert-Ludwigs Universität Freiburg; Alemania Fil: Bredesen, E.. Buck Institute for Age Research; Estados Unidos. University of California; Estados Unidos Fil: Brenner, C.. univeristy of Versailles ; Francia Fil: Castedo, M.. Inserm; Francia. Universite Paris Sud; Francia Fil: Cidlowski, J. A.. National Institutes of Health; Estados Unidos Fil: Ciechanover, A.. The Rappaport Faculty of Medicine; Israel Fil: Cohen, G. M.. University of Leicester; Reino Unido Fil: De Laurenzi, V.. Università ‘G. d’Annunzio’ Chieti Pescara; Italia Fil: De Maria, R.. Istituto Superiore di Sanità; Italia. Mediterranean Institute of Oncology; Italia Fil: Deshmukh, M.. University of North Carolina; Estados Unidos Fil: Dynlacht, B. D.. University of New York; Estados Unidos Fil: El Deiry, W. S.. University of Pennsylvania; Estados Unidos Fil: Flavell, R. A.. University of Yale; Estados Unidos Fil: Fulda, S.. University Children; Alemania Fil: Garrido, C.. Inserm; Francia. University of Burgundy; Francia Fil: Golstein, P.. Inserm; Francia. Aix Marseille Université; Francia Fil: Gougeon, M. L.. Instituto Pasteur; Francia Fil: Green, D. R.. St. Jude Children′s Research Hospital; Estados Unidos Fil: Gronemeyer, H.. Institut de Génétique et de Biologie Moléculaire et Cellulaire; Francia. Inserm; Francia Fil: Hajnóczky, G.. Thomas Jefferson University; Estados Unidos Fil: Hardwick, J. M.. Johns Hopkins University; Estados Unidos Fil: Hengartner, M.O.. University Johns Hopkins; Estados Unidos Fil: Ichijo, H.. University of Tokyo; Japón Fil: Jäättelä, M.. Institute of Cancer Biology; Dinamarca Fil: Kepp, O.. Inserm; Francia. Universite Paris Sud; Francia. Institut Gustave Roussy; Francia Fil: Kimchi, A.. Weizmann Institute of Science; Israel Fil: Klionsky, D. J.. University of Michigan; Estados Unidos Fil: Knight, R. A.. University College London; Estados Unidos Fil: Kornbluth, S.. University of Duke; Estados Unidos Fil: Kumar, S.. Hanson Institute; Australia Fil: Levine, B.. Howard Hughes Medical Institute; Estados Unidos. University of Texas; Estados Unidos Fil: Lipton, S. A.. Burnham Institute for Medical Research; Estados Unidos. The Salk Institute for Biological Studies; Estados Unidos. The Scripps Research Institute; Estados Unidos. University of California at San Diego; Estados Unidos Fil: Lugli, E.. National Institutes of Health; Estados Unidos Fil: Madeo, F.. university of Graz; Austria Fil: Malorni, W.. Istituto Superiore di Sanità; Italia Fil: Marine, J. C.. VIB; Bélgica. Ghent University; Bélgica Fil: Martin, S. J.. Trinity College; Irlanda Fil: Medema, J. P.. Academic Medical Center; Países Bajos. University of Amsterdam; Países Bajos Fil: Mehlen, P.. Centre Léon Berard; Francia. Centre National de la Recherche Scientifique; Francia. Universite Lyon 2; Francia Fil: Melino, G.. University of Leicester; Reino Unido. Göttingen Center of Molecular Biosciences; Alemania Fil: Moll, U. M.. Stony Brook University; Estados Unidos. Göttingen Center of Molecular Biosciences; Alemania. University of Göttingen; Alemania Fil: Morselli, E.. Inserm; Francia. Universite Paris Sud; Francia. Institut Gustave Roussy; Francia Fil: Nagata, S.. University of Kyoto; Japón Fil: Nicholson, D. W.. Merck Research Laboratories; Estados Unidos Fil: Nicotera, P.. University of Leicester; Reino Unido Fil: Nuñez, G.. University of Michigan; Estados Unidos Fil: Oren, M.. Weizmann Institute of Science; Israel Fil: Penninger, J.. Institute of Molecular Biotechnology of the Austrian Academy of Science; Austria Fil: Pervaiz, S.. National University of Singapore; Singapur. Duke-NUS Graduate Medical School; Singapur Fil: Peter, M. E.. University of Chicago; Estados Unidos Fil: Piacentini, M.. National Institute for Infectious Diseases IRCCS "L. Spallanzani"; Italia. University of Rome "Tor Vergata"; Italia Fil: Prehn. J. H.. Royal College of Surgeons in Ireland; Irlanda Fil: Puthalakath, H.. La Trobe University; Australia Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Rizzuto, R.. Università di Padova; Italia Fil: Rodrigues, C. M.. Universidade de Lisboa; Portugal Fil: Rubinsztein, D. C.. Cambridge Institute for Medical Research; Reino Unido Fil: Rudel, T.. University of Würzburg; Alemania Fil: Scorrano, L.. University of Geneva ; Suiza. Venetian Institute of Molecular Medicine; Italia Fil: Simon, H. U.. University of Bern; Suiza Fil: Steller, H.. Howard Hughes Medical Institute; Estados Unidos. The Rockefeller University; Estados Unidos Fil: Tschoop, J.. University of Lausanne; Suiza Fil: Tsujimoto, Y.. Osaka University Medical School; Japón Fil: Vandenabeele, P.. Ghent University; Bélgica. VIB; Bélgica Fil: Vitale, I.. Inserm; Francia. Universite Paris Sud; Francia. Institut Gustave Roussy; Francia Fil: Vousden, K. H.. The Beatson Institute for Cancer Research; Reino Unido Fil: Youle, J. R.. National Institutes of Health; Estados Unidos Fil: Yuan, J.. Harvard Medical School; Estados Unidos Fil: Zhivotovsky, B.. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia Fil: Kroemer, G.. Inserm; Francia. Universite Paris Sud; Francia. Institut Gustave Roussy; Francia
Published: 2009
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29. Effectiveness of Artificial Intelligence Methods in Personalized Aggression Risk Prediction within Inpatient Psychiatric Treatment Settings-A Systematic Review

Author: Jing Ling Tay, Ziqiang Li, Kang Sim, Lee Kong Chian School of Medicine (LKCMedicine), Institute of Mental Health, and Yong Loo Lin School of Medicine, NUS
Subjects: Artificial Intelligence, Medicine (miscellaneous), Medicine [Science], Aggression Risk
Abstract: Aggression risk assessments are vital to prevent injuries and morbidities amongst patients and staff in psychiatric settings. More recent studies have harnessed artificial intelligence (AI) methods such as machine learning algorithms to determine factors associated with aggression in psychiatric treatment settings. In this review, using Cooper's five-stage review framework, we aimed to evaluate the: (1) predictive accuracy, and (2) clinical variables associated with AI-based aggression risk prediction amongst psychiatric inpatients. Databases including PubMed, Cochrane, Scopus, PsycINFO, CINAHL were searched for relevant articles until April 2022. The eight included studies were independently evaluated using critical appraisal tools for systematic review developed by Joanna Briggs Institute. Most of the studies (87.5%) examined health records in predicting aggression and reported acceptable to excellent accuracy with specific machine learning algorithms employed (area under curve range 0.75-0.87). No particular machine learning algorithm outperformed the others consistently across studies (area under curve range 0.61-0.87). Relevant factors identified with aggression related to demographic and social profile, past aggression, forensic history, other psychiatric history, psychopathology, challenging behaviors and management domains. The limited extant studies have highlighted a potential role for the use of AI methods to clarify factors associated with aggression in psychiatric inpatient treatment settings. Published version The study was funded by West Region, Institute of Mental Health.
Published: 2022

30. Activated brown adipose tissue releases exosomes containing mitochondrial methylene tetrahydrofolate dehydrogenase (NADP dependent) 1-like protein (MTHFD1L)

Author: Melvin Khee-Shing Leow, Anantharaj Rengaraj, Kothandaraman Narasimhan, Sanjay K. Verma, Jadegoud Yaligar, Giang Le Thi Thu, Lijuan Sun, Hui Jen Goh, Priya Govindharajulu, Suresh Anand Sadananthan, Navin Michael, Wei Meng, Xavier Gallart-Palau, Lei Sun, Neerja Karnani, Newman Siu Kwan Sze, S. Sendhil Velan, Lee Kong Chian School of Medicine (LKCMedicine), School of Biological Sciences, Singapore Institute for Clinical Sciences, A*STAR, Duke-NUS Medical School, Yong Loo Lin School of Medicine, NUS, and Tan Tock Seng Hospital
Subjects: Methylenetetrahydrofolate Dehydrogenase (NADP), Biophysics, Biological sciences [Science], Cell Biology, Exosomes, Biochemistry, Rats, Tetrahydrofolate Dehydrogenase, Adipocytes, Brown, Adipose Tissue, Brown, Positron Emission Tomography Computed Tomography, Animals, Humans, Mitochondrial Protein, Brown Adipose Tissue, Medicine [Science], Energy Metabolism, Molecular Biology, NADP
Abstract: Brown adipose tissue (BAT) is a promising weapon to combat obesity and metabolic disease. BAT is thermogenic and consumes substantial amounts of glucose and fatty acids as fuel for thermogenesis and energy expenditure. To study BAT function in large human longitudinal cohorts, safe and precise detection methodologies are needed. Although regarded a gold standard, the foray of PET-CT into BAT research and clinical applications is limited by its high ionizing radiation doses. Here, we show that brown adipocytes release exosomes in blood plasma that can be utilized to assess BAT activity. In the present study, we investigated circulating protein biomarkers that can accurately and reliably reflect BAT activation triggered by cold exposure, capsinoids ingestion and thyroid hormone excess in humans. We discovered an exosomal protein, methylene tetrahydrofolate dehydrogenase (NADP+ dependent) 1-like (MTHFD1L), to be overexpressed and detectable in plasma for all three modes of BAT activation in human subjects. This mitochondrial protein is packaged as a cargo within multivesicular bodies of the endosomal compartment and secreted as exosomes via exocytosis from activated brown adipocytes into the circulation. To support MTHFD1L as a conserved BAT activation response in other vertebrates, we examined a rodent model and also proved its presence in blood of rats following BAT activation by cold exposure. Plasma concentration of exosomal MTHFD1L correlated with human BAT activity as confirmed by PET-MR in humans and supported by data from rats. Thus, we deduce that MTHFD1L appears to be overexpressed in activated BAT compared to BAT in the basal nonstimulated state. Agency for Science, Technology and Research (A*STAR) Ministry of Health (MOH) National Medical Research Council (NMRC) Published version The study was funded by the Singapore Ministry of Health’s National Medical Research Council (NMRC) Clinician Scientist Award [grant number NMRC/CSA-INV/0003/2015] awarded to A/Prof. MKSL and also partly supported by the Agency for Science, Technology and Research (A*STAR).
Published: 2022
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31. Biology of resident tissue macrophages

Author: Florent Ginhoux, Christopher Lee, School of Biological Sciences, Singapore Immunology Network, Yong Loo Lin School of Medicine, National University of Singapore, and Translational Immunology Institute, SingHealth Duke-NUS Academic Medical Centre
Subjects: Macrophage, Macrophages, Biological sciences [Science], Cell Differentiation, Kupffer Cell, Microglia, Biology, Molecular Biology, Monocytes, Developmental Biology
Abstract: Although best known for their phagocytic and immunological functions, macrophages have increasingly been recognised as key players in the development, homeostasis and regeneration of their host tissues. Early during development, macrophages infiltrate and colonise all tissues within the body, developing symbiotically with their host tissues and acquiring unique functional adaptations based on the tissue microenvironment. These embryonic resident tissue macrophages (RTMs) are ontogenically distinct from the later adult bone marrow-derived monocytes, and in some tissues are self-maintained independently of general circulation at a steady state. In this article, we briefly discuss the ontogeny, maintenance and unique tissue adaptions of RTMs focusing on microglia, Kupffer cells, Langerhans cells, intestinal macrophages, cardiac macrophages and tumour-associated macrophages, and highlight their role in development, homeostasis and dysfunction. Agency for Science, Technology and Research (A*STAR) National Research Foundation (NRF) F.G. is supported by Singapore Immunology Network (SIgN) core funding. F.G. is a European Molecular Biology Organization (EMBO) YIP awardee and is supported by the National Research Foundation Singapore Senior Investigatorship (NRFI) (NRF2016NRF-NRFI001-02). C.Z.W.L. is supported by the Agency for Science, Technology and Research (A*STAR) Graduate Scholarship.
Published: 2022
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32. Viral Dynamics and Immune Correlates of Coronavirus Disease 2019 (COVID-19) Severity

Author: Young, Barnaby E, Ong, Sean W X, Ng, Lisa F P, Anderson, Danielle E, Chia, Wan Ni, Chia, Po Ying, Ang, Li Wei, Mak, Tze-Minn, Kalimuddin, Shirin, Chai, Louis Yi Ann, Pada, Surinder, Tan, Seow Yen, Sun, Louisa, Parthasarathy, Purnima, Fong, Siew-Wai, Chan, Yi-Hao, Tan, Chee Wah, Lee, Bernett, Rötzschke, Olaf, Ding, Ying, Tambyah, Paul, Low, Jenny G H, Cui, Lin, Barkham, Timothy, Lin, Raymond Tzer Pin, Leo, Yee-Sin, Renia, Laurent, Wang, Lin-Fa, Lye, David Chien, Lim, Poh Lian, Peng Ang, Brenda Sze, Lee, Cheng Chuan, U Lee, Lawrence Soon, Ling, Li Min, Ng, Oon Tek, Chan, Monica, Marimuthu, Kalisvar, Vasoo, Shawn, Wong, Chen Seong, Lee, Tau Hong, Sadarangani, Sapna, Lin, Ray Junhao, Sadasiv, Mucheli Sharavan, Ling Ng, Deborah Hee, Choy, Chiaw Yee, En Tan, Glorijoy Shi, Tan, Yu Kit, Sutjipto, Stephanie, Lee, Pei Hua, Tay, Jun Yang, Yeo, Tsin Wen, Khoo, Bo Yan, Tay, Woo Chiao, Ng, Gabrielle, Mah, Yun Yuan, Tan, Wilnard, De, Partha Pratim, Pooja, Rao, Chia, Jonathan W Z, Constance Chen, Yuan Yi, Mendis, Shehara, Toh, Boon Kiat, Choon Fong, Raymond Kok, Lin Oh, Helen May, Fong Chien, Jaime Mei, Shafi, Humaira, Cheong, Hau Yiang, Tan, Thean Yen, Tan, Thuan Tong, Tan, Ban Hock, Wijaya, Limin, Venkatachalam, Indumathi, Chua, Ying Ying, Zhi Cherng, Benjamin Pei, Zi Chan, Yvonne Fu, Wong, Hei Man, Thien, Siew Yee, Meng Goh, Kenneth Choon, Ling Tan, Shireen Yan, Ean Oon, Lynette Lin, Chan, Kian Sing, Lin, Li, Gin Chan, Douglas Su, Ooi, Say Tat, Narayana, Deepak Rama, Somani, Jyoti, Ling Oon, Jolene Ee, Yan, Gabriel Zherong, Allen, David Michael, Jureen, Roland, Yan, Benedict, Foo, Randy, Kang, Adrian, Sivalingam, Velraj, How, Wilson, Fernandez, Norman Leo, Yeo, Nicholas Kim-Wah, Chee, Rhonda Sin-Ling, Amrun, Siti Naqiah, Lee Kong Chian School of Medicine (LKCMedicine), National Centre for Infectious Diseases, Tan Tock Seng Hospital, Yong Loo Lin School of Medicine, NUS, and Saw Swee Hock School of Public Health, NUS
Subjects: 0301 basic medicine, Microbiology (medical), biology, Viral culture, business.industry, 030106 microbiology, COVID-19, medicine.disease, 03 medical and health sciences, Pneumonia, 0302 clinical medicine, Infectious Diseases, Immune system, Immunoglobulin M, Viral pneumonia, Immunology, Severity of illness, medicine, biology.protein, Cytokines, Medicine [Science], 030212 general & internal medicine, Seroconversion, Antibody, business
Abstract: Background Key knowledge gaps remain in the understanding of viral dynamics and immune response of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Methods We evaluated these characteristics and established their association with clinical severity in a prospective observational cohort study of 100 patients with PCR-confirmed SARS-CoV-2 infection (mean age, 46 years; 56% male; 38% with comorbidities). Respiratory samples (n = 74) were collected for viral culture, serum samples for measurement of IgM/IgG levels (n = 30), and plasma samples for levels of inflammatory cytokines and chemokines (n = 81). Disease severity was correlated with results from viral culture, serologic testing, and immune markers. Results Fifty-seven (57%) patients developed viral pneumonia, of whom 20 (20%) required supplemental oxygen, including 12 (12%) with invasive mechanical ventilation. Viral culture from respiratory samples was positive for 19 of 74 patients (26%). No virus was isolated when the PCR cycle threshold (Ct) value was >30 or >14 days after symptom onset. Seroconversion occurred at a median (IQR) of 12.5 (9–18) days for IgM and 15.0 (12–20) days for IgG; 54/62 patients (87.1%) sampled at day 14 or later seroconverted. Severe infections were associated with earlier seroconversion and higher peak IgM and IgG levels. Levels of IP-10, HGF, IL-6, MCP-1, MIP-1α, IL-12p70, IL-18, VEGF-A, PDGF-BB, and IL-1RA significantly correlated with disease severity. Conclusions We found virus viability was associated with lower PCR Ct value in early illness. A stronger antibody response was associated with disease severity. The overactive proinflammatory immune signatures offer targets for host-directed immunotherapy, which should be evaluated in randomized controlled trials.
Published: 2020
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33. Venom Peptide Repertoire of the European Myrmicine Ant Manica rubida: Identification of Insecticidal Toxins

Author: Samira R. Aili, Elsa Bonnafé, Benjamin Lefranc, Graham M. Nicholson, Axel Touchard, Valentine Barassé, Mrinalini, Laurent Coquet, Alain Dejean, R. Manjunatha Kini, Thierry Jouenne, Pierre Escoubas, Michel Treilhou, Christophe Klopp, Nathan Téné, Jérôme Leprince, Biochimie et Toxicologie des Substances Bioactives (BTSB), Institut national universitaire Champollion [Albi] (INUC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, School of Environmental and Life Sciences - SELS (Callaghan, Australia), University of Newcastle [Australia] (UoN), Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRA), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ecologie des forêts de Guyane (UMR ECOFOG), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-AgroParisTech-Université de Guyane (UG)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Laboratoire Ecologie Fonctionnelle et Environnement (ECOLAB), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), Protein Science laboratory, Department of biological Sciences, Faculty of Science, National University of Singapore, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Polymères Biopolymères Surfaces (PBS), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Plate-forme de Protéomique PISSARO, Institute for Research and Innovation in Biomedicine (IRIB), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Différenciation et communication neuronale et neuroendocrine (DC2N), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plate-Forme de Recherche en Imagerie Cellulaire de Haute-Normandie (PRIMACEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Venometech, European Commission, Region Normandie through the European Regional Development Fund (ERDF), and Southeast Asian Biodiversity Genomics Center, National University of Singapore - R-154-000-648-646
Subjects: 0301 basic medicine, pyroglutamate, Peptide, Lucilia caesar, Venom, glycosylated toxin, Manica rubida, medicine.disease_cause, Biochemistry, Ant venom, 03 medical and health sciences, peptidome, medicine, Threonine, polycationic α-helix, chemistry.chemical_classification, reversible neurotoxicity, 030102 biochemistry & molecular biology, biology, Toxin, [SDV.BA]Life Sciences [q-bio]/Animal biology, General Chemistry, biology.organism_classification, medicine.disease, ANT, 030104 developmental biology, chemistry, predation, [MATH.MATH-NA]Mathematics [math]/Numerical Analysis [math.NA]
Abstract: International audience; Using an integrated transcriptomic and proteomic approach, we characterized the venom peptidome of the European red ant, Manica rubida. We identified 13 "myrmicitoxins" that share sequence similarities with previously identified ant venom peptides, one of them being identified as an EGF-like toxin likely resulting from a threonine residue modified by O-fucosylation. Furthermore, we conducted insecticidal assays of reversed-phase HPLC venom fractions on the blowfly Lucilia caesar, permitting us to identify six myrmicitoxins (i.e., U3-, U10-, U13-, U20-MYRTX-Mri1a, U10-MYRTX-Mri1b, and U10-MYRTX-Mri1c) with an insecticidal activity. Chemically synthesized U10-MYRTX-Mri1a, -Mri1b, -Mri1c, and U20-MYRTX-Mri1a irreversibly paralyzed blowflies at the highest doses tested (30-125 nmol·g-1). U13-MYRTX-Mri1a, the most potent neurotoxic peptide at 1 h, had reversible effects after 24 h (150 nmol·g-1). Finally, U3-MYRTX-Mri1a has no insecticidal activity, even at up to 55 nmol·g-1. Thus, M. rubida employs a paralytic venom rich in linear insecticidal peptides, which likely act by disrupting cell membranes.
Published: 2020
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34. Family-focused contextual factors associated with lifestyle patterns in young children from two mother-offspring cohorts: GUSTO and EDEN

Author: Airu Chia, Alexandra Descarpentrie, Rene N. Cheong, Jia Ying Toh, Padmapriya Natarajan, Ray Sugianto, Shirong Cai, Cécilia Saldanha-Gomes, Patricia Dargent-Molina, Blandine de Lauzon-Guillain, Sabine Plancoulaine, Carla Lança, Seang Mei Saw, Keith M. Godfrey, Lynette P. Shek, Kok Hian Tan, Marie-Aline Charles, Yap Seng Chong, Barbara Heude, Johan G. Eriksson, Falk Müller-Riemenschneider, Sandrine Lioret, Mary F.-F. Chong, Jonathan Y. Bernard, Clinicum, Research Programs Unit, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Saw Swee Hock School of Public Health [Singapore, Singapore], National University of Singapore (NUS), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Singapore Institute for Clinical Sciences, Agency for science, technology and research [Singapore] (A*STAR), Singapore Institute for Clinical Sciences [Singapour] (SICS), Singapore Eye Research Institute [Singapore] (SERI), NIHR Southampton Biomedical Research Centre, Yong Loo Lin School of Medicine [Singapore], KK Women's and Children's Hospital [Singapore], This research is supported by the Paris‐NUS grant (ANR‐18‐IDEX‐0001).The EDEN study is supported by Foundation for Medical Research (FRM), National Agency for Research (ANR), National Institute for Research in Public Health (IRESP: TGIR cohorte santé 2008 program), French Ministry of Health (DGS), French Ministry of Research, INSERM Bone and Joint Diseases National Research (PRO‐A), and Human Nutrition National Research Programs, Paris‐Sud University, Nestlé, French National Institute for Population Health Surveillance (InVS.), French National Institute for Health Education (INPES), the European Union FP7 programmes (FP7/2007–2013, HELIX, ESCAPE, ENRIECO, Medall projects), Diabetes National Research Program (through a collaborationwith the French Association of Diabetic Patients (AFD)), French Agency for Environmental Health Safety (now ANSES), Mutuelle Générale de l’Education Nationale a complementary health insurance (MGEN), French National Agency for Food Security, French‐speaking Association for the Study of Diabetes and Metabolism (ALFEDIAM).The GUSTO study is supported by the Singapore National Research Founda‐ tion under its Translational and Clinical Research Flagship Programme and administered by the Singapore Ministry of Health’s National Medical Research Council, Singapore ‐ NMRC/TCR/004‐NUS/2008, NMRC/TCR/012‐NUHS/2014. Additional funding is provided by the Singapore Institute for Clinical Sciences, Agency for Science Technology and Research, Singapore. KMG is supported by the UK Medical Research Council (MC_UU_12011/4), the National Institute for Health Research (NIHR Senior Investigator (NF‐SI‐0515‐10042) and NIHR South‐ ampton Biomedical Research Centre (IS‐BRC‐1215‐20004)), the European Union (Erasmus+ Programme ImpENSA 598488‐EPP‐1‐2018‐1‐DE‐EPPKA2‐ CBHE‐JP) and the British Heart Foundation (RG/15/17/3174). The funders had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript., and ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018)
Subjects: Male, QUESTIONNAIRE, Mothers, Medicine (miscellaneous), Physical Therapy, Sports Therapy and Rehabilitation, Pregnancy, FOOD, Humans, Hierarchical analysis, VALIDITY, Child, Life Style, Nutrition and Dietetics, Physical activity, Preschool children, 1184 Genetics, developmental biology, physiology, Feeding Behavior, ADULTS, Screen time, Diet, DIETARY PATTERNS, PHYSICAL-ACTIVITY, Lifestyle patterns, Child, Preschool, OBESITY, 3121 General medicine, internal medicine and other clinical medicine, Female, Television, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Family ecological model, Snacks, 3143 Nutrition, TRANSITION
Abstract: Background Integrated patterns of energy balance-related behaviours of preschool children in Asia are sparse, with few comparative analyses. Purpose Using cohorts in Singapore (GUSTO) and France (EDEN), we characterized lifestyle patterns of children and investigated their associations with family-focused contextual factors. Methods Ten behavioural variables related to child’s diet, walking, outdoor play and screen time were ascertained by parental questionnaires at age 5–6 years. Using principal component analysis, sex-specific lifestyle patterns were derived independently for 630 GUSTO and 989 EDEN children. Contextual variables were organised into distal (family socio-economics, demographics), intermediate (parental health, lifestyle habits) and proximal (parent-child interaction factors) levels of influence and analysed with hierarchical linear regression. Results Three broadly similar lifestyle patterns were identified in both cohorts: “discretionary consumption and high screen time”, “fruit, vegetables, and low screen time” and “high outdoor playtime and walking”. The latter two patterns showed small differences between cohorts and sexes. The “discretionary consumption and high screen time” pattern was consistently similar in both cohorts; distal associated factors were lower maternal education (EDEN boys), no younger siblings (GUSTO boys) and Malay/Indian ethnicity (GUSTO), while intermediate and proximal associated factors in both cohorts and sexes were poor maternal diets during pregnancy, parents allowing high child control over food intake, snacking between meals and having television on while eating. Conclusions Three similar lifestyle patterns were observed among preschool children in Singapore and France. There were more common associated proximal factors than distal ones. Cohort specific family-focused contextual factors likely reflect differences in social and cultural settings. Findings will aid development of strategies to improve child health.
Published: 2022
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35. Transitional premonocytes emerge in the periphery for host defense against bacterial infections

Author: Ye Chean Teh, Ming Yao Chooi, Dehua Liu, Immanuel Kwok, Ghee Chuan Lai, Liyana Ayub Ow Yong, Melissa Ng, Jackson L. Y. Li, Yingrou Tan, Maximilien Evrard, Leonard Tan, Ka Hang Liong, Keith Leong, Chi Ching Goh, Andrew Y. J. Chan, Nurhidaya Binte Shadan, Chinmay Kumar Mantri, You Yi Hwang, Hui Cheng, Tao Cheng, Weimiao Yu, Hong Liang Tey, Anis Larbi, Ashley St John, Veronique Angeli, Christiane Ruedl, Bernett Lee, Florent Ginhoux, Swaine L. Chen, Lai Guan Ng, Jeak Ling Ding, Shu Zhen Chong, Lee Kong Chian School of Medicine (LKCMedicine), School of Biological Sciences, Yong Loo Lin School of Medicine, NUS, National Skin Centre, and Singapore Immunology Network (SIgN), A*STAR
Subjects: Multidisciplinary, Macrophages, Biological sciences [Science], Bacterial Infections, Monocytes, Mice, Inbred C57BL, Mice, Sepsis, Host Defense, Animals, Cytokines, Humans, Medicine [Science]
Abstract: Circulating Ly6Chi monocytes often undergo cellular death upon exhaustion of their antibacterial effector functions, which limits their capacity for subsequent macrophage differentiation. This shrouds the understanding on how the host replaces the tissue-resident macrophage niche effectively during bacterial invasion to avert infection morbidity. Here, we show that proliferating transitional premonocytes (TpMos), an immediate precursor of mature Ly6Chi monocytes (MatMos), were mobilized into the periphery in response to acute bacterial infection and sepsis. TpMos were less susceptible to apoptosis and served as the main source of macrophage replenishment when MatMos were vulnerable toward bacteria-induced cellular death. Furthermore, TpMo and its derived macrophages contributed to host defense by balancing the proinflammatory cytokine response of MatMos. Consequently, adoptive transfer of TpMos improved the survival outcome of lethal sepsis. Our findings hence highlight a protective role for TpMos during bacterial infections and their contribution toward monocyte-derived macrophage heterogeneity in distinct disease outcomes. Agency for Science, Technology and Research (A*STAR) National Research Foundation (NRF) Published version This research was funded by Singapore Immunology Network (SIgN) core funding and A*STAR, Singapore. F.G. is an EMBO YIP awardee and is supported by SIgN core funding and Singapore National Research Foundation Investigatorship (NRF2016NRF-NRF1001-02). L.G.N. is supported by SIgN core funding. S.Z.C. is supported by the Ministry of Health, Singapore’s National Medical Research Council under its Open Fund-Young Individual Research Grant (OFYIRG17may036), and A*STAR Career Development Award (192D8043). Y.C.T. is a graduate scholar supported by the Ministry of Education, Singapore. M.Y.C. is a graduate scholar supported by the SIgN-NTU-NUS scholarship, Singapore. SIgN Flow Cytometry facility is supported by National Research Foundation (NRF) Singapore under Shared Infrastructure Support (SIS) (NRF2017_SISFP09).
Published: 2022

36. Rapid recruitment of p53 to DNA damage sites directs DNA repair choice and integrity

Author: Yu-Hsiu Wang, Teresa L. F. Ho, Anushya Hariharan, Hui Chin Goh, Yao Liang Wong, Nicole S. Verkaik, May Yin Lee, Wai Leong Tam, Dik C. van Gent, Ashok R. Venkitaraman, Michael P. Sheetz, David P. Lane, Molecular Genetics, School of Biological Sciences, Cancer Science Institute of Singapore, NUS, Genome Institute of Singapore, A*STAR, and Yong Loo Lin School of Medicine, NUS
Subjects: P53, Multidisciplinary, DNA End-Joining Repair, Biological sciences [Science], Nuclear Proteins, Cell Cycle Proteins, DNA-Binding Proteins, Protein Domains, Cell Line, Tumor, Tumor Suppression, Mutation, Humans, Tumor Suppressor Protein p53, Tumor Suppressor p53-Binding Protein 1, DNA Damage
Abstract: p53 is primarily known as a downstream transcriptional effector in the DNA damage-response cascade. We report that endogenous p53 rapidly accumulates at DNA damage sites within 2 s of UVA microirradiation. The kinetics of p53 recruitment mimics those of known DNA damage-response proteins, such as Ku70 and poly(- ADP-ribose) polymerase (PARP), and precedes recruitment of Nbs1, 53BP1, and DDB1. Mutations in the DNA-binding and C-terminal domains significantly suppress this rapid recruitment. The C-terminal domain of p53 contains key residues for PARP interaction that are required for rapid recruitment of p53 to DNA damage sites, as is PARP-dependent modification. The presence of p53 at damage sites influences the recruitment kinetics of 53BP1 and DDB1 and directs the choice of nonhomologous end joining repair (NHEJ) and nucleotide excision repair. Mutations that suppressed rapid recruitment of p53 promoted error-prone alternative end-joining (alt-NHEJ) and inhibited nucleotide excision repair. Our finding that p53 is a critical early responder to DNA damage stands in contrast with its extensively studied role as a downstream transcriptional regulator in DNA damage repair. We highlight an unrecognized role of p53 in directing DNA repair dynamics and integrity and suggest a parallel mode of p53 tumor suppression apart from its function as a transcription factor. Ministry of Education (MOE) National Medical Research Council (NMRC) National Research Foundation (NRF) Published version D.P.L. and T.L.F.H. were supported by A*STAR core funding. M.P.S. and Y.-H.W. were supported by the Mechanobiology Institute at the National University of Singapore, and, more recently, by a Cancer Prevention and Research Institute of Texas grant at the University of Texas Medical Branch. W.L.T. and M.Y.L. were supported by funding from the National Medical Research Council, Singapore (OFIRG17may-061, OFIRG19nov-0106, CTGIIT18may-0012, NMRC/OFLCG/002-2018), the National Research Foundation, Singapore (NRF-NRFF2015-04, NRF-CRP22- 2019-0003, NRF-CRP23-2019-0004), and the Singapore Ministry of Education under its Research Centers of Excellence initiative.
Published: 2022

37. Maternal Glycemic Dysregulation During Pregnancy and Neonatal Blood DNA Methylation: Meta-analyses of Epigenome-Wide Association Studies

Author: Elmar W. Tobi, Diana L. Juvinao-Quintero, Justiina Ronkainen, Raffael Ott, Rossella Alfano, Mickaël Canouil, Madelon L. Geurtsen, Amna Khamis, Leanne K. Küpers, Ives Y. Lim, Patrice Perron, Giancarlo Pesce, Johanna Tuhkanen, Anne P. Starling, Toby Andrew, Elisabeth Binder, Robert Caiazzo, Jerry K.Y. Chan, Romy Gaillard, Peter D. Gluckman, Elina Keikkala, Neerja Karnani, Sanna Mustaniemi, Tim S. Nawrot, François Pattou, Michelle Plusquin, Violeta Raverdy, Kok Hian Tan, Evangelia Tzala, Katri Raikkonen, Christiane Winkler, Anette-G. Ziegler, Isabella Annesi-Maesano, Luigi Bouchard, Yap Seng Chong, Dana Dabelea, Janine F. Felix, Barbara Heude, Vincent W.V. Jaddoe, Jari Lahti, Brigitte Reimann, Marja Vääräsmäki, Amélie Bonnefond, Philippe Froguel, Sandra Hummel, Eero Kajantie, Marjo-Riita Jarvelin, Regine P.M. Steegers-Theunissen, Caitlin G. Howe, Marie-France Hivert, Sylvain Sebert, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Harvard Pilgrim Health Care Institute, University of Oulu, Helmholtz Zentrum München = German Research Center for Environmental Health, Klinikums rechts der Isar, Hasselt University (UHasselt), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), The Generation R Study Group, Imperial College London, Bioinformatics Institute (A*STAR), Singapore Institute for Clinical Sciences [Singapour] (SICS), Agency for science, technology and research [Singapore] (A*STAR), Université de Sherbrooke (UdeS), Centre Hospitalier Universitaire de Sherbrooke, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Epidemiology of Allergic and Respiratory Diseases Department [iPlesp] (EPAR), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), TKK Helsinki University of Technology (TKK), Colorado School of Public Health [Aurora, CO, USA] (CSPH), University of Colorado Anschutz [Aurora], Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Emory University School of Medicine, Emory University [Atlanta, GA], Recherche translationnelle sur le diabète - U 1190 (RTD), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), KK Women's and Children's Hospital [Singapore], Duke-NUS Medical School [Singapore], Liggins Institute, University of Auckland [Auckland], Finnish Institute for Health and Welfare [Helsinki, Finland] (FIHW), Oulu University Hospital [Oulu], Bioinformatics Institute [Singapore], Yong Loo Lin School of Medicine [Singapore], Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université du Québec à Chicoutimi (UQAC), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Norwegian University of Life Sciences (NMBU), Brunel University London [Uxbridge], Geisel School of Medicine at Dartmouth, Harvard Medical School [Boston] (HMS), Massachusetts General Hospital [Boston], Salvy-Córdoba, Nathalie, Obstetrics & Gynecology, Pediatrics, Binder, Elisabeth, Küpers, Leanne K., Geurtsen, Madelon L., Raikkonen, Katri, Tuhkanen, Johanna, Felix, Janine F., ALFANO, Rossella, Winkler, Christiane, Ott, Raffael, Dabelea, Dana, Khamis, Amna, Bouchard, Luigi, Bonnefond, Amélie, Canouil, Mickaël, Karnani, Neerja, Hummel, Sandra, Tobi, Elmar W, Sebert, Sylvain, Jarvelin, Marjo-Riita, Keikkala, Elina, Heude, Barbara, Pesce, Giancarlo, Steegers-Theunissen, Regine P.M., Lim, Ives Y., REIMANN, Brigitte, Caiazzo, Robert, Hian Tan, Kok, Chan, Jerry K.Y., Ronkainen, Justiina, Ziegler, Anette-G., NAWROT, Tim, Froguel, Philippe, Gluckman, Peter D., Raverdy, Violeta, Starling, Anne P., Howe, Caitlin G., Lahti, Jari, Mustaniemi, Sanna, Hivert, Marie-France, Seng Chong, Yap, Jaddoe, Vincent W.V., Perron, Patrice, Pattou, François, Annesi-Maesano, Isabella, Juvinao-Quintero, Diana L., Gaillard, Romy, Vääräsmäki, Marja, Plusquin, Michelle, Andrew, Toby, Kajantie, Eero, and Tzala, Evangelia
Subjects: Endocrinology, Diabetes and Metabolism, MESH: Epigenome, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Epigenesis, Genetic, Endocrinology & Metabolism, Epigenome, MESH: DNA Methylation, MESH: Pregnancy, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, SDG 3 - Good Health and Well-being, HYPERGLYCEMIA, Pregnancy, Internal Medicine, Humans, MESH: Fetal Blood, MESH: Epigenesis, Genetic, Advanced and Specialized Nursing, MESH: Diabetes, Gestational, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Science & Technology, MESH: Humans, MESH: Infant, Newborn, Infant, Newborn, DNA Methylation, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Fetal Blood, Diabetes, Gestational, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Diabetes Mellitus, Type 2, Female, Life Sciences & Biomedicine, MESH: Female, MESH: Diabetes Mellitus, Type 2
Abstract: OBJECTIVE Maternal glycemic dysregulation during pregnancy increases the risk of adverse health outcomes in her offspring; a risk thought to be linearly related to maternal hyperglycemia. It is hypothesized that changes in offspring DNA methylation (DNAm) underline these associations. RESEARCH DESIGN AND METHODS To address this hypothesis, we conducted fixed-effect meta-analyses of epigenome-wide association study (EWAS) results from eight birth cohorts investigating relationships between cord blood DNAm and fetal exposure to maternal glucose (Nmax= 3,503), insulin (Nmax= 2,062), and the area under the curve of glucose (AUCgluc) following oral glucose tolerance tests (OGTT, Nmax= 1,505). We performed look-up analyses for identified CpG dinucleotides (CpGs) in independent observational cohorts to examine associations between DNAm and cardiometabolic traits as well as tissue-specific gene expression. RESULTS Greater maternal AUCgluc was associated with lower cord blood DNAm at neighboring CpGs cg26974062 (β= -0.013 [SE=2.1x10-3], PFDR= 5.1x10-3) and cg02988288 (β= -0.013 [SE=2.3x10-3], PFDR =0.031) in TXNIP. These associations were attenuated in women with GDM. Lower blood DNAm at these two CpGs near TXNIP was associated with multiple metabolic traits later in life, including type 2 diabetes. TXNIP DNAm in liver biopsies was associated with hepatic expression of TXNIP. We observed little evidence of associations between either maternal glucose or insulin and cord blood DNAm. CONCLUSION Maternal hyperglycemia, as reflected by AUCgluc, was associated with lower cord blood DNAm at TXNIP. Associations between DNAm at these CpGs and metabolic traits in subsequent look-up analyses suggest that these may be candidate loci to investigate in future causal and mediation analyses.
Published: 2022
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38. Developing a lifestyle intervention program for overweight or obese preconception, pregnant and postpartum women using qualitative methods

Author: Ku, Chee Wai, Leow, Shu Hui, Ong, Lay See, Erwin, Christina, Ong, Isabella, Ng, Xiang Wen, Tan, Jacinth JX, Yap, Fabian, Chan, Jerry Kok Yen, Loy, See Ling, Lee Kong Chian School of Medicine (LKCMedicine), Yong Loo Lin School of Medicine, NUS, KK Women’s and Children’s Hospital, and Apollo - University of Cambridge Repository
Subjects: Adult, Body Mass, Multidisciplinary, Postpartum Period, Social Support, Motivational Interviewing, Body Mass Index, Obesity, Maternal, Treatment Outcome, Behavior Therapy, Pregnancy, Surveys and Questionnaires, Humans, Medicine [Science], Female, Healthy Lifestyle, Diet, Healthy, Preconception Care, Exercise, Goals, Qualitative Research
Abstract: The time period before, during and after pregnancy represents a unique opportunity for interventions to cultivate sustained healthy lifestyle behaviors to improve the metabolic health of mothers and their offspring. However, the success of a lifestyle intervention is dependent on uptake and continued compliance. To identify enablers and barriers towards engagement with a lifestyle intervention, thematic analysis of 15 in-depth interviews with overweight or obese women in the preconception, pregnancy or postpartum periods was undertaken, using the integrated-Promoting Action on Research Implementation in Health Services framework as a guide to systematically chart factors influencing adoption of a novel lifestyle intervention. Barrier factors include time constraints, poor baseline knowledge, family culture, food accessibility, and lack of relevant data sources. Enabling factors were motivation to be healthy for themselves and their offspring, family and social support, a holistic delivery platform providing desired information delivered at appropriate times, regular feedback, goal setting, and nudges. From the findings of this study, we propose components of an idealized lifestyle intervention including (i) taking a holistic life-course approach to education, (ii) using mobile health platforms to reduce barriers, provide personalized feedback and promote goal-setting, and (iii) health nudges to cultivate sustained lifestyle habits. National Medical Research Council (NMRC) Published version This research was supported by the National Medical Research Council Singapore (Grant Number NMRC/CG/ M003/2017). The funding body did not influence either the data collection and analysis or the writing and the decision to submit the manuscript. KCW and JCKY received salary support from Singapore’s Ministry of Health’s National Medical Research Council (NMRC/MOH-000596-00 and NMRC/CSA-SI-008–2016 respectively).
Published: 2022
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39. Real-world use of sotrovimab for pre-emptive treatment in high-risk hospitalized COVID-19 patients: an observational cross-sectional study

Author: Sean W. X. Ong, Dongdong Ren, Pei Hua Lee, Stephanie Sutjipto, Christopher Dugan, Bo Yan Khoo, Jun Xin Tay, Shawn Vasoo, Barnaby E. Young, David C. Lye, Lee Kong Chian School of Medicine (LKCMedicine), National Centre for Infectious Diseases, Singapore, Tan Tock Seng Hospital, and Yong Loo Lin School of Medicine, NUS
Subjects: COVID-19, SARS-CoV-2, sotrovimab, treatment, monoclonal antibody, Microbiology (medical), Infectious Diseases, Pharmacology (medical), Medicine [Science], General Pharmacology, Toxicology and Pharmaceutics, Biochemistry, Microbiology, Sotrovimab
Abstract: Data on use of monoclonal antibodies (mAbs) in hospitalized patients are limited. In this cross-sectional study, we evaluated the use of mAbs for early treatment of unvaccinated hospitalized patients with mild-to-moderate COVID-19. All inpatients at our center were screened on 27 October 2021. Primary outcome was in-hospital deterioration as defined by a composite of oxygen requirement, intensive care unit (ICU) admission, or mortality within 28 days of admission. Ninety-four out of 410 COVID-19 inpatients were included in the final analysis, of whom 19 (20.2%) received early treatment with sotrovimab. The median age was 73 years (IQR 61–83), and 35 (37.2%) were female. Although the treatment group was significantly older and had more comorbidities, there was a lower proportion of progression to oxygen requirement (31.6% vs. 54.7%), ICU admission (10.5% vs. 24.0%), or mortality (5.3% vs. 13.3%). Kaplan–Meier curves showed a significant difference in time to in-hospital deterioration (log-rank test, p = 0.043). Cox proportional hazards model for in-hospital deterioration showed that sotrovimab treatment was protective (hazard ratio, 0.41; 95% CI, 0.17–0.99; p = 0.047) after adjustment for baseline ISARIC deterioration score. Our findings support the use of sotrovimab for early treatment in hospitalized patients with mild-to-moderate COVID-19 at a high risk of disease progression.
Published: 2022

40. Mechanism for the attenuation of neutrophil and complement hyperactivity by MSC exosomes

Author: Jia Tong Loh, Bin Zhang, Joey Kay Hui Teo, Ruenn Chai Lai, Andre Boon Hwa Choo, Kong-Peng Lam, Sai Kiang Lim, School of Biological Sciences, Singapore Immunology Network, A*STAR, and Yong Loo Lin School of Medicine, NUS
Subjects: Cancer Research, Transplantation, Neutrophils, SARS-CoV-2, Immunology, COVID-19, Biological sciences [Science], Mesenchymal Stem Cells, Cell Biology, Complement Membrane Attack Complex, Exosomes, Oncology, Immunology and Allergy, Humans, Medicine [Science], Genetics (clinical), Complements
Abstract: Complements and neutrophils are two key players of the innate immune system that are widely implicated as drivers of severe COVID-19 pathogenesis, as evident by the direct correlation of respiratory failure and mortality with elevated levels of terminal complement complex C5b-9 and neutrophils. In this study, we identified a feed-forward loop between complements and neutrophils that could amplify and perpetuate the cytokine storm seen in severe SARS-CoV-2-infected patients. We observed for the first time that the terminal complement activation complex C5b-9 directly triggered neutrophil extracellular trap (NET) release and interleukin (IL)-17 production by neutrophils. This is also the first report that the production of NETs and IL-17 induced by C5b-9 assembly on neutrophils could be abrogated by mesenchymal stem cell (MSC) exosomes. Neutralizing anti-CD59 antibodies abolished this abrogation. Based on our findings, we hypothesize that MSC exosomes could alleviate the immune dysregulation in acute respiratory failure, such as that observed in severe COVID-19 patients, by inhibiting complement activation through exosomal CD59, thereby disrupting the feed-forward loop between complements and neutrophils to inhibit the amplification and perpetuation of inflammation during SARS-CoV-2 infection. Agency for Science, Technology and Research (A*STAR) Published version This work was funded by institutional core funds from A*STAR and IAF-PP (H19H6a0026, TEx2Pharm) to SKL and KPL.
Published: 2022

41. Seroprevalence of IgG antibodies against diphtheria antitoxin among migrant workers in Singapore, 2016–2019

Author: Li Wei Ang, Qi Gao, Lin Cui, Aysha Farwin, Matthias Paul Han Sim Toh, Irving Charles Boudville, Mark I-Cheng Chen, Angela Chow, Raymond Tzer-Pin Lin, Vernon Jian Ming Lee, Yee Sin Leo, Lee Kong Chian School of Medicine (LKCMedicine), National Centre for Infectious Diseases, Saw Swee Hock School of Public Health, National University of Singapore, Tan Tock Seng Hospital, and Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Subjects: Adult, Transients and Migrants, Singapore, Basic protection, Diphtheria Toxoid, Research, Public Health, Environmental and Occupational Health, Immunity, Seroprevalence, Diphtheria, Migrant workers, complex mixtures, Antibodies, Bacterial, Diphtheria Antitoxin, Seroepidemiologic Studies, Immunoglobulin G, Humans, Medicine [Science], Public aspects of medicine, RA1-1270, geographic locations, Vaccination coverage
Abstract: Background: Since the last local case of diphtheria in 1992, there had not been any case in Singapore until an autochthonous case was reported in 2017. This fatal diphtheria case of a migrant worker raised concerns about the potential re-emergence of locally transmitted toxigenic diphtheria in Singapore. We conducted a seroprevalence study to assess the immunity levels to diphtheria among migrant workers in Singapore. Methods: Residual sera from migrant workers who hailed from Bangladesh, China, India, Indonesia, Malaysia, Myanmar and the Philippines were tested for anti-diphtheria toxoid immunoglobulin G (IgG) antibodies. These migrant workers previously participated in a survey between 2016 and 2019 and had provided blood samples as part of the survey procedure. Results: A total of 2176 migrant workers were included in the study. Their overall mean age was 27.1 years (standard deviation 5.0), range was 20–43 years. The proportion having at least basic protection against diphtheria (antitoxin titres ≥ 0.01 IU/ml) ranged from 77.9% (95% confidence interval [CI] 72.8 – 82.3%) among migrant workers from Bangladesh to 96.7% (95% CI 92.5 – 98.6%) in those hailing from Malaysia. The proportion showing full protection (antitoxin titres ≥ 0.10 IU/ml) ranged from 10.1% (95% CI 6.5 – 15.4%) in Chinese workers to 23.0% (95% CI 17.1 – 30.3%) in Malaysian workers. There were no significant differences in the proportion with at least basic protection across birth cohorts, except for those from Bangladesh where the seroprevalence was significantly lower in younger migrant workers born after 1989. Conclusions: The proportions having at least basic protection against diphtheria in migrant workers from five out of seven Asian countries (India, Indonesia, Malaysia, Myanmar and the Philippines) were higher than 85%, the threshold for diphtheria herd immunity. Seroprevalence surveys should be conducted periodically to assess the level of immunity against diphtheria and other vaccine preventable diseases in migrant worker population, so that appropriate interventions such as booster vaccination can be implemented proactively to prevent sporadic outbreaks. Published version MICC was supported by the Ministry of Health, Singapore, under the Communicable Diseases – Public Health Research Grant (grant number MOHCS‑ 15MAR001) for sample collection. Laboratory testing for the seroprevalence of diphtheria among migrant workers was supported by the National Public Health Laboratory.
Published: 2022

42. Cardiac remodelling - Part 1: From cells and tissues to circulating biomarkers. A review from the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology

Author: Arantxa González, A. Mark Richards, Rudolf A. de Boer, Thomas Thum, Henrike Arfsten, Martin Hülsmann, Inês Falcao‐Pires, Javier Díez, Roger S.Y. Foo, Mark Y. Chan, Alberto Aimo, Chukwuemeka G. Anene‐Nzelu, Magdy Abdelhamid, Stamatis Adamopoulos, Stefan D. Anker, Yuri Belenkov, Tuvia Ben Gal, Alain Cohen‐Solal, Michael Böhm, Ovidiu Chioncel, Victoria Delgado, Michele Emdin, Ewa A. Jankowska, Finn Gustafsson, Loreena Hill, Tiny Jaarsma, James L. Januzzi, Pardeep S. Jhund, Yuri Lopatin, Lars H. Lund, Marco Metra, Davor Milicic, Brenda Moura, Christian Mueller, Wilfried Mullens, Julio Núñez, Massimo F. Piepoli, Amina Rakisheva, Arsen D. Ristić, Patrick Rossignol, Gianluigi Savarese, Carlo G. Tocchetti, Sophie Van Linthout, Maurizio Volterrani, Petar Seferovic, Giuseppe Rosano, Andrew J.S. Coats, Antoni Bayés‐Genís, Center for Applied Medical Research [Plamplona] (CIMA), Universidad de Navarra [Pamplona] (UNAV), Navarra Institute for Health Research / Instituto de Investigación Sanitaria de Navarra (IdiSNA), Universidad Pública de Navarra [Espagne] = Public University of Navarra (UPNA)-Universidad de Navarra [Pamplona] (UNAV)-Clínica Universidad de Navarra [Pamplona], Instituto de Salud Carlos III [Madrid] (ISC), Yong Loo Lin School of Medicine [Singapore], National University of Singapore (NUS), University of Otago [Dunedin, Nouvelle-Zélande], University Medical Center Groningen [Groningen] (UMCG), Hannover Medical School [Hannover] (MHH), Fraunhofer Institute for Toxicology and Experimental Medicine (Fraunhofer ITEM), Fraunhofer (Fraunhofer-Gesellschaft), Medizinische Universität Wien = Medical University of Vienna, German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, Departments of Cardiology and Cardiac Surgery, and Nephrology, Clínica Universidad de Navarra, Clínica Universidad de Navarra [Pamplona], Scuola Universitaria Superiore Sant'Anna [Pisa] (SSSUP), Fondazione Toscana Gabriele Monasterio, Montreal Heart Institute - Institut de Cardiologie de Montréal, Cairo University - Faculty of Medicine, Onassis Cardiac Surgery Center [Athens] (OCSC), Charité Campus Virchow-Klinikum (CVK), Berlin-Brandenburg Center for Regenerative Medicine [Berlin, Germany] (BCRT), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Université d'État Lomonossov de Moscou = Lomonosov Moscow State University (MSU), Cardiology Department, Rabin Medical Center, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Saarland University Hospital (UKS), Emergency Institute for Cardiovascular Diseases 'Prof. Dr. C.C. Iliescu' [Bucharest, Romania], Leiden University Medical Center (LUMC), Wrocław Medical University, Hôpital national = Rigshospitalet [Copenhagen, Denmark] (HNC), Queen's University [Belfast] (QUB), Linköping University (LIU), Massachusetts General Hospital [Boston], Baim Institute for Clinical Research Boston MA, British Heart Foundation Glasgow Cardiovascular Research Centre (BHF GCRC), University of Glasgow-NHS Greater Glasgow and Clyde, Volgograd State Medical University [Russian Federation] (VSMU), Karolinska University Hospital [Stockholm], Karolinska Institutet [Stockholm], Azienda Socio Sanitaria Territoriale Spedali Civili di Brescia [Brescia], Università degli Studi di Brescia = University of Brescia (UniBs), University of Zagreb, Cardiology Department, Porto Armed Forces Hospital, University Hospital Basel [Basel], Ziekenhuis Oost-Limburg (ZOL), Universitat de València (UV), Hospital Clínico Universitario de Valencia, Cardiology Division, Castelsangiovanni Hospital, Scientific Research Institute of Cardiology and Internal Medicine [Almaty, Kazakhstan], University Clinical Centre of Serbia, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), University of Naples Federico II = Università degli studi di Napoli Federico II, IRCCS Ospedale San Raffaele [Milan, Italy], Serbian Academy of Sciences and Arts (SASA), University of Belgrade [Belgrade], St George’s University Hospitals, University of Warwick [Coventry], Germans Trias i Pujol University Hospital [Badalona, Barcelona, Spain] (GTPUH), Universitat Autònoma de Barcelona (UAB), This work was supported by grants from the Spanish Ministry of Science, Innovation and Universities Institute of Health Carlos III (ISCIII) (PI18/01469 and PI21/00946 to A.G., CB16/11/00403 to A.B.-G and CB16/11/00483 to J.D. projects co-funded by the European Regional Development Funds), the European Commission (H2020 CRUCIAL project 2019–848109-2 to A.G.), the European Research Council (ERC CoG 818715 to R.A.d.B., ERC-PoC Megfib to T.T.), the National Medical Research Council of Singapore (NMRC, NMRC/STaR/0022/2014 to A.M.R. and MOH-000280 to M.Y.C.), the Health Research Council of New Zealand (02/152, 08/070, 11/1070), National Heart Foundation of New Zealand, New Zealand Lotteries Grant Board, Foundation for Research, Science and Technology and the Christchurch Heart Institute Trust to A.M.R., the Netherlands Heart Foundation (2017-21, 2017-11, 2018-30, 2020B005) to R.A.d.B., the leDucq Foundation (Cure-PLaN) to R.A.d.B., the Deutsche Forschungsgemeinschaft (KFO311 and TRR267 to T.T., TTR 219 to M.B., and TRR 1470 to S.V.L.), the Karolinska Institutet, the Swedish Research Council (523–2014-2336), the Swedish Heart Lung Foundation (20150557, 20190310), and the Stockholm County Council (20170112, 20190525) to L.H.L., European Project, BOZEC, Erwan, H2020 CRUCIAL project 2019–848109-2 - INCOMING, and Universiteit Leiden
Subjects: Heart Failure, Tissue, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Biomarkers, Cells, Remodeling, Endothelial Cells, Humans, Ventricular Remodeling, Cardiology, Cardiology and Cardiovascular Medicine, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract: International audience; Cardiac remodelling refers to changes in left ventricular structure and function over time, with a progressive deterioration that may lead to heart failure (HF) development (adverse remodelling) or vice versa a recovery (reverse remodelling) in response to HF treatment. Adverse remodelling predicts a worse outcome, whilst reverse remodelling predicts a better prognosis. The geometry, systolic and diastolic function and electric activity of the left ventricle are affected, as well as the left atrium and on the long term even right heart chambers. At a cellular and molecular level, remodelling involves all components of cardiac tissue: cardiomyocytes, fibroblasts, endothelial cells and leucocytes. The molecular, cellular and histological signatures of remodelling may differ according to the cause and severity of cardiac damage, and clearly to the global trend toward worsening or recovery. These processes cannot be routinely evaluated through endomyocardial biopsies, but may be reflected by circulating levels of several biomarkers. Different classes of biomarkers (e.g. proteins, non-coding RNAs, metabolites and/or epigenetic modifications) and several biomarkers of each class might inform on some aspects on HF development, progression and long-term outcomes, but most have failed to enter clinical practice. This may be due to the biological complexity of remodelling, so that no single biomarker could provide great insight on remodelling when assessed alone. Another possible reason is a still incomplete understanding of the role of biomarkers in the pathophysiology of cardiac remodelling. Such role will be investigated in the first part of this review paper on biomarkers of cardiac remodelling.
Published: 2022
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43. Sustaining antimicrobial stewardship in a high-antibiotic resistance setting

Author: Tat Ming Ng, Shi Thong Heng, Boon Hou Chua, Li Wei Ang, Sock Hoon Tan, Hui Lin Tay, Min Yi Yap, Jason Quek, Christine B. Teng, Barnaby E. Young, Ray Lin, Brenda Ang, Tau Hong Lee, David C. Lye, Lee Kong Chian School of Medicine (LKCMedicine), National Centre for Infectious Diseases, Singapore, Tan Tock Seng Hospital, and Yong Loo Lin School of Medicine, NUS
Subjects: Cohort Studies, Piperacillin, Antimicrobial Stewardship, Tazobactam, Carbapenems, Antibiotic Resistance, Humans, Drug Resistance, Microbial, Medicine [Science], Prospective Studies, General Medicine, Carbapenem Derivative, Anti-Bacterial Agents
Abstract: Importance: There is a lack of studies comparing the intended and unintended consequences of prospective review and feedback (PRF) with computerized decision support systems (CDSS), especially in the longer term in antimicrobial stewardship. Objective: To examine the outcomes associated with the sequential implementation of PRF and CDSS and changes to these interventions with long-term use of antibiotics for and incidence of multidrug resistant organisms (MDROs) and other unintended outcomes. Design, Setting, and Participants: This cohort study used an interrupted time series with segmented regression analysis of data from January 2007 to December 2018. Data were extracted from the electronic medical records of patients admitted at a large university teaching hospital with high rates of antibiotic resistance in Singapore. Data were analyzed from June 2019 to June 2020. Exposures: PRF of piperacillin-tazobactam and carbapenems (intervention 1, April 2009), with the addition of hospital-wide CDSS (intervention 2, April 2011), and lifting of CDSS for half of the hospital wards for 6 months (intervention 3, March 2017). Main Outcomes and Measures: Monthly antimicrobial use was measured in defined daily doses (DDDs) per 1000 patient-days. The monthly incidence of MDROs was calculated as number of clinical isolates detected per 1000 inpatient-days over a 6-month period. Unintended outcomes examined included in-hospital mortality and age-adjusted length of stay (LOS). Results: The number of inpatients increased from 56263 in 2007 to 63572 in 2018. During the same period, the mean monthly patient days increased from 33929 in 2007 to 45603 in 2018, and the proportion of patients older than 65 years increased from 45.5% in 2007 to 56.6% in 2018. After intervention 1, there were 0.33 (95% CI, 0.18 to 0.48) more DDDs per 1000 patient-days per month of piperacillin-tazobactam and carbapenems and-11.05 (95% CI,-15.55 to-6.55) fewer DDDs per 1000 patient-days per month for other broad-spectrum antibiotics. After intervention 2, there were-0.22 (95% CI,-0.33 to-0.10) fewer DDDs per 1000 patient-days per month of piperacillin-tazobactam and carbapenems and-2.10 (95% CI,-3.13 to-1.07) fewer DDDs per 1000 patient-days per month for other broad-spectrum antibiotics. After intervention 3, use of piperacillin-tazobactam and carbapenem increased by 0.28 (95% CI, 0.02 to 0.55) DDDs per 1000 patient-days per month. After intervention 2, incidence of Clostridioides difficile decreased (estimate,-0.02 [95% CI,-0.03 to-0.01] cases per 1000 patient-days per month). Conclusions and Relevance: In this cohort study, concurrent PRF and CDSS were associated with limiting the use of piperacillin-tazobactam and carbapenems while reducing use of other antibiotics. Published version
Published: 2022

44. mRNA booster vaccination enhances antibody responses against SARS-CoV2 omicron variant in individuals primed with mRNA or inactivated virus vaccines

Author: Biyan Zhang, Jianxin Huo, Yuhan Huang, Shuan Yong Teo, Kaibo Duan, Yanfeng Li, Lim Kai Toh, Kong Peng Lam, Shengli Xu, School of Biological Sciences, Singapore Immunology Network, A*STAR, and Yong Loo Lin School of Medicine, NUS
Subjects: Pharmacology, Infectious Diseases, SARS-CoV-2, Omicron, Drug Discovery, Immunology, Biological sciences [Science], Pharmacology (medical), Medicine [Science], vaccines, omicron, booster, antibodies, B cells, COVID-19
Abstract: The advent of the Omicron variant globally has hastened the requirement for a booster vaccination dose to confer continuous protection against symptomatic SARS-CoV2 infection. However, different vaccines are available in different countries, and individuals who had adverse reactions to certain vaccine types require heterologous vaccine boosters. To understand the efficacy of different vaccination regimens in inducing humoral responses to SARS-CoV2, we examined plasma antibodies and frequencies of Omicron RBD-specific B cells in individuals who had different priming-booster vaccination regimens. We found that individuals with three homologous doses of mRNA vaccines had higher levels of IgG of all subclasses against RBD of Omicron than individuals with three homologous doses of inactivated virus vaccine. A booster with mRNA vaccine resulted in significant increases in median levels of RBD-reactive IgG1 (17–19 fold) and IgG3 (2.3–3.3 fold) as compared to individuals receiving inactivated virus booster shots regardless of priming vaccine types. More importantly, individuals who received a booster dose of mRNA vaccine, irrespective of the priming vaccine, had antibodies with higher neutralizing capability against the Omicron variant than those who received a booster dose of inactivated virus vaccine. Corroborating the antibody results, boosting with the mRNA vaccine increased the frequencies of Omicron RBD-binding B cells by (1.5–3.3 fold) regardless of priming vaccine types. Together, our data demonstrate that an mRNA vaccine (BNT162b2 or mRNA-1273) booster enhances humoral responses against the Omicron variant in individuals vaccinated with either two prior doses of mRNA or inactivated virus vaccine (CoronaVac or BBIBP-CorV), potentially providing more effective protection against SARS-CoV-2 infection, particularly by the Omicron variant.
Published: 2022

45. Prevalence of measles antibodies among migrant workers in Singapore: a serological study to identify susceptible population subgroups

Author: Li Wei Ang, Qi Gao, Lin Cui, Aysha Farwin, Matthias Paul Han Sim Toh, Irving Charles Boudville, Mark I-Cheng Chen, Angela Chow, Raymond Tzer-Pin Lin, Vernon Jian Ming Lee, Yee Sin Leo, Lee Kong Chian School of Medicine (LKCMedicine), National Centre for Infectious Diseases, Saw Swee Hock School of Public Health, National University of Singapore, Tan Tock Seng Hospital, and Yong Loo Lin School of Medicine, National University of Singapore
Subjects: Male, Transients and Migrants, Singapore, Research, Immunity, Infectious and parasitic diseases, RC109-216, Middle Aged, Antibodies, Viral, Migrant workers, Infectious Diseases, Seroepidemiologic Studies, Prevalence, Humans, Female, Medicine [Science], Vaccination coverage, Measles
Abstract: Background: In 2019, two clusters of measles cases were reported in migrant worker dormitories in Singapore. We conducted a seroprevalence study to measure the level of susceptibility to measles among migrant workers in Singapore. Methods: Our study involved residual sera of migrant workers from seven Asian countries (Bangladesh, China, India, Indonesia, Malaysia, Myanmar and the Philippines) who had participated in a survey between 2016 and 2019. Immunoglobulin G (IgG) antibody levels were first measured using a commercial enzyme-linked immunosorbent assay (ELISA) test kit. Those with equivocal or negative IgG results were further evaluated using plaque reduction neutralization test (PRNT). Results: A total of 2234 migrant workers aged 20–49 years were included in the study. The overall prevalence of measles IgG antibodies among migrant workers from the seven Asian countries was 90.5% (95% confidence interval 89.2–91.6%). The country-specific seroprevalence ranged from 80.3 to 94.0%. The seroprevalence was significantly higher among migrant workers born in 1965–1989 than those born in 1990–1999 (95.3% vs. 86.6%, p < 0.0005), whereas there was no significant difference by gender (90.8% in men vs. 89.9% in women, p = 0.508). 195 out of 213 samples with equivocal or negative ELISA results were tested positive using PRNT. Conclusion: The IgG seroprevalence in migrant workers was below the herd immunity threshold of 95% for measles. Sporadic outbreaks may occur in susceptible individuals due to high transmissibility of measles virus. Seroprevalence surveys can help identify susceptible subgroups for vaccination. Ministry of Health (MOH) Published version Sample collection was supported by the Ministry of Health, Singapore, under the Communicable Diseases—Public Health Research Grant (Grant Number MOHCS15MAR001). Laboratory testing for the seroprevalence of measles in migrant workers was supported by the National Public Health Laboratory.
Published: 2022

46. Brown adipose tissues mediate the metabolism of branched chain amino acids during the transitioning from hyperthyroidism to euthyroidism (TRIBUTE)

Author: Lijuan Sun, Hui Jen Goh, Sanjay Verma, Priya Govindharajulu, Suresh Anand Sadananthan, Navin Michael, Christiani Jeyakumar Henry, Julian Park-Nam Goh, S. Sendhil Velan, Melvin Khee-Shing Leow, Lee Kong Chian School of Medicine (LKCMedicine), Singapore Institute for Clinical Sciences, (A*STAR), Tan Tock Seng Hospital, Yong Loo Lin School of Medicine, NUS, and Duke-NUS Medical School
Subjects: endocrine system, Multidisciplinary, endocrine system diseases, Valine, Hyperthyroidism, Adipose Tissue, Brown, Fluorodeoxyglucose F18, Leucine, Branched Chain Amino Acid, Humans, Insulin, Brown Adipose Tissue, Medicine [Science], Insulin Resistance, Isoleucine, Amino Acids, Branched-Chain, hormones, hormone substitutes, and hormone antagonists
Abstract: Both hyperthyroidism and elevated plasma branched chain amino acids (BCAA) are associated with insulin resistance. BCAA utilization and clearance relative to thyroid status changes remains unclear. We investigate amino acids changes, specifically BCAA, during the transition from hyperthyroidism to euthyroidism, and the impact of active brown adipose tissue (BAT) on the metabolic effects of BCAA. Newly diagnosed Graves' disease participants were recruited. Hyperthyroidism was treated via a titration dosing regimen of thionamide anti-thyroid drug to establish euthyroidism over 12-24 weeks. All underwent energy expenditure (EE) measurement within a chamber calorimeter, 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging and plasma amino acids measurement during hyperthyroidism and euthyroidism. PET BAT maximum standardized uptake value (SUVmax), SUVmean and MR supraclavicular fat fraction (FF) quantified BAT activity. Twenty-two patients completed the study. Plasma BCAA level was significantly reduced in BAT-positive but not in BAT-negative patients during the transition from hyperthyroidism to euthyroidism. Plasma valine but not leucine and isoleucine correlated positively with insulin and HOMA-IR in hyperthyroidism. Plasma valine, leucine and isoleucine correlated with insulin and HOMA-IR in euthyroidism. Plasma valine correlated with insulin and HOMA-IR in BAT-negative but not in BAT-positive participants in both hyperthyroid and euthyroid state. However, the change (i.e. decrease) in plasma valine concentration from hyperthyroid to euthyroid state was affected by BAT-status. BAT utilizes and promotes BCAA plasma clearance from hyperthyroid to euthyroid state. Active BAT can potentially reduce circulating BCAA and may help to ameliorate insulin resistance and improve metabolic health.Clinical trial registration: The trial was registered at clinicaltrials.gov as NCT03064542. National Medical Research Council (NMRC) Published version The study was supported by the National Medical Research Council Award grant. Grant number: NMRC/ CSA-INV/0003/2015.
Published: 2022

47. Antibiotic therapy in the treatment of COVID-19 pneumonia: who and when?

Author: Tat Ming Ng, Sean W. X. Ong, Audrey Y. X. Loo, Sock Hoon Tan, Hui Lin Tay, Min Yi Yap, David C. Lye, Tau Hong Lee, Barnaby E. Young, Lee Kong Chian School of Medicine (LKCMedicine), National Centre for Infectious Diseases, Singapore, Tan Tock Seng Hospital, and Yong Loo Lin School of Medicine, NUS
Subjects: Microbiology (medical), Infectious Diseases, Antibiotics, antibiotics, COVID-19, pneumonia, bacterial infection, Pharmacology (medical), Medicine [Science], General Pharmacology, Toxicology and Pharmaceutics, Biochemistry, Microbiology
Abstract: Background: COVID-19 imposes challenges in antibiotic decision-making due to similarities between bacterial pneumonia and moderate to severe COVID-19. We evaluated the effects of antibiotic therapy on the clinical outcomes of COVID-19 pneumonia patients and diagnostic accuracy of key inflammatory markers to inform antibiotic decision-making. Methods: An observational cohort study was conducted in patients hospitalised with COVID-19 at the National Centre for Infectious Diseases and Tan Tock Seng Hospital, Singapore, from January to April 2020. Patients were defined as receiving empiric antibiotic treatment for COVID-19 if started within 3 days of diagnosis. Results: Of 717 patients included, 86 (12.0%) were treated with antibiotics and 26 (3.6%) had documented bacterial infections. Among 278 patients with COVID-19 pneumonia, those treated with antibiotics had more diarrhoea (26, 34.7% vs. 24, 11.8%, p < 0.01), while subsequent admissions to the intensive care unit were not lower (6, 8.0% vs. 10, 4.9% p = 0.384). Antibiotic treatment was not independently associated with lower 30-day (adjusted odds ratio, aOR 19.528, 95% confidence interval, CI 1.039–367.021) or in-hospital mortality (aOR 3.870, 95% CI 0.433–34.625) rates after adjusting for age, co-morbidities and severity of COVID-19 illness. Compared to white cell count and procalcitonin level, the C-reactive protein level had the best diagnostic accuracy for documented bacterial infections (area under the curve, AUC of 0.822). However, the sensitivity and specificity were less than 90%. Conclusion: Empiric antibiotic use in those presenting with COVID-19 pneumonia did not prevent deterioration or mortality. More studies are needed to evaluate strategies to diagnose bacterial co-infections in these patients.
Published: 2022

48. Demographics, radiological findings, and clinical outcomes of Klebsiella pneumonia vs. Non-Klebsiella pneumoniae pyogenic liver abscess: a systematic review and meta-analysis with trial sequential analysis

Author: Kai Siang Chan, Christopher Tze Wei Chia, Vishal G. Shelat, Lee Kong Chian School of Medicine (LKCMedicine), Tan Tock Seng Hospital, and Yong Loo Lin School of Medicine, NUS
Subjects: Microbiology (medical), Escherichia Coli, Infectious Diseases, Hepatic Abscess, General Immunology and Microbiology, Immunology and Allergy, Medicine [Science], Molecular Biology
Abstract: Pyogenic liver abscess (PLA) is a common cause of hepatobiliary sepsis. Klebsiella pneumoniae (KP) is the most common organism causing PLA. Evidence is scarce on the demographics, radiological findings, and outcomes of KPPLA versus non-KPPLA (N-KPPLA). PubMed, Embase, The Cochrane Library, and Scopus were systematically searched until 14 May 2022 for studies comparing KPPLA and N-KPPLA. Exclusion criteria were single-arm studies. Primary outcomes were mortality (30-day/in-hospital) and metastatic complications. There were 16 studies, including 5127 patients (KPPLA n = 3305, N-KPPLA n = 1822). Patients with KPPLA were younger (mean difference: −2.04 years, p = 0.02). History of hepatobiliary disease (Odds ratio (OR) 0.30, 95% CI: 0.20, 0.46) and malignancy (OR 0.26, 95% CI: 0.16, 0.42) were less common in KPPLA. KPPLA was associated with lower incidence of multiple abscesses (OR 0.52, 95% CI: 0.35, 0.76, p < 0.001) and bilobar abscesses (OR 0.60, 95% CI: 0.49, 0.74, p < 0.001). KPPLA has higher overall metastatic complications (KPPLA 9.7% vs. N-KPPLA 4.8%, OR 3.16, 95% CI: 2.00, 4.99, p < 0.001), but lower mortality (KPPLA 3.9% vs. N-KPPLA 7.6%, OR 0.51, 95% CI: 0.34, 0.78, p < 0.001). Trial sequential analysis showed conclusive evidence that KPPLA has lower mortality than N-KPPLA. In conclusion, KPPLA has lower mortality than N-KPPLA.
Published: 2022

49. MYC overexpression leads to increased chromatin interactions at superenhancers and MYC binding sites

Author: Melissa Fullwood, KAIJING CHEN, Yi Xiang See, School of Biological Sciences, Cancer Science Institute of Singapore, National University of Singapore, Yong Loo Lin School of Medicine, National University of Singapore, and Institute of Molecular and Cell Biology, A*STAR
Subjects: Biological sciences::Molecular biology [Science], Chromatin Interactions, Genetics, Biological sciences::Genetics [Science], Genetics (clinical), Cancer
Abstract: The MYC oncogene encodes for the MYC protein and is frequently dysregulated across multiple cancer cell types, making it an attractive target for cancer therapy. MYC overexpression leads to MYC binding at active enhancers, resulting in a global transcriptional amplification of active genes. Since superenhancers are frequently dysregulated in cancer, we hypothesized that MYC preferentially invades into superenhancers and alters the cancer genome organization. To that end, we performed ChIP-seq, RNA-seq, 4C-seq and SIQHiC (Spike-in Quantitative Hi-C) on the U2OS osteosarcoma cell line with tetracycline-inducible MYC. MYC overexpression in U2OS cells modulated histone acetylation and increased MYC binding at superenhancers. SIQHiC analysis revealed increased global chromatin contact frequency, particularly at chromatin interactions connecting MYC binding sites at promoters and enhancers. Immunofluorescence staining showed that MYC molecules formed punctate foci at these transcriptionally active domains after MYC overexpression. These results demonstrate the accumulation of overexpressed MYC at promoter-enhancer hubs and suggest that MYC invades into enhancers through spatial proximity. At the same time, the increased protein-protein interactions may strengthen these chromatin interactions to increase chromatin contact frequency. CTCF siRNA knockdown in MYC overexpressed U2OS cells demonstrated that removal of architectural proteins can disperse MYC and abrogate the increase in chromatin contacts. By elucidating the chromatin landscape of MYC driven cancers, we can potentially target MYC associated chromatin interactions for cancer therapy. Ministry of Education (MOE) Accepted version This research is supported by the RNA Biology Center at the Cancer Science Institute of Singapore, NUS, as part of funding under the Singapore Ministry of Education Academic Research Fund Tier 3 grant awarded to Daniel Tenen (MOE2014-T3-1-006). This research is supported by the NRF Singapore and the Singapore Ministry of Education under its Research Centres of Excellence initiative and a Singapore Ministry of Education Academic Research Fund Tier 2 grant awarded to M.J.F. (MOET2EP30120-0009).
Published: 2022

50. Therapeutics in paediatric genetic diseases: Current and future landscape

Author: Koh, Ai Ling, Jamuar, Saumya Shekhar, Lee Kong Chian School of Medicine (LKCMedicine), KK Women’s and Children’s Hospital, SingHealth Duke‑NUS Genomic Medicine Centre, Duke‑NUS Medical School, and Yong Loo Lin School of Medicine, NUS
Subjects: Antisense Oligonucleotide, Medicine [Science], Gene Therapy, General Medicine
Abstract: There are more than 7,000 paediatric genetic diseases (PGDs) but less than 5% have treatment options. Treatment strategies targeting different levels of the biological process of the disease have led to optimal health outcomes in a subset of patients with PGDs, where treatment is available. In the past 3 decades, there has been rapid advancement in the development of novel therapies, including gene therapy, for many PGDs. The therapeutic success of treatment relies heavily on knowledge of the genetic basis and the disease mechanism. Specifically, gene therapy has been shown to be effective in various clinical trials, and indeed, these trials have led to regulatory approvals, paving the way for gene therapies for other types of PGDs. In this review, we provide an overview of the treatment strategies and focus on some of the recent advancements in therapeutics for PGDs. Published version
Published: 2023
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