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1. Artemia salina Lethality and Histopathological Studies of Siam Weed, Chromolaena odorata

Author

Sirinthipaporn, Anushika; Mahidol University International College, Mahidol University, Salaya Campus, Nakhon Pathom 73170, Jiraungkoorskul, Kanitta; Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok 10400, Jiraungkoorskul, Wannee; Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok 10400, Sirinthipaporn, Anushika; Mahidol University International College, Mahidol University, Salaya Campus, Nakhon Pathom 73170, Jiraungkoorskul, Kanitta; Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok 10400, and Jiraungkoorskul, Wannee; Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok 10400

Abstract

Siam weed, Chromolaena odorata, leaves, stem, and root were extracted with aqueous and ethanol solvents within 1, 3, 5 and 24 hours. The extractions were determined amount of total phenolic compound using Folin-Ciocalteu reagent. The extract that showed the highest amount of total phenolic compound was used for evaluating the cytotoxicity test against Artemia salina at varying concentrations as 0, 50, 500, 5,000 and 50,000 ppm. The cytotoxicity data were determined the median and 90% lethal concentration, LC50 and LC90, respectively, within 24 hours. The result revealed that the highest amount of total phenolic compound was 198.02+3.96 mg of gallic acid equivalent per gram of aqueous leaf extraction in 24 h. Therefore, the 24-hour aqueous extract of C. odorata leaf expressed the 24-h LC50 and LC90 values in A. salina were 43, 551 and 78,391 ppm, respectively. The lesions were observed in intestinal parts such as edema, deformation or elongation of the enterocytes, blebbing cells, and pyknotic cells.

Published
2017

4. Report from the second cytomegalovirus and immunosenescence workshop

Author

Jan Strindhall, Natalie E. Riddell, Arne N. Akbar, Graham Pawelec, George C. Wang, Mark Beswick, Gavin M. Mason, Claudio Franceschi, Tamas Fulop, René A. W. van Lier, Calogero Caruso, Delphine Sauce, Annette Pachnio, Goronzy Joerg J, Rafael Solana, Florian Kern, Piotr Trzonkowski, Andrea B. Maier, Janko Nikolich-Zugich, Mark R. Wills, Dietmar Herndler-Brandstetter, Derek C. Macallan, Ryan Roberts, Ambarish Dutta, Matthew D. Morgan, David Melzer, Giuseppina Colonna-Romano, Sian M. Henson, Jos A. Bosch, Rosanna Vescovini, Stephen J. Griffiths, John Sinclair, Paul Klenerman, Rudi G. J. Westendorp, Paolo Sansoni, Paul Moss, Ann B. Hill, Effrossyni Gkrania-Klotsas, Richard Macaulay, Department of Medicine, University of Cambridge [UK] (CAM), Division of Infection and Immunity, University College of London [London] (UCL), School of Cancer Sciences, University of Birmingham [Birmingham], College of Life and Environmental Sciences, Social and Preventive Medicine, Universität Heidelberg [Heidelberg]-Mannheim Institute of Public Health, Department of Pathobiology and Medical and Forensic Biotechnologies, Università degli studi di Palermo - University of Palermo, Epidemiology and Public Health Group, University of Exeter, Dept. Experimental Pathology, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Research Centre on Aging, Université de Sherbrooke (UdeS), Addenbrooke's Hospital, Cambridge University NHS Trust, Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, School of Immunity and Infection, Dept Microbiology and Immunology, Oregon Health and Science University [Portland] (OHSU), BSMS, University of Sussex, Nuffield Dept of Clinical Medicine, University of Oxford [Oxford]-NIHR Biomedical Research Centre, Centre for Infection, St George's, University of London, Department of Gerontology and Geriatrics, Leiden University Medical Center (LUMC), Department of Immunobiology and the Arizona Center on Aging, University of Arizona, Department of Internal Medicine and Biomedical Sciences, University of Parma = Università degli studi di Parma [Parme, Italie], Immunité et Infection, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR113-Université Pierre et Marie Curie - Paris 6 (UPMC), Instituto Maimonides de Investigación Biomédica de Cordoba (IMIBIC), Universidad de Córdoba [Cordoba]-Hospital Universitario Reina Sofía, Department of Natural Science and Biomedicine, School of Health Sciences-Jönköping University [Sweden], Department of Clinical Immunology and Transplantology, Medical University of Gdansk, Department of Experimental Immunology, Sanquin Blood Supply Foundation, Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Department of Public Health and Primary Care, Department of Internal Medicine II, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Wills1, M, Akbar, A, Beswick, M, Bosch, JA, Caruso, C, Colonna-Romano, G, Dutta, A, Franceschi, C, Fulop, T, Gkrania-Klotsas, E, Goronzy, G, Griffiths, SJ, Henson, SM, Herndler-Brandstetter, D, Hill, A, Kern, F, Klenerman, P, Macallan, D, Macaulay, R, Maier, AB, Mason, G, Melzer, D, Morgan, M, Moss, P, Nikolich-Zugich, J, Pachnio, A, Riddell, N, Roberts, R, Sansoni, P, Sauce, D, Sinclair, J, Solana, R, Strindhall, J, Trzonkowski, P, van Lier, R, Vescovini, R, Wang, G, Westendorp, R, Pawelec, G., University of Cambridge [UK] (CAM)-Addenbrooke's Hospital, Cancer Sciences School, Advisory Board of OA Cancer, University of Amsterdam [Amsterdam] (UvA), Department of Pathobiology and Biomedical Methodologies, University of Exeter Medical School, Centro Interdipartimentale Galvani (CIG), Semmelweis University [Budapest, Hungary], Department of Molecular Microbiology and Immunology, Brighton and Sussex Medical School (BSMS), NIHR Biomedical Research Centre [London], Guy's and St Thomas' NHS Foundation Trust-King‘s College London, Department of Immunobiology, University of Arizona-College of Medicine, Department of Internal Medicine, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Immunology Unit, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)-Reina Sofia University-Hospital-University of Cordoba, Health Sciences School, Jönköping University [Sweden], Medical University of Gdańsk, Experimental Immunology, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Dipartimento di Medicina Interna e Scienze Biomediche, Section for Transplantation Immunology and Immunohaematology, University Hospital Tübingen, Wills M., Akbar A., Beswick M., Bosch J.A., Caruso C., Colonna-Romano G., Dutta A., Franceschi C., Fulop T., Gkrania-Klotsas E., Goronzy J., Griffiths S.J., Henson S., Herndler-Brandstetter D., Hill A., Kern F., Klenerman P., Macallan D., Macualay R., Maier A.B., Mason G., Melzer D., Morgan M., Moss P., Nikolich-Zugich J., Pachnio A., Riddell N., Roberts R., Sansoni P., Sauce D., Sinclair J., Solana R., Strindhall J., Trzonkowski P., van Lier R., Vescovini R., Wang G., Westendorp R., Pawelec G., Neuromechanics, BMC, Ed., University of Oxford-NIHR Biomedical Research Centre, Università degli studi di Parma = University of Parma (UNIPR), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidad de Córdoba = University of Córdoba [Córdoba]-Hospital Universitario Reina Sofía, Wills, Mark [0000-0001-8548-5729], Gkrania-Klotsas, Effrossyni [0000-0002-0930-8330], Sinclair, John [0000-0002-2616-9571], Apollo - University of Cambridge Repository, Universität Heidelberg [Heidelberg] = Heidelberg University-Mannheim Institute of Public Health, and Universiteit Leiden-Universiteit Leiden

Subjects
lcsh:Immunologic diseases. Allergy, Gerontology, Aging, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], Immunology, Congenital cytomegalovirus infection, Disease, Ageing, CMV, immunity, lcsh:Geriatrics, 0601 Biochemistry and Cell Biology, Vaccine Related, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Medicine, cytomegalovirus, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, immunosenescence, 0303 health sciences, business.industry, Geriatrics gerontology, Immunosenescence, medicine.disease, 3. Good health, lcsh:RC952-954.6, Ageing, HCMV Infection, Infectious Diseases, Commentary, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunization, lcsh:RC581-607, business, 030215 immunology
Abstract

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.; International audience; The Second International Workshop on CMV & Immunosenescence was held in Cambridge, UK, 2-4th December, 2010. The presentations covered four separate sessions: cytomegalovirus and T cell phenotypes; T cell memory frequency, inflation and immunosenescence; cytomegalovirus in aging, mortality and disease states; and the immunobiology of cytomegalovirus-specific T cells and effects of the virus on vaccination. This commentary summarizes the major findings of these presentations and references subsequently published work from the presenter laboratory where appropriate and draws together major themes that were subsequently discussed along with new areas of interest that were highlighted by this discussion.

Published
2011

5. Assessment of the safety and the anti-α-Gal immune response to an oral vaccine in captive-bred Humboldt penguins (Spheniscus humboldti)

Author

Thorel, Milan, Mateos-Hernandez, Lourdes, Mulot, Baptiste, Azzouni, Mouna Naila, Hodžić, Adnan, Gaillot, Hugues, Ruel, Yannick, Desoubeaux, Guillaume, Delaye, Jean-Baptiste, Obregon, Dasiel, Wu-Chuang, Alejandra, de La Fuente, José, Bermúdez-Humarán, Luis, Risco-Castillo, Veronica, Leclerc, Antoine, Cabezas-Cruz, Alejandro, SaBio, Instituto de Investigación en Recursos Cinegéticos (IREC), Beauval Nature, Department of Pathobiology, Institute of Parasitology, University of Veterinary Medicine [Vienna] (Vetmeduni)-University of Veterinary Medicine [Vienna] (Vetmeduni), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidade de São Paulo (USP), School of environmental sciences, University of Guelph, Biologie moléculaire et immunologie parasitaires et fongiques (BIPAR), École nationale vétérinaire - Alfort (ENVA)-Laboratoire de santé animale, sites de Maisons-Alfort et de Dozulé, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Department of Veterinary Pathobiology, Oklahoma State University [Stillwater], MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Dynamic Microbiology - EA 7380 (DYNAMIC), École nationale vétérinaire - Alfort (ENVA)-Université Paris-Est (UPE)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), BioPôle Alfort, École nationale vétérinaire - Alfort (ENVA), ZooParc de Beauval, University of Veterinary Medicine [Vienna] (Vetmeduni), Advetia Specialty Practice, Partenaires INRAE, Oklahoma State University [Stillwater] (OSU), SaBio (CSIC-UCLM-JCCM), and École nationale vétérinaire - Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université Paris-Est (UPE)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)

Subjects
MESH: Galactose, E. coli Nissle 1917, MESH: Escherichia coli, Aspergillus fumigatus, Spheniscus humboldti, α-Gal Vaccine, MESH: Immunoglobulin M, Escherichia coli Nissle, MESH: Vaccines, penguins, Anti-α-Gal immunity, probiotics, MESH: Spheniscidae, zoo, vaccine, Aspergillosis, MESH: Animals, MESH: Aspergillosis, Sphenisciformes, MESH: Probiotics, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Oral administration of Escherichia coli O86:B7 expressing high levels of galactose-α-1,3galactose (α-Gal) was previously shown to protect turkeys from aspergillosis caused by Aspergillus fumigatus. In the present study, we first tested the basal level of anti-α-Gal antibodies (Abs) in healthy Humboldt penguin (Spheniscus humboldti) sera and penguin egg yolks. We then conducted a trial to test whether modulation of α-Gal immunity by oral administration of the probiotic bacterium Escherichia coli Nissle could prevent Humboldt penguins from aspergillosis. To this aim, E. coli Nissle was administered orally to ten penguins and a placebo was concomitantly given to a control group of ten other penguins. An aspergillosis diagnostic panel (CT scans, capillary zone electrophoresis, 3-hydroxybutyrate levels, anti-A. fumigatus Abs measurements) was implemented before, during and after the interventional procedure in both penguin groups. As results, healthy penguins produced natural anti-α-Gal Abs that were also detected in the egg yolks. Surprisingly, oral administration of E. coli Nissle was associated with lower levels of anti-α-Gal and anti-A. fumigatus Abs compared with the control group. Still, a correlation was seen between anti-E.coli Abs (IgM/IgY) and anti-α-Gal Abs (IgM/IgY), only in the vaccinated penguins. E. coli Nissle is a safe probiotic to use in Humboldt penguins with potential protective effect against aspergillosis to be further tested.

Published
2022

6. Transmission of highly pathogenic avian influenza in the nomadic free-grazing duck production system in Viet Nam

Author

Anne Meyer, Pawin Padungtod, Katriina Willgert, Nhu Van Thu, Dinh Xuan Tung, Guillaume Fournié, Nguyen Thanh Thuy, Dirk U. Pfeiffer, Pham Thanh Long, Timothée Vergne, Scott H. Newman, Royal Veterinary College [London], University of London [London], Department of Pathobiology and Population Sciences, Royal Veterinary College, Veterinary Epidemiology, Economics and Public Health Group, University of Cambridge [UK] (CAM), Department of Veterinary Medicine, Disease Dynamics Unit [UK], Ausvet Europe, Institute of Environmental Health and Sustainable Development (IEHSD), Food and Agriculture Organization of the United Nations, Global Emergency Centre for Transboundary Animal Diseases (ECTAD), Ministry of Agriculture and Rural Development [Hanoï] (MARD), City University of Hong Kong [Hong Kong] (CUHK), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), This work was supported by a British Council Institutional Links grant under the Newton Fund (Grant ID: 172711836), which is administered through the UK Department for Business Innovation and Skills., Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Willgert, Katriina [0000-0003-3586-1997], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Veterinary medicine, Indirect Transmission, 040301 veterinary sciences, animal diseases, lcsh:Medicine, Biology, medicine.disease_cause, Article, law.invention, Disease Outbreaks, 0403 veterinary science, 03 medical and health sciences, law, medicine, Influenza A virus, Animals, lcsh:Science, Preventive medicine, Multidisciplinary, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Influenza A Virus, H5N1 Subtype, Viet nam, Vaccination, lcsh:R, Outbreak, virus diseases, 04 agricultural and veterinary sciences, Influenza A virus subtype H5N1, Disinfection, Motor Vehicles, 030104 developmental biology, Transmission (mechanics), Ducks, Vietnam, Influenza Vaccines, Influenza in Birds, Communicable Disease Control, lcsh:Q, Flock, Influenza virus
Abstract

The presence of free-grazing ducks (FGD) has consistently been shown to be associated with highly pathogenic avian influenza virus (HPAIV) H5N1 outbreaks in South-East Asia. However, the lack of knowledge about the transmission pathways limits the effectiveness of control efforts. To address this gap, we developed a probabilistic transmission model of HPAIV H5N1 in the nomadic FGD production system in Viet Nam, assuming different scenarios to address parameter uncertainty. Results suggested that HPAIV H5N1 could spread within the nomadic FGD production system, with an estimated flock-level effective reproduction number (re) ranging from 2.16 (95% confidence interval (CI): 1.39-3.49) to 6.10 (95%CI: 3.93-9.85) depending on the scenario. Indirect transmission via boats and trucks was shown to be the main transmission route in all scenarios. Results suggest that re could be reduced below one with 95% confidence if 86% of FGD flocks were vaccinated in the best-case scenario or 95% in the worst-case scenario. If vaccination was combined with cleaning and disinfection of transport vehicles twice a week, vaccination coverage could be lowered to 60% in the best-case scenario. These findings are of particular relevance for prioritising interventions for effective control of HPAIV in nomadic free-grazing duck production systems.

Published
2020

7. Importance of the Major Histocompatibility Complex (Swine Leukocyte Antigen) in Swine Health and Biomedical Research

Author

C. S. Ho, M. Tector, Asako Ando, Joan K. Lunney, Sabine E. Hammer, M. Charles, Claire Rogel-Gaillard, A. J. Tector, Institute of Immunology, Department of Pathobiology, University of Veterinary Medicine [Vienna] (Vetmeduni), Gift of Hope Organ & Tissu e Donor Network, Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, Génétique Animale et Biologie Intégrative (GABI), Université Paris-Saclay-AgroParisTech-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Paris Saclay (COMUE), Department of Surgery Birmingham, University of Alabama at Birmingham (UAB), Animal Parasitic Diseases Laboratory, Beltsville Agricultural Research Center, US Department of Agriculture, USDA-ARS : Agricultural Research Service, Lunney, Joan, Institut National de la Recherche Agronomique (INRA)-AgroParisTech, and Agricultural Research Service

Subjects
0301 basic medicine, Swine, [SDV]Life Sciences [q-bio], Xenotransplantation, medicine.medical_treatment, Sus scrofa, Antigen presentation, Transplants, 030230 surgery, Biology, Major histocompatibility complex, 03 medical and health sciences, 0302 clinical medicine, Antigen, Genetics, medicine, Animals, Gene, Swine Diseases, allogeneic, Chromosome 7 (human), General Veterinary, xenogeneic, Histocompatibility Antigens Class I, fungi, Haplotype, SLA polymorphism, Transplantation, 030104 developmental biology, swine leukocyte antigen, vaccine responses, Gene Expression Regulation, Models, Animal, biology.protein, Animal Science and Zoology, Biotechnology
Abstract

In pigs, the major histocompatibility complex (MHC), or swine leukocyte antigen (SLA) complex, maps to Sus scrofa chromosome 7. It consists of three regions, the class I and class III regions mapping to 7p1.1 and the class II region mapping to 7q1.1. The swine MHC is divided by the centromere, which is unique among mammals studied to date. The SLA complexspans between 2.4 and 2.7 Mb, depending on haplotype, and encodes approximately 150 loci, with at least 120 genes predicted to be functional. Here we update the whole SLA complex based on the Sscrofa11.1 build and annotate the organization for all recognized SLA genes and their allelic sequences. We present SLA nomenclature and typing methods and discuss the expression of SLA proteins, as well as their role in antigen presentation and immune, disease, and vaccine responses. Finally, we explore the role of SLA genes in transplantation and xenotransplantation and their importance in swine biomedical models.

Published
2020

9. 'Health in' and 'Health of' Social-Ecological Systems: A Practical Framework for the Management of Healthy and Resilient Agricultural and Natural Ecosystems

Author

De Garine-Wichatitsky, M., Binot, A., Ward, J., Caron, A., Perrotton, Arthur, Ross, H., Quoc, H. T., Valls-Fox, H., Gordon, I. J., Promburom, P., Ancog, R., Kock, R. A., Morand, S., Chevalier, V., Allen, W., Phimpraphai, W., Duboz, R., Echaubard, P., Animal, Santé, Territoires, Risques et Ecosystèmes (UMR ASTRE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Faculty of Veterinary Medicine [Kasetsart University, Thaïlande], Kasetsart University (KU)-Partenaires IRSTEA, Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Département Systèmes Biologiques (Cirad-BIOS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Mekong Region Futures Institute [Bangkok] (MERFI), Université Eduardo Mondlane, Stockholm University, Savoirs, ENvironnement et Sociétés (SENS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Paul-Valéry - Montpellier 3 (UPVM)-Institut de Recherche pour le Développement (IRD), School of Agriculture and Food Sciences, University of Southern Queensland (USQ), Fonctionnement écologique et gestion durable des agrosystèmes bananiers et ananas (UR GECO), Département Performances des systèmes de production et de transformation tropicaux (Cirad-PERSYST), Systèmes d'élevage méditerranéens et tropicaux (UMR SELMET), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Département Environnements et Sociétés (Cirad-ES), Fenner School of Environment and Society, Australian National University (ANU), The James Hutton Institute, Central Queensland University (CQU), Chiang Mai University (CMU), University of the Philippines Los Baños (UP Los Baños), Department of Pathobiology and Population Sciences, Royal Veterinary College, Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Faculty of Veterinary Technology, Kasetsart University (KU), Unité d'Épidémiologie et de Santé Publique [Phnom Penh], Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Learning for Sustainability [Christchurch], Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), Université de Yaoundé I-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Sorbonne Université (SU)-Institut de Recherche pour le Développement (IRD [France-Nord]), School of Oriental and African Studies (SOAS), University of London [London], CIRAD (ProPISThai International Cooperation Agency (TICA-Health Interface and TICA-Innovative Animal Health).-HEcoSEA/2018-2019), European Project, Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226, and Institut de Recherche pour le Développement (IRD [France-Nord])-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Université de Yaoundé I-Sorbonne Université (SU)

Subjects
H01 - Protection des végétaux - Considérations générales, [SDV.SA]Life Sciences [q-bio]/Agricultural sciences, Conservation of Natural Resources, [SDV]Life Sciences [q-bio], Communicable Diseases, Emerging, Santé publique, résilience des écosystèmes, résilience, Zoonoses, Animals, Humans, Politique de l'environnement, resilience, Ecosystem, Original Research, agriculture, biodiversity, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Santé, Préservation de l'écosystème, L70 - Sciences et hygiène vétérinaires - Considérations générales, health, co-learning, services écosystémiques, social-ecological systems, S50 - Santé humaine, P01 - Conservation de la nature et ressources foncières, Public Health, Écosystème
Abstract

International audience; The past two decades have seen an accumulation of theoretical and empirical evidence for the interlinkages between human health and well-being, biodiversity and ecosystem services, and agriculture. The COVID-19 pandemic has highlighted the devastating impacts that an emerging pathogen, of animal origin, can have on human societies and economies. A number of scholars have called for the wider adoption of "One Health integrated approaches" to better prevent, and respond to, the threats of emerging zoonotic diseases. However, there are theoretical and practical challenges that have precluded the full development and practical implementation of this approach. Whilst integrated approaches to health are increasingly adopting a social-ecological system framework (SES), the lack of clarity in framing the key concept of resilience in health contexts remains a major barrier to its implementation by scientists and practitioners. We propose an operational framework, based on a transdisciplinary definition of Socio-Ecological System Health (SESH) that explicitly links health and ecosystem management with the resilience of SES, and the adaptive capacity of the actors and agents within SES, to prevent and cope with emerging health and environmental risks. We focus on agricultural transitions that play a critical role in disease emergence and biodiversity conservation, to illustrate the proposed participatory framework to frame and co-design SESH interventions. Finally, we highlight critical changes that are needed from researchers, policy makers and donors, in order to engage communities and other stakeholders involved in the management of their own health and that of the underpinning ecosystems.

Published
2021

10. Enterobactin Deficiency in a Coliform Mastitis Isolate Decreases Its Fitness in a Murine Model: A Preliminary Host–Pathogen Interaction Study

Author

Amanda J Gibson, Dirk Werling, Pierre Germon, David Smith, Jonas Steenbrugge, Niels Vander Elst, Evelyne Meyer, Koen Breyne, Department of Pharmacology, Toxicology and Biochemistry, Universiteit Gent = Ghent University [Belgium] (UGENT), Department of Neurology [Boston], Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Center for Molecular Imaging Research, Harvard Medical School [Boston] (HMS), Centre of Excellence for Bovine TB, Institute of Biological, Environmental and Rural Sciences (IBERS), Aberystwyth University-Aberystwyth University, Department of Pathobiology and Population Sciences, Royal Veterinary College, School of Engineering and Physical Sciences [Edinburgh] (EPS-HWU), Heriot-Watt University [Edinburgh] (HWU), Infectiologie et Santé Publique (UMR ISP), Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), KOlimastIR-ANIHWA consortium of Era-Net, funded in the UK by DEFRA and BBSRC (Reference OD1718), Research Foundation of Flanders (FWO) grant number 1.S.236.20N, European Research Development Fund, Welsh Government., ANR-13-ANWA-0003,KOlimastIR,Controlling the impact of Escherichia coli mastitis through modulation of immune responses(2013), and Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
inorganic chemicals, INTERLEUKIN-8, Siderophore, 040301 veterinary sciences, Host–pathogen interaction, E. coli mastitis, [SDV]Life Sciences [q-bio], ANTIMICROBIAL SUSCEPTIBILITY, Context (language use), medicine.disease_cause, Microbiology, 0403 veterinary science, 03 medical and health sciences, chemistry.chemical_compound, Enterobactin, iron scavenging, In vivo, INFECTION, medicine, polycyclic compounds, Veterinary Sciences, Interleukin 8, lipocalin 2 (also known as NGAL), Escherichia coli, Original Research, 030304 developmental biology, DAIRY-COWS, 0303 health sciences, lcsh:Veterinary medicine, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, General Veterinary, biology, siderophores, IRON-METABOLISM, 04 agricultural and veterinary sciences, MAMMARY EPITHELIAL-CELLS, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, chemistry, lcsh:SF600-1100, Veterinary Science, enterobactin, CLINICAL MASTITIS, Bacteria
Abstract

International audience; Iron is an essential nutrient for bacterial growth. Therefore, bacteria have evolved chelation mechanisms to acquire iron for their survival. Enterobactin, a chelator with high affinity for ferric iron, is secreted by Escherichia coli and contributes to its improved bacterial fitness. In this preliminary study, we evaluated enterobactin deficiency both in vitro and in vivo in the context of E. coli mastitis. Firstly, we showed that expression of lipocalin 2, a protein produced by the host that is able to both bind and deplete enterobactin, is increased upon E. coli infection in the cow's mastitic mammary gland. Secondly, we demonstrated in vitro that enterobactin deficiency does not alter interleukin (IL)-8 expression in bovine mammary epithelial cells and its associated neutrophil recruitment. However, a significantly increased reactive oxygen species production of these neutrophils was observed. Thirdly, we showed there was no significant difference in bacterial in vitro growth between the enterobactin-deficient mutant and its wild-type counterpart. However, when further explored in a murine model for bovine mastitis, the enterobactin-deficient mutant vs. the wild-type strain revealed a significant reduction of the bacterial load and, consequently, a decrease in pro-inflammatory cytokines (IL-1α,-1β,-4,-6, and-8). A reduced neutrophilic influx was also observed immunohistochemically. These findings therefore identify interference of the enterobactin iron-scavenging mechanism as a potential measure to decrease the fitness of E. coli in the mastitic mammary gland.

Published
2020

15. Equine Asthma: Current Understanding and Future Directions

Author

James G. Martin, Dorothee Bienzle, K.M. Ivester, Michela Bullone, Laurent L. Couëtil, Renaud Léguillette, Nicola Pusterla, C.E. Swiderski, Artur Niedźwiedź, Jean-Pierre Lavoie, Melissa R. Mazan, Eric Richard, Jacqueline M. Cardwell, Gabriel Morán, Vinzenz Gerber, College of Veterinary Medicine, Purdue University [West Lafayette], Department of Pathobiology and Population Sciences, Royal Veterinary College, University of Calgary, Tufts University [Medford], LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), University of Guelph, University of Turin, University of Bern, Institut Suisse de Médecine Equine (ISME), Université du Québec à Montréal = University of Québec in Montréal (UQAM), Cancer Research Program, Research Institute of the McGill University Health Center, Montreal, Quebec, Canada, Universidad Austral de Chile, Wroclaw University of Environmental and Life Sciences, University of California, and Mississippi State University [Mississippi]

Subjects
medicine.medical_specialty, phenotype, 040301 veterinary sciences, Asthma phenotypes, Review, Disease, 0403 veterinary science, recurrent airway obstruction, 03 medical and health sciences, Clinical Research, biomarkers, endotype, heaves, inflammatory airway disease, medicine, Veterinary Sciences, Intensive care medicine, Lung, 030304 developmental biology, Equine asthma, 0303 health sciences, lcsh:Veterinary medicine, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, 630 Agriculture, General Veterinary, business.industry, 04 agricultural and veterinary sciences, Asthma, 3. Good health, Good Health and Well Being, Respiratory, lcsh:SF600-1100, Veterinary Science, business
Abstract

International audience; The 2019 Havemeyer Workshop brought together researchers and clinicians to discuss the latest information on Equine Asthma and provide future research directions. Current clinical and molecular asthma phenotypes and endotypes in humans were discussed and compared to asthma phenotypes in horses. The role of infectious and non-infectious causes of equine asthma, genetic factors and proposed disease pathophysiology were reviewed. Diagnostic limitations were evident by the limited number of tests and biomarkers available to field practitioners. The participants emphasized the need for more accessible, standardized diagnostics that would help identify specific phenotypes and endotypes in order to create more targeted treatments or management strategies. One important outcome of the workshop was the creation of the Equine Asthma Group that will facilitate communication between veterinary practice and research communities through published and easily accessible guidelines and foster research collaboration.

Published
2020

16. Mise à jour sur Cryptosporidium spp.: Faits saillants de la Septième Conférence Internationale sur Giardia et Cryptosporidium

Author

Loïc Favennec, Fabrice Laurent, Martin Kváč, David Carmena, Giovanni Widmer, Rachel M. Chalmers, Lihua Xiao, Boris Striepen, Gilles Gargala, Jessica C. Kissinger, Adam Sateriale, Sonia Lacroix-Lamandé, Cummings School of Veterinary Medicine, Tufts University [Medford], National Centre for Microbiology [Madrid], Instituto de Salud Carlos III [Madrid] (ISC), Institute of Parasitology [České Budějovice] (BIOLOGY CENTRE CAS), Biology Centre of the Czech Academy of Sciences (BIOLOGY CENTRE CAS), Czech Academy of Sciences [Prague] (CAS)-Czech Academy of Sciences [Prague] (CAS), University of South Bohemia, Faculty of Agriculture, Studentska 13, 370 05 Ceske Budejovice, Cryptosporidium reference unit, Public Health Wales, Swansea University Medical School [Swansea, Royaume-Uni], Swansea University, Center for Tropical and Emerging Global Diseases, University of Georgia [USA], College of Veterinary Medicine, South China Agricultural University (SCAU), Department of Pathobiology [Philadelphia], University of Pennsylvania [Philadelphia], Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre national de référence des Cryptosporidioses, CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Epidémiosurveillance de protozooses à transmission alimentaire et vectorielle (ESCAPE), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)-Université de Reims Champagne-Ardenne (URCA)

Subjects
Diarrhea, Giardiasis, medicine.medical_specialty, Genotype, Epidemiology, Veterinary (miscellaneous), [SDV]Life Sciences [q-bio], Cryptosporidium, Cryptosporidiosis, Genomics, Review Article, Biology, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Feces, Environmental health, medicine, Animals, Humans, lcsh:RC109-216, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Microbiome, One Health, 030304 developmental biology, Comparative genomics, 0303 health sciences, 030306 microbiology, Public health, Giardia, Congresses as Topic, biology.organism_classification, 3. Good health, Infectious Diseases, Insect Science, Animal Science and Zoology, Parasitology, France, Primary research
Abstract

While cryptosporidiosis is recognized as being among the most common causes of human parasitic diarrhea in the world, there is currently limited knowledge on Cryptosporidium infection mechanisms, incomplete codification of diagnostic methods, and a need for additional therapeutic options. In response, the Seventh International Giardia and Cryptosporidium Conference (IGCC 2019) was hosted from 23 to 26 June 2019, at the Rouen Normandy University, France. This trusted event brought together an international delegation of researchers to synthesize recent advances and identify key research questions and knowledge gaps. The program of the interdisciplinary conference included all aspects of host-parasite relationships from basic research to applications to human and veterinary medicine, and environmental issues associated with waterborne parasites and their epidemiological consequences. In relation to Cryptosporidium and cryptosporidiosis, the primary research areas for which novel findings and the most impressive communications were presented and discussed included: Cryptosporidium in environmental waters, seafood, and fresh produce; Animal epidemiology; Human cryptosporidiosis and epidemiology; Genomes and genomic evolution encompassing: Comparative genomics of Cryptosporidium spp., Genomic insights into biology, Acquiring and utilizing genome sequences, Genetic manipulation; Host-parasite interaction (immunology, microbiome); and Diagnosis and treatment. High quality presentations discussed at the conference reflected decisive progress and identified new opportunities that will engage investigators and funding agencies to spur future research in a "one health" approach to improve basic knowledge and the clinical and public health management of zoonotic cryptosporidiosis.Mise à jour sur Cryptosporidium spp.: Faits saillants de la Septième Conférence Internationale sur Giardia et Cryptosporidium.Bien que la cryptosporidiose soit reconnue comme l’une des premières causes de diarrhée parasitaire humaine dans le monde, la connaissance des mécanismes de l’infection par Cryptosporidium est limitée, la codification des méthodes diagnostiques est incomplète et des options thérapeutiques supplémentaires sont requises. En réponse à cette situation, la Septième Conférence Internationale sur Giardia and Cryptosporidium (IGCC 2019) s’est tenue du 23 au 26 juin 2019, à l’Université de Rouen-Normandie, France. Cet événement renommé a rassemblé une délégation internationale de chercheurs pour faire la synthèse des avancées récentes et identifier les principaux thèmes de recherche et les lacunes dans les connaissances. Le programme de cette conférence interdisciplinaire comprenait tous les aspects des relations hôte-parasite, de la recherche fondamentale aux applications à la médecine humaine et vétérinaire, ainsi que les questions environnementales liées aux parasites d’origine hydrique et leurs conséquences épidémiologiques. En ce qui concerne Cryptosporidium et la cryptosporidiose, les principaux domaines de recherche pour lesquels de nouvelles découvertes et les communications les plus impressionnantes ont été présentées et discutées comprenaient : Cryptosporidium dans les eaux environnementales, les fruits de mer et les produits frais ; Épidémiologie animale ; Cryptosporidiose et épidémiologie humaine ; Génomes et évolution génomique englobant : Génomique comparative des Cryptosporidium spp., Perspectives génomiques en biologie, Acquisition et utilisation des séquences du génome, Manipulation génétique ; Interaction hôte-parasite (immunologie, microbiome) ; Diagnostic et traitement. Les présentations de grande qualité discutées à la conférence ont fait état de progrès décisifs et ont permis de cerner de nouvelles possibilités qui inciteront les chercheurs et les organismes de financement à stimuler la recherche future dans une approche « une seule santé » afin d’améliorer les connaissances de base et la gestion clinique et de santé publique de la cryptosporidiose zoonotique.

Published
2020

17. Update on Cryptosporidium spp.: highlights from the seventh international Giardia and Cryptosporidium conference

Author

Widmer, Giovanni, Carmena, David, Kváč, Martin, Chalmers, Rachel, Kissinger, Jessica, Xiao, Lihua, Sateriale, Adam, Striepen, Boris, Laurent, Fabrice, Lacroix-Lamandé, Sonia, Gargala, Gilles, Favennec, Loïc, Cummings School of Veterinary Medicine, Tufts University [Medford], National Centre for Microbiology [Madrid], Instituto de Salud Carlos III [Madrid] (ISC), Institute of Parasitology [České Budějovice] (BIOLOGY CENTRE CAS), Biology Centre of the Czech Academy of Sciences (BIOLOGY CENTRE CAS), Czech Academy of Sciences [Prague] (CAS)-Czech Academy of Sciences [Prague] (CAS), University of South Bohemia, Faculty of Agriculture, Studentska 13, 370 05 Ceske Budejovice, Cryptosporidium reference unit, Public Health Wales, Swansea University Medical School [Swansea, Royaume-Uni], Swansea University, Center for Tropical and Emerging Global Diseases, University of Georgia [USA], College of Veterinary Medicine, South China Agricultural University (SCAU), Department of Pathobiology [Philadelphia], University of Pennsylvania [Philadelphia], Infectiologie et Santé Publique (UMR ISP), Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre national de référence des Cryptosporidioses, CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Epidémiosurveillance de protozooses à transmission alimentaire et vectorielle (ESCAPE), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)-Université de Reims Champagne-Ardenne (URCA)

Subjects
Epidemiology, [SDV]Life Sciences [q-bio], Cryptosporidium, Cryptosporidiosis, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Genomics
Abstract

International audience; While cryptosporidiosis is recognized as being among the most common causes of human parasitic diarrhea in the world, there is currently limited knowledge on Cryptosporidium infection mechanisms, incomplete codification of diagnostic methods, and a need for additional therapeutic options. In response, the Seventh International Giardia and Cryptosporidium Conference (IGCC 2019) was hosted from 23 to 26 June 2019, at the Rouen Normandy University, France. This trusted event brought together an international delegation of researchers to synthesize recent advances and identify key research questions and knowledge gaps. The program of the interdisciplinary conference included all aspects of host-parasite relationships from basic research to applications to human and veterinary medicine, and environmental issues associated with waterborne parasites and their epidemiological consequences. In relation to Cryptosporidium and cryptosporidiosis, the primary research areas for which novel findings and the most impressive communications were presented and discussed included: Cryptosporidium in environmental waters, seafood, and fresh produce; Animal epidemiology; Human cryptosporidiosis and epidemiology; Genomes and genomic evolution encompassing: Comparative genomics of Cryptosporidium spp., Genomic insights into biology, Acquiring and utilizing genome sequences, Genetic manipulation; Host-parasite interaction (immunology, microbiome); and Diagnosis and treatment. High quality presentations discussed at the conference reflected decisive progress and identified new opportunities that will engage investigators and funding agencies to spur future research in a "one health" approach to improve basic knowledge and the clinical and public health management of zoonotic cryptosporidiosis.; Bien que la cryptosporidiose soit reconnue comme l’une des premières causes de diarrhée parasitaire humaine dans le monde, la connaissance des mécanismes de l’infection par Cryptosporidium est limitée, la codification des méthodes diagnostiques est incomplète et des options thérapeutiques supplémentaires sont requises. En réponse à cette situation, la Septième Conférence Internationale sur Giardia and Cryptosporidium (IGCC 2019) s’est tenue du 23 au 26 juin 2019, à l’Université de Rouen-Normandie, France. Cet événement renommé a rassemblé une délégation internationale de chercheurs pour faire la synthèse des avancées récentes et identifier les principaux thèmes de recherche et les lacunes dans les connaissances. Le programme de cette conférence interdisciplinaire comprenait tous les aspects des relations hôte-parasite, de la recherche fondamentale aux applications à la médecine humaine et vétérinaire, ainsi que les questions environnementales liées aux parasites d’origine hydrique et leurs conséquences épidémiologiques. En ce qui concerne Cryptosporidium et la cryptosporidiose, les principaux domaines de recherche pour lesquels de nouvelles découvertes et les communications les plus impressionnantes ont été présentées et discutées comprenaient : Cryptosporidium dans les eaux environnementales, les fruits de mer et les produits frais ; Épidémiologie animale ; Cryptosporidiose et épidémiologie humaine ; Génomes et évolution génomique englobant : Génomique comparative des Cryptosporidium spp., Perspectives génomiques en biologie, Acquisition et utilisation des séquences du génome, Manipulation génétique ; Interaction hôte-parasite (immunologie, microbiome) ; Diagnostic et traitement. Les présentations de grande qualité discutées à la conférence ont fait état de progrès décisifs et ont permis de cerner de nouvelles possibilités qui inciteront les chercheurs et les organismes de financement à stimuler la recherche future dans une approche « une seule santé » afin d’améliorer les connaissances de base et la gestion clinique et de santé publique de la cryptosporidiose zoonotique.

Published
2020

18. Standardized IMGT® Nomenclature of Salmonidae IGH Genes, the Paradigm of Atlantic Salmon and Rainbow Trout: From Genomics to Repertoires

Author

Susana Magadan, Aleksei Krasnov, Saida Hadi-Saljoqi, Sergey Afanasyev, Stanislas Mondot, Delphine Lallias, Rosario Castro, Irene Salinas, Oriol Sunyer, John Hansen, Ben F. Koop, Marie-Paule Lefranc, Pierre Boudinot, LALLIAS, Delphine, Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), Norwegian Institute of Food,Fisheries and Aquaculture Research (NOFIMA), Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique Animale et Biologie Intégrative (GABI), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Department of Animal Health, Faculty of Veterinary Sciences, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), The University of New Mexico [Albuquerque], Department of Pathobiology [Philadelphia], University of Pennsylvania, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Nofima AS, AgroParisTech-Institut National de la Recherche Agronomique (INRA), and University of Pennsylvania [Philadelphia]

Subjects
lcsh:Immunologic diseases. Allergy, 0301 basic medicine, [SDV.IMM] Life Sciences [q-bio]/Immunology, Genes, Immunoglobulin Heavy Chain, [SDV]Life Sciences [q-bio], animal diseases, Pseudogene, Salmo salar, Immunology, Context (language use), Genomics, 03 medical and health sciences, 0302 clinical medicine, Antibody Repertoire, antibody repertoire, Animals, Humans, Immunology and Allergy, 14. Life underwater, Salmo, VDJ annotation, Phylogeny, comparative immunology, Salmonidae, Original Research, Genetics, biology, Computational Biology, Genetic Variation, High-Throughput Nucleotide Sequencing, Molecular Sequence Annotation, biology.organism_classification, V(D)J Recombination, [SDV] Life Sciences [q-bio], Trout, 030104 developmental biology, Gene Expression Regulation, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Oncorhynchus mykiss, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Rainbow trout, salmonid fish, lcsh:RC581-607, immunoglobulin, 030215 immunology
Abstract

In teleost fish as in mammals, humoral adaptive immunity is based on B lymphocytes expressing highly diverse immunoglobulins (IG). During B cell differentiation, IG loci are subjected to genomic rearrangements of V, D, and J genes, producing a unique antigen receptor expressed on the surface of each lymphocyte. During the course of an immune response to infections or immunizations, B cell clones specific of epitopes from the immunogen are expanded and activated, leading to production of specific antibodies. Among teleost fish, salmonids comprise key species for aquaculture. Rainbow trout (Oncorhynchus mykiss) and Atlantic salmon (Salmo salar) are especially important from a commercial point of view and have emerged as critical models for fish immunology. The growing interest to capture accurate and comprehensive antibody responses against common pathogens and vaccines has resulted in recent efforts to sequence the IG repertoire in these species. In this context, a unified and standardized nomenclature of salmonid IG heavy chain (IGH) genes is urgently required, to improve accuracy of annotation of adaptive immune receptor repertoire dataset generated by high-throughput sequencing (AIRRseq) and facilitate comparisons between studies and species. Interestingly, the assembly of salmonids IGH genomic sequences is challenging due to the presence of two large size duplicated IGH loci and high numbers of IG genes and pseudogenes. We used data available for Atlantic salmon to establish an IMGT standardized nomenclature of IGH genes in this species and then applied the IMGT rules to the rainbow trout IGH loci to set up a nomenclature, which takes into account the specificities of Salmonid loci. This unique, consistent nomenclature for Salmonid IGH genes was then used to construct IMGT sequence reference directories allowing accurate annotation of AIRRseq data. The complex issues raised by the genetic diversity of salmon and trout strains are discussed in the context of IG repertoire annotation.

Published
2019

23. Dynamic organization of Herpesvirus glycoproteins on the viral envelope revealed by super-resolution microscopy

Author

Roselyn J. Eisenberg, Frauke Beilstein, David Pasdeloup, Valérie Nicolas, Audrey Esclatine, Gary H. Cohen, Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Department of Microbiology, University of Pennsylvania, Department of Pathobiology [Philadelphia], Ingénierie et Plateformes au Service de l'Innovation Thérapeutique (IPSIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), ANR-14-CE14-0022, Pasdeloup, David, University of Pennsylvania [Philadelphia], and Institut National de la Recherche Agronomique (INRA)-Université de Tours

Subjects
Physiology, Virologie, [SDV]Life Sciences [q-bio], Cell, Cell Membranes, Glycobiology, Herpesvirus 1, Human, medicine.disease_cause, Biochemistry, Membrane Fusion, Virions, Viral Packaging, Viral Envelope Proteins, Immune Physiology, Medicine and Health Sciences, Biology (General), Receptor, chemistry.chemical_classification, 0303 health sciences, Microscopy, Immune System Proteins, biology, 030302 biochemistry & molecular biology, 3. Good health, Cell biology, medicine.anatomical_structure, Viral Envelope, Antibody, Cellular Structures and Organelles, Research Article, Cell Binding, Cell Physiology, QH301-705.5, Immunology, Virus Attachment, Viral Structure, Microbiology, Antibodies, Cell Line, 03 medical and health sciences, Viral envelope, herpesvirus, Virology, Genetics, medicine, Humans, Molecular Biology, 030304 developmental biology, Glycoproteins, glycoprotéine, enveloppe virale, Virus Glycoproteins, Virion, Lipid bilayer fusion, Biology and Life Sciences, Proteins, Cell Biology, RC581-607, Virus Internalization, Viral Replication, Herpes simplex virus, chemistry, Cell culture, biology.protein, Parasitology, imagerie haute resolution, Immunologic diseases. Allergy, Glycoprotein, fusion membranaire
Abstract

The processes of cell attachment and membrane fusion of Herpes Simplex Virus 1 involve many different envelope glycoproteins. Viral proteins gC and gD bind to cellular receptors. Upon binding, gD activates the gH/gL complex which in turn activates gB to trigger membrane fusion. Thus, these proteins must be located at the point of contact between cellular and viral envelopes to interact and allow fusion. Using super-resolution microscopy, we show that gB, gH/gL and most of gC are distributed evenly round purified virions. In contrast, gD localizes essentially as clusters which are distinct from gB and gH/gL. Upon cell binding, we observe that all glycoproteins, including gD, have a similar ring-like pattern, but the diameter of these rings was significantly smaller than those observed on cell-free viruses. We also observe that contrary to cell-free particles, gD mostly colocalizes with other glycoproteins on cell-bound particles. The differing patterns of localization of gD between cell-free and cell-bound viruses indicates that gD can be reorganized on the viral envelope following either a possible maturation of the viral particle or its adsorption to the cell. This redistribution of glycoproteins upon cell attachment could contribute to initiate the cascade of activations leading to membrane fusion., Author summary The envelopes of Herpesvirus particles contain a variety of different proteins that allow them to infect specific cell types. An essential core set of these proteins is designed to allow viral entry into the cell after adsorption by binding to specific receptors and ultimately inducing fusion between the viral and cellular membranes in a regulated way through a succession of interactions between receptor-binding and fusion-triggering viral proteins. We have identified here for the first time the localization patterns of these essential proteins at the surface of purified virions and we describe how their localization changes after cell attachment. These results illustrate how the dynamics of viral proteins at the surface of the viral particle could participate in optimizing the all-important process of cell binding and membrane fusion.

Published
2019

24. The alpha-Gal syndrome is a tick-associated and emerging IgE-mediated hypersensitivity reaction directed against the carbohydrate Gal alpha 1-3Gal beta 1-(3)4GlcNAc-R (alpha-Gal) epitope after red meat intake. Herein, we describe a clinical case of a 44-year-old French patient who suffered from recurrent anaphylactic reactions after mammalian meat consumption for five years before the final diagnosis of the alpha-Gal syndrome was established in 2018. The patient also reported multiple tick bites prior to symptom onset. This unique type of allergy has increasingly been reported across the world, but it is still unknown in many European countries. Therefore, the present clinical case should increase awareness among primary care practitioners and further improve the early diagnosis of the alpha-Gal syndrome in affected individuals

Author

Alejandro Cabezas-Cruz, Lourdes Mateos-Hernández, José de la Fuente, Adnan Hodžić, Department of Pathobiology, Institute of Parasitology, University of Veterinary Medicine [Vienna] (Vetmeduni)-University of Veterinary Medicine [Vienna] (Vetmeduni), Biologie moléculaire et immunologie parasitaires et fongiques (BIPAR), École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Laboratoire de santé animale, sites de Maisons-Alfort et de Dozulé, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University [Stillwater] (OSU)-Oklahoma State University [Stillwater] (OSU), Laboratoire de santé animale, sites de Maisons-Alfort et de Dozulé, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire d'Alfort (ENVA)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Oklahoma State University [Stillwater]-Oklahoma State University [Stillwater]

Subjects
0301 basic medicine, Francia, Adult, Allergy, Ixodes ricinus, Meat, α-gal, 030231 tropical medicine, Tick, Immunoglobulin E, Microbiology, Epitope, Anafilaxia, 03 medical and health sciences, Epitopes, 0302 clinical medicine, Ticks, medicine, Animals, Humans, Galactose-alpha-1, Hypersensitivity, Delayed, Anaphylaxis, Galactosa-α-1,3-galactosa, Tick Bites, biology, alpha-Gal, 3-galactose, Galactose, biology.organism_classification, medicine.disease, 3. Good health, Galactose-α-1,3-galactose, Diet, Hypersensitivity reaction, 030104 developmental biology, Infectious Diseases, Delayed hypersensitivity, Insect Science, Immunology, biology.protein, Parasitology, Female, IgE, France, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

The α-Gal syndrome is a tick-associated and emerging IgE-mediated hypersensitivity reaction directed against the carbohydrate Galα1-3Galβ1-(3)4GlcNAc-R (α-Gal) epitope after red meat intake. Herein, we describe a clinical case of a 44-year-old French patient who suffered from recurrent anaphylactic reactions after mammalian meat consumption for five years before the final diagnosis of the α-Gal syndrome was established in 2018. The patient also reported multiple tick bites prior to symptom onset. This unique type of allergy has increasingly been reported across the world, but it is still unknown in many European countries. Therefore, the present clinical case should increase awareness among primary care practitioners and further improve the early diagnosis of the α-Gal syndrome in affected individuals., El síndrome de α-Gal es una reacción de hipersensibilidad mediada por IgE emergente y asociada a garrapatas dirigida contra el epítopo de carbohidratos Galα1-3Galβ1-(3)4GlcNAc-R (α-Gal) después de la ingesta de carne roja. En este documento, describimos un caso clínico de un paciente francés de 44 años que sufrió reacciones anafilácticas recurrentes después del consumo de carne de mamífero durante cinco años antes de que se estableciera el diagnóstico final del síndrome α-Gal en 2018. El paciente también informó múltiples garrapatas. muerdeantes del inicio de los síntomas. Este tipo único de alergia se ha informado cada vez más en todo el mundo, pero aún se desconoce en muchos países europeos. Por lo tanto, el presente caso clínico debería aumentar la conciencia entre los médicos de atención primaria y mejorar aún más el diagnóstico precoz del síndrome de α-Gal en las personas afectadas.

Published
2019

25. Mechanism and regulation of ferrous heme-nitric oxide (NO) oxidation in NO synthases

Author

Andrew P. Hunt, Jérôme Santolini, Dennis J. Stuehr, Jesús Tejero, Nicolai Lehnert, Department of Pathobiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, affiliation inconnue, Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Département Biochimie, Biophysique et Biologie Structurale (B3S), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Stress Oxydants et Détoxication (LSOD), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Department of Chemistry, University of Michigan, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, and Cleveland Clinic

Subjects
0301 basic medicine, [SDV]Life Sciences [q-bio], Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type I, Biochemistry, ligand-protein interactions, atoms li, chemistry.chemical_compound, Mice, computational biology, enzyme kinetics, heme, Heme, education.field_of_study, biology, Chemistry, nitric oxide synthase, subunit dimerization, electron-transfer, Nitric oxide synthase, tetrahydrobiopterin, Oxidation-Reduction, kinetic-parameters, Hemeprotein, oxygenase domain, redox reaction, Stereochemistry, nitric-oxide synthase, Population, Mutation, Missense, Ferrous, 03 medical and health sciences, thermodynamics, nitric oxide, Animals, enzyme mechanism, Enzyme kinetics, l-arginine, education, heme–thiolate, Molecular Biology, 030102 biochemistry & molecular biology, catalysis, Futile cycle, Cell Biology, dioxygenation, Rats, 030104 developmental biology, Catalytic cycle, Amino Acid Substitution, Models, Chemical, heme-thiolate, gaussian-basis sets, heme protein, biology.protein, Enzymology, reaction mechanism
Abstract

International audience; Nitric oxide (NO) synthases (NOSs) catalyze the formation of NO from L-arginine. We have shown previously that the NOS enzyme catalytic cycle involves a large number of reactions, but can be characterized by a global model with three main rate-limiting steps. These are the rate of heme reduction by the flavin domain (kr); of dissociation of NO from the ferric heme‒NO complex (kd) and of oxidation of the ferrous heme‒NO complex (kox). The reaction of oxygen with the ferrous heme‒NO species is part of a futile cycle that does not directly contribute to NO synthesis, but allows a population of inactive enzyme molecules to return to the catalytic cycle, and thus enables a steady-state NO synthesis rate. Previously, we have reported that this reaction does involve the reaction of oxygen with NO-bound ferrous heme complex, but the mechanistic details of the reaction, that could proceed via either an inner-sphere or an outer-sphere mechanism, remains unclear. Here we present additional experiments with neuronal NOS (nNOS) and inducible NOS (iNOS) variants (nNOS W409F and iNOS K82A and V346I) and computational methods to study how changes in heme access and electronics affect the reaction. Our results support an inner-sphere mechanism and indicate that the particular heme-thiolate environment of the NOS enzymes can stabilize an N-bound FeIII-N(O)OO- intermediate species and thereby catalyze this reaction, which otherwise is not observed or favorable in proteins like globins that contain a histidine-coordinated heme.

Published
2019

27. Origin of Public Memory B Cell Clones in Fish After Antiviral Vaccination

Author

Magadan, Susana, Jouneau, Luc, Puelma Touzel, Maximilian, Marillet, Simon, Chara, Wahiba, Six, Adrien, Quillet, Edwige, Mora, Thierry, Walczak, Aleksandra, Cazals, Frédéric, Sunyer, Oriol, Fillatreau, Simon, Boudinot, Pierre, Unité de recherche Virologie et Immunologie Moléculaires (VIM), Institut National de la Recherche Agronomique (INRA), Laboratoire de Physique Théorique de l'ENS (LPTENS), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Algorithms, Biology, Structure (ABS), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Immunologie - Immunopathologie - Immunothérapie (I3), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Génétique Animale et Biologie Intégrative (GABI), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Laboratoire de Physique Statistique de l'ENS (LPS), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Department of Pathobiology [Philadelphia], University of Pennsylvania [Philadelphia], Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Deutsches Rheuma-ForschungsZentrum (DRFZ), Deutsches Rheuma-ForschungsZentrum, Hopital Saint-Louis, Assistance Publique – Hôpitaux de Paris (AP-HP), Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AgroParisTech-Institut National de la Recherche Agronomique (INRA), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Universités (COMUE), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), University of Pennsylvania, European Commission under the Work Programme 2012 of the 7th Framework Programme for Research and Technological Development of the European Union [306312, 600391], FishRNAVax [ANR-16-CE20-0002-01], INRA-INRIA contract Young scientist, NIH [R01-GM085207-08], NSF [IOS-1457282], ANR-16-CE20-0002,Fish-RNAvax,Vaccins ARN éco-compatibles pour l'induction de réponses immunitaires protectrices chez le poisson d'élevage(2016), European Project: 311993,EC:FP7:KBBE,FP7-KBBE-2012-6-singlestage,TARGETFISH(2012), ProdInra, Migration, Targeted disease prophylaxis in European fish farming - TARGETFISH - - EC:FP7:KBBE2012-10-01 - 2017-09-30 - 311993 - VALID, Laboratoire de Physique Théorique de l'ENS [École Normale Supérieure] (LPTENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV]Life Sciences [q-bio], Immunology, [SDV.GEN] Life Sciences [q-bio]/Genetics, [SDV.GEN.GA] Life Sciences [q-bio]/Genetics/Animal genetics, [INFO.INFO-CG]Computer Science [cs]/Computational Geometry [cs.CG], Novirhabdovirus, Hemorrhagic Septicemia, Viral, Animals, antibodies, comparative immunology, ComputingMilieux_MISCELLANEOUS, Original Research, B-Lymphocytes, B cells, [SDV.GEN]Life Sciences [q-bio]/Genetics, RepSeq, Vaccination, Fishes, repertoire, Viral Vaccines, V(D)J Recombination, Clone Cells, [SDV] Life Sciences [q-bio], public response, fish immunology, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, Immunoglobulin M, Immunologic Memory
Abstract

International audience; Vaccination induces "public" antibody clonotypes common to all individuals of a species, that may mediate universal protection against pathogens. Only few studies tried to trace back the origin of these public B-cell clones. Here we used Illumina sequencing and computational modeling to unveil the mechanisms shaping the structure of the fish memory antibody response against an attenuated Viral Hemorrhagic Septicemia rhabdovirus. After vaccination, a persistent memory response with a public VH5JH5 IgM component was composed of dominant antibodies shared among all individuals. The rearrangement model showed that these public junctions occurred with high probability indicating that they were already favored before vaccination due to the recombination process, as shown inmammals. In addition, these clonotypes were in the naive repertoire associated with larger similarity classes, composed of junctions differing only at one or two positions by amino acids with comparable properties. The model showed that this property was due to selective processes exerted between the recombination and the naive repertoire. Finally, our results showed that public clonotypes greatly expanded after vaccination displayed several VDJ junctions differing only by one or two amino acids with similar properties, highlighting a convergent response. The fish public memory antibody response to a virus is therefore shaped at three levels: by recombination biases, by selection acting on the formation of the pre-vaccination repertoire, and by convergent selection of functionally similar clonotypes during the response. We also show that naive repertoires of IgM and IgT have different structures and sharing between individuals, due to selection biases. In sum, our comparative approach identifies three conserved features of the antibody repertoire associated with public memory responses. These features were already present in the last common ancestors of fish and mammals, while other characteristics may represent species-specific solutions.

Published
2018

28. Parallel Evolution in the Emergence of Highly Pathogenic Avian Influenza A Viruses

Author

Oliver G. Pybus, J.R. Keown, Marina Escalera-Zamudio, Julien Thézé, Loic Carrique, Michael Golden, Thomas A. Bowden, Bernardo Gutierrez, Department of Zoology, University of Oxford [Oxford], The Wellcome Trust Centre for Human Genetics [Oxford], Department of Pathobiology and Population Sciences, and Royal Veterinary College

Subjects
animal diseases, Datasets as Topic, General Physics and Astronomy, medicine.disease_cause, Genome, lcsh:Science, Phylogeny, Genetics, 0303 health sciences, Multidisciplinary, Virulence, Phylogenetic tree, Protein Stability, 030302 biochemistry & molecular biology, virus diseases, Publisher Correction, Phenotype, 3. Good health, Phylogenetics, Influenza A virus, Viral evolution, Parallel evolution, Science, Highly pathogenic, Genome, Viral, Biology, General Biochemistry, Genetics and Molecular Biology, Article, Birds, Evolution, Molecular, Viral Proteins, 03 medical and health sciences, Molecular evolution, Influenza, Human, medicine, Animals, Humans, Selection, Genetic, 030304 developmental biology, Base Sequence, 030306 microbiology, Outbreak, General Chemistry, Influenza A virus subtype H5N1, Influenza in Birds, Mutation, lcsh:Q, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Influenza virus, Sequence Alignment
Abstract

Parallel molecular evolution and adaptation are important phenomena commonly observed in viruses. Here, we exploit parallel molecular evolution to understand virulence evolution in avian influenza viruses (AIV). Highly-pathogenic AIVs evolve independently from low-pathogenic ancestors via acquisition of polybasic cleavage sites. Why some AIV lineages but not others evolve in this way is unknown. We hypothesise that the parallel emergence of highly-pathogenic AIV may be facilitated by permissive or compensatory mutations occurring across the viral genome. We combine phylogenetic, statistical and structural approaches to discover parallel mutations in AIV genomes associated with the highly-pathogenic phenotype. Parallel mutations were screened using a statistical test of mutation-phenotype association and further evaluated in the contexts of positive selection and protein structure. Our resulting mutational panel may help to reveal new links between virulence evolution and other traits, and raises the possibility of predicting aspects of AIV evolution., Highly pathogenic avian influenza viruses (HPAIV) can evolve via acquisition of polybasic cleavage sites, but the contribution of other mutations remains unclear. Here, the authors combine phylogenetic, statistical and structural approaches, and identify parallel mutations that are associated with HPAIV phenotype.

Published
2018

29. Spatial and temporal variation in the abundance of Culicoides biting midges (Diptera: Ceratopogonidae) in nine European countries

Author

Renke Lühken, Delphine Delecolle, Ignace Rakotoarivony, Sonja Steinke, Bruno Mathieu, Xavier Allene, Javier Lucientes, Katharina Brugger, Lene Jung Kjær, Henrik Skovgård, Carsten Kirkeby, Jan Chirico, Anders Lindström, Franz Rubel, Bethsabée Scheid, Ståle Sviland, David Chavernac, Carlos Barceló, Petter Hopp, Wesley Tack, Miguel Ángel Miranda Chueca, Søren Nielsen, Jonathan Lhoir, Claire Garros, Ellen Kiel, R. Estrada, Ana Carolina Cuellar, Roger Venail, Jean-Claude Delécolle, Anders Stockmarr, Franz Josef Conraths, Thomas Balenghien, Jörn Gethmann, Inger Sofie Hamnes, Magdalena Larska, Rene Bødker, Gunnar Andersson, Marie-Laure Setier-Rio, Alexander Mathis, Technical University of Denmark [Lyngby] (DTU), Aarhus University [Aarhus], Roskilde University, Department of Applied Mathematics and Computer Science, National Veterinary Institute, Bernhard Nocht Institute for Tropical Medicine - Bernhard-Nocht-Institut für Tropenmedizin [Hamburg, Germany] (BNITM), University of Oldenburg, Friedrich-Loeffler-Institut (FLI), National Veterinary Research Institute [Pulawy, Pologne] (NVRI), Norwegian Veterinary Institute [Oslo], Institute of Veterinary Public Health, Partenaires INRAE, Animal, Santé, Territoires, Risques et Ecosystèmes (UMR ASTRE), Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Université de Strasbourg (UNISTRA), Entente Interdépartementale pour la Démoustication du Littoral Méditerranéen, Avia-GIS, Laboratory of Zoology, University of the Balearic Islands (UIB), University of Zaragoza - Universidad de Zaragoza [Zaragoza], Department of Pathobiology, Institute of Parasitology, EMIDA ERA-NET through the Federal Office for Agriculture and Food [314-06.01-2811ERA248], and Cuellar, Ana Carolina

Subjects
Culicoides imicola, [SDV]Life Sciences [q-bio], African Horse Sickness Virus, Population Dynamics, Peste équine africaine, L73 - Maladies des animaux, Ceratopogonidae, 0403 veterinary science, 0302 clinical medicine, Vector season, Abundance (ecology), African Horse Sickness, Analyse du risque, Dynamique des populations, media_common, biology, Geography, Ecology, Culicoides, Schmallenberg virus, 04 agricultural and veterinary sciences, Ruminants, Europe, Variation saisonnière, Infectious Diseases, Vecteur de maladie, Entomologie, Seasons, Fièvre catarrhale du mouton, Banque de données, L72 - Organismes nuisibles des animaux, Bétail, Seasonal abundance, Farms, 040301 veterinary sciences, Distribution géographique, Ruminant, 030231 tropical medicine, Culicoides abundance, Spatial pattern, Temporal trend, Culicoides distribution, Vector-borne disease, Spatial distribution, Bluetongue, Virus des animaux, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Species Specificity, media_common.cataloged_instance, Animals, Surveillance épidémiologique, lcsh:RC109-216, European union, Population Density, Cartographie, Research, Distribution spatiale, 15. Life on land, biology.organism_classification, Insect Vectors, Parasitology, U30 - Méthodes de recherche
Abstract

Background Biting midges of the genus Culicoides (Diptera: Ceratopogonidae) are vectors of bluetongue virus (BTV), African horse sickness virus and Schmallenberg virus (SBV). Outbreaks of both BTV and SBV have affected large parts of Europe. The spread of these diseases depends largely on vector distribution and abundance. The aim of this analysis was to identify and quantify major spatial patterns and temporal trends in the distribution and seasonal variation of observed Culicoides abundance in nine countries in Europe. Methods We gathered existing Culicoides data from Spain, France, Germany, Switzerland, Austria, Denmark, Sweden, Norway and Poland. In total, 31,429 Culicoides trap collections were available from 904 ruminant farms across these countries between 2007 and 2013. Results The Obsoletus ensemble was distributed widely in Europe and accounted for 83% of all 8,842,998 Culicoides specimens in the dataset, with the highest mean monthly abundance recorded in France, Germany and southern Norway. The Pulicaris ensemble accounted for only 12% of the specimens and had a relatively southerly and easterly spatial distribution compared to the Obsoletus ensemble. Culicoides imicola Kieffer was only found in Spain and the southernmost part of France. There was a clear spatial trend in the accumulated annual abundance from southern to northern Europe, with the Obsoletus ensemble steadily increasing from 4000 per year in southern Europe to 500,000 in Scandinavia. The Pulicaris ensemble showed a very different pattern, with an increase in the accumulated annual abundance from 1600 in Spain, peaking at 41,000 in northern Germany and then decreasing again toward northern latitudes. For the two species ensembles and C. imicola, the season began between January and April, with later start dates and increasingly shorter vector seasons at more northerly latitudes. Conclusion We present the first maps of seasonal Culicoides abundance in large parts of Europe covering a gradient from southern Spain to northern Scandinavia. The identified temporal trends and spatial patterns are useful for planning the allocation of resources for international prevention and surveillance programmes in the European Union. Electronic supplementary material The online version of this article (10.1186/s13071-018-2706-y) contains supplementary material, which is available to authorized users.

Published
2018

30. Establishment of an in vitro chicken epithelial cell line model to investigate Eimeria tenella gamete development

Author

Anne Silvestre, Nicholas Smith, Pascale Quéré, Françoise I. Bussière, Alix Sausset, Robert A. Walker, Fabrice Laurent, Evelyne Esnault, Alisson Niepceron, Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Department of Pathobiology, Institute of Parasitology, Research School of Biology, Australian National University (ANU), Bussière, Françoise I., and Institut National de la Recherche Agronomique (INRA)-Université de Tours

Subjects
0301 basic medicine, Chicken epithelial cells, Short Report, poulet, Mycology & Parasitology, gamète, Models, Biological, Eimeria, Macrogametes, Microbiology, lcsh:Infectious and parasitic diseases, Cell Line, 03 medical and health sciences, Tropical Medicine, Gene expression, Eimeria tenella, Microgametes, parasitic diseases, medicine, Parasite hosting, Animals, lcsh:RC109-216, Gene, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, biology, Coccidiosis, Microbiology and Parasitology, Wild type, cellule épithéliale, Epithelial Cells, biology.organism_classification, Microbiologie et Parasitologie, 030104 developmental biology, Infectious Diseases, medicine.anatomical_structure, Germ Cells, Médecine vétérinaire et santé animal, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Cell culture, biology.protein, Gamete, Parasitology, Veterinary medicine and animal Health, Antibody, Chickens
Abstract

© 2018 The Author(s). Background: Eimeria tenella infection leads to acute intestinal disorders responsible for important economic losses in poultry farming worldwide. The life-cycle of E. tenella is monoxenous with the chicken as the exclusive host; infection occurs in caecal epithelial cells. However, in vitro, the complete life-cycle of the parasite has only been propagated successfully in primary chicken kidney cells, which comprise undefined mixed cell populations; no cell line model has been able to consistently support the development of the sexual stages of the parasite. We therefore sought to develop a new model to study E. tenella gametogony in vitro using a recently characterised chicken cell line (CLEC-213) exhibiting an epithelial cell phenotype. Methods: CLEC-213 were infected with sporozoites from a precocious strain or with second generation merozoites (merozoites II) from wild type strains. Sexual stages of the parasite were determined both at the gene and protein levels. Results: To our knowledge, we show for the first time in CLEC-213, that sporozoites from a precocious strain of E. tenella were able to develop to gametes, as verified by measuring gene expression and by using antibodies to a microgamete-specific protein (EtFOA1: flagellar outer arm protein 1) and a macrogamete-specific protein (EtGAM-56), but oocysts were not observed. However, both gametes and oocysts were observed when cells were infected with merozoites II from wild type strains, demonstrating that completion of the final steps of the parasite cycle is possible in CLEC-213 cells. Conclusion: The epithelial cell line CLEC-213 constitutes a useful avian tool for studying Eimeria epithelial cell interactions and the effect of drugs on E. tenella invasion, merogony and gametogony.

Published
2018

31. Inhibition of Acetyl-CoA Carboxylase by Phosphorylation or the Inhibitor ND-654 Suppresses Lipogenesis and Hepatocellular Carcinoma

Author

Gregory R. Steinberg, Robert A. Foster, Wenyan Miao, Ting Wang, Vanessa P. Houde, Naoto Fujiwara, Hailing Sun, Jeremy R. Greenwood, Jennifer Rocnik, Geraldine Harriman, Danielle K. DePeralta, Theodoros Tsakiridis, Asish K. Saha, Lan Wei, Jamie Bates, Alexander E. Anagnostopoulos, Alice Wang, Henry Liu, Kenneth K. Tanabe, Omeed Moaven, Paola Muti, Yujin Hoshida, Derek J. Erstad, William F. Westlin, Rebecca J. Ford, Ricard Masia, James S. V. Lally, Bryan C. Fuchs, Adrian S. Ray, H. James Harwood, Lindsay A. Broadfield, Sarani Ghoshal, Rosana Kapeller, Vivian Leong, Sathesh Bhat, daulny, anne, Cell circuits as targets and biomarkers for liver disease and cancer prevention - HEPCIR - - H20202016-01-01 - 2020-12-31 - 671231 - VALID, Department of Medicine [Hamilton, ON, Canada], McMaster University [Hamilton, Ontario], Division of Surgical Oncology [Boston, MA, USA], Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital Cancer Center [Boston, MA, USA], Department of Pathology [Boston, MA, USA], Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Harold C. Simmons Comprehensive Cancer Center [Dallas, TX, États-Unis], University of Texas Southwestern Medical Center [Dallas], Department of Internal Medicine [Dallas, TX, USA], Department of Oncology [Hamilton, ON, Canada], Department of Pathobiology [Guelph, ON, Canada], University of Guelph-Ontario Veterinary College [Guelph, ON, Canada], Gilead Sciences, Inc. [Foster City, CA, USA], Department of Medicine and Physiology [Boston, MA, USA], Boston University [Boston] (BU)-School of Medicine, Endocrinology, Diabetes, and Nutrition [Boston, MA, USA], Schrodinger [New York, NY, USA], Nimbus Therapeutics [Cambridge, MA, USA], Department of Biochemistry and Biomedical Sciences [Hamilton, ON, Canada], This work was supported by grants from the National Cancer Institute (T32 CA071345 to D.K.D., O.M., and K.K.T. and K01 CA140861 to B.C.F.), the Uehara Memorial Foundation (N.F.), the National Institute of Diabetes and Digestive and Kidney Diseases (DK099558 to Y.H.), the European Union (ERC-2014-AdG-671231 HEPCIR to Y.H.), the Irma T. Hirschl Trust (Y.H.), the U.S. Department of Defense (W81XWH-16-1-0363 to Y.H.), the Canadian Cancer Society Research and Innovation Fund (G.R.S.), the Canadian Institutes of Health Research (G.R.S. 125980-1, 144625-1), Nimbus Therapeutics (to B.C.F.), and Gilead Sciences (to B.C.F.). A.E.G received a scholarship from the Canadian Liver Foundation. G.R.S. is supported by a Canada Research Chair and by the J. Bruce Duncan Chair in Metabolic Diseases., and European Project: 671231,H2020,ERC-2014-ADG,HEPCIR(2016)

Subjects
0301 basic medicine, Sorafenib, Male, Carcinoma, Hepatocellular, Physiology, cancer metabolism, Article, fructose, 03 medical and health sciences, Mice, 0302 clinical medicine, malonyl-CoA, NAFLD, medicine, Animals, Humans, Phosphorylation, Rats, Wistar, Protein kinase A, Molecular Biology, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Chemistry, Lipogenesis, Fatty liver, fibrosis, Liver Neoplasms, Acetyl-CoA carboxylase, NASH, AMPK, non-alcoholic fatty liver disease, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Cell Biology, Hep G2 Cells, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Rats, 030104 developmental biology, inflammation, Hepatocellular carcinoma, Cancer research, non-alcoholic steatohepatitis, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug, Acetyl-CoA Carboxylase
Abstract

International audience; The incidence of hepatocellular carcinoma (HCC) is rapidly increasing due to the prevalence of obesity and non-alcoholic fatty liver disease, but the molecular triggers that initiate disease development are not fully understood. We demonstrate that mice with targeted loss-of-function point mutations within the AMP-activated protein kinase (AMPK) phosphorylation sites on acetyl-CoA carboxylase 1 (ACC1 Ser79Ala) and ACC2 (ACC2 Ser212Ala) have increased liver de novo lipogenesis (DNL) and liver lesions. The same mutation in ACC1 also increases DNL and proliferation in human liver cancer cells. Consistent with these findings, a novel, liver-specific ACC inhibitor (ND-654) that mimics the effects of ACC phosphorylation inhibits hepatic DNL and the development of HCC, improving survival of tumor-bearing rats when used alone and in combination with the multi-kinase inhibitor sorafenib. These studies highlight the importance of DNL and dysregulation of AMPK-mediated ACC phosphorylation in accelerating HCC and the potential of ACC inhibitors for treatment.

Published
2017

32. Lungworms and gastrointestinal parasites of domestic cats: a European perspective

Author

Martin Knaus, Alessio Giannelli, Emanuele Brianti, Viorica Mircean, Carla Maia, Andrei Daniel Mihalca, Luís Madeira de Carvalho, Cinzia Cantacessi, Anja Joachim, Barbara Hinney, Maria Stefania Latrofa, Maria Alfonsa Cavalera, Ettore Napoli, Frederic Beugnet, Elias Papadopoulos, Giada Annoscia, Ana Margarida Alho, Lénaïg Halos, Magalie René-Martellet, Claudia Tamponi, Gioia Capelli, Luís Cardoso, Domenico Otranto, Bertrand Losson, Róbert Farkas, Zvezdelina Kirkova, Manuela Schnyder, Vito Colella, Antonio Varcasia, Guadalupe Miró, Cantacessi, Cinzia [0000-0001-6863-2950], Apollo - University of Cambridge Repository, Dipartimento di Medicina Veterinaria, Università degli studi di Bari, Istituto Zooprofilattico Sperimentale delle Venezie, Department of Pathobiology, Institute of Parasitology, University of Veterinary Medicine, Faculty of Veterinary Medicine, Liège, Department of Parasitology, Faculty of Medicine, Unité de recherche d'Épidémiologie Animale (UEA), Institut National de la Recherche Agronomique (INRA), Épidémiologie des Maladies Animales et Zoonotiques - UMR 346 (EPIA), Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Laboratory of Parasitology and Parasitic Diseases, Aristotle University of Thessaloniki, Department of Parasitology and Zoology, Dipartimento di Scienze Veterinarie, Università degli Studi di Messina, Università degli studi di Milano [Milano], Faculty of Veterinary Medicine, University of Lisbon, CIISA Interdisciplinary, Universidade de Trás-os-Montes e Alto Douro, Global Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa (NOVA), Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid [Madrid] (UCM), University of Zurich, Department of Veterinary Medicine, University of Cambridge [UK] (CAM), Kathrinenhof Research Center, Merial GmbH, Merial S.A.S., Università degli studi di Bari Aldo Moro (UNIBA), Istituto Zooprofilattico Sperimentale delle Venezie (IZSVe), Faculty of Veterinary Medicine, University of Liège, Université de Liège, Unité Mixte de Recherche d'Épidémiologie des maladies Animales et zoonotiques (UMR EPIA), Dipartimento di Medicina Veterinaria (DIMEVET), Università degli Studi di Milano [Milano] (UNIMI), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), and Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM)

Subjects
0301 basic medicine, Male, Veterinary medicine, medicine.medical_specialty, diagnosis, Lung Diseases, Parasitic, [SDV]Life Sciences [q-bio], Parasitic Diseases, Animal, 030231 tropical medicine, Cat Diseases, 03 medical and health sciences, Feces, 0302 clinical medicine, Animal science, broadline®, Risk Factors, Epidemiology, medicine, Prevalence, Parasite hosting, Animals, Intestinal Diseases, Parasitic, gastrointestinal parasites, Strongylida Infections, Cats, lungworms, gastrointestinal parasites, epidemiology, treatment, diagnosis, broadline®, Aelurostrongylus abstrusus, CATS, biology, treatment, 030108 mycology & parasitology, Broadline®, DNA, Helminth, biology.organism_classification, 3. Good health, Gastrointestinal parasites, Praziquantel, Europe, Metastrongyloidea, Infectious Diseases, Larva, Cats, lungworms, Parasitology, epidemiology, Female, Lungworm, medicine.drug
Abstract

With the exception of Aelurostrongylus abstrusus, feline lungworms have been poorly studied. Information on their distribution is patchy and mostly limited to case reports. In this study, the occurrence of feline lungworms and co-infecting gastrointestinal parasites has been investigated in 12 European countries (i.e. Austria, Belgium, Bulgaria, France, Greece, Hungary, Italy, Portugal, Romania, Spain, Switzerland and the United Kingdom). An average of 10 domestic cats, with regular outdoor access, was sampled each month for 12 months, and freshly passed faeces were collected. Stools were processed using a McMaster assay and a quantitative Baermann-Wetzel method. Animals positive for lungworms and/or gastrointestinal parasites were treated with a formulation containing fipronil, (S)-methoprene, eprinomectin, and praziquantel (Broadline®, Merial), and re-sampled 28 days post-treatment. The association between lungworm infection and risk factors was analysed using statistical medians/means and the efficacy of the treatment against each lungworm species was assessed. Of 1990 cats sampled, 613 (30.8%) were positive for at least one parasite, while 210 (10.6%) were infected by lungworms. The prevalence of lungworm infection varied between the sampled sites, with the highest recorded in Bulgaria (35.8%) and the lowest in Switzerland (0.8%). None of the cats from Austria or the United Kingdom were infected by lungworms. Aelurostrongylus abstrusus was the species most frequently detected (78.1%), followed by Troglostrongylus brevior (19.5%), Eucoleus aerophilus (14.8%) and Oslerus rostratus (3.8%). The overall efficacy of the treatment was 99% for A. abstrusus and 100% for T. brevior, O. rostratus and E. aerophilus. Data presented provide a comprehensive account of the diagnosis, epidemiology and treatment of feline lungworms in Europe, as well as of the occurrence of co-infections by gastrointestinal parasites.

Published
2016

33. A protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis

Author

Richard H. Duerr, Dalin Li, Ming-Hsi Wang, Tariq Ahmad, John D. Rioux, Patrick Sulem, Daniel B. Graham, Steven R. Brant, Severine Vermeire, Mark Tremelling, James Lee, Leena Halme, K. de Lane, Miguel Regueiro, M Parkes, David C. Wilson, Alain Bitton, R. Milgrom, Daniel G. MacArthur, Marijn C. Visschedijk, Sören Mucha, Kenneth Croitoru, Alison Simmons, Mark S. Silverberg, Rinse K. Weersma, Jonas Halfvarson, Daniel L. Rice, J. M. Stempak, Christopher J. Hawkey, Mauro D'Amato, Christopher G. Mathew, Philippe Goyette, Frauke Degenhardt, Daniel F. Gudbjartsson, Mark J. Daly, Kari Stefansson, Beryl B. Cummings, Maarit Lappalainen, Päivi Saavalainen, Paulina Paavola-Sakki, P. Fleshner, Talin Haritunians, Joshua C. Randall, Elaine R. Nimmo, Taru Tukiainen, Christine Stevens, Subra Kugathasan, Monkol Lek, Andre Franke, Kimmo Kontula, Unnur Thorsteinsdottir, Andrew Hart, Martin O. Pollard, Gabrielle Boucher, Natalie J. Prescott, Benjamin M. Neale, Holm H. Uhlig, Carl A. Anderson, Ashwin N. Ananthakrishnan, Luke Jostins, C. Mowatt, Judy H. Cho, B. Newman, A. Nicole Desch, Yang Luo, Dermot P.B. McGovern, Clara Abraham, Ingileif Jonsdottir, Jeffrey C. Barrett, John C. Mansfield, Jean-Paul Achkar, Charlie W. Lees, Martti Färkkilä, Ramnik J. Xavier, S. R. Targan, Manuel A. Rivas, Deborah D. Proctor, Johan Van Limbergen, Nicholas A. Kennedy, Christopher A. Lamb, Jürgen Glas, Vito Annese, Yashoda Sharma, Phil Schumm, Graham A. Heap, Cathryn Edwards, Lotta L. E. Koskinen, Jack Satsangi, Mitja I. Kurki, Aarno Palotie, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA deCODE Genetics, Amgen Inc., 101 Reykjavik, Iceland Research Center, Montreal Heart Institute, Montréal, Québec, Canada H1T1C8 School of Engineering and Natural Sciences, University of Iceland, 101 Reykjavik, Iceland Department of Immunology, Landspitali, the National University Hospital of Iceland, 101 Reykjavik, Iceland Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 24118 Kiel, Germany F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California 90048 USA Department of Biosciences and Nutrition, Karolinska Institutet, 14183 Stockholm, Sweden BioCruces Health Research Institute and IKERBASQUE, Basque Foundation for Science, 48903 Bilbao, Spain Unit of Gastroenterology, Istituto di Ricovero e Cura a Carattere Scientifico-Casa Sollievo della Sofferenza (IRCCS-CSS) Hospital, 71013 San Giovanni Rotondo, Italy Strutture Organizzative Dipartimentali (SOD) Gastroenterologia 2, Azienda Ospedaliero Universitaria (AOU) Careggi, 50134 Florence, Italy Department of Clinical and Experimental Medicine, Translational Research in GastroIntestinal Disorders (TARGID), Katholieke Universiteit (KU) Leuven, Leuven 3000, Belgium Division of Gastroenterology, University Hospital Gasthuisberg, BE-3000 Leuven, Belgium Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, The Netherlands Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, SE 701 82 Örebro, Sweden Department of Medicine, University of Helsinki, 00100 Helsinki, Finland Helsinki University Hospital, 00100 Helsinki, Finland Clinic of Gastroenterology, Helsinki University Hospital, 00100 Helsinki, Finland Research Programs Unit, Immunobiology, and Department of Medical and Clinical Genetics, University of Helsinki, 00014 Helsinki, Finland Department of Transplantation and Liver Surgery, University of Helsinki, 00100 Helsinki, Finland Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, 00100 Helsinki, Finland Gastroenterology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA Division of Medical Sciences, Harvard Medical School, Boston, Massachusetts 02114, USA Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK IBD Pharmacogenetics, Royal Devon and Exeter NHS Trust, Exeter EX2 5DW, UK Graham A. Heap Peninsula College of Medicine and Dentistry, Exeter PL6 8BU, UK Meyerhoff Inflammatory Bowel Disease Center, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, 21205, USA Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, 21205, USA Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania 15261, USA Department of Medicine, Inflammatory Bowel Disease Centre, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5 Department of Genetics, Yale School of Medicine, New Haven, Connecticut 06510, USA Institute for Molecular Medicine Finland, University of Helsinki, 00100 Helsinki, Finland Massachusetts General Hospital, Center for Human Genetic Research, Psychiatric and Neurodevelopmental Genetics Unit, Boston, Massachusetts 02114, USA Research Programs Unit, Immunobiology, University of Helsinki, 00100 Helsinki, Finland Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada H3T 1J4 Department of Gastroenterology, Torbay Hospital, Devon, UK Department of Medicine, St. Mark’s Hospital, Middlesex, UK Nottingham Digestive Disease Centre, Queens Medical Centre, Nottingham, UK Wellcome Trust Centre for Human Genetics, University of Oxford, Headington, UK Christ Church, University of Oxford, Oxford, UK Gastrointestinal Unit, Wester General Hospital, University of Edinburgh, Edinburgh, UK Newcastle University, Newcastle upon Tyne, UK Inflammatory Bowel Disease Research Group, Addenbrooke’s Hospital, Cambridge, UK Department of Medical and Molecular Genetics, Guy’s Hospital, London, UK Department of Medical and Molecular Genetics, King’s College London School of Medicine, Guy’s Hospital, London, UK Department of Medicine, Ninewells Hospital and Medical School, Dundee, UK Genetic Medicine, Manchester Academic Health Science Centre, Manchester, UK The Manchester Centre for Genomic Medicine, University of Manchester, Manchester, UK Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh, UK Translational Gastroenterology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK Gastroenterology & General Medicine, Norfolk and Norwich University Hospital, Norwich, UK Translational Gastroenterology Unit and the Department of Pediatrics, University of Oxford, Oxford, UK Pediatric Gastroenterology and Nutrition, Royal Hospital for Sick Children, Edinburgh, UK Child Life and Health, University of Edinburgh, Edinburgh, UK Section of Digestive Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA Division of Gastroenterology, Royal Victoria Hospital, Montréal, Québec, Canada Inflammatory Bowel Disease Group, Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA Division of Pediatric Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Toronto, Ontario, Canada Department of Public Health Sciences, University of Chicago, Chicago, Illinois, USA Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA, Department of Medicine, Clinicum, Gastroenterologian yksikkö, Immunobiology Research Program, Research Programs Unit, Department of Medical and Clinical Genetics, Medicum, II kirurgian klinikka, Department of Surgery, Institute for Molecular Medicine Finland, Aarno Palotie / Principal Investigator, Immunomics, Kimmo Kontula Research Group, and Genomics of Neurological and Neuropsychiatric Disorders

Subjects
0301 basic medicine, AAI12, Chemistry(all), SUSCEPTIBILITY LOCI, Science, Population, General Physics and Astronomy, Physics and Astronomy(all), OF-FUNCTION VARIANTS, Inflammatory bowel disease, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, NUMBER, medicine, Ring finger, IMPUTATION, Allele, education, POPULATION, RISK, education.field_of_study, Multidisciplinary, biology, Biochemistry, Genetics and Molecular Biology(all), MUTATIONS, General Chemistry, ASSOCIATION, medicine.disease, Inflammatory Bowel Diseases, Ulcerative colitis, digestive system diseases, 3. Good health, Ubiquitin ligase, Transport protein, Transmembrane domain, 030104 developmental biology, medicine.anatomical_structure, RARE VARIANTS, Immunology, biology.protein, Cancer research, 3111 Biomedicine, INFLAMMATORY-BOWEL-DISEASE
Abstract

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access. Protein-truncating variants protective against human disease provide in vivo validation of therapeutic targets. Here we used targeted sequencing to conduct a search for protein-truncating variants conferring protection against inflammatory bowel disease exploiting knowledge of common variants associated with the same disease. Through replication genotyping and imputation we found that a predicted protein-truncating variant (rs36095412, p.R179X, genotyped in 11,148 ulcerative colitis patients and 295,446 controls, MAF=up to 0.78%) in RNF186, a single-exon ring finger E3 ligase with strong colonic expression, protects against ulcerative colitis (overall P=6.89 × 10(-7), odds ratio=0.30). We further demonstrate that the truncated protein exhibits reduced expression and altered subcellular localization, suggesting the protective mechanism may reside in the loss of an interaction or function via mislocalization and/or loss of an essential transmembrane domain. National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) DK064869 DK062432 National Human Genome Research Institute (NHGRI) DK064869 DK043351 HG005923 Crohns and Colitis Foundation 3765 Leona M. & Harry B. Helmsley Charitable Trust 2015PG-IBD001 Amgen 2013583217 CCFA 3765 Cedars-Sinai F. Widjaja Foundation, info:eu-repo/grantAgreement/EC/FP7/305479, European Union DK062413 AI067068 U54DE023789-01 Leona M. and Harry B. Helmsley Charitable Trust Crohn's and Colitis Foundation of America NIH DK062431 U01 DK062429 U01 DK062422 R01 DK092235 U01 DK062420 Medical Research Council, UK MR/J00314X/1 Wellcome Trust WT091310 098051 Inflammatory Bowel Disease Genetic Research Chair at the University of Pittsburgh PO1DK046763

Published
2016

34. Discovery of a tyrosine-rich sporocyst wall protein in Eimeria tenella

Author

Robert A. Walker, Laura Sedano, Nicholas Smith, Adrian B. Hehl, Chandra Ramakrishnan, Fabien Brossier, Alisson Niepceron, Queensland Tropical Health Alliance Research Laboratory, Australian Institute of Tropical Health and Medicine, James Cook University (JCU), Department of Pathobiology, Institute of Parasitology, Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Australian Research Council for Discovery Project DP0664013, and Institut National de la Recherche Agronomique (INRA)-Université de Tours

Subjects
0301 basic medicine, CROSS-LINKING, animal diseases, Protozoan Proteins, Mycology & Parasitology, Oocyst, Eimeria, Coccidia, Apicomplexa, Sporocyst, Dityrosine bond, I-TASSER SERVER, OOCYST WALL, NIESCHULZI COCCIDIA, MAXIMA, PREDICTIONS, APICOMPLEXA, VACCINATION, EXPRESSION, PARASITE, Cell Wall, 1108 Medical Microbiology, 1117 Public Health and Health Services, Tyrosine, biology, Microbiology and Parasitology, activité biochimique, Microbiologie et Parasitologie, 3. Good health, Cell biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, paroi cellulaire, Eimeria tenella, sporocyste, Short Report, Microbiology, Cell wall, 03 medical and health sciences, Tropical Medicine, parasitic diseases, Gene, Oocysts, biology.organism_classification, 030104 developmental biology, Parasitology, Targeted disruption
Abstract

Background Eimeria is an important genus of apicomplexan parasites. A defining feature of these parasites is the oocyst, which is transmitted into the environment via the faeces of definitive hosts. The oocyst wall contains cross-linked, tyrosine-rich proteins and protects eight infectious sporozoites, housed in pairs within a second walled structure, the sporocyst. The biochemical basis for sporocyst wall formation is not known. Findings Here, we report the discovery of a novel tyrosine-rich protein, EtSWP1, in Eimeria tenella. Like the tyrosine-rich proteins of the oocyst wall, EtSWP1 is an intrinsically disordered protein with the tyrosine residues concentrated in a specific region of the protein, located immediately following the region of intrinsic disorder. We engineered E. tenella to express mCherry-tagged EtSWP1 and showed that the tagged protein localises specifically to sporocyst walls, indicating that the biochemistry of sporocyst wall assembly is analagous to that of oocyst walls. Conclusions Tyrosine-rich proteins are known to be key components of the oocyst wall and we now demonstrate, using gene and protein analyses combined with genetic manipulation, that a novel tyrosine-rich protein is specific for the sporocyst wall. This finding is important because it shows that the biochemistry of these two distinct walls is similar and, hence, brings targeted disruption of sporulation and, therefore, potential neutralisation of oocysts in the environment, a step closer. Electronic supplementary material The online version of this article (doi:10.1186/s13071-016-1410-z) contains supplementary material, which is available to authorized users.

Published
2016

35. Inflammatory Airway Disease of Horses-Revised Consensus Statement

Author

Jean-Pierre Lavoie, Eric Richard, Renaud Léguillette, Jacqueline M. Cardwell, Vinzenz Gerber, Laurent L. Couëtil, College of Veterinary Medicine, Purdue University [West Lafayette], Department of Pathobiology and Population Sciences, Royal Veterinary College, Department of Clinical Research and Veterinary Public Health, University of Bern, Department of Clinical Sciences, Faculty of Veterinary Medicine, Faculty of Veterinary Medicine, University of Calgary, University of Calgary, LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)

Subjects
Lung Diseases, 0301 basic medicine, medicine.medical_specialty, 040301 veterinary sciences, Statement (logic), ACVIM Consensus Statement, Performance, education, 0403 veterinary science, 03 medical and health sciences, medicine, Animals, Horses, Animal Husbandry, Intensive care medicine, Respiratory disease, Equine asthma, Inflammation, lcsh:Veterinary medicine, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, General Veterinary, 630 Agriculture, business.industry, Consensus Statement, 04 agricultural and veterinary sciences, 030104 developmental biology, Airway disease, Cough, Practice Guidelines as Topic, Physical therapy, lcsh:SF600-1100, Heaves, Horse Diseases, business
Abstract

International audience; The purpose of this manuscript is to revise and update the previous consensus statement on inflammatory airway disease (IAD) in horses. Since 2007, a large number of scientific articles have been published on the topic and these new findings have led to a significant evolution of our understanding of IAD.

Published
2016
Full Text
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36. Assessing prognosis and optimizing treatment in patients with postchemotherapy viable nonseminomatous germ-cell tumors (NSGCT): results of the sCR2 international study

Author

J. Bouzy, Hans-Joachim Schmoll, I. Chen, Gedske Daugaard, M. De Santis, Joerg T. Hartmann, U. De Giorgi, Aude Flechon, Karim Fizazi, G. Fromont, Jan Oldenburg, Ariane Dunant, Sergei Tjulandin, Roberto Salvioni, Sophie D. Fosså, Génomes et cancer (GC (FRE2939)), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Department of Pathobiology [Auburn], Auburn University (AU), College of Veterinary Medicine, Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Dept of Oncology, Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Laboratory of Clinical Genetics, Institute of Clinical Oncology, Departments of Clinical Cancer Research and genetics, and Rikshospitalet-Radiumhospitalet Trust

Subjects
Male, MESH: Orchiectomy, MESH: Combined Modality Therapy, Time Factors, International Cooperation, medicine.medical_treatment, 030232 urology & nephrology, MESH: Risk Assessment, Cohort Studies, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, MESH: Cohort Studies, MESH: Testicular Neoplasms, MESH: Treatment Outcome, MESH: Statistics, Nonparametric, MESH: Middle Aged, Biopsy, Needle, Hematology, Middle Aged, Neoplasms, Germ Cell and Embryonal, Prognosis, Combined Modality Therapy, Immunohistochemistry, Chemotherapy regimen, 3. Good health, MESH: Antineoplastic Combined Chemotherapy Protocols, Treatment Outcome, Oncology, Chemotherapy, Adjuvant, MESH: Chemotherapy, Adjuvant, MESH: Survival Analysis, 030220 oncology & carcinogenesis, MESH: Neoplasms, Germ Cell and Embryonal, Cohort study, Adult, MESH: Biopsy, Needle, medicine.medical_specialty, Adolescent, Urology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Risk Assessment, Disease-Free Survival, Statistics, Nonparametric, MESH: Multivariate Analysis, MESH: Prognosis, 03 medical and health sciences, Testicular Neoplasms, medicine, Humans, Progression-free survival, Survival analysis, Retrospective Studies, MESH: Adolescent, Chemotherapy, MESH: Humans, business.industry, MESH: Time Factors, MESH: Adult, MESH: Immunohistochemistry, MESH: Retrospective Studies, Retrospective cohort study, Seminoma, medicine.disease, Survival Analysis, MESH: Male, Surgery, MESH: International Cooperation, Multivariate Analysis, MESH: Disease-Free Survival, Germ cell tumors, business, Orchiectomy
Abstract

BACKGROUND: The purpose of this study was to validate a prognostic index [surgical complete response 1 (sCR1)] in patients with postchemotherapy viable nonseminomatous germ-cell tumors (NSGCT). PATIENTS AND METHODS: Data and specimens from 61 patients with normalized tumor markers and postchemotherapy viable nonteratomatous NSGCT treated in 13 institutions were collected. RESULTS: With a median follow-up of 5.4 years, the 5-year progression-free survival (PFS) rate was 65%; the 5-year overall survival (OS) rate was 72%. Favorable PFS was predicted by a complete resection

Published
2008

37. The Swine Leukocyte Antigen (SLA) nomenclature system of the International Society for Animal Genetics (ISAG) and the International Union of Immunological Societies (IUIS): Update 2015

Author

Hammer, Sabine E., Ando, Asako, Rogel Gaillard, Claire, Lee, Jun-Heon, Schook, Lawrence B., Smith, Douglas M., Lunney, Joan K., Ho, Chak-Sum, Institute of Immunology, Department of Pathobiology, University of Veterinary Medicine [Vienna] (Vetmeduni), Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, Génétique Animale et Biologie Intégrative (GABI), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Université Paris Saclay (COmUE), Department of Animal Science and Biotechnology, College of Agriculture and Life Sciences, Chungnam National University (CNU), Institute for Genomic Biology, University of Illinois System, independent, Animal Parasitic Diseases Laboratory, BARC, USDA-ARS : Agricultural Research Service, Histocompatibility Laboratory, Gift of Life Michigan, and Veterinary Vaccinology Workshop.

Subjects
[SDV.GEN]Life Sciences [q-bio]/Genetics, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2015

38. RNA Seq analysis of the Eimeria tenella gametocyte transcriptome reveals clues about the molecular basis for sexual reproduction and oocyst biogenesis

Author

Adrian B. Hehl, Michal J. Okoniewski, Chandra Ramakrishnan, Fabien Brossier, Catherine M. Miller, Ramon M. Eichenberger, Peter Deplazes, Robert A. Walker, Nicholas Smith, Philippa A Sharman, Christoph Lippuner, Queensland Tropical Health Alliance Research Laboratory, Australian Institute of Tropical Health and Medicine, James Cook University (JCU), Department of Pathobiology, Institute of Parasitology, Universität Zürich [Zürich] = University of Zurich (UZH), Functional Genomics Center Zurich, Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Australian Research Council [DP0664013], NCS, Australian Government Department of Innovation, Industry, Science and Research International Science Linkage [FR110089], Bellberry Foundation, Swiss Government Excellence Scholarship: Postdoctoral Scholarship from the Swiss Confederation, Australian Postgraduate Award Scholarship, Australian Society for Parasitology Researcher Exchange, Training and Travel Award, University of Zurich, Smith, Nicholas C, and Institut National de la Recherche Agronomique (INRA)-Université de Tours

Subjects
10078 Institute of Parasitology, [SDV]Life Sciences [q-bio], Protozoan Proteins, Eimeria tenella, RNA Seq, Microgametocyte, Macrogametocyte, Oocyst, Fertilisation, Transmission, Transcriptome, 0302 clinical medicine, 600 Technology, Parasite hosting, Genetics, 0303 health sciences, biology, Recombinant Proteins, 3. Good health, Coccidiosis, Sporozoites, 1305 Biotechnology, Oxidoreductases, Research Article, Biotechnology, Molecular Sequence Data, 030231 tropical medicine, 610 Medicine & health, 10071 Functional Genomics Center Zurich, Eimeria, 03 medical and health sciences, Coccidia, 1311 Genetics, parasitic diseases, medicine, Gametocyte, Animals, Amino Acid Sequence, Gene, 030304 developmental biology, Merozoites, Sequence Analysis, RNA, Oocysts, Toxoplasma gondii, biology.organism_classification, medicine.disease, 10187 Department of Farm Animals, Microscopy, Fluorescence, 570 Life sciences, RNA, Chickens, Genome, Protozoan, Sequence Alignment
Abstract

Background The protozoan Eimeria tenella is a common parasite of chickens, causing avian coccidiosis, a disease of on-going concern to agricultural industries. The high prevalence of E. tenella can be attributed to the resilient oocyst stage, which is transmitted between hosts in the environment. As in related Coccidia, development of the eimerian oocyst appears to be dependent on completion of the parasite’s sexual cycle. RNA Seq transcriptome profiling offers insights into the mechanisms governing the biology of E. tenella sexual stages (gametocytes) and the potential to identify targets for blocking parasite transmission. Results Comparisons between the sequenced transcriptomes of E. tenella gametocytes and two asexual developmental stages, merozoites and sporozoites, revealed upregulated gametocyte transcription of 863 genes. Many of these genes code for proteins involved in coccidian sexual biology, such as oocyst wall biosynthesis and fertilisation, and some of these were characterised in more depth. Thus, macrogametocyte-specific expression and localisation was confirmed for two proteins destined for incorporation into the oocyst wall, as well as for a subtilisin protease and an oxidoreductase. Homologues of an oocyst wall protein and oxidoreductase were found in the related coccidian, Toxoplasma gondii, and shown to be macrogametocyte-specific. In addition, a microgametocyte gamete fusion protein, EtHAP2, was discovered. Conclusions The need for novel vaccine candidates capable of controlling coccidiosis is rising and this panel of gametocyte targets represents an invaluable resource for development of future strategies to interrupt parasite transmission, not just in Eimeria but in other Coccidia, including Toxoplasma, where transmission blocking is a relatively unexplored strategy. Electronic supplementary material The online version of this article (doi:10.1186/s12864-015-1298-6) contains supplementary material, which is available to authorized users.

Published
2015

39. Intercellular Spreading of Porphyromonas gingivalis Infection in Primary Gingival Epithelial Cells

Author

Özlem Yilmaz, Philippe Verbeke, Richard J. Lamont, David M. Ojcius, Department of Pathobiology, University of Washington [Seattle], Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Oral Biology College of Dentistry, University of Florida [Gainesville] (UF), School of Natural Sciences, University of California [Merced], University of California-University of California, and University of Florida [Gainesville]

Subjects
Immunology, Cell, Gingiva, Microbiology, Flow cytometry, Periodontal pathogen, 03 medical and health sciences, chemistry.chemical_compound, Immune system, Bacteroidaceae Infections, Extracellular, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Porphyromonas gingivalis, Cells, Cultured, Cytoskeleton, 030304 developmental biology, Cytochalasin D, 0303 health sciences, Cellular Microbiology: Pathogen-Host Cell Molecular Interactions, biology, medicine.diagnostic_test, 030306 microbiology, Epithelial Cells, Extracellular Fluid, Flow Cytometry, biology.organism_classification, Actins, 3. Good health, Cell biology, Kinetics, Infectious Diseases, medicine.anatomical_structure, Microscopy, Fluorescence, chemistry, Parasitology, Intracellular
Abstract

Porphyromonas gingivalis , an important periodontal pathogen, is an effective colonizer of oral tissues. The organism successfully invades, multiplies in, and survives for extended periods in primary gingival epithelial cells (GECs). It is unknown whether P. gingivalis resides in the cytoplasm of infected cells throughout the infection or can spread to adjacent cells over time. We developed a technique based on flow cytofluorometry and fluorescence microscopy to study propagation of the organism at different stages of infection of GECs. Results showed that P. gingivalis spreads cell to cell and that the amount of spreading increases gradually over time. There was a very low level of propagation of bacteria to uninfected cells early in the infection (3 h postinfection), but there were 20-fold and 45-fold increases in the propagation rate after 24 h and 48 h, respectively, of infection. Immunofluorescence microscopy of infected cells suggested that intercellular translocation of P. gingivalis may be mediated through actin-based membrane protrusions, bypassing the need for release of bacteria into extracellular medium. Consistent with these observations, cytochalasin D treatment of infected cells resulted in significant inhibition of bacterial spreading. This study shows for the first time that P. gingivalis disseminates from cell to cell without passing through the extracellular space. This mechanism of spreading may allow P. gingivalis to colonize oral tissues without exposure to the humoral immune response.

Published
2006

40. IL-17 in severe asthma. Where do we stand?

Author

Julie Chesné, Sophie Brouard, Guillaume Mahay, Antoine Magnan, Marc Aronica, Faouzi Braza, Le Bihan, Sylvie, Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Médecine Personnalisée des Maladies Chroniques [CHU Nantes] (DHU 2020), Centre hospitalier universitaire de Nantes (CHU Nantes)-Direction de la Recherche Département Partenariats et Innovation ( DHU 2020)-Direction de la Recherche/Département Partenariats et Innovation [CHU Nantes] (DRDPI - Nantes), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Service de pneumologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Pathobiology [Cleveland, OH, USA], Cleveland Clinic, Respiratory Institute [Cleveland, OH, USA], Vaincre la Mucoviscidose., Fondation de la Recherche Médicale (FRM)., Genavie., Région Pays de La Loire., Fondation du Souffle., and Société Française d’Allergologie.

Subjects
Pulmonary and Respiratory Medicine, severe asthma, Neutrophils, Severe asthma, Drug Resistance, Induced sputum, macromolecular substances, Critical Care and Intensive Care Medicine, Pathogenesis, medicine, Humans, Anti-Asthmatic Agents, Asthma, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Interleukin-17, Epithelial Cells, Smooth muscle contraction, medicine.disease, neutrophilic asthma, respiratory tract diseases, IL-17, Chronic disease, Immunology, Airway Remodeling, Th17 Cells, Interleukin 17, Th17, business, Airway, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Signal Transduction
Abstract

International audience; Asthma is a major chronic disease ranging from mild to severe refractory disease and is classified into various clinical phenotypes. Severe asthma is difficult to treat and frequently requires high doses of systemic steroids. In some cases, severe asthma even responds poorly to steroids. Several studies have suggested a central role of IL-17 (also called IL-17A) in severe asthma. Indeed, high levels of IL-17 are found in induced sputum and bronchial biopsies obtained from patients with severe asthma. The recent identification of a steroid-insensitive pathogenic Th17 pathway is therefore of major interest. In addition, IL-17A has been described in multiple aspects of asthma pathogenesis, including structural alterations of epithelial cells and smooth muscle contraction. In this perspective article, we frame the topic of IL-17A effects in severe asthma by reviewing updated information from human studies. We summarize and discuss the implications of IL-17 in the induction of neutrophilic airway inflammation, steroid insensitivity, the epithelial cell profile, and airway remodeling.

Published
2014

41. Teleost fish mount complex clonal IgM and IgT responses in spleen upon systemic viral infection

Author

Luc Jouneau, Simon Fillatreau, Oriol Sunyer, Marie-Paule Lefranc, Adrien Six, Frédéric Cazals, Rosario Castro, Véronique Giudicelli, Pierre Boudinot, Edwige Quillet, Olivier Bouchez, Hang-Phuong Pham, Abdenour Benmansour, Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), Immunologie - Immunopathologie - Immunothérapie (I3), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Laboratoire de Génétique Cellulaire (LGC), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Laboratoire d'ImmunoGénétique Moléculaire (LIGM), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 2 - Sciences et Techniques (UM2), Génétique Animale et Biologie Intégrative (GABI), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Algorithms, Biology, Structure (ABS), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Deutsches RheumaForschungszentrum, Leibniz Institute - German Rheumatism Research Centre (DRFZ), Department of Pathobiology [Philadelphia], University of Pennsylvania [Philadelphia], Unité de recherche Virologie et Immunologie Moléculaires (VIM), Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), International ImMunoGeneTics Information System (IMGT), AgroParisTech-Institut National de la Recherche Agronomique (INRA), Department for Innovation in Biological, Agro-Food and Forest Systems, University of Tuscia, Università degli studi della Tuscia [Viterbo], Boudinot, Pierre, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT), and University of Pennsylvania

Subjects
[SDV]Life Sciences [q-bio], Adaptive Immunity, Immunoglobulin D, Fish Diseases, Mice, 0302 clinical medicine, Biology (General), Immune Response, Pathogen, infections à rhabdoviridae, Novirhabdovirus, 0303 health sciences, biology, 04 agricultural and veterinary sciences, General Medicine, Immunohistochemistry, 3. Good health, medicine.anatomical_structure, Oncorhynchus mykiss, anticorps, Antibody, Research Article, Fish Proteins, QH301-705.5, Immunology, B-Lymphocyte Subsets, Immunoglobulins, Spleen, Aquatic Science, Microbiology, Virus, Evolution, Molecular, 03 medical and health sciences, rhabdovirus des poisson, Species Specificity, Virology, pathogène, Genetics, medicine, Animals, Humans, Environmental Chemistry, Biology, Immunity to Infections, Molecular Biology, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, Mucous Membrane, Staining and Labeling, Immunity, Immune Defense, Sequence Analysis, DNA, RC581-607, biology.organism_classification, Clone Cells, Immunoglobulin M, biology.protein, 040102 fisheries, 0401 agriculture, forestry, and fisheries, Parasitology, Viral hemorrhagic septicemia, Immunologic diseases. Allergy, 030215 immunology, truite arc en ciel
Abstract

Upon infection, B-lymphocytes expressing antibodies specific for the intruding pathogen develop clonal responses triggered by pathogen recognition via the B-cell receptor. The constant region of antibodies produced by such responding clones dictates their functional properties. In teleost fish, the clonal structure of B-cell responses and the respective contribution of the three isotypes IgM, IgD and IgT remain unknown. The expression of IgM and IgT are mutually exclusive, leading to the existence of two B-cell subsets expressing either both IgM and IgD or only IgT. Here, we undertook a comprehensive analysis of the variable heavy chain (VH) domain repertoires of the IgM, IgD and IgT in spleen of homozygous isogenic rainbow trout (Onchorhynchus mykiss) before, and after challenge with a rhabdovirus, the Viral Hemorrhagic Septicemia Virus (VHSV), using CDR3-length spectratyping and pyrosequencing of immunoglobulin (Ig) transcripts. In healthy fish, we observed distinct repertoires for IgM, IgD and IgT, respectively, with a few amplified μ and τ junctions, suggesting the presence of IgM- and IgT-secreting cells in the spleen. In infected animals, we detected complex and highly diverse IgM responses involving all VH subgroups, and dominated by a few large public and private clones. A lower number of robust clonal responses involving only a few VH were detected for the mucosal IgT, indicating that both IgM+ and IgT+ spleen B cells responded to systemic infection but at different degrees. In contrast, the IgD response to the infection was faint. Although fish IgD and IgT present different structural features and evolutionary origin compared to mammalian IgD and IgA, respectively, their implication in the B-cell response evokes these mouse and human counterparts. Thus, it appears that the general properties of antibody responses were already in place in common ancestors of fish and mammals, and were globally conserved during evolution with possible functional convergences., Author Summary In humans and mice, a broad and robust antibody response is the most effective system of defense against pathogens. While all vertebrates but the most ancient use an antibody system, it remains unknown if the clonal selection rules are conserved across vertebrates. Using high-throughput sequencing and antibody repertoire analysis, we show in teleost fish that virus infection induces a typical antibody response with clonal expansions. In spleen, the antibody response mainly consists in IgM, which is found across vertebrates, with a significant contribution of the fish-specific mucosal antibody IgT. IgD does not contribute as already observed in mammals. Although antibody molecules can be of different nature and structure across species, the general features of adaptive immunity were already in place in common ancestors of fish and mammals, and globally conserved during evolution while the anatomy and physiology of the immune system diverged.

Published
2013

42. The astonishing diversity of lg classes and B cell repertoires in teleost fish

Author

Adrien Six, J. Oriol Sunyer, Pierre Boudinot, Rosario Castro, Simon Fillatreau, Susanna Magadan, Boudinot, Pierre, Deutsches RheumaForschungszentrum, Immunologie - Immunopathologie - Immunothérapie (I3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), Department of Pathobiology [Philadelphia], University of Pennsylvania [Philadelphia], Institut National de la Recherche Agronomique, European Community [222719 LIFECYCLE], European Commission under European Union [311993 TARGETFISH], Unité de recherche Virologie et Immunologie Moléculaires (VIM), University of Pennsylvania, HAL UPMC, Gestionnaire, and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)

Subjects
lcsh:Immunologic diseases. Allergy, fish, antibody, repertoire, evolution, B cells, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, Review Article, Biology, Immunoglobulin E, Immunoglobulin D, 03 medical and health sciences, 0302 clinical medicine, Immune system, biology.animal, medicine, Immunology and Allergy, 14. Life underwater, Zebrafish, B cell, 030304 developmental biology, Genetics, 0303 health sciences, Vertebrate, biology.organism_classification, Evolution of fish, medicine.anatomical_structure, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Antibody, lcsh:RC581-607, 030215 immunology
Abstract

International audience; With lymphoid tissue anatomy different than mammals, and diverse adaptations to all aquatic environments, fish constitute a fascinating group of vertebrate to study the biology of B cell repertoires in a comparative perspective. Fish B lymphocytes express immunoglobulin (Ig) on their surface and secrete antigen-specific antibodies in response to immune challenges. Three antibody classes have been identified in fish, namely IgM, IgD, and IgT, while IgG, IgA, and IgE are absent. IgM and IgD have been found in all fish species analyzed, and thus seem to be primordial antibody classes. IgM and IgD are normally co-expressed from the same mRNA through alternative splicing, as in mammals. Tetrameric IgM is the main antibody class found in serum. Some species of fish also have IgT, which seems to exist only in fish and is specialized in mucosal immunity. IgM/IgD and IgT are expressed by two different sub-populations of B cells. The tools available to investigate B cell responses at the cellular level in fish are limited, but the progress of fish genomics has started to unravel a rich diversity of IgH and immunoglobulin light chain locus organization, which might be related to the succession of genome remodelings that occurred during fish evolution. Moreover, the development of deep sequencing techniques has allowed the investigation of the global features of the expressed fish B cell repertoires in zebrafish and rainbow trout, in steady state or after infection. This review provides a description of the organization of fish Ig loci, with a particular emphasis on their heterogeneity between species, and presents recent data on the structure of the expressed Ig repertoire in healthy and infected fish.

Published
2013

43. Heme binding properties of glyceraldehyde-3-phosphate dehydrogenase

Author

Ritu Chakravarti, Jérôme Santolini, Dennis J. Stuehr, Rajesh Vempati, Pierre Dorlet, Julie Brassard, Daniel P. Collins, Luciana Hannibal, John H. Dawson, Department of Pathobiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, affiliation inconnue, University of South Carolina [Columbia], Agriculture and Agri-Food [Ottawa] (AAFC), Stress Oxydants et Détoxication (LSOD), Département Biochimie, Biophysique et Biologie Structurale (B3S), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), National Institutes of Health (NIH), Agriculture and Agri-Food - AAFC (CANADA), Agriculture and Agri-Food [Ottawa] ( AAFC ), Stress Oxydants et Détoxication ( LSOD ), Département Biochimie, Biophysique et Biologie Structurale ( B3S ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), and Agriculture and Agri-Food (AAFC)

Subjects
inorganic chemicals, Porphyrins, Heme binding, Stereochemistry, Heme, Ligands, Spectrum Analysis, Raman, Ferric Compounds, Biochemistry, Article, Protein Structure, Secondary, 03 medical and health sciences, chemistry.chemical_compound, stomatognathic system, medicine, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Ferrous Compounds, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Glyceraldehyde 3-phosphate dehydrogenase, 030304 developmental biology, chemistry.chemical_classification, Carbon Monoxide, 0303 health sciences, biology, Ligand, Circular Dichroism, 030302 biochemistry & molecular biology, Electron Spin Resonance Spectroscopy, Glyceraldehyde-3-Phosphate Dehydrogenases, Porphyrin, Conjugated protein, Nitric oxide synthase, chemistry, Potentiometry, biology.protein, Ferric, Rabbits, Oxidation-Reduction, Protein Binding, medicine.drug
Abstract

International audience; Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a glycolytic enzyme that also functions in transcriptional regulation, oxidative stress, vesicular trafficking, and apoptosis. Because GAPDH is required for the insertion of cellular heme into inducible nitric oxide synthase [Chakravarti, R., et al. (2010) Proc. Natl. Acad. Sci. U.S.A. 107, 18004-18009], we extensively characterized the heme binding properties of GAPDH. Substoichiometric amounts of ferric heme bound to GAPDH (one heme per GAPDH tetramer) to form a low-spin complex with UV-visible maxima at 362, 418, and 537 nm and when reduced to ferrous gave maxima at 424, 527, and 559 nm. Ferric heme association and dissociation rate constants at 10 °C were as follows: k(on) = 17800 M(-1) s(-1), k(off1) = 7.0 × 10(-3) s(-1), and k(off2) = 3.3 × 10(-4) s(-1) (giving approximate affinities of 19-390 nM). Ferrous heme bound more poorly to GAPDH and dissociated with a k(off) of 4.2 × 10(-3) s(-1). Magnetic circular dichroism, resonance Raman, and electron paramagnetic resonance spectroscopic data on the ferric, ferrous, and ferrous-CO complexes of GAPDH showed that the heme is bis-ligated with His as the proximal ligand. The distal ligand in the ferric complex was not displaced by CN(-) or N(3)(-) but in the ferrous complex could be displaced by CO at a rate of 1.75 s(-1) (for >0.2 mM CO). Studies with heme analogues revealed selectivity toward the coordinating metal and porphyrin ring structure. The GAPDH-heme complex was isolated from bacteria induced to express rabbit GAPDH in the presence of δ-aminolevulinic acid. Our finding of heme binding to GAPDH expands the protein's potential roles. The strength, selectivity, reversibility, and redox sensitivity of heme binding to GAPDH are consistent with it performing heme sensing or heme chaperone-like functions in cells.

Published
2012

44. The Swine Leukocyte Antigen (SLA) nomenclature system: current status after 10 years of its establishment

Author

Ho, Chak-Sum, Ando, Asako, Essler, Sabine, Gaillard, Claire, Lee, Jun-Heon, Lunney, Joan K., Schook, Lawrence B., Smith, Douglas M., Histocompatibility Laboratory, Gift of Life Michigan, Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, Institute of Immunology, Department of Pathobiology, University of Veterinary Medicine [Vienna] (Vetmeduni), Génétique Animale et Biologie Intégrative (GABI), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Department of Animal Science and Biotechnology, College of Agriculture and Life Sciences, Chungnam National University (CNU), Animal Parasitic Diseases Laboratory, BARC, United States Department of Agriculture, Institute for Genomic Biology, University of Illinois System, and AgroParisTech-Institut National de la Recherche Agronomique (INRA)

Subjects
[SDV]Life Sciences [q-bio]
Abstract

absent

Published
2012

45. Arg375 tunes tetrahydrobiopterin functions and modulates catalysis by inducible nitric oxide synthase

Author

Mohammed Fadlalla, Ashis Biswas, Jérôme Santolini, Zhi Qiang Wang, Chin Chuan Wei, Dennis J. Stuehr, Mohammad Mahfuzul Haque, Jesús Tejero, Kent State University, Department of Pathobiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, affiliation inconnue, Southern Illinois University [Edwardsville] ( SIUE ), Stress Oxydants et Détoxication ( LSOD ), Département Biochimie, Biophysique et Biologie Structurale ( B3S ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), National Institutes of Health Grants GM51491 and CA53914, American Heart Association Beginning Grant-in-aid 0565297B, KSU Farris Innovation Award, KSU Tuscarawas Faculty Professional Development Release Time Award, Southern Illinois University [Edwardsville] (SIUE), Stress Oxydants et Détoxication (LSOD), Département Biochimie, Biophysique et Biologie Structurale (B3S), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)

Subjects
MECHANISM, Nitric Oxide Synthase Type II, Biochemistry, [ CHIM ] Chemical Sciences, Protein Structure, Secondary, Hydroxylation, chemistry.chemical_compound, 0302 clinical medicine, ELECTRON-TRANSFER, Pterin, Heme, 0303 health sciences, Tetrahydrobiopterin, biology, Nitric oxide synthase, BINDING-SITE, Single turn over, Protein Binding, inorganic chemicals, Stereochemistry, OXYGENASE DOMAIN, Arginine, Redox, Catalysis, Article, Cofactor, Ferrous, NO, Inorganic Chemistry, 03 medical and health sciences, HEME-DIOXY REDUCTION, [CHIM]Chemical Sciences, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Arg375, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, SINGLE-TURNOVER, Hydrogen Bonding, Biopterin, STOPPED-FLOW ANALYSIS, HYDROXY-L-ARGININE, RADICAL FORMATION, chemistry, Mutagenesis, Site-Directed, biology.protein, Steady state (chemistry), NEURONAL NO SYNTHASE, Protein Multimerization, 030217 neurology & neurosurgery, Midpoint potential
Abstract

International audience; NO synthase enzymes (NOS) support unique single-electron transitions of a bound H(4)B cofactor during catalysis. Previous studies showed that both the pterin structure and surrounding protein residues impact H(4)B redox function during catalysis. A conserved Arg residue (Arg375 in iNOS) forms hydrogen bonds with the H(4)B ring. In order to understand the role of this residue in modulating the function of H(4)B and overall NO synthesis of the enzyme, we generated and characterized three mutants R375D, R375K and R375N of the oxygenase domain of inducible NOS (iNOSoxy). The mutations affected the dimer stability of iNOSoxy and its binding affinity toward substrates and H(4)B to varying degrees. Optical spectra of the ferric, ferrous, ferrous dioxy, ferrous-NO, ferric-NO, and ferrous-CO forms of each mutant were similar to the wild-type. However, mutants displayed somewhat lower heme midpoint potentials and faster ferrous heme-NO complex reactivity with O(2). Unlike the wild-type protein, mutants could not oxidize NOHA to nitrite in a H(2)O(2)-driven reaction. Mutation could potentially change the ferrous dioxy decay rate, H(4)B radical formation rate, and the amount of the Arg hydroxylation during single turnover Arg hydroxylation reaction. All mutants were able to form heterodimers with the iNOS G450A full-length protein and displayed lower NO synthesis activities and uncoupled NADPH consumption. We conclude that the conserved residue Arg375 (1) regulates the tempo and extent of the electron transfer between H(4)B and ferrous dioxy species and (2) controls the reactivity of the heme-based oxidant formed after electron transfer from H(4)B during steady state NO synthesis and H(2)O(2)-driven NOHA oxidation. Thus, Arg375 modulates the redox function of H(4)B and is important in controlling the catalytic function of NOS enzymes.

Published
2012

46. VHH against DARC

Author

Smolarek, Dorota, Hattab, Claude, Hassanzadeh-Ghassabeh, Gholamreza, Cochet, Sylvie, Gutiérrez, Carlos, De Brevern, Alexandre, Udomsangpetch, Rachanee, Picot, Julien, Grodecka, Magdalena, Wasniowska, Kazimiera, Muyldermans, Serge, Colin, Yves, Le Van Kim, Caroline, Czerwinski, Marcin, Bertrand, Olivier, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polska Akademia Nauk = Polish Academy of Sciences (PAN), Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Cellular and Molecular Immunology, University of California [Irvine] (UCI), University of California-University of California, Department of Molecular and Cellular Interactions, Vrije Universiteit Brussel (VUB), Department Of Animal Medicine And Surgery, University of Las Palmas, Department of Pathobiology, Mahidol University [Bangkok], and D.S. was supported by scholarship from Ambassade de France à Varsovie and from the Flemish government. Project was supported by grant no. N N302 118835 from the Ministry of Science and Higher Education of Poland and in part by a Polonium Partenariat Hubert Curien grant.

Subjects
MESH: Immunoglobulins, VHH, MESH: Carrier Proteins, Immunoaffinity, MESH: Recombinant Proteins, HIV, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH: Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, atypical chemokine receptor, Cancer, MESH: Receptors, Cell Surface, Inflammation, MESH: Humans, MESH: Blood Group Antigens, MESH: Erythrocytes, MESH: Camels, MESH: Receptors, Antigen, MESH: Chemokines, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], MESH: Plasmodium vivax, MESH: Interleukin-8, MESH: Duffy Blood-Group System, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Plasmodium vivax, Duffy Antigen Receptor for Chemokines, MESH: Receptors, Chemokine
Abstract

International audience; Fy blood group antigens are carried by the Duffy antigen receptor for chemokines (DARC), a red cells receptor for Plasmodium vivax broadly implicated in human health and diseases. Recombinant VHHs, or nanobodies, the smallest intact antigen binding fragment derivative from the heavy chain-only antibodies present in camelids, were prepared from a dromedary immunized against DARC N-terminal extracellular domain and selected for DARC binding. A described VHH, CA52, does recognize native DARC on cells. It inhibits P. vivax invasion of erythrocytes and displaces interleukin-8 bound to DARC. The targeted epitope overlaps the well-defined DARC Fy6 epitope. K (D) of CA52-DARC equilibrium is sub-nanomolar, hence ideal to develop diagnostic or therapeutic compounds. Immunocapture by immobilized CA52 yielded highly purified DARC from engineered K562 cells. This first report on a VHH with specificity for a red blood cell protein exemplifies VHHs' potentialities to target, to purify, and to modulate the function of cellular markers.

Published
2010

47. Detection and molecular analysis of West Nile virus infections in birds of prey in the eastern part of Austria in 2008 and 2009

Author

Herbert Weissenböck, Susanne Richter, Sandra Revilla-Fernández, Norbert Nowotny, Petra Winter, Eveline Wodak, Zoltán Bagó, Austrian Agency for Health and Food Safety (AGES), Department of Pathobiology, University of Veterinary Medicine, and Zoonoses and Emerging Infections Group

Subjects
Male, viruses, Enzyme-Linked Immunosorbent Assay, goshawk, Antibodies, Viral, Microbiology, Virus, Disease Outbreaks, Flaviviridae, Mice, Neutralization Tests, medicine, Animals, Cells, Cultured, Phylogeny, Specific-pathogen-free, Ovum, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, General Veterinary, biology, Raptors, Bird Diseases, Reverse Transcriptase Polymerase Chain Reaction, Flavivirus, Zoonosis, Antibody titer, Embryonated, virus diseases, Accipiter, General Medicine, zoonosis, biology.organism_classification, medicine.disease, Virology, Austria, RNA, Viral, mosquito-borne flavivirus, Female, Chickens, West Nile virus, West Nile Fever
Abstract

The emergence of West Nile virus (WNV) was expected in Austria since the initial discovery of the infection in neighbouring Hungary in 2003/2004. In 2008 six cases of West Nile disease were diagnosed at the Institute for Veterinary Disease Control Modling, Austrian Agency for Health and Food Safety (AGES), involving five goshawks (Accipiter gentilis) and one gyrfalcon (Falco rusticolus), which were found dead in the eastern Austrian federal states of Lower Austria, Vienna and Styria, respectively. Pathomorphological and immunohistochemical findings suggested a WNV infection. Virus was isolated in embryonated specific pathogen free chicken eggs and propagated in mouse neuroblastoma cells (NA), in which a cytopathic effect occurred. The virus was identified and characterised by electron microscopic examination and molecular detection using RT-PCR, sequencing, and phylogenetic analysis. The Austrian WNV sequences exhibited nucleotide identities of 99.9% to the lineage 2 WNV sequences described in Hungary since 2004. In addition, 71 sera of 14 different bird species were screened for the presence of WNV antibodies using a commercial ELISA: 43.7% of the tested samples showed antibody titers. Selected positive sera were also subjected to WNV neutralisation tests, in which the ELISA results were verified in 66%. The results of this study confirm unambiguously the presence of a lineage 2 WNV infection in birds of prey in the eastern part of Austria.

Published
2010

48. VHH against DARC

Author

Alexandre G. de Brevern, Rachanee Udomsangpetch, Caroline Le Van Kim, Kazimiera Wasniowska, Magdalena Grodecka, Claude Hattab, Olivier Bertrand, Serge Muyldermans, Julien Picot, Yves Colin, Dorota Smolarek, Sylvie Cochet, Marcin Czerwinski, Carlos Gutierrez, Gholamreza Hassanzadeh-Ghassabeh, Cellular and Molecular Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polska Akademia Nauk = Polish Academy of Sciences (PAN), Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Cellular and Molecular Immunology, University of California [Irvine] (UCI), University of California-University of California, Department of Molecular and Cellular Interactions, Vrije Universiteit Brussel (VUB), Department Of Animal Medicine And Surgery, University of Las Palmas, Department of Pathobiology, Mahidol University [Bangkok], and D.S. was supported by scholarship from Ambassade de France à Varsovie and from the Flemish government. Project was supported by grant no. N N302 118835 from the Ministry of Science and Higher Education of Poland and in part by a Polonium Partenariat Hubert Curien grant.

Subjects
Erythrocytes, MESH: Immunoglobulins, Plasmodium vivax, Epitope, law.invention, MESH: Recombinant Proteins, 0302 clinical medicine, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Duffy antigen receptor for chemokines, MESH: Animals, Receptor, MESH: Receptors, Cell Surface, Cancer, 0303 health sciences, biology, MESH: Erythrocytes, MESH: Camels, MESH: Receptors, Antigen, MESH: Chemokines, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Recombinant Proteins, 3. Good health, MESH: Plasmodium vivax, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Blood Group Antigens, Recombinant DNA, Molecular Medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Receptors, Chemokine, Chemokines, Antibody, Camelus, Immunoglobulins, Receptors, Cell Surface, MESH: Carrier Proteins, VHH, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, HIV, Antigen, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, atypical chemokine receptor, Molecular Biology, 030304 developmental biology, Pharmacology, MESH: Humans, MESH: Blood Group Antigens, Interleukin-8, Cell Biology, biology.organism_classification, Virology, Molecular biology, MESH: Interleukin-8, MESH: Duffy Blood-Group System, immunoaffinity, Receptors, Antigen, Red blood cell, inflammation, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Carrier Proteins, Duffy Blood-Group System, MESH: Receptors, Chemokine, K562 cells
Abstract

International audience; Fy blood group antigens are carried by the Duffy antigen receptor for chemokines (DARC), a red cells receptor for Plasmodium vivax broadly implicated in human health and diseases. Recombinant VHHs, or nanobodies, the smallest intact antigen binding fragment derivative from the heavy chain-only antibodies present in camelids, were prepared from a dromedary immunized against DARC N-terminal extracellular domain and selected for DARC binding. A described VHH, CA52, does recognize native DARC on cells. It inhibits P. vivax invasion of erythrocytes and displaces interleukin-8 bound to DARC. The targeted epitope overlaps the well-defined DARC Fy6 epitope. K (D) of CA52-DARC equilibrium is sub-nanomolar, hence ideal to develop diagnostic or therapeutic compounds. Immunocapture by immobilized CA52 yielded highly purified DARC from engineered K562 cells. This first report on a VHH with specificity for a red blood cell protein exemplifies VHHs' potentialities to target, to purify, and to modulate the function of cellular markers.

Published
2010

49. A recombinant dromedary antibody fragment (VHH or nanobody) directed against human Duffy antigen receptor for chemokines

Author

Smolarek, Dorota, Hattab, Claude, Hassanzadeh-Ghassabeh, Gholamreza, Cochet, Sylvie, Gutiérrez, Carlos, de Brevern, Alexandre, Udomsangpetch, Rachanee, Picot, Julien, Grodecka, Magdalena, Wasniowska, Kazimiera, Muyldermans, Serge, Colin, Yves, Le van Kim, Caroline, Czerwinski, Marcin, Bertrand, Olivier, de Brevern, Alexandre G., Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polska Akademia Nauk = Polish Academy of Sciences (PAN), Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Cellular and Molecular Immunology, University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), Department of Molecular and Cellular Interactions, Vrije Universiteit Brussel (VUB), Department Of Animal Medicine And Surgery, University of Las Palmas, Department of Pathobiology, Mahidol University [Bangkok], and D.S. was supported by scholarship from Ambassade de France à Varsovie and from the Flemish government. Project was supported by grant no. N N302 118835 from the Ministry of Science and Higher Education of Poland and in part by a Polonium Partenariat Hubert Curien grant.

Subjects
MESH: Immunoglobulins, [SDV.IMM] Life Sciences [q-bio]/Immunology, VHH, MESH: Carrier Proteins, Immunoaffinity, MESH: Recombinant Proteins, HIV, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, atypical chemokine receptor, Cancer, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Receptors, Cell Surface, Inflammation, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], MESH: Humans, MESH: Blood Group Antigens, MESH: Erythrocytes, MESH: Camels, MESH: Receptors, Antigen, MESH: Chemokines, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], MESH: Plasmodium vivax, MESH: Interleukin-8, MESH: Duffy Blood-Group System, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Plasmodium vivax, Duffy Antigen Receptor for Chemokines, MESH: Receptors, Chemokine
Abstract

International audience; Fy blood group antigens are carried by the Duffy antigen receptor for chemokines (DARC), a red cells receptor for Plasmodium vivax broadly implicated in human health and diseases. Recombinant VHHs, or nanobodies, the smallest intact antigen binding fragment derivative from the heavy chain-only antibodies present in camelids, were prepared from a dromedary immunized against DARC N-terminal extracellular domain and selected for DARC binding. A described VHH, CA52, does recognize native DARC on cells. It inhibits P. vivax invasion of erythrocytes and displaces interleukin-8 bound to DARC. The targeted epitope overlaps the well-defined DARC Fy6 epitope. K (D) of CA52-DARC equilibrium is sub-nanomolar, hence ideal to develop diagnostic or therapeutic compounds. Immunocapture by immobilized CA52 yielded highly purified DARC from engineered K562 cells. This first report on a VHH with specificity for a red blood cell protein exemplifies VHHs' potentialities to target, to purify, and to modulate the function of cellular markers.

Published
2010

50. Fast ferrous heme-NO oxidation in nitric oxide synthases

Author

Jérôme Santolini, Dennis J. Stuehr, Jesús Tejero, Department of Pathobiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, affiliation inconnue, Stress Oxydants et Détoxication (LSOD), Département Biochimie, Biophysique et Biologie Structurale (B3S), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), National Institutes of Health Grants CA53914, GM51491, HL76491American Heart Association postdoctoral fellowship 0625632B, Stress Oxydants et Détoxication ( LSOD ), Département Biochimie, Biophysique et Biologie Structurale ( B3S ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Institut de Biologie Intégrative de la Cellule ( I2BC ), and Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS )

Subjects
MECHANISM, Chemical Phenomena, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type I, Biochemistry, TETRAHYDROBIOPTERIN, Mice, chemistry.chemical_compound, 0302 clinical medicine, Dioxygenase, Heme, IN-VIVO, 0303 health sciences, L-ARGININE, biology, Tetrahydrobiopterin, CO BINDING, Nitric oxide synthase, redox, medicine.drug, inorganic chemicals, Hemeprotein, OXYGENASE DOMAIN, Redox, Article, Nitric oxide, Ferrous, FLASH-PHOTOLYSIS, 03 medical and health sciences, nitric oxide, medicine, Animals, enzyme mechanism, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, KINETICS, 030304 developmental biology, Cell Biology, Combinatorial chemistry, Rats, FLAVOHEMOGLOBIN, Oxygen, chemistry, heme-thiolate, DIOXYGENASE, heme protein, biology.protein, Nitric Oxide Synthase, 030217 neurology & neurosurgery
Abstract

International audience; During catalysis, the heme in nitric oxide synthase (NOS) binds NO before releasing it to the environment. Oxidation of the NOS ferrous heme-NO complex by O2 is key for catalytic cycling, but the mechanism is unclear. We utilized stopped-flow methods to study the reaction of O2 with ferrous heme-NO complexes of inducible and neuronal NOS enzymes. We found that the reaction does not involve heme-NO dissociation, but instead proceeds by a rapid direct reaction of O2 with the ferrous heme-NO complex. This behavior is novel and may distinguish heme-thiolate enzymes, such as NOS, from related heme proteins.

Published
2009

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