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1. Exercise in lung Cancer, the healthcare providers opinion (E.C.H.O.): Results of the EORTC lung cancer Group (LCG) survey

Author: Sara Pilotto, Alice Avancini, Jessica Menis, Isabella Sperduti, Matteo Giaj Levra, Thierry Berghmans, Paolo Bironzo, Mariana Brandão, Dirk De Ruysscher, John Edwards, Corinne Faivre-Finn, Nicolas Girard, Laurent Greillier, Lizza Hendriks, Sylvie Lantuejoul, Murielle Mauer, Silvia Novello, Mary O'Brien, Martin Reck, Noemi Reguart, Jordi Remon, Jan von der Thüsen, Anne-Marie C. Dingemans, Benjamin Besse, Michele Milella, Centre Hospitalier Universitaire [Grenoble] (CHU), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto = University of Porto, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Royal Holloway [University of London] (RHUL), University of Manchester [Manchester], Méthodes computationnelles pour la prise en charge thérapeutique en oncologie : Optimisation des stratégies par modélisation mécaniste et statistique (COMPO), 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)-Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Multidisciplinary Oncology and Therapeutic Innovations Unit, Hôpital Nord [CHU - APHM], Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), School for Oncology and Developmental Biology [Maastricht] (GROW), Maastricht University [Maastricht]-Maastricht University Medical Centre (MUMC), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Organisation for Research and Treatment of Cancer [Bruxelles] (EORTC), European Cancer Organisation [Bruxelles] (ECCO), Università degli studi di Torino = University of Turin (UNITO), German Center for Lung Research, August Pi i Sunyer Biomedical Research Institute - IDIBAPS [Barcelona, Spain], Centro Integral Oncologico Clara Campal, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Radiotherapie, Pulmonologie, Pathology, and Pulmonary Medicine
Subjects: Pulmonary and Respiratory Medicine, REHABILITATION, Cancer Research, Lung Neoplasms, Facilitators, Clinicians, Health Personnel, [SDV.CAN]Life Sciences [q-bio]/Cancer, AMERICAN-COLLEGE, GUIDELINES, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, MESH: Referral and Consultation, SDG 3 - Good Health and Well-being, QUALITY-OF-LIFE, Surveys and Questionnaires, Humans, Barriers, Current practice, Exercise, Lung cancer, Oncologist, Physical activity, Recommendation, Referral and Consultation, MESH: Surveys and Questionnaires, MEDICINE ROUND-TABLE, MESH: Humans, RANDOMIZED CONTROLLED-TRIAL, CHEMOTHERAPY, MESH: Lung Neoplasms, PHYSICAL-ACTIVITY, Oncology, MESH: Exercise, MESH: Health Personnel, INTERVENTION
Abstract: Objectives: Exercise has been reported to alleviate disease as well as treatment impact in patients with lung cancer. Nevertheless, there is limited information available regarding the perception of lung cancer dedicated healthcare professionals’ and their advice on exercise. Materials and Methods: An online survey exploring healthcare professionals’ practice patterns, perceptions, barriers, and facilitators of exercise in patients with lung cancer was conducted within members of the EORTC Lung Cancer Group (LCG). Results: One hundred forty-one healthcare providers completed the survey, mainly medical and radiation oncologists. Overall, 63% of the study participants declared that they frequently assessed exercise level in their patients, and 43% of them reinforced the importance of exercise. However, only 10% referred patients to an exercise program or specialist. Although the majority of the respondents had a positive perception regarding the benefits and safety of exercise (even in patients with advanced disease and/or bone metastasis), two-thirds of clinicians reported not having adequate training about exercise counselling. Moreover, 53% reported to lack of knowledge of guidelines referring to exercise in patients with cancer. Several obstacles and facilitators to improve exercise promotion in lung cancer care were identified. Conclusion: Healthcare providers recognize the relevance and feasibility of exercise as part of cancer treatment intervention, but specific pathways to do the referral are frequently missing. Future structured and well-designed strategies and initiatives are needed to support an effective referral in order to implement exercise interventions routinely in clinical practice.
Published: 2022
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2. Circulating Biomarkers and Cardiac Structure and Function in Rheumatoid Arthritis

Author: Masatake Kobayashi, Maria Betânia Ferreira, Rita Quelhas Costa, Tomás Fonseca, José Carlos Oliveira, António Marinho, Henrique Cyrne Carvalho, Nicolas Girerd, Patrick Rossignol, Faiez Zannad, Patrícia Rodrigues, João Pedro Ferreira, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Hospital da Luz Arrabida, V. N. Gaia, Portugal, Universidade do Porto, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Centro Hospitalar de Entre o Douro e Vouga, Centro Hospitalar do Porto, Universidade do Porto = University of Porto, and BOZEC, Erwan
Subjects: rheumatoid arthritis, heart failure with preserved ejection fraction, medicine.medical_specialty, Inflammation, Cardiovascular Medicine, 030204 cardiovascular system & hematology, Asymptomatic, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Diseases of the circulatory (Cardiovascular) system, 030212 general & internal medicine, Original Research, biology, business.industry, circulating biomarkers, PTX3, medicine.disease, Troponin, echocardiogram, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Rheumatoid arthritis, Heart failure, RC666-701, Cohort, Cardiology, biology.protein, prognosis, medicine.symptom, Heart failure with preserved ejection fraction, business, Cardiology and Cardiovascular Medicine
Abstract: Background: Rheumatoid arthritis (RA) increases the risk for abnormalities of the cardiac structure and function, which may lead to heart failure (HF). Studying the association between circulating biomarkers and echocardiographic parameters is important to screen patients with RA with a higher risk of cardiac dysfunction.Aim: To study the association between circulating biomarkers and echocardiographic parameters in patients with RA.Methods: Echocardiography was performed in 355 patients with RA from RA Porto cohort and the associations between echocardiographic characteristics and 94 circulating biomarkers were assessed. These associations were also assessed in the Metabolic Road to Diastolic Heart Failure (MEDIA-DHF) [392 patients with HF with preserved ejection fraction (HFpEF)] and the Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux (STANISLAS) (1,672 healthy population) cohorts.Results: In the RA Porto cohort, mean age was 58 ± 13 years, 23% were males and mean RA duration was 12 ± 10 years. After adjustment and multiple testing correction, left ventricular mass index (LVMi), left atrial volume index (LAVi), and E/e′ were independently associated with biomarkers reflecting inflammation [i.e., bone morphogenetic protein 9 (BMP9), pentraxin-related protein 3 (PTX3), tumor necrosis factor receptor superfamily member 11a (TNFRSF11A)], extracellular matrix remodeling [i.e., placental growth factor (PGF)], congestion [i.e., N-terminal pro-brain natriuretic peptide (NT-proBNP), adrenomedullin (ADM)], and myocardial injury (e.g., troponin). Greater LVMi [hazard ratio (HR) (95% CI) per 1 g/m2 = 1.03 (1.02–1.04), p < 0.001], LAVi [HR (95% CI) per 1 ml/m2 = 1.03 (1.01–1.06), p < 0.001], and E/e′ [HR (95% CI) per 1 = 1.08 (1.04–1.13), p < 0.001] were associated with higher rates of cardiovascular events. These associations were externally replicated in patients with HFpEF and asymptomatic individuals.Conclusion: Circulating biomarkers reflecting inflammation, extracellular matrix remodeling, congestion, and myocardial injury were associated with underlying alterations of cardiac structure and function. Biomarkers might be used for the screening of cardiac alterations in patients with RA.
Published: 2021
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3. Interleukin-10 induces interferon-γ-dependent emergency myelopoiesis

Author: Ana, Cardoso, Ana Catarina, Martins, Ana Raquel, Maceiras, Wei, Liu, Isabel, Castro, António G, Castro, António, Bandeira, James P, Di Santo, Ana, Cumano, Yan, Li, Paulo, Vieira, Margarida, Saraiva, Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto = University of Porto, Instituto de Biologia Molecular e Celular - institute for molecular and cell biology [Porto, Portugal] (IBMC), Lymphocytes et Immunité - Lymphocytes and Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Medical School (University of Nanjing), Nanjing University (NJU), University of Minho [Braga], Cellule Pasteur, Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Immunité Innée - Innate Immunity, A. Cardoso (SFRH/BD/84704/2012) and A.C.M. (SFRH/BD/136800/2018) were supported by the Portuguese Foundation for Science and Technology (FCT) through PhD grants.This study was partially supported by grants from the National Key Research and Development Program of China (2019YFA0802900), National Natural Science Foundation of China (32070942), and Fundamental Research Funds for the Central Universities.The M.S. lab was financed by a FCT-ANR grant (MyeloTEN-FCTANR/ BIM-MEC/0007/2013). We acknowledge the GenomePT project (POCI-01-0145-FEDER-022184), supported by COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Lisboa Portugal Regional Operational Programme (Lisboa2020), Algarve Portugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by FCT.This work was funded by National Funds through FCT, I.P., under the project UIDB/04293/2020, and backed by the COST Action BM1404 European Network of Investigators Triggering Exploratory Research on Myeloid Regulatory Cells (http://www.mye-euniter.eu), which is supported by the Horizon 2020—EU Framework Program Research and Innovation Programme. M.S. is funded by FCT through Estímulo Individual ao Emprego Científico.A. Cumano and P.V. were financed by ANR Twothyme and by REVIVE (Investissement d’Avenir, ANR-10-LABX-73). A.B., A. Cumano, and P.V. were also financed by the Institut Pasteur, INSERM, and ANR (project MYELOTEN, ANR-13-ISV1-0003-01)., We thank Vincent Rouilly for statistical advice and Werner Müller (University of Manchester), Rui Appelberg (i3S), and Bruno Silva-Santos (iMM) for providing the IL-10Rα-, IFN-γ-, and TCRγδ-deficient animals, respectively. We thank Anne O’Garra for helpful discussions and for critical reading of the manuscript. We also thank Delfim Duarte and Maria José Teles for helpful discussions and for helping with the hemogram quantification. We thank Caetano Reis e Sousa for help with the preparation of the graphical abstract. We thank the support of the personnel in the animal facilities, the i3S scientific platforms Translational Cytometry (TraCy), and Histology and Electron Microscopy (HEMS). HEMS is a member of the national infrastructure PPBI (Portuguese Platform of Bioimaging, PPBI-POCI-01-0145-FEDER-022122)., ANR-10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010), ANR-13-ISV1-0003,MYELOTEN,DEREGULATION DE L'HEMATOPOIESE PAR LA SUREXPRESSION DE L'INTERLEUKINE-10 : IMPLICATIONS DANS LE DEVELOPPEMENT DE PATHOLOGIES HEMATOLOGIQUES(2013), European Project, Vougny, Marie-Christine, Laboratoires d'excellence - Stem Cells in Regenerative Biology and Medicine - - REVIVE2010 - ANR-10-LABX-0073 - LABX - VALID, Blanc – Accords bilatéraux 2013 - DEREGULATION DE L'HEMATOPOIESE PAR LA SUREXPRESSION DE L'INTERLEUKINE-10 : IMPLICATIONS DANS LE DEVELOPPEMENT DE PATHOLOGIES HEMATOLOGIQUES - - MYELOTEN2013 - ANR-13-ISV1-0003 - Blanc – Accords bilatéraux 2013 - VALID, COST Action BM1404 MyeEUNITER - INCOMING, Universidade do Porto, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: CD4-Positive T-Lymphocytes, Mice, Knockout, Myelopoiesis, [SDV.IMM] Life Sciences [q-bio]/Immunology, T cells, emergency myelopoiesis, CD8-Positive T-Lymphocytes, Interleukin-10, Interferon-gamma, Mice, IL-10, Animals, [SDV.IMM]Life Sciences [q-bio]/Immunology, IFN-γ, Myeloid Progenitor Cells
Abstract: International audience; In emergency myelopoiesis (EM), expansion of the myeloid progenitor compartment and increased myeloid cell production are observed and often mediated by the pro-inflammatory cytokine interferon gamma (IFN-γ). Interleukin-10 (IL-10) inhibits IFN-γ secretion, but paradoxically, its therapeutic administration to humans causes hematologic changes similar to those observed in EM. In this work, we use different in vivo systems, including a humanized immune system mouse model, to show that IL-10 triggers EM, with a significant expansion of the myeloid progenitor compartment and production of myeloid cells. Hematopoietic progenitors display a prominent IFN-γ transcriptional signature, and we show that IFN-γ mediates IL-10-driven EM. We also find that IL-10, unexpectedly, reprograms CD4 and CD8 T cells toward an activation state that includes IFN-γ production by these T cell subsets in vivo. Therefore, in addition to its established anti-inflammatory properties, IL-10 can induce IFN-γ production and EM, opening additional perspectives for the design of IL-10-based immunotherapies.
Published: 2021
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4. Anti-neoplastic and demethylating activity of a newly synthetized flavanone-derived compound in Renal Cell Carcinoma cell lines

Author: Ângela Marques-Magalhães, Carmen Jerónimo, Inês Graça, Vera Miranda-Gonçalves, Rui Henrique, Marie Lopez, Paola B. Arimondo, Instituto Português de Oncologia do Porto / Portuguese Oncology Institute of Porto (IPO Porto), Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto = University of Porto, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Chimie biologique épigénétique - Epigenetic Chemical Biology (EpiCBio), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), The authors would like to acknowledge the support of the Programa Operacional Competitividade e Internacionalização (POCI), in the component FEDER, and by national funds (OE) through FCT/MCTES, in the scope of the project HyTherCaP (PTDC/MECONC/ 29030/2017) and Research Center of the Portuguese Oncology Institute of Porto (CI-IPOP-FBGEBC-27). This work was developed within the scope of the COST ACTION CM1406-Epichembio. IG was supported by COMPETE/FEDER/FCT_CI-IPOP-BPD/UID/DTP/00776/2013. POCI-01-0145-FEDER-2943 supports the junior researcher contract of VM-G., Universidade do Porto, and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Cell Survival, DNA damage, Angiogenesis, [SDV]Life Sciences [q-bio], Antineoplastic Agents, Chick Embryo, RM1-950, urologic and male genital diseases, 03 medical and health sciences, 0302 clinical medicine, Renal cell carcinoma, Cell Line, Tumor, medicine, Animals, Humans, MTT assay, Viability assay, Carcinoma, Renal Cell, Pharmacology, 3-nitroflavanones, DNA methylation, Dose-Response Relationship, Drug, Chemistry, Anticancer therapy, Renal Cell Carcinoma, General Medicine, medicine.disease, Kidney Neoplasms, Demethylation, 3. Good health, DNMT inhibitors, 030104 developmental biology, Cell culture, Apoptosis, 030220 oncology & carcinogenesis, Flavanones, Cancer research, Therapeutics. Pharmacology
Abstract: International audience; Renal Cell Carcinoma (RCC) is on the top 10 of the most incident cancers worldwide, being a third of patients diagnosed with advanced disease, for which no curative therapies are currently available. Thus, new effective therapeutic strategies are urgently needed. Herein, we tested the antineoplastic effect of newly synthesized 3-nitroflavanones (MLo1302) on RCC cell lines. 786-O, Caki2, and ACHN cell lines were cultured and treated with newly synthesized 3-nitroflavanones. IC50 values were calculated based on the effect on cell viability assessed by MTT assay, after 72 h of exposure. MLo1302 displayed antineoplastic properties in RCC cell lines through marked reduction of cell viability, increased apoptosis and DNA damage, and morphometric alterations indicating a less aggressive phenotype. MLo1302 induced a significant reduction of global DNA methylation and DNMT mRNA levels, increasing global DNA hydroxymethylation and TET expression. Moreover, MLo1302 decreased DNMT3A activity in RCC cell lines, demethylated and re-expressed hypermethylated genes in CAM-generated tumors. A marked in vivo decrease in tumor growth and angiogenesis was also disclosed. MLo1302 disclosed antineoplastic and demethylating activity in RCC cell lines, constituting a potential therapeutic agent for RCC patients.
Published: 2021
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5. Overview of Cattle Diseases Listed Under Category C, D or E in the Animal Health Law for Which Control Programmes Are in Place Within Europe

Author: Hodnik, Jaka Jakob, Acinger-Rogi��, ��aklin, Alishani, Mentor, Autio, Tiina, Balseiro, Ana, Berezowski, John, Carmo, Luis Pedro, Chaligiannis, Ilias, Conrady, Beate, Costa, Lina, Cvetkovikj, Iskra, Davidov, Ivana, Dispas, Marc, Djadjovski, Igor, Duarte, Elsa Leclerc, Faverjon, C��line, Fourichon, Christine, Fr��ssling, Jenny, Gerilovych, Anton, Gethmann, J��rn, Gomes, Jacinto, Graham, David, Guelbenzu, Maria, Gunn, George J, Henry, Madeleine K, Hopp, Petter, Houe, Hans, Irimia, Elena, Je��ek, Jo��ica, Juste, Ramon A, Kalaitzakis, Emmanouil, Kaler, Jasmeet, Kaplan, Selcuk, Kostoulas, Polychronis, Kovalenko, Kaspars, Kne��evi��, Nada, Knific, Tanja, Koleci, Xhelil, Madouasse, Aur��lien, Malakauskas, Alvydas, Mandelik, Rene, Meletis, Eleftherios, Mincu, Madalina, M��tus, Kerli, Mu��oz-G��mez, Violeta, Niculae, Mihaela, Nikitovi��, Jelena, Ocepek, Matja��, Tangen-Opsal, Marie, ��zsv��ri, L��szl��, Papadopoulos, Dimitrios, Papadopoulos, Theofilos, Pelkonen, Sinikka, Polak, Miroslaw Pawel, Pozzato, Nicola, Rapaliut��, Egl��, Ribbens, Stefaan, Niza-Ribeiro, Jo��o, Roch, Franz-Ferdinand, Rosenbaum Nielsen, Liza, Saez, Jose Luis, Nielsen, S��ren Saxmose, van Schaik, Gerdien, Schwan, Ebba, Sekovska, Blagica, Stari��, Jo��e, Strain, Sam, ��atran, Petr, ��eri��-Hara��i��, Sabina, Tamminen, Lena-Mari, Thulke, Hans-Hermann, Toplak, Ivan, Tuunainen, Erja, Verner, Sharon, Vil��ek, ��tefan, Yildiz, Ramazan, Santman-Berends, Inge M G A, University of Ljubljana, Ministry of Agriculture [Zagreb, Croatia], University of Prishtina, Finnish Food Authority, Partenaires INRAE, Universidad de León [León], University of Bern, Aristotle University of Thessaloniki, Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU), Complexity Science Hub Vienna (CSHV), Politécnico de Portalegre = Polytechnic Institute of Portalegre, Ss. Cyril and Methodius University in Skopje, University of Novi Sad, Sciensano [Bruxelles], Réseau International des Instituts Pasteur (RIIP), Universidade de Évora, Ausvet Europe, Biologie, Epidémiologie et analyse de risque en Santé Animale (BIOEPAR), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), National Veterinary Institute [Uppsala] (SVA), V.N. Karazin Kharkiv National University (KhNU), National Scientific Centre - Institute for Experimental and Clinical Veterinary Medicine [Kharkiv, Ukraine] (NSC - IECVM), Friedrich-Loeffler-Institut (FLI), Instituto Nacional de Investigação Agrária e Veterinária = National Institute for Agrarian and Veterinary Research [Oeiras, Portugal] (INIAV), Animal Health Ireland (AHI), Scotland's Rural College (SRUC), Norwegian Veterinary Institute [Oslo], Research and Development Institute for Bovine Balotesti (RDIB), Instituto Vasco de Investigación y Desarrollo Agrario [Derio] (NEIKER), University of Nottingham, UK (UON), Tekirdag Namik Kemal University (NKÜ), University of Thessaly [Volos] (UTH), University of Latvia (LU), Podravka d.d, Agricultural University of Tirana, Lithuanian University of Health Sciences [Kaunas, Lithuania], University of Veterinary Medicine and Pharmacy [Košice, Slovakia], Estonian University of Life Sciences (EMU), University of Zurich, Vetsuisse-Faculty, University of Agricultural Sciences and Veterinary Medicine Cluj Napoca, University of Banja Luka, Norwegian Food Safety Authority, University of Veterinary Medicine [Budapest, Hungary], National Veterinary Research Institute [Pulawy, Pologne] (NVRI), Istituto Zooprofilattico Sperimentale delle Venezie (IZSVe), Animal Health Care Flanders, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto, University of Veterinary Medicine [Vienna] (Vetmeduni), Ministry of Agriculture, Fisheries and Food, Utrecht University [Utrecht], Royal GD [Deventer], Farm and Animal Health, Animal Health and Welfare Northern Ireland, State Veterinary Institute Prague, University of Sarajevo, UNIVERZITET U SARAJEVU, Swedish University of Agricultural Sciences (SLU), Department of Ecological Modelling [UFZ Leipzig], Helmholtz Zentrum für Umweltforschung = Helmholtz Centre for Environmental Research (UFZ), Animal Health ETT, Burdur Mehmet Akif Ersoy University, This article is based upon work fromCOST Action Standardising output-based surveillance to control non-regulated diseases of cattle in the European Union (SOUND control) CA17110 supported by COST (European Cooperation in Science and Technology)3. COST is a funding agency for research and innovation networks. Actions help connect research initiatives across Europe and enable scientists to grow their ideas by sharing them with their peers. This boosts their research, career and innovation., Balseiro Morales, Ana María [0000-0002-5121-7264], FAH Evidence based Veterinary Medicine, FAH veterinaire epidemiologie, dFAH AVR, Dep Gezondheidszorg Landbouwhuisdieren, and Balseiro Morales, Ana María
Subjects: Europe, 630 Agriculture, General Veterinary, Control programmes, Disease control, [SDV]Life Sciences [q-bio], Output-based standards, SOUND control, Veterinary Science, Cattle, veterinary(all), Original Research
Abstract: 13 páginas, 5 figuras, 3 tablas., The COST action “Standardising output-based surveillance to control non-regulated diseases of cattle in the European Union (SOUND control),” aims to harmonise the results of surveillance and control programmes (CPs) for non-EU regulated cattle diseases to facilitate safe trade and improve overall control of cattle infectious diseases. In this paper we aimed to provide an overview on the diversity of control for these diseases in Europe. A non-EU regulated cattle disease was defined as an infectious disease of cattle with no or limited control at EU level, which is not included in the European Union Animal health law Categories A or B under Commission Implementing Regulation (EU) 2020/2002. A CP was defined as surveillance and/or intervention strategies designed to lower the incidence, prevalence, mortality or prove freedom from a specific disease in a region or country. Passive surveillance, and active surveillance of breeding bulls under Council Directive 88/407/EEC were not considered as CPs. A questionnaire was designed to obtain country-specific information about CPs for each disease. Animal health experts from 33 European countries completed the questionnaire. Overall, there are 23 diseases for which a CP exists in one or more of the countries studied. The diseases for which CPs exist in the highest number of countries are enzootic bovine leukosis, bluetongue, infectious bovine rhinotracheitis, bovine viral diarrhoea and anthrax (CPs reported by between 16 and 31 countries). Every participating country has on average, 6 CPs (min–max: 1–13) in place. Most programmes are implemented at a national level (86%) and are applied to both dairy and non-dairy cattle (75%). Approximately one-third of the CPs are voluntary, and the funding structure is divided between government and private resources. Countries that have eradicated diseases like enzootic bovine leukosis, bluetongue, infectious bovine rhinotracheitis and bovine viral diarrhoea have implemented CPs for other diseases to further improve the health status of cattle in their country. The control of non-EU regulated cattle diseases is very heterogenous in Europe. Therefore, the standardising of the outputs of these programmes to enable comparison represents a challenge.
Published: 2021
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6. Yolk sac, but not hematopoietic stem cell–derived progenitors, sustain erythropoiesis throughout murine embryonic life

Author: Soares-Da-Silva, Francisca, Freyer, Laina, Elsaid, Ramy, Burlen-Defranoux, Odile, Iturri, Lorea, Sismeiro, Odile, Pinto-Do-Ó, Perpétua, Gomez-Perdiguero, Elisa, Cumano, Ana, Gestionnaire, Hal Sorbonne Université, Appel à projets générique - Deux progéniteurs hématopoïétiques différents établissent le compartiment de lymphocytes T: tester un nouveau paradigme du développement T. - - Twothyme2014 - ANR-14-CE11-0022 - Appel à projets générique - VALID, Bases moléculaires de la spécification vers le lignage lymphoïde : une approche comparative trans-espèce - - Epi-Dev2019 - ANR-19-CE14-0018 - AAPG2019 - VALID, Lymphocytes et Immunité - Lymphocytes and Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Universidade do Porto = University of Porto, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Macrophages et Cellules endothéliales / Macrophages and Endothelial Cells, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Cellule Pasteur UPMC, Institut Pasteur [Paris] (IP)-Sorbonne Université (SU), Sorbonne Université (SU), Pôle Biomics (C2RT), Centre de Ressources et de Recherche Technologique - Center for Technological Resources and Research (C2RT), Institut Pasteur [Paris] (IP)-Institut Pasteur [Paris] (IP), Agence Nationale de la Recherche (Twothyme, EPI-DEV)European Research Council (2016-StG-715320)Fundação para a Ciência e a Tecnologia (POCI-01-0145-FEDER-032656, PD/BD/114128/2015, POCI-0100145-FEDER-01638)Institut National de la Santé et de la Recherche Médicale (NO AWARD)Institut Pasteur (NO AWARD), ANR-14-CE11-0022,Twothyme,Deux progéniteurs hématopoïétiques différents établissent le compartiment de lymphocytes T: tester un nouveau paradigme du développement T.(2014), ANR-19-CE14-0018,Epi-Dev,Bases moléculaires de la spécification vers le lignage lymphoïde : une approche comparative trans-espèce(2019), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Universidade do Porto, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Sorbonne Université (SU), and Institut Pasteur [Paris]-Institut Pasteur [Paris]
Subjects: Mice, Knockout, Erythrocytes, Macrophages, [SDV]Life Sciences [q-bio], Stem Cells & Regeneration, Embryonic Development, Article, Hematopoiesis, Mice, Inbred C57BL, [SDV] Life Sciences [q-bio], Mice, Proto-Oncogene Proteins c-myb, Pregnancy, embryonic structures, Animals, Cell Lineage, Erythropoiesis, Female, Erythropoietin, Megakaryocyte Progenitor Cells, Yolk Sac
Abstract: Yolk sac erythropoiesis is not replaced by hematopoietic stem cell–derived progeny up until birth. Yolk sac–derived erythroid progenitors require 10-fold lower concentrations of erythropoietin for differentiation, which confers a competitive advantage over progenitors of hematopoietic stem cell origin., In the embryo, the first hematopoietic cells derive from the yolk sac and are thought to be rapidly replaced by the progeny of hematopoietic stem cells. We used three lineage-tracing mouse models to show that, contrary to what was previously assumed, hematopoietic stem cells do not contribute significantly to erythrocyte production up until birth. Lineage tracing of yolk sac erythromyeloid progenitors, which generate tissue resident macrophages, identified highly proliferative erythroid progenitors that rapidly differentiate after intra-embryonic injection, persisting as the major contributors to the embryonic erythroid compartment. We show that erythrocyte progenitors of yolk sac origin require 10-fold lower concentrations of erythropoietin than their hematopoietic stem cell–derived counterparts for efficient erythrocyte production. We propose that, in a low erythropoietin environment in the fetal liver, yolk sac–derived erythrocyte progenitors efficiently outcompete hematopoietic stem cell progeny, which fails to generate megakaryocyte and erythrocyte progenitors.
Published: 2021
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7. Sperm Morphology Assessment in the Era of Intracytoplasmic Sperm Injection: Reliable Results Require Focus on Standardization, Quality Control, and Training

Author: Ahmad Majzoub, Simryn Covarrubias, Mara Simopoulou, Sajal Gupta, Florence Boitrelle, Donald P. Evenson, Jonathan Ramsay, Rupin Shah, Camila Pompeu, Edmund Y. Ko, Pallav Sengupta, Hassan N. Sallam, Sunil Jindal, Marlon Martinez, Mohamed Arafa, Andrea Belo, Raha Sadeghi, Sarah Madani, Sara Darbandi, Rafael F. Ambar, Ashok Agarwal, Gian Maria Busetto, Paraskevi Vogiatzi, Sheena E.M. Lewis, Neel Parekh, Manesh Kumar Panner Selvam, Ralf Henkel, Mahsa Darbandi, Juan G. Alvarez, Neha Singh, Christina Anagnostopoulou, Kambiz Gilany, Damayanthi Durairajanayagam, Jaime Gosálvez, Armand Zini, Hussein Kandil, Marco G. Alves, Israel Maldonado, Renata Finelli, Ramadan A Saleh, Rakesh Sharma, Cleveland Clinic, Tulane University, Imperial College London, University of the Western Cape, Universiti Teknologi MARA [Shah Alam] (UiTM ), Instituto Ideia Fèrtil, University of Sciences and Technology Houari Boumediene [Alger] (USTHB), Huntington Centro de Medicina Reproditiva, NOVA IVF, University of San Francisco (USF), Fetal Health Research Center, Biologie de la Reproduction, Environnement, Epigénétique & Développement (BREED), Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-École nationale vétérinaire d'Alfort (ENVA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), CHI Poissy-Saint-Germain, National and Kapodistrian University of Athens (NKUA), Sohag University, Hamad medical corporation, Weill Cornell Medicine [Qatar], McGill University = Université McGill [Montréal, Canada], Loma Linda University, UNIVERSITY OF SANTO TOMAS MANILA PHL, 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), Hammersmith Hospital NHS Imperial College Healthcare, Alexandria University [Alexandrie], Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto, Queens University Belfast, Queen's University [Belfast] (QUB), and Universidad Autonoma de Madrid (UAM)
Subjects: Aging, Standardization, medicine.medical_treatment, 030232 urology & nephrology, Intracytoplasmic sperm injection, 0302 clinical medicine, KARTAGENERS-SYNDROME, STRICT CRITERIA, HUMAN SPERMATOZOA, Pharmacology (medical), Andrology, FERTILIZATION RATES, media_common, 030219 obstetrics & reproductive medicine, Abnormality, medicine.diagnostic_test, stain, Health Policy, teratozoospermia, Urology & Nephrology, Morphology, stain, 3. Good health, Psychiatry and Mental health, Sperm morphology, Life Sciences & Biomedicine, Morphology, medicine.medical_specialty, Urology, media_common.quotation_subject, Semen analysis, Endocrinology & Metabolism, 03 medical and health sciences, medicine, Quality (business), Intensive care medicine, Science & Technology, business.industry, urogenital system, MALE-INFERTILITY, Public Health, Environmental and Occupational Health, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, DNA FRAGMENTATION, Abnormality, teratozoospermia, SEMEN PARAMETERS, PREDICTIVE-VALUE, Sperm, Health Care Sciences & Services, Reproductive Medicine, Male fertility, ACROSOME REACTION, CIGARETTE-SMOKING, business, Quality assurance
Abstract: International audience; Semen analysis is the first, and frequently, the only step in the evaluation of male fertility. Although the laboratory procedures are conducted according to the World Health Organization (WHO) guidelines, semen analysis and especially sperm morphology assessment is very difficult to standardize and obtain reproducible results. This is mainly due to the highly subjective nature of their evaluation. ICSI is the choice of treatment when sperm morphology is severely abnormal (teratozoospermic). Hence, the standardization of laboratory protocols for sperm morphology evaluation represents a fundamental step to ensure reliable, accurate and consistent laboratory results that avoid misdiagnoses and inadequate treatment of the infertile patient. This article aims to promote standardized laboratory procedures for an accurate evaluation of sperm morphology, including the establishment of quality control and quality assurance policies. Additionally, the clinical importance of sperm morphology results in assisted reproductive outcomes is discussed, along with the clinical management of teratozoospermic patients.
Published: 2021
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8. Dietary glycerol inclusion decreases growth performance and nitrogen retention efficiency in rainbow trout (Oncorhynchus mykiss)

Author: Leonardo J. Magnoni, Stéphane Panserat, Ivan Viegas, Rodrigo O. A. Ozório, Mariana Palma, João Rito, Paulo Rema, Francisca Silva-Brito, Interdisciplinary Centre of Marine and Environmental Research [Matosinhos, Portugal] (CIIMAR), Universidade do Porto, CECAV, University of Trás-os-Montes and Alto Douro, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Centre for Functional Ecology, Department of Life Sciences, University of Coimbra, Center for Neuroscience and Cell Biology (CNC) (CNC), University of Coimbra [Portugal] (UC)-Neuroscience Research Domain, Nutrition, Métabolisme, Aquaculture (NuMéA), Université de Pau et des Pays de l'Adour (UPPA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Fundaçao para a Ciencias e Tecnologia (FCT, Portugal), Compete 2020 (PTDC/CVT-NUT/2851/2014), Centro2020 (ReNATURE Centro-01-0145-FEDER-000007), UID/Multi/04423/2019 (CIIMAR), UID/BIA/04004/2019 (CFE), and FCT (IF/01314/2014/CP1231/CT0001)
Subjects: Energy balance, Aquatic Science, Feed conversion ratio, Excretion, 03 medical and health sciences, chemistry.chemical_compound, Animal science, Glycerol, Protein efficiency, Fish growth, Feces, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, biology, [SDV.BA]Life Sciences [q-bio]/Animal biology, 04 agricultural and veterinary sciences, biology.organism_classification, Nitrogen excretion, Trout, chemistry, Digestibility, Digestive enzyme, 040102 fisheries, biology.protein, 0401 agriculture, forestry, and fisheries, Rainbow trout, Dietary glycerol, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Glycerol is an inexpensive source of dietary energy, although its inclusion in compound feeds has been barely investigated in fish. The effects of dietary refined glycerol inclusion on growth performance, nitrogen and energy balance, as well as its digestibility and intestinal digestive enzyme activities was studied in rainbow trout. Fish (initial BW 20.2 ± 0.1 g, mean ± SE) were divided into nine tanks (1.66 kg m−3), each one assigned to the experimental diets, in triplicates. Fish were fed twice a day to apparent satiation for 60 days three diets including 0, 25, or 50 g kg−1 of refined glycerol (G0, G25, and G50, respectively) with similar digestible protein to energy ratios (22 mg kJ−1). A digestibility trial was conducted in parallel to the growth trial by using a Choubert System to collect feces, in triplicates. Refined glycerol was well digested (ADCglycerol > 99.7%) when included up to 50 g kg−1. Specific growth rate (SGR) decreased as glycerol inclusion levels increased in the diet (P = 0.029). Feed intake was enhanced with increasing dietary inclusion levels of glycerol (P = 0.013). The feed efficiency decreased linearly as the glycerol inclusion levels increased in the diet, reflected in a higher FCR ratio, particularly in the G50 group compared to the G0 or G25 groups (1.04 ± 0.02, 0.90 ± 0.02 and 0.91 ± 0.02, respectively). Total ammonia nitrogen excretion rate (TANER) was measured in trout at the end of the growth trial, displaying increased values with higher dietary glycerol inclusion levels (P
Published: 2021
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9. Subclinical ventricular dysfunction in rheumatoid arthritis

Author: Rita Costa, João Pedro Ferreira, João Loureiro Pinto, Sofia Cabral, Nicolas Girerd, António Marinho, Olivier Huttin, Patrícia Rodrigues, Betânia Ferreira, Erwan Bozec, Francisca Saraiva, Henrique Carvalho, Tomás Fonseca, Unit for Multidisciplinary Research in Biomedicine - UMIB [Porto, Portugal] (Department of Anatomy), Universidade do Porto-Institute of Biomedical Sciences Abel Salazar - ICBAS [Porto, Portugal], Centro Hospitalar Universitário Do Porto (Cardiology Department), Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto, Hospital de Santo António, Centro Hospitalar do Porto, Unit of Multidisciplinary Research in Biomedicine (UMIB), Hospital da Luz Arrabida, V. N. Gaia, Portugal, Centro Hospitalar Universitário Do Porto (Internal Medicine Department), Department of Surgery and Physiology, Cardiovascular Research and Development Center, Faculty of Medicine, University of Porto, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), F. A. Saraiva is supported by Universidade do Porto/FMUP and FSE-Fundo Social Europeu, NORTE 2020-Programa Operacional Regional do Norte, NORTE-08-5369-FSE-000024-Programas Doutorais, and Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
Subjects: Male, Systolic dysfunction, Heart disease, Echocardiogram, Comorbidity, Disease, 030204 cardiovascular system & hematology, Ventricular Function, Left, Arthritis, Rheumatoid, Ventricular Dysfunction, Left, 0302 clinical medicine, Diastole, Risk Factors, Prevalence, Prospective Studies, Prospective cohort study, Subclinical infection, Age Factors, Middle Aged, 3. Good health, Echocardiography, Rheumatoid arthritis, Cardiology, Diastolic dysfunction, Female, Cardiology and Cardiovascular Medicine, Adult, medicine.medical_specialty, Systole, Concordance, Risk Assessment, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Predictive Value of Tests, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Aged, 030203 arthritis & rheumatology, Portugal, business.industry, Stroke Volume, medicine.disease, Heart failure, Asymptomatic Diseases, business, Biomarkers
Abstract: International audience; Patients with rheumatoid arthritis (RA) are at higher risk for having underdiagnosed heart failure, however there are no recommendations regarding echocardiographic screening. We aimed to determine the prevalence of subclinical ventricular dysfunction in RA applying current echocardiographic guidelines, its association with patients' characteristics, biomarkers and prognostic parameters and compare the 2016 guidelines to the recommendations from 2009. Prospective study of RA patients without known heart disease, categorized as preserved ventricular function (PVF), systolic dysfunction (SD), isolated diastolic dysfunction (DD) or indeterminate diastolic function (IDF) as per the 2016 echocardiography guidelines-or any ventricular dysfunction (AVD) comprehending the last 3. The median age was 58 years and 78% were females. The majority had PVF (73%), followed by DD (13%), IDF (11%) and SD (4%). Concordance with the 2009 echocardiographic guidelines was low. Compared with PVF, AVD patients were older (65 vs 55 years, p 57 years) was the only independent predictor of AVD or DD. AVD was significantly associated with higher NT-proBNP and lower distance in 6-min walk test. There were no significant independent associations between characteristics of RA disease and ventricular function. A total of 17% of RA patients without known cardiovascular disease presented subclinical systolic or diastolic dysfunction, which was associated with older age. The echocardiographic screening may have clinical value in identifying subclinical ventricular dysfunction, especially in older RA patients.
Published: 2020
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10. Orally administrated chitosan microspheres bind Helicobacter pylori and decrease gastric infection in mice

Author: Henriques, Patrícia, Costa, Lia, Seabra, Catarina, Antunes, Bernardo, Silva-Carvalho, Ricardo, Junqueira-Neto, Susana, Maia, André, Oliveira, Pedro, Magalhães, Ana, Reis, Celso, Gärtner, Fátima, Touati, Eliette, Gomes, Joana, Costa, Paulo, Martins, M Cristina L, Gonçalves, Inês, Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Instituto de Engenharia Biomédica [Porto, Portugal] (INEB), Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Instituto de Biologia Molecular e Celular - institute for molecular and cell biology [Porto, Portugal] (IBMC), Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Faculdade de Medicina da Universidade do Porto (FMUP), Pathogenèse de Helicobacter / Helicobacter Pathogenesis, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Pharmaceutical Technology Laboratory [Porto], Faculdade de Farmácia da Universidade do Porto (FFUP), Universidade do Porto-Universidade do Porto, This work was financed by PTDC/CTM-BIO/4043/2014 and by Portuguese funds from FCT UID/BIM/04293/2019, UID/Multi/04378/2019, EXPL/CTM-BIO/0762/2013 and by L'OrealPortugal/FCT/UNESCO. Authors wish to thank FCT for Inês C. Gonçalves research position (IF/01479/2015), Patricia C. Henriques PhD grant (SFRH/BD/120154/2016) and Catarina L. Seabra PhD grant (SFRH/BD/89001/2012)., The authors acknowledge the support of i3S Scientific Platforms, namely the Bioimaging Center for Biomaterials and Regenerative Therapies (b.IMAGE), and the BioSciences Screening for the imaging data acquisition using equipment maintained by the platforms, both members of the PPBI (PPBI-POCI-01-0145-feder-022122), and CCGEN and Paula Magalhães, for the help during the PCR analysis., Universidade do Porto = University of Porto, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Universidade do Porto = University of Porto-Universidade do Porto = University of Porto
Subjects: Biomaterials, Bacteria adhesion, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, In vivo, Mucoadhesion, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Microparticles, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials
Abstract: International audience; Persistent Helicobacter pylori (H. pylori) infection is related to 90% of gastric cancers. With bacterial resistance rising and treatment inefficiency affecting 15% of the patients, alternative treatments urge. Chitosan microspheres (ChMics) have been proposed as an H. pylori-binding system. This work evaluates ChMics biocompatibility, mucopenetration and capacity to treat H. pylori infection in mice after oral administration. ChMics of different size (XL, ∼120 µm and XS, ∼40 µm) and degree of acetylation (6% and 16%) were developed and revealed to be able to adhere both human and mouse-adapted H. pylori strains without cytotoxicity towards human gastric cells. Ex vivo studies showed that smaller (XS) microspheres penetrate further within the gastric foveolae, suggesting their ability to reach deeply adherent bacteria. In vivo assays showed 88% reduction of infection when H. pylori-infected mice (C57BL/6) were treated with more mucoadhesive XL6 and XS6 ChMics. Overall, ChMics clearly demonstrate ability to reduce H. pylori gastric infection in mice, with chitosan degree of acetylation being a dominant factor over microspheres' size on H. pylori removal efficiency. These results evidence the strong potential of this strategy as an antibiotic-free approach to fight H. pylori infection, where microspheres are orally administered, bind H. pylori in the stomach, and remove them through the gastrointestinal tract. STATEMENT OF SIGNIFICANCE: Approximately 90% of gastric cancers are caused by the carcinogenic agent Helicobacter pylori, which infects >50% of the world population. Bacterial resistance, reduced antibiotic bioavailability, and the intricate distribution of bacteria in mucus and within gastric foveolae hamper the success of most strategies to fight H. pylori. We demonstrate that an antibiotic-free therapy based on bare chitosan microspheres that bind and remove H. pylori from stomach can achieve 88% reduction of infection from H. pylori-infected mice. Changing size and mucoadhesive properties, microspheres can reach different areas of gastric mucosa: smaller and less mucoadhesive can penetrate deeper into the foveolae. This promising, simple and inexpensive strategy paves the way for a faster bench-to-bedside transition, therefore holding great potential for clinical application.
Published: 2020
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11. Characterization of Endogenous SERINC5 Protein as Anti-HIV-1 Factor

Author: Jens Bohne, Daniel Todt, Steppich K, Sergej Franz, Angelina Malassa, Thomas Zillinger, Eike Steinmann, Xu S, Nicoletta Casartelli, Passos, Christine Goffinet, Winfried Barchet, Wachs As, Oliver Schwartz, Schilling H, Kathrin Sutter, Ulf Dittmer, Centre for Experimental and Clinical Infection Research [Hanover] (TWINCORE), Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto, Institute of Clinical Chemistry and Clinical Pharmacology [Bonn, Allemagne], University of Bonn, Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Hannover Medical School [Hannover] (MHH), Ruhr University Bochum (RUB), University of Duisburg-Essen, German Centre for Infection Research (DZIF), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health (BIH), Vânia Passos and Sergej Franz are supported by the Infection Biology International Ph.D. Program of the Hannover Biomedical Research School. Vânia Passos is supported by the GABBA Ph.D. Program and the Fundação para a Ciência e Tecnologia (FCT). Thomas Zillinger and Winfried Barchet acknowledge Bonfor and DZIF funding and German Research Foundation (Deutsche Forschungsgemeinschaft [DFG]) grants EXC1023: ImmunoSensation and CRCs 670 and 704. This work is supported by DFG funding to Christine Goffinet (Collaborative Research Centre SFB900, Microbial Persistence and its Control, project C8 and Priority Program 1923, Innate Sensing and Restriction of Retroviruses, GO2153/4 grant) and funding from the HZI and the Berlin Institute of Health (BIH) to Christine Goffinet., Universidade do Porto = University of Porto, Universität Bonn = University of Bonn, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Universität Duisburg-Essen = University of Duisburg-Essen [Essen], and TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.
Subjects: MESH: Gene Editing, MESH: CRISPR-Cas Systems, T-Lymphocytes, Mutant, Medizin, HIV Infections, Endogeny, Jurkat cells, Epitope, MESH: HIV-1, MESH: Genotype, Gene Knockout Techniques, SERINC5, MESH: nef Gene Products, Human Immunodeficiency Virus, MESH: Anti-HIV Agents, Internalization, media_common, MESH: Gene Knockout Techniques, Gene Editing, 0303 health sciences, human immunodeficiency virus, 030302 biochemistry & molecular biology, virus diseases, MESH: HIV Infections, MESH: Gene Expression Regulation, Virus-Cell Interactions, 3. Good health, Cell biology, interferons, MESH: HEK293 Cells, Host-Pathogen Interactions, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Virion, MESH: Membrane Proteins, MESH: Interferon-alpha, Genotype, Anti-HIV Agents, media_common.quotation_subject, Immunology, Alpha interferon, Heterologous, Biology, Microbiology, Cell Line, 03 medical and health sciences, Virology, Nitriles, Humans, nef Gene Products, Human Immunodeficiency Virus, antiviral factor, CRISPR/Cas9, 030304 developmental biology, Nef, MESH: Humans, Cell Membrane, MESH: Host-Pathogen Interactions, Virion, Interferon-alpha, Membrane Proteins, Subcellular localization, MESH: Cell Line, HEK293 Cells, Pyrimidines, MESH: T-Lymphocytes, Gene Expression Regulation, Insect Science, HIV-1, Pyrazoles, CRISPR-Cas Systems, MESH: Pyrazoles, MESH: Cell Membrane
Abstract: SERINC5 is the long-searched-for antiviral factor that is counteracted by the HIV-1 accessory gene product Nef. Here, we engineered, via CRISPR/Cas9 technology, T-cell lines that express endogenous SERINC5 alleles tagged with a knocked-in HA epitope. This genetic modification enabled us to study basic properties of endogenous SERINC5 and to verify proposed mechanisms of HIV-1 Nef-mediated counteraction of SERINC5. Using this unique resource, we identified the susceptibility of endogenous SERINC5 protein to posttranslational modulation by type I IFNs and suggest uncoupling of Nef-mediated functional antagonism from SERINC5 exclusion from virions., When expressed in virus-producing cells, the cellular multipass transmembrane protein SERINC5 reduces the infectivity of HIV-1 particles and is counteracted by HIV-1 Nef. Due to the unavailability of an antibody of sufficient specificity and sensitivity, investigation of SERINC5 protein expression and subcellular localization has been limited to heterologously expressed SERINC5. We generated, via CRISPR/Cas9-assisted gene editing, Jurkat T-cell clones expressing endogenous SERINC5 bearing an extracellularly exposed hemagglutinin (HA) epitope [Jurkat SERINC5(iHA knock-in) T cells]. This modification enabled quantification of endogenous SERINC5 protein levels and demonstrated a predominant localization in lipid rafts. Interferon alpha (IFN-α) treatment enhanced cell surface levels of SERINC5 in a ruxolitinib-sensitive manner in the absence of modulation of mRNA and protein quantities. Parental and SERINC5(iHA knock-in) T cells shared the ability to produce infectious wild-type HIV-1 but not an HIV-1 Δnef mutant. SERINC5-imposed reduction of infectivity involved a modest reduction of virus fusogenicity. An association of endogenous SERINC5 protein with HIV-1 Δnef virions was consistently detectable as a 35-kDa species, as opposed to heterologous SERINC5, which presented as a 51-kDa species. Nef-mediated functional counteraction did not correlate with virion exclusion of SERINC5, arguing for the existence of additional counteractive mechanisms of Nef that act on virus-associated SERINC5. In HIV-1-infected cells, Nef triggered the internalization of SERINC5 in the absence of detectable changes of steady-state protein levels. These findings establish new properties of endogenous SERINC5 expression and subcellular localization, challenge existing concepts of HIV-1 Nef-mediated antagonism of SERINC5, and uncover an unprecedented role of IFN-α in modulating SERINC5 through accumulation at the cell surface. IMPORTANCE SERINC5 is the long-searched-for antiviral factor that is counteracted by the HIV-1 accessory gene product Nef. Here, we engineered, via CRISPR/Cas9 technology, T-cell lines that express endogenous SERINC5 alleles tagged with a knocked-in HA epitope. This genetic modification enabled us to study basic properties of endogenous SERINC5 and to verify proposed mechanisms of HIV-1 Nef-mediated counteraction of SERINC5. Using this unique resource, we identified the susceptibility of endogenous SERINC5 protein to posttranslational modulation by type I IFNs and suggest uncoupling of Nef-mediated functional antagonism from SERINC5 exclusion from virions.
Published: 2019
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12. Population genetics-informed meta-analysis in seven genes associated with risk to dengue fever disease

Author: Anavaj Sakuntabhai, Luísa Pereira, Verónica Fernandes, María G. Guzmán, Beatriz Sierra, Isabelle Casademont, Nourdin Harich, Bruno Cavadas, Marisa Oliveira, Lotfi Cherni, Nicole Pedro, Farida Alshamali, Fanny Koeth, Diana P. Saraiva, Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Dubai Police General Headquarters, Université Chouaib Doukkali (UCD), Université de Tunis El Manar (UTM), Université de Monastir - University of Monastir (UM), Pedro Kouri Institute of Tropical Medicine, Génomique évolutive, modélisation et santé (CNRS-UMR2000), Faculdade de Medicina da Universidade do Porto (FMUP), The research leading to these results has received funding from the European Commission Seventh Framework Programme [FP7/2007-2013] for the DENFREE project under Grant Agreement no. 282378. MO has a PhD grant from FCT (The Portuguese Foundation for Science and Technology - SFRH/BD/95626/2013). IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT, FEDER and COMPETE (PEst-C/SAU/LA0003/2013)., European Project: 282378,EC:FP7:HEALTH,FP7-HEALTH-2011-single-stage,DENFREE(2012), Universidade do Porto = University of Porto, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Génomique évolutive, modélisation et santé (GEMS)
Subjects: Genetic Markers, 0301 basic medicine, Microbiology (medical), Candidate gene, Genotype, Population, Population genetics, Disease, Biology, Polymorphism, Single Nucleotide, Microbiology, Worldwide diversity, Dengue fever, Dengue, 03 medical and health sciences, Genetic drift, Dengue disease, Genetics, medicine, Humans, Genetic Predisposition to Disease, education, Global risk, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Genetic association, education.field_of_study, Odds ratio, East Asian and Latin American cohorts, medicine.disease, 3. Good health, Meta-analysis, 030104 developmental biology, Infectious Diseases, Gene Expression Regulation, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Demography
Abstract: International audience; Population genetics theory predicted that rare frequent markers would be the main contributors for heritability of complex diseases, but meta-analyses of genome-wide association studies are revealing otherwise common markers, present in all population groups, as the identified candidate genes. In this work, we applied a population-genetics informed meta-analysis to 10 markers located in seven genes said to be associated with dengue fever disease. Seven markers (in PLCE1, CD32, CD209, OAS1 and OAS3 genes) have high-frequency and the other three (in MICB and TNFA genes) have intermediate frequency. Most of these markers have high discriminatory power between population groups, but their frequencies follow the rules of genetic drift, and seem to have not been under strong selective pressure. There was a good agreement in directional consistency across trans-ethnic association signals, in East Asian and Latin American cohorts, with heterogeneity generated by randomness between studies and especially by low sample sizes. This led to confirm the following significant associations: with DF, odds ratio of 0.67 for TNFA-rs1800629-A; with DHF, 0.82 for CD32-rs1801274-G; with DSS, 0.55 for OAS3-rs2285933-G, 0.80 for PLCE1-rs2274223-G and 1.32 for MICB-rs3132468-C. The overall genetic risks confirmed sub-Saharan African populations and descendants as the best protected against the severer forms of the disease, while Southeast and Northeast Asians are the least protected ones. European and close neighbours are the best protected against dengue fever, while, again, Southeast and Northeast Asians are the least protected ones. These risk scores provide important predictive information for the largely na\"ive European and North American regions, as well as for Africa where misdiagnosis with other hemorrhagic diseases is of concern.
Published: 2018
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13. Hypoxia, but Not an Electrolyte-Imbalanced Diet, Reduces Feed Intake, Growth and Oxygen Consumption in Rainbow Trout ( Oncorhynchus Mykiss )

Author: Johan W. Schrama, Inge Geurden, Leonardo J. Magnoni, Patrick Prunet, Rodrigo O. A. Ozório, Isabelle Leguen, Ep H. Eding, Laboratoire de Physiologie et Génomique des Poissons (LPGP), Institut National de la Recherche Agronomique (INRA)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Nutrition, Métabolisme, Aquaculture (NuMéA), Institut National de la Recherche Agronomique (INRA)-Université de Pau et des Pays de l'Adour (UPPA), Aquaculture and Fisheries Group, Wageningen Institute of Animal Science, The aquatic metabolic unit used in this study was cofounded by The Netherlands Organization for Scientific Research (code 805-34.025). The present study was funded by the EU-FP7 project AQUAEXCEL (262336). L.J. Magnoni is currently supported by a FCT research position with exploratory grant IF/01314/2014/CP1231/CT0001 from Portugal., European Project: 262336,EC:FP7:INFRA,FP7-INFRASTRUCTURES-2010-1,AQUAEXCEL(2011), Interdisciplinary Centre of Marine and Environmental Research [Matosinhos, Portugal] (CIIMAR), Universidade do Porto = University of Porto, Instituto de Investigaciones Biotecnológicas [San Martín] (IIB-INTECH), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Universidad Nacional de San Martin (UNSAM), Wageningen University and Research [Wageningen] (WUR), and Instituto de Ciências Biomédicas de Abel Salazar (ICBAS)
Subjects: 030110 physiology, 0301 basic medicine, Water-Electrolyte Imbalance, Energy balance, lcsh:Medicine, oxygène dissous, Aquaculture, 7. Clean energy, Eating, Nutrient, Aquaculture and Fisheries, Hypoxia, lcsh:Science, Animal biology, Multidisciplinary, biology, Aquacultuur en Visserij, Chemistry, [SDV.BA]Life Sciences [q-bio]/Animal biology, Hypoxia (environmental), Thermogenesis, Water-Electrolyte Balance, prise alimentaire, Trout, Oncorhynchus mykiss, Body Composition, consommation d'oxygène, Animal feed, Article, 03 medical and health sciences, Oxygen Consumption, Animal science, Biologie animale, Animals, Life Science, Dry matter, 14. Life underwater, business.industry, Body Weight, lcsh:R, Nutritional Requirements, hypoxie, biology.organism_classification, croissance, Animal Feed, électrolyte, 030104 developmental biology, WIAS, lcsh:Q, Rainbow trout, Energy Metabolism, business
Abstract: Oxygen limitation and dietary imbalances are key aspects influencing feed intake (FI) and growth performance in cultured fish. This study investigated the combined effects of hypoxia and dietary electrolyte balance on the growth performance, body composition and nutrient utilization in a rainbow trout (Oncorhynchus mykiss) isogenic line. Fish were fed ad libitum two experimental diets: electrolyte-balanced or -imbalanced diets (DEB 200 or 700 mEq kg−1, respectively) and exposed to normoxia or hypoxia (7.9 or 4.5 mg O2 l−1, respectively) for 42 days. DEB did not affect FI, growth performance or body composition. Nevertheless, hypoxia had a negative impact, reducing FI (6%), growth rate (8%), oxygen consumption (19%), energy (5%) and lipid (42%) contents. Digestible energy intake and heat production were higher in normoxic fish (40% and 23%, respectively), retaining 64% more energy in lipid or protein. Hypoxia reduced the apparent digestibility of dry matter, ash, protein, lipid, carbohydrates and energy. Trout fed DEB 700 diet were energetically less efficient, reflected in higher heat production and energy requirements for maintenance. FI was inhibited by low dissolved oxygen levels, but not by electrolyte-imbalanced diet, in spite of the higher energy requirements for maintenance. This study highlights the importance that dietary-electrolyte content and DO levels have on energy balance and growth performance when fish are fed to satiation.
Published: 2018
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14. Impact of dietary electrolyte balance (DEB) and dissolved O2 (DO) level on feed intake, growth and O2 consumption In rainbow trout Oncorhynchus mykiss

Author: Magnoni, Leonardo J., Eding, E., Leguen, Isabelle, Prunet, Patrick, Geurden, Inge, Ozório, Rodrigo, Schrama, J.W., CIIMAR (Centro Interdisciplinar de Investigação Marinha e Ambiental), IIB-INTECH, Wageningen University and Research Centre (WUR), Laboratoire de Physiologie et Génomique des Poissons (LPGP), Institut National de la Recherche Agronomique (INRA)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Nutrition, Métabolisme, Aquaculture (NuMéA), Institut National de la Recherche Agronomique (INRA)-Université de Pau et des Pays de l'Adour (UPPA), Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto, European Project: 262336,EC:FP7:INFRA,FP7-INFRASTRUCTURES-2010-1,AQUAEXCEL(2011), and Universidade do Porto = University of Porto
Subjects: [SDV.BA]Life Sciences [q-bio]/Animal biology, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2017

15. Three-dimensional scaffolds of fetal decellularized hearts exhibit enhanced potential to support cardiac cells in comparison to the adult

Author: Mário A. Barbosa, Ana Catarina Silva, Diana S. Nascimento, Maria José Oliveira, Sólveig Thorsteinsdóttir, Tatiana P. Resende, Andreia Nunes, Joana Caldeira, Vasco Sampaio-Pinto, Perpétua Pinto-do-Ó, S.C. Rodrigues, Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto = University of Porto, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Instituto de Engenharia Biomédica (INEB), Centre for Ecology, Evolution and Environmental Change [Lisboa], Universidade de Lisboa = University of Lisbon (ULISBOA), Lymphopoïèse (Lymphopoïèse (UMR_1223 / U1223 / U-Pasteur_4)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was financed by PTDC/SAUORG/118297/2010, FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Inovação in the framework of the project 'Institute for Research and Innovation in Health Sciences'- POCI-01-0145-FEDER-007274 and individual fellowships (SFRH/BD/88780/2012 to A.C.S., BI-PTDC/SAU-ORG/118297/2010 to A.M.N., SFRH/BPD/78187/2011 to J.C., SFRH/BPD/80588/2011 to T.P.R and SFRH/BD/111799/2015 to V.S.P.). PPO was recipient of an invited scientist grant by Institut Pasteur, Paris, France. MJO is Portuguese Science Foundation Fellow (FCT-Investigator 2012)., European Project: 118297,FCT::,PTDC/2010,PTDC/SAU-ORG/118297/2010(2012), European Project: SFRH/BD/88780/2012,FCT::Doutoramento,SFRH/2012,SFRH/BD/88780/2012(2013), European Project: SFRH/BPD/78187/2011,FCT::Pós-Doutoramento,SFRH/2011,SFRH/BPD/78187/2011(2012), European Project: SFRH/BPD/80588/2011,FCT::Pós-Doutoramento,SFRH/2011,SFRH/BPD/80588/2011(2012), Universidade do Porto [Porto], centre for ecology, evolution and environmental change, Universidade de Lisboa, Centro de Biologia Ambiental/Departamento de Biologia Animal, University of Porto, Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidade do Porto, and Universidade de Lisboa (ULISBOA)
Subjects: 0301 basic medicine, Scaffold, Aging, Cell Survival, 3D scaffolds, [SDV]Life Sciences [q-bio], Biophysics, Bioengineering, Fetal microenvironments, 030204 cardiovascular system & hematology, Cardiac tissue engineering, Biomaterials, Extracellular matrix, 03 medical and health sciences, Mice, 0302 clinical medicine, Fetal Heart, Tissue engineering, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Cell Movement, Animals, Myocytes, Cardiac, Progenitor cell, Cells, Cultured, Decellularization, Three dimensional scaffolds, Fetus, Cell-Free System, Tissue Engineering, Tissue Scaffolds, Chemistry, Cell biology, Mice, Inbred C57BL, 030104 developmental biology, Mechanics of Materials, Printing, Three-Dimensional, Ceramics and Composites, Feasibility Studies, [SDV.IMM]Life Sciences [q-bio]/Immunology, Biomedical engineering, Explant culture
Abstract: International audience; A main challenge in cardiac tissue engineering is the limited data on microenvironmental cues that sustain survival, proliferation and functional proficiency of cardiac cells. The aim of our study was to evaluate the potential of fetal (E18) and adult myocardial extracellular matrix (ECM) to support cardiac cells. Acellular three-dimensional (3D) bioscaffolds were obtained by parallel decellularization of fetal- and adult-heart explants thereby ensuring reliable comparison. Acellular scaffolds retained main constituents of the cardiac ECM including distinctive biochemical and structural meshwork features of the native equivalents. In vitro, fetal and adult ECM-matrices supported 3D culture of heart-derived Sca-1(+) progenitors and of neonatal cardiomyocytes, which migrated toward the center of the scaffold and displayed elongated morphology and excellent viability. At the culture end-point, more Sca-1(+) cells and cardiomyocytes were found adhered and inside fetal bioscaffolds, compared to the adult. Higher repopulation yields of Sca-1(+) cells on fetal ECM relied on β1-integrin independent mitogenic signals. Sca-1(+) cells on fetal bioscaffolds showed a gene expression profile that anticipates the synthesis of a permissive microenvironment for cardiomyogenesis. Our findings demonstrate the superior potential of the 3D fetal microenvironment to support and instruct cardiac cells. This knowledge should be integrated in the design of next-generation biomimetic materials for heart repair.
Published: 2016
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16. Spectral Cytometry Has Unique Properties Allowing Multicolor Analysis of Cell Suspensions Isolated from Solid Tissues

Author: Sophie Novault, Sandrine Schmutz, Ana Cumano, Mariana Valente, Cytométrie (Plate-forme), Institut Pasteur [Paris], Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto, Lymphopoïèse (Lymphopoïèse (UMR_1223 / U1223 / U-Pasteur_4)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cellule Pasteur, Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Instituto de Investigação e Inovação em Saúde (I3S), This work was supported by the Pasteur Institute, Institut National de la Santé et de la Recherche Médicale (INSERM), Swiss National Science Foundation (SS), Pasteur Bourse Roux (SS), Fundação para a Ciência e a Tecnologia - SFRH/BD/74218/2010 (MV), Université Paris Diderot (AC), and the Agence Nationale de la Recherche (ANR) project Twothyme and the ANR Program REVIVE (Investment for the Future) (AC)., ANR-14-CE11-0022,Twothyme,Deux progéniteurs hématopoïétiques différents établissent le compartiment de lymphocytes T: tester un nouveau paradigme du développement T.(2014), ANR-10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010), Institut Pasteur [Paris] (IP), Universidade do Porto = University of Porto, Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vougny, Marie-Christine, Appel à projets générique - Deux progéniteurs hématopoïétiques différents établissent le compartiment de lymphocytes T: tester un nouveau paradigme du développement T. - - Twothyme2014 - ANR-14-CE11-0022 - Appel à projets générique - VALID, and Laboratoires d'excellence - Stem Cells in Regenerative Biology and Medicine - - REVIVE2010 - ANR-10-LABX-0073 - LABX - VALID
Subjects: Male, 0301 basic medicine, Luminescence, Cell, lcsh:Medicine, Bioinformatics, Epithelium, Emission Spectra, Mice, White Blood Cells, 0302 clinical medicine, Animal Cells, Intestine, Small, Medicine and Health Sciences, Independent parameter, Lymphocytes, Emission spectrum, lcsh:Science, Cells, Cultured, Staining, Multidisciplinary, medicine.diagnostic_test, Physics, Electromagnetic Radiation, Cell Staining, Heart, Flow Cytometry, Fluorescence, Microspheres, medicine.anatomical_structure, Optical Equipment, 030220 oncology & carcinogenesis, Physical Sciences, Engineering and Technology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Cellular Types, Anatomy, Biological system, Surface protein, Research Article, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immune Cells, Immunology, Materials Science, Material Properties, Spectral flow, Equipment, Biology, Research and Analysis Methods, Flow cytometry, 03 medical and health sciences, medicine, Animals, Fluorescent Dyes, Blood Cells, Lasers, lcsh:R, Biology and Life Sciences, Epithelial Cells, Cell Biology, Mice, Inbred C57BL, Gastrointestinal Tract, Biological Tissue, 030104 developmental biology, Specimen Preparation and Treatment, lcsh:Q, Digestive System, Cytometry
Abstract: International audience; Flow cytometry, initially developed to analyze surface protein expression in hematopoietic cells, has increased in analytical complexity and is now widely used to identify cells from different tissues and organisms. As a consequence, data analysis became increasingly difficult due the need of large multi-parametric compensation matrices and to the eventual auto-fluorescence frequently found in cell suspensions obtained from solid organs. In contrast with conventional flow cytometry that detects the emission peak of fluorochromes, spectral flow cytometry distinguishes the shapes of emission spectra along a large range of continuous wave lengths. The data is analyzed with an algorithm that replaces compensation matrices and treats auto-fluorescence as an independent parameter. Thus, spectral flow cytometry should be capable to discriminate fluorochromes with similar emission peaks and provide multi-parametric analysis without compensation requirements. Here we show that spectral flow cytometry achieves a 21-parametric (19 fluorescent probes) characterization and deals with auto-fluorescent cells, providing high resolution of specifically fluorescence-labeled populations. Our results showed that spectral flow cytometry has advantages in the analysis of cell populations of tissues difficult to characterize in conventional flow cytometry, such as heart and intestine. Spectral flow cytometry thus combines the multi-parametric analytical capacity of the highest performing conventional flow cytometry without the requirement for compensation and enabling auto-fluorescence management.
Published: 2016
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17. The Impact of Nutritional and Environmental Stressors on the Immune Response, Oxidative Stress and Energy Use of Rainbow Trout (Oncorhynchus Mykiss)

Author: Ep H. Eding, Sara C. Novais, Rodrigues Ozório, Isabelle Leguen, Patrick Prunet, Leonardo J. Magnoni, Marco F.L. Lemos, Carla O. Silva, Inge Geurden, Johan W. Schrama, Nutrition, Métabolisme, Aquaculture (NuMéA), Institut National de la Recherche Agronomique (INRA)-Université de Pau et des Pays de l'Adour (UPPA), Laboratoire de Physiologie et Génomique des Poissons (LPGP), Institut National de la Recherche Agronomique (INRA)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), NOVELTIS [Sté], CIIMAR (Centro Interdisciplinar de Investigação Marinha e Ambiental), IIB-INTECH, MARE-IPLeiria, Partenaires INRAE, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto, Wageningen University and Research Centre (WUR), Marine and Environmental Sciences Centre (MARE). PRT., European Project: 262336,EC:FP7:INFRA,FP7-INFRASTRUCTURES-2010-1,AQUAEXCEL(2011), and Universidade do Porto = University of Porto
Subjects: 0106 biological sciences, Global and Planetary Change, 010504 meteorology & atmospheric sciences, 010604 marine biology & hydrobiology, [SDV]Life Sciences [q-bio], [SDV.BA]Life Sciences [q-bio]/Animal biology, Stressor, Zoology, Ocean Engineering, Aquatic Science, Biology, Oceanography, medicine.disease_cause, 01 natural sciences, Fishery, No keyword, Immune system, medicine, Rainbow trout, [INFO]Computer Science [cs], Oxidative stress, ComputingMilieux_MISCELLANEOUS, 0105 earth and related environmental sciences, Water Science and Technology
Abstract: International audience
Published: 2016
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18. A Safe and Stable Neonatal Vaccine Targeting GAPDH Confers Protection against Group B Streptococcus Infections in Adult Susceptible Mice

Author: Maria Teresa Baltazar, Paula Ferreira, Luis M.M. Vieira, Félix Carvalho, Ricardo Jorge Dinis-Oliveira, Pedro Madureira, Adília Ribeiro, Joana Alves, Patrick Trieu-Cuot, José Alberto Duarte, Leandro Barros, Liliana Oliveira, Elva Bonifácio Andrade, Instituto de Biologia Molecular e Celular (IBMC), Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto = University of Porto, Instituto de Investigação e Inovação em Saúde (I3S), Serviço de Toxicologia da Faculdade (REQUIMTE), Farmácia da Universidade do Porto, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie des Bactéries pathogènes à Gram-positif, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Universidade do Porto, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Faculdade de Desporto, Faculdade de Farmácia, Faculdade de Medicina, Lassailly-Bondaz, Anne, Universidade do Porto [Porto], Institut Cochin (UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris] - Centre National de la Recherche Scientifique (CNRS)
Subjects: Serotype, lcsh:Medicine, medicine.disease_cause, Group B, Streptococcus agalactiae, Mice, Streptococcal Infections, medicine, Animals, lcsh:Science, Pathogen, Multidisciplinary, biology, Streptococcus, lcsh:R, Streptococcal Vaccines, Glyceraldehyde-3-Phosphate Dehydrogenases, Antibodies, Bacterial, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Disease Models, Animal, Animals, Newborn, Immunization, Immunology, Toxicity, biology.protein, Cytokines, lcsh:Q, Female, Inflammation Mediators, Antibody, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Biomarkers, Research Article
Abstract: International audience; Group B Streptococcus (GBS), a commensal organism, can turn into a life-threatening pathogen in neonates and elderly, or in adults with severe underlying diseases such as diabetes. We developed a vaccine targeting the GBS glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a glycolytic enzyme detected at the bacterial surface, which was proven to be effective in a neonatal mouse model of infection. Since this bacterium has emerged as an important pathogen in non-pregnant adults, here we investigated whether this vaccine also confers protection in an adult susceptible and in a diabetic mouse model of infection. For immunoprotection studies, sham or immunized adult mice were infected with GBS serotype Ia and V strains, the two most prevalent serotypes isolated in adults. Sham and vaccinated mice were also rendered diabetic and infected with a serotype V GBS strain. For toxicological (pre-clinical) studies, adult mice were vaccinated three times, with three concentrations of recombinant GAPDH adjuvanted with Allydrogel, and the toxicity parameters were evaluated twenty-four hours after the last immunization. For the stability tests, the vaccine formulations were maintained at 4°C for 6 and 12 months prior immunization. The results showed that all tested doses of the vaccine, including the stability study formulations, were immunogenic and that the vaccine was innocuous. The organs (brain, blood, heart, and liver) of vaccinated susceptible or diabetic adult mice were significantly less colonized compared to those of control mice. Altogether, these results demonstrate that the GAPDH-based vaccine is safe and stable and protects susceptible and diabetic adult mice against GBS infections. It is therefore a promising candidate as a global vaccine to prevent GBS-induced neonatal and adult diseases.
Published: 2015
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19. Interleukin-1 signaling pathway as a therapeutic target in transthyretin amyloidosis

Author: Nádia Gonçalves, Paulo Vieira, Maria João Saraiva, Department of Molecular Neurobiology, Institute for Molecular and Cell Biology, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto = University of Porto, Développement des Lymphocytes, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by FEDER funds through the Operational Competitiveness Program - COMPETE, a grant from Cordex and by national funding from Portuguese Foundation for Science and Technology (FCT) under the project PTDC/BIM-MEC/0282/2012, and fellowship to NPG (SFRH/BD/74304/2010)., Universidade do Porto, and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Interleukin-1beta, Gene Expression, Apoptosis, neuroinflammation, Mice, 0302 clinical medicine, Ganglia, Spinal, Prealbumin, Transgenes, HSF1, Glyceraldehyde 3-phosphate dehydrogenase, 0303 health sciences, biology, neurodegeneration, Sciatic Nerve, 3. Good health, Anakinra, [SDV.IMM]Life Sciences [q-bio]/Immunology, Original Article, Binding immunoglobulin protein, Signal transduction, Signal Transduction, medicine.drug, Injections, Subcutaneous, Mice, Transgenic, Protein Aggregation, Pathological, Proinflammatory cytokine, familial amyloidotic polyneuropathy, Protein Aggregates, 03 medical and health sciences, peripheral nervous system, Internal Medicine, medicine, Animals, 030304 developmental biology, Amyloid Neuropathies, Familial, Nerve Fibers, Unmyelinated, familial amyloidotic, cytokines, Disease Models, Animal, Interleukin 1 Receptor Antagonist Protein, Oxidative Stress, Transthyretin, Immunology, biology.protein, Cancer research, Unfolded protein response, polyneuropathy, 030217 neurology & neurosurgery
Abstract: Introduction: Inflammation is a key pathological hallmark of several neurodegenerative disorders including Alzheimer’s disease, Parkinson’s disease and familial amyloidotic polyneuropathy (FAP). Among all inflammatory cytokines associated with FAP, IL-1b, in particular, has been implicated in playing a key pathogenic role. In the present study, we sought to investigate whether blocking IL-1b signaling provides disease-modifying benefits in an FAP mouse model. Methods: We assessed the effect of chronic administration of Anakinra, an IL-1 antagonist, on FAP pathogenesis in vivo, using real-time polymerase chain reaction (qPCR), semi-quantitative immunohistochemistry (SQ-IHC), western blot and nerve morphometric analyses. Results: We found that treatment with Anakinra prevents transthyretin (TTR) extracellular deposition in sciatic nerve, protecting unmyelinated nerve fibers from aggregate-induced degeneration. Moreover, Anakinra administration significantly suppressed IL-1 signaling pathway and inhibited apoptosis and nitrative stress. Conclusions: The present work highlights the relevance of the IL-1 signaling pathway in the pathophysiology of FAP. Our results bring to light the importance of non-amyloid targets in the therapeutic strategies for this disorder. Thus, we propose the use of Anakinra as a potential therapeutic agent for TTR-related amyloidosis. Abbreviations: BiP: binding immunoglobulin protein; DRG: dorsal root ganglia; ER: endoplasmic reticulum; FAP: familial amyloidotic polyneuropathy; Gapdh: glyceraldehyde 3-phosphate dehydrogenase; Hsf-1: heat shock factor 1; IL-1: interleukin-1; Hsp-27: heat shock protein-27; IL-1Ra: interleukin-1 receptor antagonist; Irak1: interleukin-1 receptor associated kinase-1; Myd88: myeloid differentiation primary response gene 88; NF-kB: nuclear factor kB; PBS: phosphate buffer saline; qPCR: real-time polymerase chain reaction; RAGE: receptor for advanced glycation end products; SEM: standard error of the mean; siRNA: small interfering RNA; mRNA: messenger RNA; SQ-IHC: semi-quantitative immunohistochemistry; TNF-a: tumor necrosis factor a; TTR: transthyretin; UPR: unfolded protein response; V30M: valine 30 methionine
Published: 2014
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20. Structural, Biochemical, and Functional Characterization of the Cyclic Nucleotide Binding Homology Domain from the Mouse EAG1 Potassium Channel

Author: João H. Morais-Cabral, Guillaume Gabant, Maria J. Marques-Carvalho, Martine Cadene, Nirakar Sahoo, Roland Schönherr, Frederick W. Muskett, Ricardo S. Vieira-Pires, Instituto de Biologia Molecular e Celular (IBMC), Jena University Hospital [Jena], University of Leicester, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto, Centre de biophysique moléculaire (CBM), and Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
Subjects: Calmodulin, Crystallography, X-Ray, Homology (biology), 03 medical and health sciences, Mice, Structural Biology, Cyclic nucleotide binding, Animals, Nucleotide, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Binding site, Molecular Biology, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Binding Sites, biology, 030302 biochemistry & molecular biology, Potassium channel, Ether-A-Go-Go Potassium Channels, Protein Structure, Tertiary, Crystallography, chemistry, Cyclic nucleotide-binding domain, biology.protein, Biophysics, Potassium, Nucleotides, Cyclic
Abstract: International audience; KCNH channels are voltage-gated potassium channels with important physiological functions. In these channels, a C-terminal cytoplasmic region, known as the cyclic nucleotide binding homology (CNB-homology) domain displays strong sequence similarity to cyclic nucleotide binding (CNB) domains. However, the isolated domain does not bind cyclic nucleotides. Here, we report the X-ray structure of the CNB-homology domain from the mouse EAG1 channel. Through comparison with the recently determined structure of the CNB-homology domain from the zebrafish ELK (eag-like K(+)) channel and the CNB domains from the MlotiK1 and HCN (hyperpolarization-activated cyclic nucleotide-gated) potassium channels, we establish the structural features of CNB-homology domains that explain the low affinity for cyclic nucleotides. Our structure establishes that the "self-liganded" conformation, where two residues of the C-terminus of the domain are bound in an equivalent position to cyclic nucleotides in CNB domains, is a conserved feature of CNB-homology domains. Importantly, we provide biochemical evidence that suggests that there is also an unliganded conformation where the C-terminus of the domain peels away from its bound position. A functional characterization of this unliganded conformation reveals a role of the CNB-homology domain in channel gating.
Published: 2012
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21. The European university landscape: A micro characterization based on evidence from the Aquameth project

Author: Andrea Bonaccorsi, Carsten Pohl, Maria Olivares, Harold O. Fried, Gustavo Crespi, Ben Jongbloed, Annamaria Inzelt, Stig Slipersaeter, Elena Castro-Martínez, Aldo Geuna, Laurent Bach, Ignacio Fernández de Lucio, Benedetto Lepori, Cinzia Daraio, Cláudia S. Sarrico, Maria João Rosa, Patrick Llerena, Peter Bogetoft, Pedro Teixeira, Adela García-Aracil, Gerhard Kempkes, Margarida Fonseca Cardoso, Léopold Simar, Tarmo Räty, Mireille Matt, Philippe Vanden Eeckaut, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], University of Torino, Università degli studi di Torino (UNITO), Bureau d'Économie Théorique et Appliquée (BETA), Institut National de la Recherche Agronomique (INRA)-Université de Strasbourg (UNISTRA)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Innovation, INGENIO (CSIC-UPV), Business Management and Economics, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Laboratoire d'Economie Appliquée = Grenoble Applied Economics Laboratory (GAEL), Université Pierre Mendès France - Grenoble 2 (UPMF)-Institut National de la Recherche Agronomique (INRA), Imagerie Guilloz [CHRU Nancy] (Service d'imagerie Guilloz), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Faculty of Behavioural, Management and Social Sciences, European Commission, Sapienza University [Rome], Technische Universität Dresden (TUD), Laboratoire d'Economie Appliquée de Grenoble (GAEL), Institut National de la Recherche Agronomique (INRA)-Université Pierre Mendès France - Grenoble 2 (UPMF), University of Bologna/Università di Bologna, University of Pisa - Università di Pisa, Università degli studi di Torino = University of Turin (UNITO), Department of Economics 'S. Cognetti de Martiis', BRICK (Bureau of Resarch on Innovation, Complexity and Knowledge), Collegio Carlo Alberto, EESC-GEM Grenoble Ecole de Management, Università della Svizzera italiana = University of Italian Switzerland (USI), Copenhagen Business School [Copenhagen] (CBS), Interdisciplinary Centre of Marine and Environmental Research [Matosinhos, Portugal] (CIIMAR), Universidade do Porto = University of Porto, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universitat Politècnica de València (UPV)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Inter-American Development Bank (IDB), Inter-American Development Bank, Union College, Corvinus University of Budapest, Center for Higher Education Policy Studies, University of Twente, Deutsche Bundesbank, Universität Zürich [Zürich] = University of Zurich (UZH), Institut für Angewandte Biowissenschaften (IAB), Karlsruher Institut für Technologie (KIT), Finnish Forest Research Institute (METLA), Natural Resources Institute Finland (LUKE), Centre de Recherche du Centro de Investigação de Políticas do Ensino Superior (CIPES), Centro de Investigação de Políticas do Ensino Superior, Universidade de Aveiro, Université Catholique de Louvain = Catholic University of Louvain (UCL), Nordic Institute for Studies in Innovation, Research and Education (NIFU), Faculdade de Economia (LIACC), Université de Lille, Funding support by the European Commission through the PRIME Network of Excellence – Aquameth project (coordinated by Andrea Bonaccorsi and Cinzia Daraio) is gratefully acknowledged., University of Zurich, and Daraio, Cinzia
Subjects: productivity, Universities, Strategy and Management, growth, Management Science and Operations Research, size, 10004 Department of Business Administration, specialization, differentiation, universities, Management of Technology and Innovation, IR-103467, 0502 economics and business, 1408 Strategy and Management, Regional science, CROISSANCE, 1405 Management of Technology and Innovation, 14. Life underwater, Productivity, SPECIALIZATION, METIS-271192, PRODUCTIVITY, Spécialisation, 05 social sciences, 050301 education, 1803 Management Science and Operations Research, SPECIALISATION, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, 330 Economics, DIFFERENCIATION, Geography, SIZE, DIFFERENTIATION, Economy, Différentiation, TAILLE, GROWTH, UNIVERSITY, 0503 education, 050203 business & management
Abstract: Special Section on Heterogeneity and University-Industry Relations.-- et al., This paper provides a new and systematic characterization of 488 universities, from 11 European countries: Finland, France, Germany, Hungary, Italy, Netherlands, Norway, Portugal, Spain, Switzerland and UK. Using micro indicators built on the integrated Aquameth database, we characterize the European university landscape according to the following dimensions: history/foundation of university, dynamics of growth, specialization pattern, subject mix, funding composition, offer profile and productivity. © 2010 Elsevier B.V. All rights reserved., Funding support by the European Commission through the PRIME Network of Excellence – Aquameth project (coordinated by Andrea Bonaccorsi and Cinzia Daraio) is gratefully acknowledged.
Published: 2011
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22. The effect of long-term depuration on levels of oxidative stress biomarkers in mullets (Mugil cephalus) chronically exposed to contaminants

Author: Maria Armanda Reis-Henriques, Pedro Moradas-Ferreira, Marta Ferreira, ICBAS – Instituto de Ciências Biomédicas de Abel Salazar, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto-Universidade do Porto, CIIMAR – Centro Interdisciplinar de Investigação Marinha e Ambiental, IBMC – Instituto de Biologia Molecular e Celular, and Instituto de Biologia Molecular e Celular (IBMC)
Subjects: Antioxidant, medicine.medical_treatment, 010501 environmental sciences, Aquatic Science, Oceanography, medicine.disease_cause, 01 natural sciences, Mullet, Superoxide dismutase, Lipid peroxidation, 03 medical and health sciences, chemistry.chemical_compound, medicine, Animals, Seawater, 14. Life underwater, Food science, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0105 earth and related environmental sciences, chemistry.chemical_classification, Glutathione Peroxidase, 0303 health sciences, Reactive oxygen species, biology, Superoxide Dismutase, Glutathione peroxidase, Life Sciences, General Medicine, Catalase, biology.organism_classification, Pollution, Smegmamorpha, Oxidative Stress, chemistry, Biochemistry, 13. Climate action, biology.protein, Biological Assay, Lipid Peroxidation, Biomarkers, Water Pollutants, Chemical, Oxidative stress, Environmental Monitoring
Abstract: The present study aimed to obtain additional data on the effect of long-term depuration on the levels of oxidative stress biomarkers, and to clarify the role of mullets for monitoring pollution in River Douro estuary. Mullets chronically exposed to a mixture of contaminants in Douro estuary were captured in Spring of 2001, 2002 and 2003. The activities of antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPX); and oxidative damages in lipids (lipid peroxidation) and in proteins (protein carbonyl content) were assessed at capture day and after transfer to unpolluted seawater for 1, 4 and 8 months. An overall decrease in the activities of the antioxidant enzymes was detected, except for the GPX after 4 months depuration. CAT activity exhibited the more significant decrease at the end of the long-term depuration. The decrease in SOD activity after 1 month of depuration was then maintained during the remaining depuration period. Regarding oxidative damages, a decrease in lipid peroxidation as well as the content of oxidised proteins was observed during depuration. Indeed, at capture the activities of antioxidant defences were higher as a result of the formation of reactive oxygen species (ROS) from the metabolism of pollutants. The oxidative damaged molecules were repaired or degraded during the depuration period, supporting the use of such damages as indicators of exposure to pro-oxidant pollutants.
Published: 2007
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23. Streptococcus agalactiae GAPDH Is a Virulence-Associated Immunomodulatory Protein

Author: Patrick Trieu-Cuot, Delfina Tavares, Pedro Madureira, Ana Camelo, Paula Ferreira, Adília Ribeiro, Marina Baptista, Vanessa Magalhães, Marta Vieira, Manuel Vilanova, Liliana Oliveira, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto = University of Porto, Instituto de Biologia Molecular e Celular (IBMC), Biologie des Bactéries pathogènes à Gram-positif, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Universidade do Porto, and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, MESH: Interleukin-10, MESH: Glyceraldehyde-3-Phosphate Dehydrogenases, MESH: Virulence, Lymphocyte Activation, medicine.disease_cause, law.invention, Mice, law, Immunology and Allergy, MESH: Animals, MESH: Bacterial Proteins, B-Lymphocytes, 0303 health sciences, Virulence, MESH: Immunologic Factors, breakpoint cluster region, Glyceraldehyde-3-Phosphate Dehydrogenases, Interleukin-10, medicine.anatomical_structure, Recombinant DNA, Virulence Factors, MESH: Mice, Transgenic, Immunology, Mice, Transgenic, Biology, Streptococcus agalactiae, Microbiology, 03 medical and health sciences, Bacterial Proteins, Antigen, MESH: Mice, Inbred C57BL, MESH: B-Lymphocytes, medicine, Animals, Immunologic Factors, MESH: Lymphocyte Activation, Escherichia coli, MESH: Mice, B cell, 030304 developmental biology, MESH: Virulence Factors, Antigens, Bacterial, 030306 microbiology, Molecular biology, MESH: Streptococcus agalactiae, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, In vitro, MESH: Male, Mice, Inbred C57BL, MESH: Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating), Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating), MESH: Antigens, Bacterial
Abstract: Certain extracellular proteins produced by several pathogenic microorganisms interfere with the host immune system facilitating microbial colonization and were thus designated virulence-associated immunomodulatory proteins. In this study, a protein with B lymphocyte stimulatory activity was isolated from culture supernatants of Streptococcus agalactiae strain NEM316. This protein, with an apparent molecular mass of 45 kDa, was identified as GAPDH by N-terminal amino acid sequencing. The gapC gene was cloned and expressed in Escherichia coli for the production of a recombinant histidyl-tagged protein. The recombinant GAPDH (rGAPDH), purified in an enzymatically active form, induced in vitro an up-regulation of CD69 expression on B cells from normal and BCR transgenic mice. In addition, rGAPDH induced an increase in the numbers of total, but not of rGAPDH-specific, splenic Ig-secreting cells in C57BL/6 mice treated i.p. with this protein. These in vitro- and in vivo-elicited B cell responses suggest that the B cell stimulatory effect of rGAPDH is independent of BCR specificity. A S. agalactiae strain overexpressing GAPDH showed increased virulence as compared with the wild-type strain in C57BL/6 mice. This virulence was markedly reduced in IL-10-deficient and anti-rGAPDH antiserum-treated mice. These results suggest that IL-10 production, which was detected at higher concentrations in the serum of rGAPDH-treated mice, is important in determining the successfulness of the host colonization by S. agalactiae and they highlight the direct role of GAPDH in this process. Taken together, our data demonstrate that S. agalactiae GAPDH is a virulence-associated immunomodulatory protein.
Published: 2007
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24. Collisions of ionized hydrogen clusters with helium atoms: electron capture as a function of the cluster size

Author: Ginette Jalbert, S. Louc, M. C. Bacchus-Montabonel, N. Gonçalves, M. Carré, N. V. de Castro Faria, H. Luna, J. P. Buchet, Bernadette Farizon, M.J. Gaillard, Michel Farizon, Institut de Physique Nucléaire de Lyon (IPNL), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Department of Biology and Environmental Science, Department of Molecular Neurobiology, Institute for Molecular and Cell Biology, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto, Departamento de Ciência da Computação [Minas Gerais] (DCC - UFMG), Universidade Federal de Minas Gerais [Belo Horizonte] (UFMG), Service de Cardiologie (HIA BREST - Cardio), HIA - BREST, Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), and Universidade do Porto = University of Porto
Subjects: Nuclear and High Energy Physics, Hydrogen, Helium atom, Electron capture, [PHYS.PHYS.PHYS-ATM-PH]Physics [physics]/Physics [physics]/Atomic and Molecular Clusters [physics.atm-clus], chemistry.chemical_element, 01 natural sciences, 010305 fluids & plasmas, Ion, chemistry.chemical_compound, chemistry, Ionization, 0103 physical sciences, Cluster (physics), Molecule, Physics::Atomic Physics, Atomic physics, 010306 general physics, Instrumentation, Helium
Abstract: IPM; International audience; Electron capture cross sections of hydrogen cluster ions Hn+ colliding with atomic helium have been measured in a large range of cluster size (5⩽n⩽35) for the same velocity (1.5v0, 60 keV/u). While the electron capture cross section decreases from the H+ ion to the H3+ one, the cluster electron capture cross section is found to be independent of the cluster size and nearly equal to the capture cross section of the H3+ ion. Electron capture by hydrogen clusters on a helium atom is a process involving only the H3+ core of the cluster where the positive charge is localized. It appears that this very localized electron capture is not disturbed by the presence of molecules, up to sixteen, around the H3+ core.
Published: 1998
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24 results on '"Instituto de Ciências Biomédicas de Abel Salazar (ICBAS)"'

1. Exercise in lung Cancer, the healthcare providers opinion (E.C.H.O.): Results of the EORTC lung cancer Group (LCG) survey

2. Circulating Biomarkers and Cardiac Structure and Function in Rheumatoid Arthritis

3. Interleukin-10 induces interferon-γ-dependent emergency myelopoiesis

4. Anti-neoplastic and demethylating activity of a newly synthetized flavanone-derived compound in Renal Cell Carcinoma cell lines

5. Overview of Cattle Diseases Listed Under Category C, D or E in the Animal Health Law for Which Control Programmes Are in Place Within Europe

6. Yolk sac, but not hematopoietic stem cell–derived progenitors, sustain erythropoiesis throughout murine embryonic life

7. Sperm Morphology Assessment in the Era of Intracytoplasmic Sperm Injection: Reliable Results Require Focus on Standardization, Quality Control, and Training

8. Dietary glycerol inclusion decreases growth performance and nitrogen retention efficiency in rainbow trout (Oncorhynchus mykiss)

9. Subclinical ventricular dysfunction in rheumatoid arthritis

10. Orally administrated chitosan microspheres bind Helicobacter pylori and decrease gastric infection in mice

11. Characterization of Endogenous SERINC5 Protein as Anti-HIV-1 Factor

12. Population genetics-informed meta-analysis in seven genes associated with risk to dengue fever disease

13. Hypoxia, but Not an Electrolyte-Imbalanced Diet, Reduces Feed Intake, Growth and Oxygen Consumption in Rainbow Trout ( Oncorhynchus Mykiss )

14. Impact of dietary electrolyte balance (DEB) and dissolved O2 (DO) level on feed intake, growth and O2 consumption In rainbow trout Oncorhynchus mykiss

15. Three-dimensional scaffolds of fetal decellularized hearts exhibit enhanced potential to support cardiac cells in comparison to the adult

16. Spectral Cytometry Has Unique Properties Allowing Multicolor Analysis of Cell Suspensions Isolated from Solid Tissues

17. The Impact of Nutritional and Environmental Stressors on the Immune Response, Oxidative Stress and Energy Use of Rainbow Trout (Oncorhynchus Mykiss)

18. A Safe and Stable Neonatal Vaccine Targeting GAPDH Confers Protection against Group B Streptococcus Infections in Adult Susceptible Mice

19. Interleukin-1 signaling pathway as a therapeutic target in transthyretin amyloidosis

20. Structural, Biochemical, and Functional Characterization of the Cyclic Nucleotide Binding Homology Domain from the Mouse EAG1 Potassium Channel

21. The European university landscape: A micro characterization based on evidence from the Aquameth project

22. The effect of long-term depuration on levels of oxidative stress biomarkers in mullets (Mugil cephalus) chronically exposed to contaminants

23. Streptococcus agalactiae GAPDH Is a Virulence-Associated Immunomodulatory Protein

24. Collisions of ionized hydrogen clusters with helium atoms: electron capture as a function of the cluster size

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