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1. How Molecular Mobility, Physical State, and Drug Distribution Influence the Naproxen Release Profile from Different Mesoporous Silica Matrices

Author: Mirtha A.O. Lourenço, Paula Ferreira, Piedade d’Orey, João Sotomayor, Inês Matos, Teresa Cordeiro, Isabel Fonseca, Natália T. Correia, Madalena Dionísio, Florence Danede, Laboratorio Associado para a Quimica Verde (LAQV), Requimte, Universidade do Porto = University of Porto-Departamento de Química (DQ), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto = University of Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Italian Institute of Technology (IIT), Unité Matériaux et Transformations - UMR 8207 (UMET), and Centrale Lille-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Materials science, amorphous, Pharmaceutical Science, 02 engineering and technology, Conductivity, 030226 pharmacology & pharmacy, 03 medical and health sciences, Drug Delivery Systems, 0302 clinical medicine, Differential scanning calorimetry, X-Ray Diffraction, Spectroscopy, Fourier Transform Infrared, Drug Discovery, naproxen, [PHYS.COND.CM-DS-NN]Physics [physics]/Condensed Matter [cond-mat]/Disordered Systems and Neural Networks [cond-mat.dis-nn], Particle Size, mesoporous Silica, Drug Carriers, Calorimetry, Differential Scanning, Hydrogen bond, Water, Mesoporous silica, Silicon Dioxide, 021001 nanoscience & nanotechnology, control release, drug distribution, Solubility, Chemical engineering, Attenuated total reflection, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], Molecular Medicine, Adsorption, Crystallization, 0210 nano-technology, Drug carrier, Mesoporous material, Glass transition, Hydrophobic and Hydrophilic Interactions, Porosity, [PHYS.COND.CM-SCM]Physics [physics]/Condensed Matter [cond-mat]/Soft Condensed Matter [cond-mat.soft]
Abstract: International audience; Aiming to evaluate how the release profile of naproxen (nap) is influenced by its physical state, molecular mobility, and distribution in the host, this pharmaceutical drug was loaded in three different mesoporous silicas differing in their architecture and surface composition. Unmodified and partially silylated MCM-41 matrices, respectively MCM-41 and MCM-41sil, and a biphenylene-bridged periodic mesoporous organic matrix, PMOBph, were synthetized and used as drug carriers, having comparable pore sizes (∼3 nm) and loading percentages (∼30% w/w). The loaded guest was investigated by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), and dielectric relaxation spectroscopy (DRS). DSC and XRD confirmed amorphization of a nap fraction incorporated inside the pores. A narrower glass transition was detected for PMOBph_nap, taken as an indication of the impact of host ordering, which also hinders the guest molecular mobility inside the pores as probed by DRS. While the PMOBph matrix is highly hydrophobic, the unmodified MCM-41 readily adsorbs water, accelerating the nap relaxation rate in the respective composite. In the dehydrated state, the faster dynamics was found for the silylated matrix since guest–host hydrogen bond interactions were inhibited to some extent by methylation. Nevertheless, in all the prepared composites, bulk-like crystalline drug deposits outside pores in a greater extent in PMOBph_nap. The DRS measurements analyzed in terms of conductivity show that, upon melting, nap easily migrates into pores in MCM-41-based composites, while it stays in the outer surface in the ordered PMOBph, determining a faster nap delivery from the latter matrix. On the other side, the mobility enhancement in the hydrated state controls the drug delivery in the unmodified MCM-41 matrix vs the silylated one. Therefore, DRS proved to be a suitable technique to disclose the influence of the ordering of the host surface and its chemical modification on the guest behavior, and, through conductivity depletion, it provides a mean to monitor the guest entrance inside the pores, easily followed even by untrained spectroscopists.
Published: 2021

2. Accuracy of the clinical pulmonary infection score to differentiate ventilator-associated tracheobronchitis from ventilator-associated pneumonia

Author: Alexandre Gaudet, Ignacio Martin-Loeches, Pedro Povoa, Alejandro Rodriguez, Jorge Salluh, Alain Duhamel, Saad Nseir, TAVeM study group, NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Hospital de S. Francisco Xavier (EPE), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Universitat Rovira i Virgili, Instituto de Salud Carlos III [Madrid] (ISC), D'Or Institute for Research and Education [Rio de Janeiro], Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Lille Inflammation Research International Center - U 995 (LIRIC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille, LillOA, Université de Lille, CNRS, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL], Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], Institut d'Investigacions Biomèdiques August Pi i Sunyer [IDIBAPS], Universidade Nova de Lisboa = NOVA University Lisbon [NOVA], METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694, and Lille Inflammation Research International Center (LIRIC) - U995
Subjects: medicine.medical_specialty, medicine.medical_treatment, Youden's J statistic, Critical Care and Intensive Care Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Lower respiratory tract infection, 03 medical and health sciences, CPIS, 0302 clinical medicine, Mechanical ventilation, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Intensive care, Anesthesiology, Internal medicine, Tracheobronchitis, Medicine, Pneumonia, Receiver operating characteristic, business.industry, Research, Ventilator-associated pneumonia, lcsh:Medical emergencies. Critical care. Intensive care. First aid, 030208 emergency & critical care medicine, lcsh:RC86-88.9, medicine.disease, respiratory tract diseases, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Background Differentiating Ventilator-Associated Tracheobronchitis (VAT) from Ventilator-Associated Pneumonia (VAP) may be challenging for clinicians, yet their management currently differs. In this study, we evaluated the accuracy of the Clinical Pulmonary Infection Score (CPIS) to differentiate VAT and VAP. Methods We performed a retrospective analysis based on the data from 2 independent prospective cohorts. Patients of the TAVeM database with a diagnosis of VAT (n = 320) or VAP (n = 369) were included in the derivation cohort. Patients admitted to the Intensive Care Centre of Lille University Hospital between January 1, 2016 and December 31, 2017 who had a diagnosis of VAT (n = 70) or VAP (n = 139) were included in the validation cohort. The accuracy of the CPIS to differentiate VAT from VAP was assessed within the 2 cohorts by calculating sensitivity and specificity values, establishing the ROC curves and choosing the best threshold according to the Youden index. Results The areas under ROC curves of CPIS to differentiate VAT from VAP were calculated at 0.76 (95% CI [0.72–0.79]) in the derivation cohort and 0.67 (95% CI [0.6–0.75]) in the validation cohort. A CPIS value ≥ 7 was associated with the highest Youden index in both cohorts. With this cut-off, sensitivity and specificity were respectively found at 0.51 and 0.88 in the derivation cohort, and at 0.45 and 0.89 in the validation cohort. Conclusions A CPIS value ≥ 7 reproducibly allowed to differentiate VAT from VAP with high specificity and PPV and moderate sensitivity and NPV in our derivation and validation cohorts.
Published: 2020

3. The SOUL family of heme-binding proteins: Structure and function 15 years later

Author: Jean-Marc Moulis, Susana S. Aveiro, Anjos L. Macedo, Gloria C. Ferreira, Ana Luísa Carvalho, Alastair G. McEwen, Leonildo Delgado, Brian J. Goodfellow, João E. Rodrigues, Filipe Freire, Peggy Charbonnier, Catherine Birck, Pierre Poussin-Courmontagne, CICECO, Departamento de Química, Instituto de Biologia Experimental e Tecnológica (IBET), Instituto de Tecnologia Química e Biológica António Xavier (ITQB), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Unidade de Ciencias Biomoleculares Aplicadas (UCIBIO), Requimte, Departamento de Química (DQ), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto, GreenCoLab - Associação Oceano Verde, Universidade do Algarve, Métaux et Organes (MET&OR), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Equity Analyst Biotech & Healthcare, Morsani College of Medicine [Tampa, USA], University of South Florida [Tampa] (USF), Center for Neuroscience and Cell Biology (CNC) (CNC), University of Coimbra [Portugal] (UC)-Neuroscience Research Domain, Centre for Integrative Biology - CBI (Inserm U964 - CNRS UMR7104 - IGBMC), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universidade do Porto = University of Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto = University of Porto-Departamento de Química (DQ), and Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)
Subjects: Heme binding, Globular protein, Protein Data Bank (RCSB PDB), Inorganic Chemistry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Protein structure, NMR spectroscopy, Materials Chemistry, HEBP1, [CHIM.COOR]Chemical Sciences/Coordination chemistry, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Physical and Theoretical Chemistry, HEBP2, Function, Heme, Histidine, 030304 developmental biology, X-ray crystallography, chemistry.chemical_classification, 0303 health sciences, Tetrapyrrole binding, Structure, chemistry, SOUL protein, 030220 oncology & carcinogenesis, Biophysics, Heteronuclear single quantum coherence spectroscopy
Abstract: International audience; The SOUL, or heme-binding protein HBP/SOUL, family represents a group of evolutionary conservedputative heme-binding proteins that contains a number of members in animal, plant and bacterial spe-cies. The structures of the murine form of HEBP1, or p22HBP, and the human form of HEBP2, or SOUL,have been determined in 2006 and 2011 respectively.In this work we discuss the structures of HEBP1 and HEBP2 in light of new X-ray data for heme boundmurine HEBP1. The interaction between tetrapyrroles and HEBP1, initially proven to be hydrophobic innature, was thought to also involve electrostatic interactions between heme propionate groups and pos-itively charged amino acid side chains. However, the new X-ray structure, and results from murine HEBP1variants and human HEBP1, confirm the hydrophobic nature of the heme-HEBP1 interaction, resulting inKdvalues in the low nanomolar range, and rules out any electrostatic stabilization. Results from NMRrelaxation time measurements for human HEBP1 describe a rigid globular protein with no change inmotional regime upon heme binding.X-ray structures deposited in the PDB for human HEBP2 are very similar to each other and to the newheme-bound murine HEBP1 X-ray structure (backbone rmsd ca. 1 Å). Results from a HSQC spectrum cen-tred on the histidine side chain Nd-proton region for HEBP2 confirm that HEBP2 does not bind heme viaH42 as no chemical shift differences were observed upon heme addition for backbone NH and Ndprotons.A survey of the functions attributed to HEBP1 and HEBP2 over the last 20 years span a wide range ofcellular pathways. Interestingly, many of them are specific to higher eukaryotes, particularly mammalsand a potential link between heme release under oxidative stress and human HEBP1 is also examinedusing recent data. However, at the present moment, trying to relate function to the involvement of hemehttps://doi.org/10.1016/j.ccr.2021.2141890010-8545/Ó2021 Elsevier B.V. All rights reserved.Abbreviations:HEBP1, Heme-binding protein 1 (or p22HBP); HEBP2, Heme-binding protein 2 (or SOUL); BH3, Bcl-2 homology 3; HSQC, heteronuclear single quantumcoherence spectroscopy; TROSY, transverse relaxation optimized spectroscopy; FQ, fluorescence quenching; PPIX, protoporphyrin IX; sGC, solubleGuanylyl Cyclase; hetNOE,heteronuclear nuclear Overhauser effect; rmsd, root mean squared deviation; BMRB, biological magnetic resonance bank; VAST, vector alignment search tool; MEL, murineerythroleukemia.⇑Corresponding authors.E-mail addresses:brian.goodfellow@ua.pt(B.J. Goodfellow),mdam@fct.unl(A.L. Macedo).Coordination Chemistry Reviews 448 (2021) 214189Contents lists available atScienceDirectCoordination Chemistry Reviewsjournal homepage: www.elsevier.com/locate/ccr
Published: 2021

4. Successful dissemination of plasmid-mediated extended-Spectrum β-lactamases in enterobacterales over humans to wild fauna

Author: Richard Bonnet, Frédéric Robin, Patrícia Poeta, Racha Beyrouthy, Giberto Igrejas, Carolina Sabença, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Centre National de Référence de la Résistance aux Antibiotiques [CHU Clermont-Ferrand] (CNR), CHU Clermont-Ferrand, Universidade de Trás-os-Montes e Alto Douro (UTAD), Universidade do Trás-os-Montes e Alto Douro, Laboratorio Associado para a Quimica Verde (LAQV), Requimte, Departamento de Química (DQ), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto = University of Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto = University of Porto, Ministere de la Recherche et de la Technologie, Inserm (UMR 1071), INRAe (USC-2018), Programa de Accoes Universitarias Integradas Luso-Francesas [TC-14/2017], Portuguese Foundation for Science and Technology [[UID/QUI/50006/2019], ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016), European Project: 323209,EC:FP7:HEALTH,FP7-JPROG-2012-RTD,JPIAMR(2012), Molé, Christine, CAP 20-25 - - CAP 20-252016 - ANR-16-IDEX-0001 - IDEX - VALID, Coordination Action for the early implementation of the Joint Programming Initiative on Antimicrobial Resistance - JPIAMR - - EC:FP7:HEALTH2012-09-01 - 2016-02-29 - 323209 - VALID, Universidade do Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto-Departamento de Química (DQ), and Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)
Subjects: Microbiology (medical), QH301-705.5, medicine.disease_cause, Microbiology, Genome, Article, 03 medical and health sciences, Plasmid, Polymorphism (computer science), Virology, plasmid, medicine, Escherichia coli, IncI1-ST3, CTX-M-1, Biology (General), Gene, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, 030304 developmental biology, Synteny, 2. Zero hunger, Genetics, 0303 health sciences, biology, 030306 microbiology, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, bacterial infections and mycoses, β-lactamase, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Multilocus sequence typing, beta-lactamase, Bacteria
Abstract: Background: The emergence of multidrug-resistant bacteria remains poorly understood in the wild ecosystem and at the interface of habitats. Here, we explored the spread of Escherichia coli containing IncI1-ST3 plasmid encoding resistance gene cefotaximase-Munich-1 (blaCTX-M-1) in human-influenced habitats and wild fauna using a genomic approach. Methods. Multilocus sequence typing (MLST), single-nucleotide polymorphism comparison, synteny-based analysis and data mining approaches were used to analyse a dataset of genomes and circularised plasmids. Results. CTX-M-1 E. coli sequence types (STs) were preferentially associated with ecosystems. Few STs were shared by distinct habitats. IncI1-ST3-blaCTX-M-1 plasmids are disseminated among all E. coli phylogroups. The main divergences in plasmids were located in a shuffling zone including blaCTX-M-1 inserted in a conserved site. This insertion hot spot exhibited diverse positions and orientations in a zone-modulating conjugation, and the resulting synteny was associated with geographic and biological sources. Conclusions. The ecological success of IncI1-ST3-blaCTX-M-1 appears less linked to the spread of their bacterial recipients than to their ability to transfer in a broad spectrum of bacterial lineages. This feature is associated with the diversity of their shuffling conjugation region that contain blaCTX-M-1. These might be involved in the resistance to antimicrobials, but also in their spread.
Published: 2021

5. Acting on observed social exclusion and pro-social behaviour in autism spectrum disorder

Author: Catarina Silva, Christine Deruelle, D. Da Fonseca, Francisco Esteves, Chloé Jover, Instituto polictecnico Leira, Service de Pédopsychiatrie, Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Center for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), and Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)
Subjects: Adult, Male, Adolescent, Autism Spectrum Disorder, [SDV]Life Sciences [q-bio], media_common.quotation_subject, Approachability, Altruism, Developmental psychology, Social Skills, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Developmental and Educational Psychology, medicine, Humans, Interpersonal Relations, 0501 psychology and cognitive sciences, Social isolation, Child, 10. No inequality, ComputingMilieux_MISCELLANEOUS, media_common, Motivation, 05 social sciences, 16. Peace & justice, medicine.disease, Psychological Distance, Prosocial behavior, Autism spectrum disorder, Autism, Female, Social exclusion, medicine.symptom, Psychology, Inclusion (education), 030217 neurology & neurosurgery, 050104 developmental & child psychology
Abstract: International audience; Humans are commonly motivated towards cooperation and prosociality. In this study, we examined this motivational predisposition in autistic individuals. Using an adaptation of the Cyberball paradigm, we investigated subsequent pro-social behaviour after witnessing social exclusion. Participants witnessed and played a series of Cyberball games, rated their affective state and valued emotional faces with respect to their approachability. Results showed that participants from both groups were aware of the social exclusion. However, while neurotypically developing participants engaged in pro-social behaviour in reaction to the exclusion, autistic participants showed less alterations, in terms of either behaviour or affective state. The current findings suggest a distinct motivational drive and processing of social reward stimuli in autism, which may result in behavioural responses divergent from typical development when engaging in the social world.
Published: 2019

6. Heterogeneity of the pharmacologic treatment of allergic rhinitis in Europe based on MIDAS and OTCims platforms

Author: Torsten Zuberbier, Julia Saueressig, Joaquim Mullol, Glenis Scadding, João Fonseca, G. Walter Canonica, Eric Van Ganse, Claus Bachert, Bolesław Samoliński, Olga Lourenço, Oliver Pfaar, Philippe Devillier, Ann-Kathrin Stroh, Wienczyslawa Czarlewski, Jean Bousquet, Ludger Klimek, Elísio Costa, Piotr Kuna, Detlef Schroder-Bernhardi, Victoria Cardona, Sophie Scheire, Nhan Pham Thi, Institut Català de la Salut, [Bousquet J] Charité Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany. Department of Dermatology and Allergy, Comprehensive Allergy Center, Berlin Institute of Health, Berlin, Germany. University Hospital Montpellier, Montpellier, France. MACVIA-France, Montpellier, France. [Schröder-Bernhardi D] IQVIA Consumer Health, Frankfurt, Germany. [Bachert C] Upper Airways Research Laboratory, ENT Dept, Ghent University Hospital, Ghent, Belgium. International Airway Research Center, First Affiliated Hospital Guangzou, Sun Yat-sen University, Guangzou, China. Division of ENT Diseases, CLINTEC, Karolinska Institutet, Stockholm, Sweden. Department of ENT Diseases, Karolinska University Hospital, Stockholm, Sweden. [Canonica GW] Personalized Medicine Asthma, & Allergy Clinic-Humanitas University & Research Hospital, IRCCS-Milano, Milano, Italy. [Cardona V] Servei d’Al·lergologia, Servei de Medicina Interna, Vall d'Hebron Hospital Universitari, Barcelona, Spain. ARADyAL Research Network, Barcelona, Spain. [Costa EM] UCIBIO, REQUINTE, Faculty of Pharmacy and Competence Center on Active and Healthy Ageing of University of Porto (Porto4Ageing), Porto, Portugal, Vall d'Hebron Barcelona Hospital Campus, uBibliorum, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health (BIH), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), IQVIA, Ghent University Hospital, Sun Yat-Sen University [Guangzhou] (SYSU), Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], IRCCS Istituto Nazionale dei Tumori [Milano], Vall d'Hebron University Hospital [Barcelona], Unidade de Ciencias Biomoleculares Aplicadas (UCIBIO), Requimte, Universidade do Porto = University of Porto-Departamento de Química (DQ), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto = University of Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Hôpital Foch [Suresnes], Universidade do Porto = University of Porto, University Medical Center [Mainz], Medical University of Łódź (MUL), University of Beira Interior [Portugal] (UBI), Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Philipps Universität Marburg = Philipps University of Marburg, Institut de Recherche Biomédicale des Armées (IRBA), Medical University of Warsaw - Poland, University College of London [London] (UCL), Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, and Retiveau, Nolwenn
Subjects: 0301 basic medicine, Allergy, IMPACT, Database analysis, Medications, costs, MESH: Allergy and Immunology, Medication, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Allergic rhinitis, 0302 clinical medicine, medications, MESH: Anti-Allergic Agents, Anti-Allergic Agents, Medicine and Health Sciences, Medicine, Immunology and Allergy, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Practice Patterns, Physicians', health care economics and organizations, International market, Medication use, Units, enfermedades respiratorias::enfermedades nasales::rinitis::rinitis alérgica [ENFERMEDADES], Medicaments - Prescripció - Europa, Europe, MESH: Rhinitis, Allergic, [SDV.IMM]Life Sciences [q-bio]/Immunology, preparados farmacéuticos::medicamentos por prescripción [COMPUESTOS QUÍMICOS Y DROGAS], localizaciones geográficas::Europa (continente) [DENOMINACIONES GEOGRÁFICAS], MIDAS, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, Rinitis - Tractament - Europa, Healthcare system, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, Respiratory Tract Diseases::Nose Diseases::Rhinitis::Rhinitis, Allergic [DISEASES], Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Geographic Locations::Europe [GEOGRAPHICALS], Eu countries, PERSON-CENTERED CARE, Pharmacological treatment, 03 medical and health sciences, units, Environmental health, Allergy and Immunology, MANAGEMENT, Humans, Pharmaceutical Preparations::Prescription Drugs [CHEMICALS AND DRUGS], MESH: Humans, allergic rhinitis, OTC Medicines, business.industry, PATHWAYS, Al·lèrgia - Tractament - Europa, AIR-POLLUTION, medicine.disease, Rhinitis, Allergic, Costs, 030104 developmental biology, 030228 respiratory system, Analytics, Family medicine, MESH: Practice Patterns, Physicians', ASTHMA, MESH: Europe, business
Abstract: Rinitis al·lèrgica; Costos; Medicaments Rinitis alérgica; Costos; Medicamentos Allergic rhinitis; Costs; Medications Background The practice of allergology varies widely between countries, and the costs and sales for the treatment of rhinitis differ depending on practices and health systems. To understand these differences and their implications, the rhinitis market was studied in some of the EU countries. Methods We conducted a pharmaco-epidemiological database analysis to assess the medications that were being prescribed for allergic rhinitis in the years 2016, 2017 and 2018. We used the IQVIA platforms for prescribed medicines (MIDAS®—Meaningful Integration of Data, Analytics and Services) and for OTC medicines (OTC International Market Tracking—OTCims). We selected the five most important markets in the EU (France, Germany, Italy, Poland and Spain). Results Intranasal decongestants were excluded from the analyses because they are rarely prescribed for allergic rhinitis. For both Standard Units (SU) and costs, France is leading the other countries. In terms of SU, the four other countries are similar. For costs, Poland is lower than the three others. However, medication use differs largely. For 2018, in SU, intranasal corticosteroid is the first treatment in Poland (70.0%), France (51.3%), Spain (51.1%) and Germany (50.3%), whereas the Italian market is dominated by systemic antihistamines (41.4%) followed by intranasal corticosteroids (30.1%). Results of other years were similar. Discussion There are major differences between countries in terms of rhinoconjunctivitis medication usage.
Published: 2021

7. Electrochemical Activity of Cytochrome P450 1A2: The Relevance of O 2 Control and the Natural Electron Donor

Author: Wissam Ghach, Mathieu Etienne, Sofia A. Pereira, Célia M. Silveira, Patricia Rodrigues, Francisco de Assis Esteves, Michel Kranendonk, M. Gabriela Almeida, Unidade de Ciencias Biomoleculares Aplicadas (UCIBIO), Requimte, Departamento de Química (DQ), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto, Instituto de Tecnologia Química e Biológica António Xavier (ITQB), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), School of Medicine [Cardiff], Cardiff University-Institute of Medical Genetics [Cardiff], Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centro de Estudos de Doenças Crónicas (CEDOC), NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), and Center for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology
Subjects: 0303 health sciences, biology, Cytochrome p450 oxidoreductase, CYP1A2, Cytochrome P450, O2 reduction, Electron donor, 010402 general chemistry, Electrochemistry, 01 natural sciences, Combinatorial chemistry, Catalysis, 0104 chemical sciences, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, 03 medical and health sciences, chemistry.chemical_compound, chemistry, biology.protein, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: International audience
Published: 2021

8. International Survey to Establish Prioritized Outcomes for Trials in People With Coronavirus Disease 2019

Author: Andrew Conway Morris, Ning Shen, Nicole Evangelidis, Sally Crowe, Derek P. Chew, Mervyn Mer, Saad Nseir, Alan R. Smyth, Emma Liu, Peter Horby, Luciano Cesar Pontes Azevedo, Andrea K. Viecelli, Ella Flemyng, Deena Lynch, Andrew D. Bersten, Jonathan C. Craig, Laila Woc-Colburn, Antoni Torres, Anne McKenzie, Martin Howell, Yeoungjee Cho, Julian Elliott, Sebastián Cabrera, Eduardo Lorca, John C. Marshall, Junhua Zhang, Paula R Williamson, Yasser Sakr, Andrea Matus Gonzalez, Steve Webb, Sangeeta Mehta, Jaehee Lee, Amanda Baumgart, Giovanni F.M. Strippoli, Charlie McLeod, Mark Reid, Ivor S. Douglas, Allison Tong, Tari Turner, Valeria Saglimbene, Pedro Póvoa, Patrizia Natale, Lilia Cervantes, Chandana Guha, Tom Snelling, Armando Teixeira-Pinto, Tess E Cooper, The University of Sydney, Monash University [Melbourne], Flinders University [Adelaide, Australia], University of Colorado [Denver], University of Oxford [Oxford], Kyungpook National University [Daegu], Universidad de Chile = University of Chile [Santiago] (UCHILE), University of Toronto, University of the Witwatersrand [Johannesburg] (WITS), University of Cambridge [UK] (CAM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille, Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Jena University Hospital [Jena], University of Nottingham, UK (UON), Università degli studi di Bari Aldo Moro (UNIBA), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), University of Liverpool, Baylor College of Medecine, Tianjin University (TJU), University of Queensland [Brisbane], CNRS, University of Oxford, Kyungpook National University [Daegu] [KNU], Universidad de Chile = University of Chile [Santiago] [UCHILE], University of the Witwatersrand [Johannesburg] [WITS], University of Cambridge [UK] [CAM], Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576, Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], Universidade Nova de Lisboa = NOVA University Lisbon [NOVA], University of Nottingham, UK [UON], Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro [UNIBA], Institut d'Investigacions Biomèdiques August Pi i Sunyer [IDIBAPS], Centro de Investigación Biomédica en Red Enfermedades Respiratorias [CIBERES], Tianjin University [TJU], Kyungpook National University [Daegu] (KNU), and Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA)
Subjects: Research design, Male, Psychological intervention, coronavirus, Disease, Critical Care and Intensive Care Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, patients, Health Services Accessibility, Health Priorities/organization & administration, sepsis, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Pandemic, Outcome Assessment, Health Care, Pandemics/prevention & control, Randomized Controlled Trials as Topic, Pneumonia, Viral/prevention & control, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, clinical trial, Middle Aged, 3. Good health, Research Design, Preparedness, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Anxiety, Female, medicine.symptom, Symptom Assessment, Coronavirus Infections, Adult, medicine.medical_specialty, Critical Care, Patients, Pneumonia, Viral, MEDLINE, critical care, infection, 03 medical and health sciences, Betacoronavirus, medicine, Humans, Clinical Investigation, Pandemics, Aged, Randomized Controlled Trials as Topic/standards, business.industry, Health Priorities, SARS-CoV-2, COVID-19, 030208 emergency & critical care medicine, Coronavirus Infections/drug therapy, Health Services Accessibility/standards, COVID-19 Drug Treatment, Coronavirus, Clinical trial, 030228 respiratory system, Family medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Supplemental Digital Content is available in the text., Objectives: There are over 4,000 trials conducted in people with coronavirus disease 2019. However, the variability of outcomes and the omission of patient-centered outcomes may diminish the impact of these trials on decision-making. The aim of this study was to generate a consensus-based, prioritized list of outcomes for coronavirus disease 2019 trials. Design: In an online survey conducted in English, Chinese, Italian, Portuguese, and Spanish languages, adults with coronavirus disease 2019, their family members, health professionals, and the general public rated the importance of outcomes using a 9-point Likert scale (7–9, critical importance) and completed a Best-Worst Scale to estimate relative importance. Participant comments were analyzed thematically. Setting: International. Subjects: Adults 18 years old and over with confirmed or suspected coronavirus disease 2019, their family members, members of the general public, and health professionals (including clinicians, policy makers, regulators, funders, and researchers). Interventions: None. Measurements: None. Main Results: In total, 9,289 participants from 111 countries (776 people with coronavirus disease 2019 or family members, 4,882 health professionals, and 3,631 members of the public) completed the survey. The four outcomes of highest priority for all three groups were: mortality, respiratory failure, pneumonia, and organ failure. Lung function, lung scarring, sepsis, shortness of breath, and oxygen level in the blood were common to the top 10 outcomes across all three groups (mean > 7.5, median ≥ 8, and > 70% of respondents rated the outcome as critically important). Patients/family members rated fatigue, anxiety, chest pain, muscle pain, gastrointestinal problems, and cardiovascular disease higher than health professionals. Four themes underpinned prioritization: fear of life-threatening, debilitating, and permanent consequences; addressing knowledge gaps; enabling preparedness and planning; and tolerable or infrequent outcomes. Conclusions: Life-threatening respiratory and other organ outcomes were consistently highly prioritized by all stakeholder groups. Patients/family members gave higher priority to many patient-reported outcomes compared with health professionals.
Published: 2020
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9. Quantitative Proteomics Identifies Metabolic Pathways Affected by Babesia Infection and Blood Feeding in the Sialoproteome of the Vector Rhipicephalus bursa

Author: Maria Margarida Santos-Silva, Margarita Villar, Gustavo Seron Sanches, Olga Moreira, Ana Sofia Santos, José de la Fuente, Lourdes Mateos-Hernández, Joao P. Nobre, Joana Ferrolho, Ana Domingos, Joana Couto, Sandra Antunes, Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Global Health and Tropical Medicine [Lisbonne, Portugal] (GHTM), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana [Espagne] (FISABIO), Biochemistry Section, Faculty of Science and Chemical Technologies, Regional Centre for Biomedical Research ((CRIB)), University of Castilla-La Mancha (UCLM)-University of Castilla-La Mancha (UCLM)-Regional Centre for Biomedical Research ((CRIB)), University of Castilla-La Mancha (UCLM)-University of Castilla-La Mancha (UCLM), Biologie moléculaire et immunologie parasitaires et fongiques (BIPAR), École nationale vétérinaire d'Alfort (ENVA)-Laboratoire de santé animale, sites de Maisons-Alfort et de Dozulé, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), Instituto de Saúde Ambiental, Faculdade de Medicina, Universidade de Lisboa (ULISBOA)-Universidade de Lisboa (ULISBOA), Instituto Nacional de Investigação Agraria e Veterinaria, Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University [Stillwater]-Oklahoma State University [Stillwater], Fundacao para a Ciencia e Tecnologia (FCT) under the project TickOmic PTDC/CVT-CVT/29073/2017Portuguese Foundation for Science and TechnologySFRH/BD/121946/2016, Fundação para a Ciência e a Tecnologia (Portugal), and École nationale vétérinaire - Alfort (ENVA)-Laboratoire de santé animale, sites de Maisons-Alfort et de Dozulé
Subjects: 0301 basic medicine, 030231 tropical medicine, Immunology, Quantitative proteomics, Babesia, lcsh:Medicine, UB2N, Tick, Proteomics, ticks, 03 medical and health sciences, Ticks, 0302 clinical medicine, Antigen, Drug Discovery, parasitic diseases, Pharmacology (medical), ub2n, pcca, Pathogen, proteomic, Infecções Sistémicas e Zoonoses, Pharmacology, biology, Transmission (medicine), lcsh:R, Proteomic, rnai, biology.organism_classification, PCCA, 3. Good health, babesia, 030104 developmental biology, Infectious Diseases, RNAi, Vector (epidemiology), [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract: The negative impact of ticks and tick-borne diseases on animals and human health is driving research to discover novel targets affecting both vectors and pathogens. The salivary glands are involved in feeding and pathogen transmission, thus are considered as a compelling target to focus research. In this study, proteomics approach was used to characterize Rhipicephalus bursa sialoproteome in response to Babesia ovis infection and blood feeding. Two potential tick protective antigens were identified and its influence in tick biological parameters and pathogen infection was evaluated. Results demonstrate that the R. bursa sialoproteome is highly affected by feeding but infection is well tolerated by tick cells. The combination of both stimuli shifts the previous scenario and a more evident pathogen manipulation can be suggested. Knockdown of ub2n led to a significative increase of infection in tick salivary glands but a brusque decrease in the progeny, revealing its importance in the cellular response to pathogen infection, which is worth pursuing in future studies. Additionally, an impact in the recovery rate of adults (62%), the egg production efficiency (45.75%), and the hatching rate (88.57 %) was detected. Building knowledge on vector and/or pathogen interplay bridges the identification of protective antigens and the development of novel control strategies., This research was funded by Fundação para a Ciência e Tecnologia (FCT) under the project TickOmic (PTDC/CVT-CVT/29073/2017). JC and JF are the recipients of Ph.D. grants supported by the FCT (SFRH/BD/121946/2016, SFRH/BD/122894/2016, respectively).
Published: 2020

10. Inter-laboratory calibration of quantitative analyses of antibiotic resistance genes

Author: Popi Karaolia, Jaqueline Rocha, Thomas U. Berendonk, Célia M. Manaia, Despo Fatta-Kassinos, Ioannis D. Kampouris, Thomas Schwartz, Hélène Guilloteau, Eddie Cytryn, Christophe Merlin, Roberto B. M. Marano, Damiano Cacace, Thomas Jäger, Centro de Química Fina e Biotecnologia (CQFB), Requimte, Departamento de Química (DQ), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto, Institut für Hydrobiologie, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institute of Functional Interfaces, Karlsruhe Institute of Technology (KIT), Institute of Soil, Water and Environmental Sciences, Agricultural Research Organization - the Volcani Center, University of Cyprus (UCY), and Veritati - Repositório Institucional da Universidade Católica Portuguesa
Subjects: Life sciences, biology, 0301 basic medicine, Calibration (statistics), Inter-laboratory calibration, Computational biology, 010501 environmental sciences, Biology, Wastewater, Antibiotic resistance gene, 01 natural sciences, 03 medical and health sciences, Quantitative PCR, Plasmid, Antibiotic resistance, ddc:570, Chemical Engineering (miscellaneous), Inter-laboratory, Waste Management and Disposal, Gene, ComputingMilieux_MISCELLANEOUS, 0105 earth and related environmental sciences, [SDV.EE]Life Sciences [q-bio]/Ecology, environment, Process Chemistry and Technology, 16S ribosomal RNA, Pollution, 6. Clean water, 030104 developmental biology, Real-time polymerase chain reaction, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Antibiotic resistance genes
Abstract: Antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) are widely distributed in the environment where they represent potential public health threats. Quantitative PCR (qPCR) is a suitable approach to detect and quantify ARGs in environmental samples. However, the comparison of gene quantification data between different laboratories is challenging since the data are predominantly obtained under non-harmonized conditions, using different qPCR protocols. This study aimed at carrying out an inter-laboratory calibration in order to assess the variability inherent to the qPCR procedures for quantification of ARGs. With this aim, samples of treated wastewater collected in three different countries were analysed based on common DNA extract pools and identical protocols as well as distinct equipment, reagents batches, and operators. The genes analysed were the 16S rRNA, vanA, blaTEM, qnrS, sul1, blaCTXM-32 and intI1 and the artificial pNORM1 plasmid containing fragments from the seven targeted genes was used as a reference. The 16S rRNA gene was the most abundant, in all the analysed samples, followed by intI1, sul1, qnrS, and blaTEM, while blaCTXM-32 and vanA were below the limit of quantification in most or all the samples. For the genes 16S rRNA, sul1, intI1, blaTEM and qnrS the inter-laboratory variation was below 28% (3-8%, 6-18%, 8-21%, 10-24%, 15-28%, respectively). While it may be difficult to fully harmonize qPCR protocols due to equipment, reagents and operator variations, the inter-laboratory calibration is an adequate and necessary step to increase the reliability of comparative data on ARGs abundance in different environmental compartments and/or geographic regions.
Published: 2020

11. Impact of Chronic Obstructive Pulmonary Disease on Incidence, Microbiology and Outcome of Ventilator-Associated Lower Respiratory Tract Infections

Author: Jorge I. F. Salluh, Nassima Ramdane, Saad Nseir, Marion Houard, Pedro Póvoa, Anahita Rouzé, Ignacio Martin-Loeches, Pauline Boddaert, Alejandro Rodriguez, Université de Lille, CNRS, Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576, Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], Lille Inflammation Research International Center (LIRIC) - U995, Institut d'Investigacions Biomèdiques August Pi i Sunyer [IDIBAPS], St James's University Hospital, Universidade Nova de Lisboa = NOVA University Lisbon [NOVA], METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694, D'Or Institute for Research and Education [Rio de Janeiro], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Leeds Teaching Hospitals NHS Trust, Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille
Subjects: Microbiology (medical), medicine.medical_treatment, mechanical ventilation, Microbiology, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Article, law.invention, chronic obstructive pulmonary disease, 03 medical and health sciences, Mechanical ventilation, 0302 clinical medicine, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Intensive care, Tracheobronchitis, medicine, pneumonia, lcsh:QH301-705.5, intensive care, COPD, biology, Respiratory tract infections, business.industry, Chronic obstructive pulmonary disease, Incidence (epidemiology), ventilator-associated, Ventilator-associated, 030208 emergency & critical care medicine, Pneumonia, medicine.disease, biology.organism_classification, Intensive care unit, Lower respiratory tract infections, 3. Good health, respiratory tract diseases, lower respiratory tract infections, tracheobronchitis, Stenotrophomonas maltophilia, lcsh:Biology (General), 030228 respiratory system, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Objectives: To determine the impact of chronic obstructive pulmonary disease (COPD) on incidence, microbiology, and outcomes of ventilator-associated lower respiratory tract infections (VA-LRTI). Methods: Planned ancillary analysis of TAVeM study, including 2960 consecutive adult patients who received invasive mechanical ventilation (MV) &gt, 48 h. COPD patients (n = 494) were compared to non-COPD patients (n = 2466). The diagnosis of ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP) was based on clinical, radiological and quantitative microbiological criteria. Results: No significant difference was found in VAP (12% versus 13%, p = 0.931), or VAT incidence (13% versus 10%, p = 0.093) between COPD and non-COPD patients. Among patients with VA-LRTI, Escherichia coli and Stenotrophomonas maltophilia were significantly more frequent in COPD patients as compared with non-COPD patients. However, COPD had no significant impact on multidrug-resistant bacteria incidence. Appropriate antibiotic treatment was not significantly associated with progression from VAT to VAP among COPD patients who developed VAT, unlike non-COPD patients. Among COPD patients, patients who developed VAT or VAP had significantly longer MV duration (17 days (9&ndash, 30) or 15 (8&ndash, 27) versus 7 (4&ndash, 12), p &lt, 0.001) and intensive care unit (ICU) length of stay (24 (17&ndash, 39) or 21 (14&ndash, 40) versus 12 (8&ndash, 19), p &lt, 0.001) than patients without VA-LRTI. ICU mortality was also higher in COPD patients who developed VAP (44%), but not VAT(38%), as compared to no VA-LRTI (26%, p = 0.006). These worse outcomes associated with VA-LRTI were similar among non-COPD patients. Conclusions: COPD had no significant impact on incidence or outcomes of patients who developed VAP or VAT.
Published: 2020

12. Systematic bioinformatic analysis of nutrigenomic data of flavanols in cell models of cardiometabolic disease

Author: Ken Declerck, Maria Annunziata Carluccio, Cláudia N. Santos, Begoña Muguerza, Anna Arola-Arnal, Ana Rodriguez-Mateos, Francisca Isabel Bravo, Nadia Calabriso, Emilie Combet, Marika Massaro, Wim Vanden Berghe, Eileen R. Gibney, E. Kistanova, Egeria Scoditti, Dragan Milenkovic, Manuel Suárez, Andreia Gomes, Irena Krga, Tatjana Ruskovska, Marie Paule Gonthier, Pedro Mena, Christine Morand, Sonia de Pascual-Teresa, University Goce Delcev (UGD), Institute of Clinical Physiology (IFC), National Research Council [Italy] (CNR), Universitat Rovira i Virgili, Universiteit Antwerpen [Antwerpen], University of Glasgow, University College Dublin [Dublin] (UCD), Instituto de Biologia Experimental e Tecnológica (IBET), Instituto de Tecnologia Química e Biológica António Xavier (ITQB), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Diabète athérothrombose et thérapies Réunion Océan Indien (DéTROI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de La Réunion (UR), Bulgarian Academy of Sciences (BAS), University of Belgrade [Belgrade], Department of Food Science, Human Nutrition Unit, The Phi² Laboratory of Phytochemicals in Physiology - LS9 Bioactives and Health, Interlab Group, University of Parma = Università degli studi di Parma [Parme, Italie], Unité de Nutrition Humaine (UNH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centro de Estudos de Doenças Crónicas (CEDOC), NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Institute of Food Science, Technology and Nutrition (ICTAN-CSIC), King‘s College London, Natl Res Council CNR, Inst Biol & Agr Biotechnol IBBA, Res Unit Pisa, Pisa, Italy, European Cooperation in Science and Technology (COST) FA1403, European Commission, Universiteit Antwerpen = University of Antwerpen [Antwerpen], Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Università degli studi di Parma = University of Parma (UNIPR)
Subjects: 0301 basic medicine, Cell type, Flavonols, Computational biology, Biology, Models, Biological, 03 medical and health sciences, 0302 clinical medicine, Nutrigenomics, microRNA, Gene expression, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Gene, Regulation of gene expression, Mechanism (biology), Pharmacology. Therapy, GATA2, Computational Biology, Lipid metabolism, General Medicine, 3. Good health, Chemistry, 030104 developmental biology, flavanol, Cardiovascular Diseases, 030220 oncology & carcinogenesis, Food Science
Abstract: Flavanol intake positively influences several cardiometabolic risk factors in humans. However, the specific molecular mechanisms of action of flavanols, in terms of gene regulation, in the cell types relevant to cardiometabolic disease have never been systematically addressed. On this basis, we conducted a systematic literature review and a comprehensive bioinformatic analysis of genes whose expression is affected by flavanols in cells defining cardiometabolic health: hepatocytes, adipocytes, endothelial cells, smooth muscle cells and immune cells. A systematic literature search was performed using the following pre-defined criteria: treatment with pure compounds and metabolites (no extracts) at low concentrations that are close to their plasma concentrations. Differentially expressed genes were analyzed using bioinformatics tools to identify gene ontologies, networks, cellular pathways and interactions, as well as transcriptional and post-transcriptional regulators. The systematic literature search identified 54 differentially expressed genes at the mRNA level in in vitro models of cardiometabolic disease exposed to flavanols and their metabolites. Global bioinformatic analysis revealed that these genes are predominantly involved in inflammation, leukocyte adhesion and transendothelial migration, and lipid metabolism. We observed that, although the investigated cells responded differentially to flavanol exposure, the involvement of anti-inflammatory responses is a common mechanism of flavanol action. We also identified potential transcriptional regulators of gene expression: transcriptional factors, such as GATA2, NFKB1, FOXC1 or PPARG, and post-transcriptional regulators: miRNAs, such as mir-335-5p, let-7b-5p, mir-26b-5p or mir-16-5p. In parallel, we analyzed the nutrigenomic effects of flavanols in intestinal cells and demonstrated their predominant involvement in the metabolism of circulating lipoproteins. In conclusion, the results of this systematic analysis of the nutrigenomic effects of flavanols provide a more comprehensive picture of their molecular mechanisms of action and will support the future setup of genetic studies to pave the way for individualized dietary recommendations., COST (European Cooperation in Science and Technology) Action FA1403.
Published: 2020

13. The Henna pigment Lawsone activates the Aryl Hydrocarbon Receptor and impacts skin homeostasis

Author: Marion Klemm, Ulrike Zedler, Anne-Britta Koehler, Maria Leite-de-Moraes, Marina Bechtle, Hans-Joachim Mollenkopf, Stefan H. E. Kaufmann, Annika Kreuchwig, Gerd Krause, Andreas Puyskens, Manuela Stäber, Teresa Domaszewska, January Weiner, Ute Guhlich-Bornhof, António Jacinto, Bogdan Silviu Ungureanu, Robert Hurwitz, Carolina Lage Crespo, Pedro Moura-Alves, Ioana Florina Mihai, Ioana Streata, Laura Lozza, Jens Furkert, Marcus Maurer, Frank Siebenhaar, Leibniz Institut für Molekulare Pharmakolgie (FMP), Leibniz Association, Cell Biology, Institute of Environmental Sciences, Jagiellonian University [Krakow] (UJ), Chronic Diseases Research Center (CEDOC), NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa (NOVA)-Universidade Nova de Lisboa (NOVA), Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Dermatology, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin -Medical School, Universität Heidelberg [Heidelberg], NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), Centro de Estudos de Doenças Crónicas (CEDOC), Leibniz Forschungsinstitut für Molekulare Pharmakolgie = Leibniz Institute for Molecular Pharmacology [Berlin, Allemagne] (FMP), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), and Medical School-Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
Subjects: 0301 basic medicine, EXPRESSION, Immunology, AHR, TETRACHLORODIBENZO-PARA-DIOXIN, lcsh:Medicine, Inflammation, Context (language use), Article, TOXICITY, Lawsone, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Nuclear receptors, DIOXIN, medicine, Receptor, lcsh:Science, General, ComputingMilieux_MISCELLANEOUS, Multidisciplinary, Epidermis (botany), biology, integumentary system, IDENTIFICATION, Chemistry, Regeneration (biology), 2,3,7,8, INDUCTION, lcsh:R, KERATINOCYTES, Aryl hydrocarbon receptor, 3. Good health, Cell biology, DERMATITIS, 030104 developmental biology, DIFFERENTIATION, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, lcsh:Q, medicine.symptom, Wound healing, 030217 neurology & neurosurgery
Abstract: International audience; As a first host barrier, the skin is constantly exposed to environmental insults that perturb its integrity. tight regulation of skin homeostasis is largely controlled by the aryl hydrocarbon receptor (AhR). Here, we demonstrate that Henna and its major pigment, the naphthoquinone Lawsone activate AhR, both in vitro and in vivo. In human keratinocytes and epidermis equivalents, Lawsone exposure enhances the production of late epidermal proteins, impacts keratinocyte differentiation and proliferation, and regulates skin inflammation. To determine the potential use of Lawsone for therapeutic application, we harnessed human, murine and zebrafish models. In skin regeneration models, Lawsone interferes with physiological tissue regeneration and inhibits wound healing. Conversely, in a human acute dermatitis model, topical application of a Lawsone-containing cream ameliorates skin irritation. Altogether, our study reveals how a widely used natural plant pigment is sensed by the host receptor AhR, and how the physiopathological context determines beneficial and detrimental outcomes. The skin acts as an important first barrier of the body, which is constantly exposed to diverse environmental and mechanical insults, such as pollution, infection, injury and radiation, amongst others 1. Additionally, the application of cosmetics and other agents can have a major impact on skin homeostasis 1. Among the most widely used skin dyes, are the extracts of Lawsonia inermis, commonly known as Henna 2. In traditional medicine, Henna has been widely used to treat bacterial and fungal infections, inflammation, cancer and various skin pathologies 3 , but the underlying mechanisms remain insufficiently understood. Major side effects of Henna preparations are caused by the additive para-phenylenediamine (PPD) that has been associated with allergic contact dermatitis 4,5. As natural product, Henna comprises a mixture of numerous compounds most of which are poorly characterized opeN There are amendments to this paper
Published: 2019

14. Opioids and the Blood-Brain Barrier: A Dynamic Interaction with Consequences on Drug Disposition in Brain

Author: Salvatore Cisternino, Xavier Declèves, Catarina Chaves, Fernando Remião, Variabilité de réponse aux Psychotropes (VariaPsy - U1144), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Requimte, Universidade do Porto = University of Porto-Departamento de Química (DQ), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), and Decleves, Xavier
Subjects: 0301 basic medicine, opioids, Abcg2, [SDV]Life Sciences [q-bio], ATP-binding cassette transporter, Pharmacology, P-glycoprotein, Article, neuroinflammation, 03 medical and health sciences, 0302 clinical medicine, Medicine, Animals, Humans, Pharmacology (medical), TLR4, Neuroinflammation, biology, business.industry, Brain, Biological Transport, General Medicine, 3. Good health, Solute carrier family, [SDV] Life Sciences [q-bio], Analgesics, Opioid, Psychiatry and Mental health, 030104 developmental biology, Neurology, Opioid, ABC transporters, Nonlinear Dynamics, Blood-Brain Barrier, biology.protein, ATP-Binding Cassette Transporters, Neurology (clinical), Efflux, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: International audience; Background: Opioids are widely used in pain management, acting via opioid receptors and/or Toll-like receptors (TLR) present at the central nervous system (CNS). At the blood-brain barrier (BBB), several influx and efflux transporters, such as the ATP-binding cassette (ABC) P-glycoprotein (P-gp, ABCB1), Breast Cancer Resistance Protein (BCRP, ABCG2) and multidrug resistance-associated proteins (MRP, ABCC) transporters, and solute carrier transporters (SLC), are responsible for the transport of xenobiotics from the brain into the bloodstream or vice versa.Objective: ABC transporters export several clinically employed opioids, altering their neuropharmacokinetics and CNS effects. In this review, we explore the interactions between opioids and ABC transporters, and decipher the molecular mechanisms by which opioids can modify their expression at the BBB.Results: P-gp is largely implicated in the brain-to-blood efflux of opioids, namely morphine and oxycodone. Long-term exposure to morphine and oxycodone has proven to up-regulate the expression of ABC transporters, such as P-gp, BCRP and MRPs, at the BBB, which may lead to increased tolerance to the antinociceptive effects of such drugs. Recent studies uncover two mechanisms by which morphine may up-regulate P-gp and BCRP at the BBB: 1) via a glutamate, NMDA-receptor and COX-2 signaling cascade, and 2) via TLR4 activation, subsequent development of neuroinflammation, and activation of NF-kB, presumably via glial cells.Conclusion: The BBB-opioid interaction can culminate in bilateral consequences, since ABC transporters condition the brain disposition of opioids, while opioids also affect the expression of ABC transporters at the BBB, which may result in increased CNS drug pharmacoresistance.
Published: 2017

15. Berry-Enriched Diet in Salt-Sensitive Hypertensive Rats: Metabolic Fate of (Poly)Phenols and the Role of Gut Microbiota

Author: Andreia C. Gomes, Maria-José Motilva, Catherine Brenner, Carole Oudot, Tom Van de Wiele, Alba Macià, Derek Stewart, Alexandre Foito, Cláudia N. Santos, Diogo Carregosa, David Berry, Centro de Estudos de Doenças Crónicas (CEDOC), NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Institut National de la Santé et de la Recherche Médicale (INSERM), Universitat de Lleida, The James Hutton Institute, Instituto de Biologia Experimental e Tecnológica (IBET), Universiteit Gent = Ghent University [Belgium] (UGENT), University of Vienna [Vienna], Universidad Internacional de la Rioja (UNIR), Centre National de la Recherche Scientifique (CNRS), Agence Nationale de la Recherche (France), Fundação para a Ciência e a Tecnologia (Portugal), Austrian Science Fund, European Research Council, Scottish Government's Rural and Environment Science and Analytical Services, European Commission, Chronic Diseases Research Center (CEDOC), and INSERM, UMR-S1180
Subjects: Male, 0301 basic medicine, Agriculture and Food Sciences, [SDV]Life Sciences [q-bio], Phytochemicals, BLOOD-PRESSURE, Berry, 030204 cardiovascular system & hematology, Gut flora, Feces, chemistry.chemical_compound, 0302 clinical medicine, Glycosides, Food science, HUMAN PLASMA, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, Nutrition and Dietetics, biology, cardiovascular, dysbiosis, 3. Good health, POSTMENOPAUSAL WOMEN, CARDIOVASCULAR-DISEASE, ARTERIAL STIFFNESS, lcsh:Nutrition. Foods and food supply, lcsh:TX341-641, OIL PHENOLIC-COMPOUNDS, Article, CHLOROGENIC ACIDS, 03 medical and health sciences, Phenols, INTESTINAL MICROBIOTA, COLONIC METABOLITES, gut metabolism, medicine, Animals, polyphenols, Rats, Inbred Dahl, Biology and Life Sciences, Sodium, Dietary, Metabolism, IN-VITRO, medicine.disease, biology.organism_classification, Diet, Gastrointestinal Microbiome, Rats, 030104 developmental biology, Strawberry tree, chemistry, high salt intake, Polyphenol, Fruit, Dysbiosis, Food Science
Abstract: Diets rich in (poly)phenols are associated with a reduced reduction in the incidence of cardiovascular disorders. While the absorption and metabolism of (poly)phenols has been described, it is not clear how their metabolic fate is affected under pathological conditions. This study evaluated the metabolic fate of berry (poly)phenols in an in vivo model of hypertension as well as the associated microbiota response. Dahl salt-sensitive rats were fed either a low-salt diet (0.26% NaCl) or a high-salt diet (8% NaCl), with or without a berry mixture (blueberries, blackberries, raspberries, Portuguese crowberry and strawberry tree fruit) for 9 weeks. The saltenriched diet promoted an increase in the urinary excretion of berry (poly)phenol metabolites, while the abundance of these metabolites decreased in faeces, as revealed by UPLC¿MS/MS. Moreover, salt and berries modulated gut microbiota composition as demonstrated by 16S rRNA analysis. Some changes in the microbiota composition were associated with the high-salt diet and revealed an expansion of the families Proteobacteria and Erysipelotrichaceae. However, this effect was mitigated by the dietary supplementation with berries. Alterations in the metabolic fate of (poly)phenols occur in parallel with the modulation of gut microbiota in hypertensive rats. Thus, beneficial effects of (poly)phenols could be related with these interlinked modifications, between metabolites and microbiota environments., C.B., C.N.d.S., C.O. were funded by ANR (ANR-13-ISV1-0001-01) and FCT (FCTANR/BEX-BCM/0001/2013). D.B. was funded by the Austrian Science Fund (FWF P26127-B20) and European Research Council (Starting Grant: FunKeyGut 741623). D.S. and A.F. acknowledge support from Scottish Government: Rural and Environment Science and Analytical Services. We also acknowledge the Investment for the Future program ANR-11-IDEX-0003-01 within the LABEX ANR-10-LABX-0033 (C.B., C.O.), Fundação para a Ciência e Tecnologia financial support of A.G. (SFRH/BD/103155/2014) and C.N.d.S. (IF/01097/2013). iNOVA4Health Research Unit (LISBOA-01-0145-FEDER-007344), which is cofounded by FCT through national funds, and by FEDER under the PT2020 Partnership Agreement, is acknowledged.
Published: 2019
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16. Hemorrhagic pancreatic cyst during third trimester of pregnancy: A case-report

Author: P. Amaro, L. Duminil, T. Piardi, René Gabriel, S. Bonneau, Olivier Graesslin, J. Cousson, Emilie Raimond, Departamento de Fìsica [Lisboa] (DF), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Laboratoire Kastler Brossel (LKB (Lhomond)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Reims (CHU Reims), and Institut Mère Enfant Alix de Champagne
Subjects: medicine.medical_specialty, Pregnancy, 030219 obstetrics & reproductive medicine, Obstetrics, business.industry, [SDV]Life Sciences [q-bio], Obstetrics and Gynecology, Third trimester, medicine.disease, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Reproductive Medicine, Pancreatic cyst, medicine, 030211 gastroenterology & hepatology, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019

17. Simulation of an Early Warning Fire System

Author: Alessandro Fantoni, Paulo Lourenço, Manuela Vieira, Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Centre of Technology and Systems (CTS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Instituto Superior de Engenharia de Lisboa (ISEL), Luis M. Camarinha-Matos, Ricardo Almeida, José Oliveira, TC 5, and WG 5.5
Subjects: Power transmission, Warning system, Computer science, Wireless network, Event (computing), Fire detection, Real-time computing, Terrain, 02 engineering and technology, MMI coupler, WSN, FDTD simulations, 030507 speech-language pathology & audiology, 03 medical and health sciences, 020210 optoelectronics & photonics, 13. Climate action, Surface plasmon resonance, 0202 electrical engineering, electronic engineering, information engineering, Early warning system, [INFO]Computer Science [cs], 0305 other medical science, Wireless sensor network
Abstract: Part 9: Communication Systems; International audience; In this paper, we will be using separate software tools (wireless network and Finite Differences Time Domain based simulators) to simulate the implementation of a wireless sensor network model based on low-rate/power transmission technology. The system operates in an unlicensed frequency range and the sensing nodes rely on surface plasmon resonance phenomenon for the detection of combustion by-products. More specifically, our simulations contemplate a system for early detection of fire in densely forested areas, which will then issue a warning in an automated way. As late detection of these events usually leads to severe flora, terrain, wild life and societal impact, an early warning system will provide better event assessment conditions, thus enabling efficient resources allocation, adequate response and would certainly be a promising improvement in minimizing such disruptive impairments.
Published: 2019

18. CSRP3 mediates polyphenols-induced cardioprotection in hypertension

Author: Jocelyne Hamelin, Helena L. A. Vieira, Valérie Nicolas, Patrizia Gena, Giuseppe Calamita, Morgane Le Gall, Cédric Broussard, Philippe Chaffey, Maria Mastrodonato, Cláudia N. Santos, Andreia Gomes, Antoinette Lemoine, Jean-Luc Perfettini, Catherine Brenner, Carole Oudot, Rodolphe Fischmeister, Centre de pharmacologie et innovation dans le diabète (CPID), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1), Centro de Estudos de Doenças Crónicas (CEDOC), NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Plateforme Recombinaison Homologue, Transfert d'Embryons et Cryoconservation [Institut Cochin] (PRHTEC), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Dipartimento di Fisiologia Generale ed Ambientale, Università degli studi di Bari Aldo Moro (UNIBA), Radiothérapie moléculaire (UMR 1030), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Physiopathogenèse et Traitement des Maladies du Foie [Villejuif], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11), Signalisation et physiopathologie cardiaque, Université Paris-Sud - Paris 11 (UP11)-IFR141-Institut National de la Santé et de la Recherche Médicale (INSERM), Human Language Technology Interest Group (HULTIG), Universidade de Beira Interior, INSERM, UMR-S1180, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre National de la Recherche Scientifique (CNRS), Universidade Nova de Lisboa (NOVA)-Universidade Nova de Lisboa (NOVA), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Bari, Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Signalisation et physiopathologie cardiovasculaire (UMRS1180), Institut National de la Santé et de la Recherche Médicale (INSERM), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Ingénierie et Plateformes au Service de l'Innovation Thérapeutique (IPSIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Plateforme protéomique 3P5 [Institut Cochin] (3P5), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Radiothérapie Moléculaire et Innovation Thérapeutique (RaMo-IT), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, and FISCHMEISTER, RODOLPHE
Subjects: Male, 0301 basic medicine, Cardiotonic Agents, Endocrinology, Diabetes and Metabolism, Metabolite, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Muscle Proteins, Cardiomegaly, Cardioprotection, 030204 cardiovascular system & hematology, Pharmacology, Biochemistry, Nitric oxide, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Fibrosis, medicine, Animals, Myocyte, Myocytes, Cardiac, CSRP3, Molecular Biology, Phenylephrine, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, Rats, Inbred Dahl, Nutrition and Dietetics, Chemistry, Polyphenols, Sarcomere, Heart, Berries, LIM Domain Proteins, medicine.disease, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Disease Models, Animal, 030104 developmental biology, Strawberry tree, Fruit, Heart failure, Hypertension, medicine.drug
Abstract: International audience; Berries contain bioactive polyphenols, whose capacity to prevent cardiovascular diseases has been established recently in animal models as well in human clinical trials. However, cellular processes and molecular targets of berries polyphenols remain to be identified. The capacity of a polyphenol-enriched diet (i.e., blueberries, blackberries, raspberries, strawberry tree fruits and Portuguese crowberries berries mixture) to promote animal survival and protect cardiovascular function from salt-induced hypertension was evaluated in a chronic salt-sensitive Dahl rat model. The daily consumption of berries improved survival of Dahl/ salt-sensitive rats submitted to high-salt diet and normalized their body weight, renal function and blood pressure. In addition, a prophylactic effect was observed at the level of cardiac hypertrophy and dysfunction, tissue cohesion and cardiomyocyte hypertrophy. Berries also protected the aorta from fibrosis and modulated the expression of aquaporin-1, a channel involved in endothelial water and nitric oxide permeability. Left ventricle proteomics analysis led to the identification of berries and salt metabolites targets, including cystein and glycin-rich protein 3 (CSRP3), a protein involved in myocyte cytoarchitecture. In neonatal rat ventricular cardiomyocytes, CSRP3 was validated as a target of a berries-derived polyphenol metabolite, 4-methylcatechol sulfate, at micromolar concentrations, mimicking physiological conditions of human plasma circulation. Accordingly, siRNA silencing of CSRP3 and 4-methylcatechol sulfate pretreatment reversed cardiomyocyte hypertrophy and CSRP3 overexpression induced by phenylephrine. Our systemic study clearly supports the modulation of CSRP3 by a polyphenol-rich berries diet as an efficient cardioprotective strategy in hypertension-induced heart failure.
Published: 2019

19. Interplay between SUMOylation and NEDDylation regulates RPL11 localization and function

Author: Carmen Rivas, Rune Matthiesen, Sabela Da Silva-Álvarez, Manuel Collado, Ahmed El Motiam, Ana Sofia Carvalho, Hans Christian Beck, Carlos F. de la Cruz-Herrera, Maite Baz-Martínez, Anxo Vidal, Dimitris P. Xirodimas, Santiago Vidal, Rocío Seoane, Manuel S. Rodriguez, Molecular Medicine and Chronic Diseases Research Centre [Santiago de Compostela, Spain] (CIMUS), Universidade de Santiago de Compostela [Spain] (USC ), Centro de Biología Molecular Severo Ochoa [Madrid] (CBMSO), Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en Biologie Cellulaire (CRBM), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Centro de Estudos de Doenças Crónicas (CEDOC), NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Department of Clinical Biochemistry and Pharmacology, OdenseUniversity Hospital, Sdr. Boulevard 29, CIMUS Biomedical Research Institute [Santiago de Compostela], Centro Nacional de Biotecnología [Madrid] (CNB-CSIC), Biocomputing Unit [Madrid], Department of Molecular Genetics, Donnelly Centre for Cellular and Biomolecular Research, Department of Molecular Genetics, University of Toronto, University of Toronto, Hospital Clínico Universitario Santiago de Compostela, Institut des Technologies Avancées en sciences du Vivant (ITAV), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie et de biologie structurale (IPBS), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université Montpellier 2 - Sciences et Techniques (UM2), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Odense University Hospital, Odense, Molecular and Cellular Biology, Hospital Clinico Universitario de Santiago de Compostela, Universidad Autónoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Instituto de Investigación Sanitaria de Santiago de Compostela / Health Research Institute of Santiago de Compostela (IDIS), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en Biologie cellulaire de Montpellier (CRBM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Ribosomal Proteins, 0301 basic medicine, p53, NEDD8 Protein, Nucleolus, [SDV]Life Sciences [q-bio], SUMO protein, Regulator, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, SUMO2, Biochemistry, NEDD8, environment and public health, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Ribosomal protein, Neoplasms, Tumor Cells, Cultured, Genetics, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Ubiquitins, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Chemistry, Sumoylation, ARF, Cell biology, HEK293 Cells, 030104 developmental biology, SUMO, Small Ubiquitin-Related Modifier Proteins, Neddylation, Protein Processing, Post-Translational, 030217 neurology & neurosurgery, Biotechnology
Abstract: The ribosomal protein L11 (RPL11) integrates different types of stress into a p53-mediated response. Here, we analyzed the impact of the ubiquitin-like protein SUMO on the RPL11-mouse double-minute 2 homolog-p53 signaling. We show that small ubiquitin-related modifier (SUMO)1 and SUMO2 covalently modify RPL11. We find that SUMO negatively modulates the conjugation of the ubiquitin-like protein neural precursor cell-expressed developmentally downregulated 8 (NEDD8) to RPL11 and promotes the translocation of the RP outside of the nucleoli. Moreover, the SUMO-conjugating enzyme, Ubc9, is required for RPL11-mediated activation of p53. SUMOylation of RPL11 is triggered by ribosomal stress, as well as by alternate reading frame protein upregulation. Collectively, our data identify SUMO protein conjugation to RPL11 as a new regulator of the p53-mediated cellular response to different types of stress and reveal a previously unknown SUMO-NEDD8 interplay.-El Motiam, A, Vidal, S., de la Cruz-Herrera, C. F., Da Silva-Álvarez, S., Baz-Martínez, M., Seoane, R., Vidal, A., Rodríguez, M. S., Xirodimas, D. P., Carvalho, A. S., Beck, H. C., Matthiesen, R., Collado, M., Rivas, C. Interplay between SUMOylation and NEDDylation regulates RPL11 localization and function.
Published: 2019

20. Convergent recombination cessation between mating-type genes and centromeres in selfing anther-smut fungi

Author: Sara Branco, Tatiana Giraud, Alodie Snirc, Marco A. Coelho, Michael E. Hood, Ricardo C. Rodríguez de la Vega, Fantin Carpentier, Ecologie Systématique et Evolution (ESE), Université Paris-Sud - Paris 11 (UP11)-AgroParisTech-Centre National de la Recherche Scientifique (CNRS), Departamento de Ciencias da Vida (DCV), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), University of Massachusetts [Amherst] (UMass Amherst), University of Massachusetts System (UMASS), UCIBIO - Applied Molecular Biosciences Unit, and DCV - Departamento de Ciências da Vida
Subjects: 0303 health sciences, Mating type, Natural selection, Selfing, Biology, Mating system, Genome, 03 medical and health sciences, 0302 clinical medicine, Evolutionary biology, Genetic linkage, Phylogenetics, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, Genetics(clinical), Allele, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, 030217 neurology & neurosurgery, Genetics (clinical), [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, 030304 developmental biology
Abstract: grant 1115765 R15GM119092 The degree of selfing has major impacts on adaptability and is often controlled by molecular mechanisms determining mating compatibility. Changes in compatibility systems are therefore important evolutionary events, but their underlying genomic mechanisms are often poorly understood. Fungi display frequent shifts in compatibility systems, and their small genomes facilitate elucidation of the mechanisms involved. In particular, linkage between the pre- and postmating compatibility loci has evolved repeatedly, increasing the odds of gamete compatibility under selfing. Here, we studied the mating-type chromosomes of two anther-smut fungi with unlinked mating-type loci despite a self-fertilization mating system. Segregation analyses and comparisons of high-quality genome assemblies revealed that these two species displayed linkage between mating-type loci and their respective centromeres. This arrangement renders the same improved odds of gamete compatibility as direct linkage of the two mating-type loci under the automictic mating (intratetrad selfing) of anther-smut fungi. Recombination cessation was found associated with a large inversion in only one of the four linkage events. The lack of trans-specific polymorphism at genes located in nonrecombining regions and linkage date estimates indicated that the events of recombination cessation occurred independently in the two sister species. Our study shows that natural selection can repeatedly lead to similar genomic patterns and phenotypes, and that different evolutionary paths can lead to distinct yet equally beneficial responses to selection. Our study further highlights that automixis and gene linkage to centromeres have important genetic and evolutionary consequences, while being poorly recognized despite being present in a broad range of taxa. publishersversion published
Published: 2019

21. Fermentation innovation through complex hybridization of wild and domesticated yeasts

Author: Paula Gonçalves, Ursula Bond, Quinn K. Langdon, David Peris, Diego Libkind, Huu-Vang Nguyen, José Paulo Sampaio, Chris Todd Hittinger, Dana A. Opulente, EmilyClare P. Baker, Genome Center of Wisconsin, University of Wisconsin-Madison, Great Lakes Bioenergy Research Center (GLBRC), Department of Food Biotechnology, Instituto de Agroquímica y Tecnología de Alimentos - Institute of Agrochemistry and Food Technology [Valencia] (IATA-CSIC), Microbiology Doctoral Training Program, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Department of Microbiology, Trinity College Dublin, Unidade de Ciencias Biomoleculares Aplicadas (UCIBIO), Requimte, Universidade do Porto = University of Porto-Departamento de Química (DQ), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto = University of Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), National Science Foundation (NSF)DEB-1253634DGE-1256259USDA National Institute of Food and Agriculture Hatch Project 10032581020204United States Department of Energy (DOE)DE-SC0018409DE-FC02-07ER64494United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA5T32GM007133European Union (EU)747775Louis and Elsa Thomsen Wisconsin Distinguished Graduate Fellowship Horizon 2020 MSCA-ITN grant 764364Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET)PIP 392FONCyTPICT 3677Universidad Nacional del Comahue B199Pew Charitable Trusts Vilas Trust Estate Office of the Vice Chancellor for Research and Graduate Education Wisconsin Alumni Research Foundation, European Project: 0747775(2008), European Commission, National Science Foundation (US), National Institute of Food and Agriculture (US), Universidade do Porto-Departamento de Química (DQ), and Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto-Departamento de Química (DQ)
Subjects: Mitochondrial DNA, Lineage (evolution), Saccharomyces cerevisiae, BEER, INGENIERÍAS Y TECNOLOGÍAS, CEREVISIAE, Saccharomyces, Article, MITOCHONDRIAL GENOMES, Biotecnología Industrial, 03 medical and health sciences, YEAST, MALTOTRIOSE UTILIZATION, Gene, X SACCHAROMYCES-KUDRIAVZEVII, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Hybrid, Genetics, 0303 health sciences, Ecology, biology, 030306 microbiology, Bioproductos, Biomateriales, Bioplásticos, Biocombustibles, Bioderivados, etc, STRAINS, purl.org/becyt/ford/2.9 [https], R-PACKAGE, Beer, food and beverages, GENOME SEQUENCE, biology.organism_classification, Yeast, POPULATION GENOMICS, EVOLUTION, ALPHA-GLUCOSIDE TRANSPORTER, purl.org/becyt/ford/2 [https], DOMESTICATION, Fermentation, [SDE]Environmental Sciences, Hybridization, Genetic, Adaptation, HYBRIDIZATION
Abstract: The most common fermented beverage, lager beer, is produced by interspecies hybrids of the brewing yeast Saccharomyces cerevisiae and its wild relative S. eubayanus. Lager-brewing yeasts are not the only example of hybrid vigour or heterosis in yeasts, but the full breadth of interspecies hybrids associated with human fermentations has received less attention. Here we present a comprehensive genomic analysis of 122 Saccharomyces hybrids and introgressed strains. These strains arose from hybridization events between two to four species. Hybrids with S. cerevisiae contributions originated from three lineages of domesticated S. cerevisiae, including the major wine-making lineage and two distinct brewing lineages. In contrast, the undomesticated parents of these interspecies hybrids were all from wild Holarctic or European lineages. Most hybrids have inherited a mitochondrial genome from a parent other than S. cerevisiae, which recent functional studies suggest could confer adaptation to colder temperatures. A subset of hybrids associated with crisp flavour profiles, including both lineages of lager-brewing yeasts, have inherited inactivated S. cerevisiae alleles of critical phenolic off-flavour genes and/or lost functional copies from the wild parent through multiple genetic mechanisms. These complex hybrids shed light on the convergent and divergent evolutionary trajectories of interspecies hybrids and their impact on innovation in lager brewing and other diverse fermentation industries., Work supported by the National Science Foundation (grant nos. DEB-1253634 to C.T.H. and DGE-1256259 (Graduate Research Fellowship to Q.K.L.), the USDA National Institute of Food and Agriculture Hatch Project (nos. 1003258 and 1020204 to C.T.H.) and in part by the DOE Great Lakes Bioenergy Research Center (DOE BER Office of Science nos. DE-SC0018409 and DE-FC02-07ER64494). Q.K.L. was also supported by the Predoctoral Training Program in Genetics, funded by the National Institutes of Health (grant no. 5T32GM007133). D.P. is a Marie Sklodowska-Curie fellow of the European Union’s Horizon 2020 research and innovation programme (grant no. 747775).
Published: 2019

22. Next-generation Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines for allergic rhinitis based on Grading of Recommendations Assessment, Development and Evaluation (GRADE) and real-world evidence

Author: Piotr Kuna, J. C. Ivancevich, Dana Wallace, Alvaro A. Cruz, Igor Kaidashev, Louis-Philippe Boulet, Anna Bedbrook, Marek L. Kowalski, Ioana Agache, Hae-Sim Park, Gregoire Mercier, Mario Sánchez-Borges, Karl-Christian Bergmann, Tomohisa Iinuma, Peter Hellings, Graham Roberts, Erkka Valovirta, Antonella Muraro, Robyn E O'Hehir, Oliver Pfaar, Luis Caraballo, Mohamed H. Shamji, Torsten Zuberbier, Guy Brusselle, Nicolas Roche, Dermot Ryan, Holger J. Schünemann, Ignacio J. Ansotegui, Erik Melén, V. Cardona, Wienczyslawa Czarlewski, Mike Bewick, Ana-Maria Todo Bom, Susan Waserman, Sinthia Bosnic-Anticevich, Ludger Klimek, Isabelle Bosse, Sanna Toppila-Salmi, Giovanni Passalacqua, Daniel Laune, Lan Le, Despo Ierodiakonou, Gert Marien, Derek K. Chu, Akdis Togias, M. T. Ventura, Marek Jutel, Désirée Larenas-Linnemann, João Fonseca, Elísio Costa, Motohiro Ebisawa, Mark S. Dykewicz, Roy Gerth van Wijk, Musa Khaitov, Pedro Carreiro-Martins, Ioana Tsiligianni, Ettore Novellino, Wytske Fokkens, Nelson Rosario, Thomas B. Casale, Philippe Bonniaud, Bolesław Samoliński, Omer Kalayci, Olga Lourenço, Yoshitaka Okamoto, Moises A. Calderon, Stefania La Grutta, Gennaro D'Amato, Glenis Scadding, Bilun Gemicioglu, Petr Panzner, Philippe Devillier, Ralph Mosgues, Susanne Halken, Susanne Lau, Violeta Kvedariene, Aziz Sheikh, Samantha Walker, Marylin Valentin-Rostan, Martina Erhola, Nhan Pham-Thi, Christine Rolland, H. Neffen, Jean Bousquet, Jean-François Fontaine, Jacques Bouchard, Jean-Louis Fauquert, Arunas Valiulis, Claus Bachert, Lorenzo Cecchi, Jorg Kleine Tebbe, Walter Canonica, David Price, Tari Haahtela, Ken Ohta, Philipp Lieberman, Leyla Namazova, Karin C. Lødrup Carlsen, Joaquim Mullol, Enrica Menditto, Arzu Yorgancioglu, Jan Brozek, Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA), Humboldt-Universität zu Berlin, McMaster University [Hamilton, Ontario], National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Upper Airways Research Laboratory, Universiteit Gent = Ghent University [Belgium] (UGENT), National Institute for Health and Welfare [Helsinki], University Hospitals Leuven [Leuven], VU University Medical Center [Amsterdam], Center for Rhinology and Allergology Wiesbaden, University Hospital Mannheim, Philipps Universität Marburg, Nova Southeastern University (NSU), Hospital Quirónsalud Bizkaia [Bilbao], Transilvania University of Brasov, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], iQ4U consultants Ltd, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Woolcock Institute of Medical Research [Sydney], The University of Sydney, Allergist [La Rochelle], Laval University Medical center, Université Laval [Québec] (ULaval), Quebec Heart and Lung Institute, Ghent University Hospital, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Humanitas University [Milan] (Hunimed), Institute for Immunological Research (University of Cartagena), Vall d'Hebron University Hospital [Barcelona], RETIC ARADyAL, University of South Florida [Tampa] (USF), SOS Allergology and Clinical Immunology, Unidade de Ciencias Biomoleculares Aplicadas (UCIBIO), Requimte, Departamento de Química (DQ), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto, ProAR – Nucleo de Excelencia em Asma, Universidade Federal da Bahia (UFBA), Medical Consulting Czarlewski, 'Federico II' University of Naples Medical School, Laboratoire de Pharmacologie Respiratoire UPRES EA220, UPRES EA 220, Pôle des maladies respiratoires, Hôpital Foch, Washington University School of Medecine [Saint Louis, MO], Sagamihara National Hospital, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Department of Otorhinolaryngology [Amsterdam], Academic Medical Centre [Amsterdam], University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Center of Research in Health Technologies and Information Systems (CINTESIS), Universidade do Porto, Allergist [Reims], Cerrahpasa Faculty of Medicine, Istanbul University, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Skin and allergy hospital [Helsinki, Finland], Odense University Hospital [Odense, Denmark], University General Hospital of Heraklion, Chiba University Hospital, Servicio de Alergia e ImmunologiaBuenos Aires (Clinica Santa Isabel), Wroclaw Medical University [Wrocław, Pologne], Ukrainina Medical Stomatological Academy [Poltava, Ukraine], Federal Medicobiological Agency [Moscow, Russian Federation], Hacettepe University School of Medicine, DRK Kliniken Berlin, Westend, Medical University of Łódź (MUL), Barlicki University Hospital, Vilnius University [Vilnius], Institute of Biomedicine and Molecular Immunology (IBIM), Hospital Medica Sur [Mexico City, Mexico], KYomed INNOV [Montpellier], Ho Chi Minh City University of Medicine, The University of Tennessee Health Science Center [Memphis] (UTHSC), Oslo University Hospital [Oslo], University of Beira Interior [Portugal] (UBI), Centro Hospitalar de Lisboa Central E.P.E, NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Sachs’ Children and Youth Hospital [Stockholm, Sweden], Karolinska Institutet [Stockholm], Center for Allergy and Immunology and Respiratory Diseases, Département d'Information Médicale [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), University Hospital of Cologne [Cologne], Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), University Hospital of Padua, Pirogov Russian National Research Medical University [Moscow, Russia], Monash University [Melbourne], Tokyo National Hospital, Ajou University, Charles University [Prague] (CU), Ospedale Policlinico San Martino [Genoa], Centre Médical de l'Institut Pasteur, Institut Pasteur [Paris], Observational and Pragmatic Research Institute, Singapore, Singapore, The David Hide Asthma and Allergy Research Centre, St Mary's Hospital-University Hospital Southampton NHS Foundation Trust, Département des maladies respiratoires [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Association Asthme et Allergies, Universidade Federal do Parana [Curitiba] (UFPR), Universidade Federal do Paraná (UFPR), University of Edinburgh, Medical University of Warsaw - Poland, Centro Médico Docente La Trinidad, The Royal National TNE Hospital, University College of London [London] (UCL), Imperial College London, Usher Institute of Population Health Sciences and Informatics [Edinburgh, U.K.], University of Coimbra [Portugal] (UC), University of Helsinki, University of Crete [Heraklion] (UOC), Allergist, University of Turku, Terveystalo Pulssi, University of Bari Aldo Moro (UNIBA), Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, (MRC), Guy's Hospital [London], Manisa Celal Bayar University, uBibliorum, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Humboldt University Of Berlin, Universiteit Gent = Ghent University (UGENT), Philipps Universität Marburg = Philipps University of Marburg, Universidade do Porto = University of Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto = University of Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Washington University School of Medicine [Saint Louis, MO], Sagamihara National Hospital [Kanagawa, Japan], Universidade do Porto = University of Porto, Wrocław Medical University, Azienda Ospedale Università di Padova = Hospital-University of Padua (AOUP), Pirogov Russian National Research Medical University, Centre Médical de l'Institut Pasteur (CMIP), Institut Pasteur [Paris] (IP), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Internal Medicine, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Universidade do Porto-Departamento de Química (DQ), and CCSD, Accord Elsevier
Subjects: MESH: Asthma, Allergy, [INFO.INFO-DS] Computer Science [cs]/Data Structures and Algorithms [cs.DS], Disease, Allergic Rhinitis and Its Impact on Asthma, medicine.disease_cause, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Allergic rhinitis, Grading of Recommendations Assessment, law.invention, 0302 clinical medicine, Allergen, Randomized controlled trial, MESH: Practice Guidelines as Topic, law, HDE ALER, HEALTH LITERACY, Immunology and Allergy, 030212 general & internal medicine, guidelines, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, MASK-RHINITIS, mHealth, PLACEBO, LORATADINE, MOBILE TECHNOLOGY, 3. Good health, Evidence-Based Practice, Practice Guidelines as Topic, MESH: Rhinitis, Allergic, AZELASTINE NASAL SPRAY, Life Sciences & Biomedicine, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, Algorithms, medicine.medical_specialty, Evidence-based practice, Visual analogue scale, [INFO.INFO-DS]Computer Science [cs]/Data Structures and Algorithms [cs.DS], Immunology, MESH: Algorithms, MACVIA-ARIA, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, Pharmacotherapy, medicine, Humans, QUALITY, Development and Evaluation, real-world evidence, Intensive care medicine, Asthma, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, MESH: Humans, Science & Technology, business.industry, MESH: Evidence-Based Practice, medicine.disease, EFFICACY, Rhinitis, Allergic, 030228 respiratory system, ONSET, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, business
Abstract: The selection of pharmacotherapy for patients with allergic rhinitis aims to control the disease and depends on many factors. Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines have considerably improved the treatment of allergic rhinitis. However, there is an increasing trend toward use of real-world evidence to inform clinical practice, especially because randomized controlled trials are often limited with regard to the applicability of results. The Contre les Maladies Chroniques pour un Vieillissement Actif (MACVIA) algorithm has proposed an allergic rhinitis treatment by a consensus group. This simple algorithm can be used to step up or step down allergic rhinitis treatment. Next-generation guidelines for the pharmacologic treatment of allergic rhinitis were developed by using existing GRADE-based guidelines for the disease, real-world evidence provided by mobile technology, and additive studies (allergen chamber studies) to refine the MACVIA algorithm. ispartof: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY vol:145 issue:1 pages:70-+ ispartof: location:United States status: published
Published: 2019

23. Type 2 diabetes mellitus and osteoarthritis

Author: André Scheen, René Rizzoli, Roland Roth, Lucio C. Rovati, Marc C. Hochberg, Mila Vlaskovska, Elaine M. Dennison, Nicola Veronese, Daniel Uebelhart, Emmanuel Maheu, Jean-François Kaux, Gabriel Herrero-Beaumont, Olivier Bruyère, Jaime Branco, Roland Chapurlat, Cyrus Cooper, Nasser M. Al-Daghri, Jean-Yves Reginster, Gestionnaire, Hal Sorbonne Université, Italian National Research Council [Padova, Italy], MRC Lifecourse Epidemiology Unit [Southampton, UK], University of Southampton, NIHR Musculoskeletal Biomedical Research Unit [Oxford, UK], University of Oxford, WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging [Liège, Belgium], Department of Public Health, Epidemiology and Health Economics [Liège, Belgium], Université de Liège-CHU Sart Tilman [Liege, Belgium], Chair for Biomarkers of Chronic Diseases [Riyadh, Kingdom of Saudi Arabia] (Biochemistry Department), Qassim University [Kingdom of Saudi Arabia]-College of Science [Riyadh, Kingdom of Saudi Arabia], Medical Care Clinical Center [Baltimore, MD, USA], VA Maryland Health Care System [Baltimore, MD, USA], Division of Rheumatology & Clinical Immunology [Baltimore, MD, USA] (Department of Medicine), University of Maryland School of Medicine, University of Maryland System-University of Maryland System, Geriatric Research [Baltimore, MD, USA], Education and Clinical Center [Baltimore, MD, USA], Centro de Estudos de Doenças Crónicas (CEDOC), NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Bone and Joint Research Unit [Madrid, Spain] (Department of Rheumatology), IIS‑Fundación Jiménez Diaz‑Autonoma University [Madrid, Spain], Department of Physical & Rehabilitation Medicine and Sports Traumatology, SPORTS-2 [Liège, Belgium], Université de Liège-Centre Hospitalier Universitaire de Liège (CHU-Liège)-FIFA Medical Centre of Excellence [Liège, Belgium], Service de rhumatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Division of Bone Diseases [Geneva, Switzerland] (Faculty of Medicine), Hôpitaux Universitaires de Genève (HUG), Chiropractic, Naturopathy and Orthopaedics practice [Essen-Suedviertel, Germany], School of Medicine and Surgery [Milan, Italy], Università degli Studi di Milano = University of Milan (UNIMI), Department of Clinical Research [Monza, Italy], Rottapharm Biotech [Monza, Italy], Division of Musculoskeletal, Internal Medicine and Oncological Rehabilitatio [Crans-Montana, Switzerland] (Orthopaedics and Traumatology), Hôpital du Valais [Crans-Montana, Switzerland] (HVS)-Centre Hospitalier du Valais Romand [Crans-Montana, Switzerland] (CHVR), Department of Pharmacology [Sofia, Bulgaria] (Medical Faculty), Medical University-Sofia [Sofia, Bulgaria], Division of Diabetes, Nutrition and Metabolic Disorders [Liège, Belgium] (Department of Medicine), Clinical Pharmacology Unit [Liège, Belgium], The meeting was funded by the ESCEO, a Belgian not-for-profitorganization., UAM. Departamento de Medicina, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), University of Oxford [Oxford], Centre Hospitalier Universitaire de Liège (CHU-Liège)-Université de Liège-FIFA Medical Centre of Excellence [Liège, Belgium], Università degli Studi di Milano [Milano] (UNIMI), Veronese, N., Cooper, C., Reginster, J.-Y., Hochberg, M., Branco, J., Bruyère, O., Chapurlat, R., Al-Daghri, N., Dennison, E., Herrero-Beaumont, G., Kaux, J.-F., Maheu, E., Rizzoli, R., Roth, R., Rovati, L.C., Uebelhart, D., Vlaskovska, M., and Scheen, A.
Subjects: medicine.medical_specialty, Evidence-based practice, type 2 diabetes mellitu, endocrine system diseases, Medicina, Osteoarthritis, Overweight, Pathophysiology, Article, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Rheumatology, Internal medicine, Type 2 diabetes mellitus, Medicine, Humans, 030212 general & internal medicine, Obesity, Risk factor, 030203 arthritis & rheumatology, ddc:616, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, business.industry, Type 2 Diabetes Mellitus, nutritional and metabolic diseases, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, 3. Good health, Institutional repository, Anesthesiology and Pain Medicine, Diabetes Mellitus, Type 2, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Disease Progression, osteoarthriti, medicine.symptom, Insulin Resistance, Safety, business
Abstract: Objectives: Type 2 diabetes mellitus (T2DM) and osteoarthritis (OA) are common diseases that frequently co-exist, along with overweight/obesity. While the mechanical impact of excess body weight on joints may explain lower limb OA, we sought to explore whether T2DM is linked to OA outside of excess weight and whether T2DM may play a role in OA pathophysiology. The consequence of T2DM on OA outcomes is a question of research interest. Methods: We conducted a critical review of the literature to explore the association between T2DM and OA, whether any association is site-specific for OA, and whether the presence of T2DM impacts on OA outcomes. We also reviewed the literature to assess the safety of anti-OA treatments in patients with T2DM. Results: T2DM has a pathogenic effect on OA through 2 major pathways involving oxidative stress and low-grade chronic inflammation resulting from chronic hyperglycemia and insulin resistance. T2DM is a risk factor for OA progression and has a negative impact on arthroplasty outcomes. Evidence is mounting for safety concerns with some of the most frequently prescribed anti-OA medications, including paracetamol, non-steroidal anti-inflammatory drugs, and corticosteroid injections, while other anti-OA medications may be safely prescribed in OA patients with T2DM, such as glucosamine and intra-articular hyaluronic acid. Conclusions: Future research is needed to better understand whether diabetes control and prevention can modulate OA occurrence and progression. The selection of therapy to treat OA symptoms in patients with T2DM may require careful consideration of the evidence based to avoid untoward safety issues., The meeting was funded by the ESCEO, a Belgian not-for-profit organization. The authors thank the Chair for Biomarkers of Chronic Diseases and the International Scientific Partnership Program (ISPP#0111) at King Saud University, Riyadh, Saudi Arabia for their support
Published: 2019

24. Accurate Determination of Human CPR Conformational Equilibrium by smFRET Using Dual Orthogonal Noncanonical Amino Acid Labeling

Author: Emmanuel Margeat, Robert B. Quast, Michel Kranendonk, Gilles Truan, Fataneh Fatemi, Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Protein Research Center, Shahid Beheshti University, Center for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Centre de Biochimie Structurale [Montpellier] (CBS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-13-ISV5-0001, ANR/FCT program [Portuguese national funds through the Fundacao para a Ciencia e a Tecnologia] [FCT-ANR/BEX-BCM/0002/2013], ANR-10-INBS-04, GIS 'IBiSA: Infrastructures en Biologie Sante et Agronomie', 'Access grant' from the France-BioImaging infrastructure, ANR-13-ISV5-0001,DODYCOEL,Dynamique de domaines dans le contrôle du flux d'électrons(2013), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), Universidade Nova de Lisboa (NOVA)-Universidade Nova de Lisboa (NOVA), ProdInra, Archive Ouverte, Blanc – Accords bilatéraux 2013 - Dynamique de domaines dans le contrôle du flux d'électrons - - DODYCOEL2013 - ANR-13-ISV5-0001 - Blanc – Accords bilatéraux 2013 - VALID, Développment d'une infrastructure française distribuée coordonnée - - France-BioImaging2010 - ANR-10-INBS-0004 - INBS - VALID, Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Phenylalanine, Molecular Conformation, Biotechnologies, 010402 general chemistry, 01 natural sciences, 7. Clean energy, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, Molecular dynamics, colorant fluorescent, bioorthogonal double labeling, biophysics, conformation analysis, Escherichia coli, Fluorescence Resonance Energy Transfer, Molecule, Humans, Cyanine, Cloning, Molecular, Molecular Biology, 030304 developmental biology, Fluorescent Dyes, NADPH-Ferrihemoprotein Reductase, noncanonical amino acids, chemistry.chemical_classification, 0303 health sciences, Microscopy, Confocal, 010405 organic chemistry, Chemistry, Lysine, Organic Chemistry, protein engineering, Protein engineering, Carbocyanines, Genetic code, Fluorescence, Single Molecule Imaging, 0104 chemical sciences, Amino acid, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, Förster resonance energy transfer, Ionic strength, Biophysics, Molecular Medicine
Abstract: Conjugation of fluorescent dyes to proteins - a prerequisite for the study of conformational dynamics by single molecule Förster resonance energy transfer (smFRET) - can lead to substantial changes of the dye’s photophysical properties, ultimately biasing the quantitative determination of inter-dye distances. In particular the popular cyanine dyes and their derivatives, which are by far the most used dyes in smFRET experiments, exhibit such behavior. To overcome this, a general strategy to site-specifically equip proteins with FRET pairs by chemo-selective reactions using two distinct non-canonical amino acids simultaneously incorporated through genetic code expansion inEscherichia coliwas developed. Applied to human NADPH- cytochrome P450 reductase (CPR), the importance of homogenously labeled samples for accurate determination of FRET efficiencies was demonstrated. Furthermore, the effect of NADP+ on the ionic strength dependent modulation of the conformational equilibrium of CPR was unveiled. Given its generality and accuracy, the presented methodology establishes a new benchmark to decipher complex molecular dynamics on single molecules.
Published: 2019

25. Epidemiology and antimicrobial resistance of methicillin-resistant Staphylococcus aureus isolates colonizing pigs with different exposure to antibiotics

Author: Hermínia de Lencastre, Laurent Poirel, Marta Aires-de-Sousa, Elizeth Lopes, Teresa Conceição, Instituto de Tecnologia Química e Biológica António Xavier (ITQB), Laboratory of Molecular Genetics [Oeiras, Portugal], Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Emerging Antibiotic Resistance Unit [Fribourg, Suisse], Medical and Molecular Microbiology [Fribourg, Suisse], Faculty of Science and Medicine [Fribourg, Suisse], University of Fribourg-University of Fribourg-Faculty of Science and Medicine [Fribourg, Suisse], University of Fribourg-University of Fribourg, Inserm European Unit [Fribourg, Suisse], Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-University of Fribourg, National Reference Center for Emerging Antibiotic Resistance [Fribourg, Suisse] (NARA), University of Fribourg, Laboratory of Microbiology and Infectious Diseases [New York, NY, États-Unis], Rockefeller University [New York], Escola Superior de Saúde da Cruz Vermelha Portuguesa [Lisbonne, Portugal], This work was partly supported by project PTDC/DTP-EPI/0842/2014 from Fundação para a Ciência e a Tecnologia (FCT), Portugal, and Project LISBOA-01-0145-FEDER-007660 (Microbiologia Molecular, Estrutural e Celular) funded by FEDER funds through COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI) and by national funds through FCT. This work was also partially supported by ONEIDA project (LISBOA-01-0145-FEDER-016417) co-funded by FEEI - 'Fundos Europeus Estruturais e de Investimento' from 'Programa Operacional Regional Lisboa 2020' and by national funds from FCT. Elizeth Lopes was supported by grant 03/BI/2017 from FCT, Portugal., and Bodescot, Myriam
Subjects: Swine, Staphylococcus, Antibiotics, Drug resistance, medicine.disease_cause, Drug Resistance, Multiple, Bacterial, Pathology and laboratory medicine, 2. Zero hunger, Mammals, Swine Diseases, 0303 health sciences, Multidisciplinary, Lincosamides, Agricultural and Biological Sciences(all), Antimicrobials, Eukaryota, Drugs, Agriculture, Medical microbiology, Staphylococcal Infections, Antimicrobial, 3. Good health, Anti-Bacterial Agents, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Vertebrates, Carrier State, Medicine, Pathogens, medicine.drug, Research Article, Methicillin-Resistant Staphylococcus aureus, Staphylococcus aureus, Farms, medicine.drug_class, Science, Biology, Nose, Microbiology, 03 medical and health sciences, Antibiotic resistance, Microbial Control, medicine, Animals, General, 030304 developmental biology, Medicine and health sciences, Pharmacology, Bacteria, Portugal, Whole Genome Sequencing, 030306 microbiology, Colistin, Biochemistry, Genetics and Molecular Biology(all), Organisms, Biology and Life Sciences, Amoxicillin, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses, Methicillin-resistant Staphylococcus aureus, Animal Feed, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Microbial pathogens, Chloramphenicol, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Antibiotic Resistance, Amniotes, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Bacterial pathogens, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Antimicrobial Resistance, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract: BackgroundIn 2016, very high rates of methicillin-resistant Staphylococcus aureus (MRSA)-ST398 (99%) were found in Portuguese pig farms that used colistin, amoxicillin, and zinc oxide as feed additives. Since then, farms A and B banned the use of colistin, and farm C banned the use of both antibiotics.ObjectiveThe aim of the present study was to evaluate the impact of the ban of colistin and amoxicillin on pig MRSA carriage rates, clonal types and antimicrobial resistance, compared to the results obtained in 2016.MethodsIn 2018, 103 pigs (52 from farm B using amoxicillin only as a feed additive and 51 from farm C where no antibiotics were included in the feed regimen) were nasally swabbed for MRSA colonization. Isolates were tested for antimicrobial susceptibility, and characterised by spa typing, SCCmec typing and MLST. Whole genome sequencing (WGS) was performed for representative isolates.ResultsOverall, 96% of the pigs swabbed in 2018 carried MRSA, mostly ST398-SCCmec V-spa types t011/t108. MRSA from pigs not receiving antibiotics in the feed regimen showed susceptibility to a higher number of antibiotics, namely erythromycin, ciprofloxacin, gentamicin, and chloramphenicol. Notably, most of these isolates (n = 52) presented an unusual erythromycin-susceptibility/clindamycin-resistance phenotype. WGS showed that these isolates lacked the erm and the lnu genes encoding resistance to macrolides and lincosamides, respectively, but carried the vgaALC gene encoding resistance to lincosamides, which is here firstly identified in S. aureus ST398.ConclusionAfter two years the ban of colistin and amoxicillin as feed additives had no significant impact on the MRSA nasal carriage rates. Nevertheless, the MRSA strains circulating in those farms showed resistance to a lower number of antibiotic classes.
Published: 2019

26. Probing the Role of the Hinge Segment of Cytochrome P450 Oxidoreductase in the Interaction with Cytochrome P450

Author: Bruno Gomes, Thomas Lautier, José Rueff, Gilles Truan, Bernardo Brito Palma, Francisco de Assis Esteves, Diana Campelo, Michel Kranendonk, Philippe Urban, Center for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Portuguese Fundacao para a Ciencia e a Tecnologia [FCT-ANR/ BEXBCM/0002/2013, SFRH/BPD/110633/2015], Portuguese Fundacao para a Ciencia e a Tecnologia [Research Center for Toxicogenomics and Human Health (ToxOmics)] [UID/BIM/0009/2016], ANR-13-ISV5-0001,DODYCOEL,Dynamique de domaines dans le contrôle du flux d'électrons(2013), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Universidade Nova de Lisboa (NOVA)-Universidade Nova de Lisboa (NOVA), Agence Nationale de la Recherche [ANR-13-ISV5-0001], Centre for Toxicogenomics and Human Health (ToxOmics), and NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
Subjects: 0301 basic medicine, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Cytochrome, Microsomal cytochrome p450 (CYP), Mutant, nadph, Protein dynamics, Reductase, Cytochrome P-450 CYP2A6, protein-protein interaction, lcsh:Chemistry, Cytochrome b5 (CYB5), Protein-protein interaction, Cytochrome P-450 Enzyme System, NADPH-cytochrome P450 reductase (CPR), microsomal cytochrome P450 (CYP), Cytochrome b(5) (CYB5), protein dynamics, electron-transfer (ET), Cytochrome P-450 CYP3A, lcsh:QH301-705.5, Spectroscopy, chemistry.chemical_classification, biology, General Medicine, Computer Science Applications, cytochrome p450, Protein Binding, adn codant, Stereochemistry, Electron-transfer (ET), education, Biotechnologies, Catalysis, Article, Protein–protein interaction, Inorganic Chemistry, Electron Transport, 03 medical and health sciences, Cytochrome P-450 CYP1A2, Cytochrome b5, transfert d'électrons, Humans, cinétique enzymatique, mutant, Physical and Theoretical Chemistry, Molecular Biology, Organic Chemistry, Cell Membrane, Cytochrome P450, Kinetics, 030104 developmental biology, Enzyme, protein–protein interaction, chemistry, lcsh:Biology (General), lcsh:QD1-999, Mutation, biology.protein
Abstract: NADPH-cytochrome P450 reductase (CPR) is the unique redox partner of microsomal cytochrome P450s (CYPs). CPR exists in a conformational equilibrium between open and closed conformations throughout its electron transfer (ET) function. Previously, we have shown that electrostatic and flexibility properties of the hinge segment of CPR are critical for ET. Three mutants of human CPR were studied (S243P, I245P and R246A) and combined with representative human drug-metabolizing CYPs (isoforms 1A2, 2A6 and 3A4). To probe the effect of these hinge mutations different experimental approaches were employed: CYP bioactivation capacity of pre-carcinogens, enzyme kinetic analysis, and effect of the ionic strength and cytochrome b5 (CYB5) on CYP activity. The hinge mutations influenced the bioactivation of pre-carcinogens, which seemed CYP isoform and substrate dependent. The deviations of Michaelis-Menten kinetic parameters uncovered tend to confirm this discrepancy, which was confirmed by CYP and hinge mutant specific salt/activity profiles. CPR/CYB5 competition experiments indicated a less important role of affinity in CPR/CYP interaction. Overall, our data suggest that the highly flexible hinge of CPR is responsible for the existence of a conformational aggregate of different open CPR conformers enabling ET-interaction with structural varied redox partners. publishersversion published
Published: 2018

27. Multiple convergent supergene evolution events in mating-type chromosomes

Author: Stéphanie Le Prieur, Sara Branco, Marco A. Coelho, Fantin Carpentier, Alodie Snirc, Tatiana Giraud, Hélène Badouin, Damien M. de Vienne, Michael E. Hood, Dominik Begerow, Fanny E. Hartmann, Ricardo C. Rodríguez de la Vega, Ecologie Systématique et Evolution (ESE), Université Paris-Sud - Paris 11 (UP11)-AgroParisTech-Centre National de la Recherche Scientifique (CNRS), Montana State University (MSU), Centre National de la Recherche Scientifique (CNRS), Sexe et évolution, Département PEGASE [LBBE] (PEGASE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Departamento de Ciencias da Vida (DCV), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Bioinformatique, phylogénie et génomique évolutive (BPGE), Ruhr-Universität Bochum [Bochum], University of Virginia [Charlottesville], and University of Virginia
Subjects: 0301 basic medicine, Mating type, Science, General Physics and Astronomy, Genomics, Biology, Genome, Article, General Biochemistry, Genetics and Molecular Biology, Evolution, Molecular, 03 medical and health sciences, Genetic linkage, Phylogenetics, lcsh:Science, Gene, Phylogeny, Recombination, Genetic, Multidisciplinary, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Fungi, Fungal genetics, Chromosome, General Chemistry, Genes, Mating Type, Fungal, 3. Good health, 030104 developmental biology, Evolutionary biology, lcsh:Q, Chromosomes, Fungal
Abstract: Convergent adaptation provides unique insights into the predictability of evolution and ultimately into processes of biological diversification. Supergenes (beneficial gene linkage) are striking examples of adaptation, but little is known about their prevalence or evolution. A recent study on anther-smut fungi documented supergene formation by rearrangements linking two key mating-type loci, controlling pre- and post-mating compatibility. Here further high-quality genome assemblies reveal four additional independent cases of chromosomal rearrangements leading to regions of suppressed recombination linking these mating-type loci in closely related species. Such convergent transitions in genomic architecture of mating-type determination indicate strong selection favoring linkage of mating-type loci into cosegregating supergenes. We find independent evolutionary strata (stepwise recombination suppression) in several species, with extensive rearrangements, gene losses, and transposable element accumulation. We thus show remarkable convergence in mating-type chromosome evolution, recurrent supergene formation, and repeated evolution of similar phenotypes through different genomic changes., Supergenes result from beneficial linkage and recombination suppression between two or more genes. Giraud and colleagues use whole genome sequencing data to show convergent evolution of supergenes on mating-type chromosomes in multiple closely-related fungal lineages.
Published: 2018

28. Yamadazyma barbieri f.a. sp. nov., an ascomycetous anamorphic yeast isolated from a Mid-Atlantic Ridge hydrothermal site (−2300 m) and marine coastal waters

Author: Stella Debaets, Mário Gadanho, Carlos A. Rosa, Gaëtan Burgaud, Serge Casaregola, Noémie Jacques, José Paulo Sampaio, Monika Coton, Natália O. P. Maciel, Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, CIRM-Levures, Departamento de Microbiologia, Universidade Federal de Minas Gerais, Biosystems and Integrative Sciences Institute (BioISI), University of Lisbon, Unidade de Ciencias Biomoleculares Aplicadas (UCIBIO), Requimte, Departamento de Química (DQ), Faculdade de Ciências e Tecnologia (FCT NOVA), Universidade Nova de Lisboa (NOVA)-Universidade Nova de Lisboa (NOVA)-Faculdade de Ciências e Tecnologia (FCT NOVA), Universidade Nova de Lisboa (NOVA)-Universidade Nova de Lisboa (NOVA)-Universidade do Porto [Porto]-Departamento de Química (DQ), Universidade Nova de Lisboa (NOVA)-Universidade Nova de Lisboa (NOVA)-Universidade do Porto [Porto], FCT Portugal [UID/Multi/04378/2013, UID/Multi/04046/2013], European Project: 311975, Universidade de Lisboa = University of Lisbon (ULISBOA), Universidade do Porto = University of Porto-Departamento de Química (DQ), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto = University of Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Universidade do Porto [Porto]-Departamento de Química (DQ), Universidade Nova de Lisboa (NOVA)-Universidade Nova de Lisboa (NOVA), Universidade de Lisboa (ULISBOA), Universidade do Porto-Departamento de Química (DQ), and Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto-Departamento de Química (DQ)
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Yamadazyma, Mid-Atlantic Ridge, Biology, Microbiology, 03 medical and health sciences, Hydrothermal Vents, Genus, Phylogenetics, Botany, 14. Life underwater, Internal transcribed spacer, DNA, Fungal, Mycological Typing Techniques, milieu marin, Atlantic Ocean, Phylogeny, Ecology, Evolution, Behavior and Systematics, caractérisation de souche, MycoBank, flore levurienne, Sequence Analysis, DNA, General Medicine, biology.organism_classification, Yeast, identification d'espèce, 030104 developmental biology, RNA, Ribosomal, ocean environment, Saccharomycetales, Brazil, Hydrothermal vent
Abstract: Two yeast strains that are members of the same species were isolated from different marine habitats, i.e. one from Mid-Atlantic Ridge ocean water samples located in the direct vicinity of black smokers near the Rainbow deep-sea hydrothermal vent and one from Brazilian marine water samples off the Ipanema beach. Strains CLIB 1964(T) and CLIB 1965 are anamorphic ascomycetous yeasts affiliated to the Yamadazyma clade of Saccharomycetales. Interestingly, these strains were phylogenetically and distinctly positioned into a group of species comprising all species of the genus Yamadazyma isolated from marine habitats including deep-sea hydrothermal vents, i.e. Candida atmosphaerica, C. spencermartinsiae, C. atlantica, C. oceani and C. taylorii. These strains differed significantly in their D1/D2 domain sequences of the LSU rRNA gene from the closely related species mentioned above, by 2.6, 3.0, 3.4, 3.8 and 6.0 %, respectively. Internal transcribed spacer region sequence divergence was also significant and corresponded to 4.6, 4.7, 4.7, 12.0 and 24.7% with C. atlantica, C. atmosphaerica, C. spencermartinsiae, C. oceani and C. taylorii, respectively. Phenotypically, strains CLIB 1964(T) and CLIB 1965 could be distinguished from closely related species by their inability to assimilate L-sorbose. CLIB 1964(T) (= CBS 14301(T) = UBOCC-A-214001(T)) is the designated type strain for Yamadazyma barbieri sp. nov. The MycoBank number is MB 815884.
Published: 2016

29. Crowdsourced assessment of common genetic contribution to predicting anti-TNF treatment response in rheumatoid arthritis

Author: Sieberts, Solveig K., Zhu, Fan, García-García, Javier, Stahl, Eli, Pratap, Abhishek, Pandey, Gaurav, Pappas, Dimitrios, Aguilar, Daniel, Anton, Bernat, Bonet, Jaume, Eksi, Ridvan, Fornés, Oriol, Guney, Emre, Li, Hongdong, Marín, Manuel Alejandro, Panwar, Bharat, Planas-Iglesias, Joan, Poglayen, Daniel, Cui, Jing, Falcao, Andre O., Suver, Christine, Hoff, Bruce, Balagurusamy, Venkat S. K., Dillenberger, Donna, Neto, Elias Chaibub, Norman, Thea, Aittokallio, Tero, Ammad-ud-din, Muhammad, Azencott, Chloe-Agathe, Bellón, Víctor, Boeva, Valentina, Bunte, Kerstin, Chheda, Himanshu, Cheng, Lu, Corander, Jukka, Dumontier, Michel, Goldenberg, Anna, Gopalacharyulu, Peddinti, Hajiloo, Mohsen, Hidru, Daniel, Jaiswal, Alok, Kaski, Samuel, Khalfaoui, Beyrem, Khan, Suleiman Ali, Kramer, Eric R., Marttinen, Pekka, Mezlini, Aziz M., Molparia, Bhuvan, Pirinen, Matti, Saarela, Janna, Samwald, Matthias, Stoven, Véronique, Tang, Hao, Tang, Jing, Torkamani, Ali, Vert, Jean-Phillipe, Wang, Bo, Wang, Tao, Wennerberg, Krister, Wineinger, Nathan E., Xiao, Guanghua, Xie, Yang, Yeung, Rae, Zhan, Xiaowei, Zhao, Cheng, Calaza, Manuel, Elmarakeby, Haitham, Heath, Lenwood S., Long, Quan, Moore, Jonathan D., Opiyo, Stephen Obol, Savage, Richard S., Zhu, Jun, Greenberg, Jeff, Kremer, Joel, Michaud, Kaleb, Barton, Anne, Coenen, Marieke, Mariette, Xavier, Miceli, Corinne, Shadick, Nancy, Weinblatt, Michael, de Vries, Niek, Tak, Paul P., Gerlag, Danielle, Huizinga, Tom W. J., Kurreeman, Fina, Allaart, Cornelia F., Louis Bridges Jr., S., Criswell, Lindsey, Moreland, Larry, Klareskog, Lars, Saevarsdottir, Saedis, Padyukov, Leonid, Gregersen, Peter K., Friend, Stephen, Plenge, Robert, Stolovitzky, Gustavo, Oliva, Baldo, Guan, Yuanfang, Mangravite, Lara M., Bridges, S. Louis, Intelligent Systems, Institute for Molecular Medicine Finland, Department of Mathematics and Statistics, Helsinki Institute for Information Technology, Jukka Corander / Principal Investigator, Department of Computer Science, Janna Saarela / Principal Investigator, Krister Wennerberg / Principal Investigator, Biostatistics Helsinki, Statistical and population genetics, AII - Amsterdam institute for Infection and Immunity, Clinical Immunology and Rheumatology, Zhejiang University, Universidad del Pais Vasco / Euskal Herriko Unibertsitatea [Espagne] (UPV/EHU), Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), DYNBIO LEGOS, Laboratoire d'études en Géophysique et océanographie spatiales (LEGOS), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Institut d'Ecologia Aquàtica, Universitat de Girona (UdG), Department of Medical Genetics, Faculty of Medicine-Child and Family Research Institute-Centre for Molecular Medicine and Therapeutics-University of British Columbia (UBC), China Agricultural University (CAU), Computational Intelligence Research Group (CA3), Centre of Technology and Systems (CTS), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Bioinformatique (CBIO), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Hefei University of Technology (HFUT), Stanford Center for BioMedical Informatics Research (BMIR), Stanford University, Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Technical Research Centre of Finland, VTT Technical Research Centre of Finland (VTT), U.S. Food and Drug Administration (FDA), Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), Profium Oy [Helsinki], Chinese Academy of Agricultural Sciences (CAAS), Business School [Hohai University], Hohai University, Institute of Industrial Economics [Hohai University], State Key Laboratory of Medical Genetics of China, Hunan Medical College, State Key Laboratory of Advanced Special Steel, Shanghai University, Quantitative Biomedical Research Center (QBRC), University of Texas Southwestern Medical Center [Dallas], Harold C. Simmons Comprehensive Cancer Center [Dallas, TX, États-Unis], Laboratoire de recherche en Hydrodynamique, Énergétique et Environnement Atmosphérique (LHEEA), École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), China National Research Center of Intelligent Equipment for Agriculture [Beijing] (NRCIEA), Centro Nacional de Análisi Genómico (CNAG), Centro Nacional de Análisis Genómico, Gregor Mendel Institute of Molecular Plant Biology (GMI), Austrian Academy of Sciences (OeAW), Department of Mechanical and Aerospace Engineering [Univ California Davis] (MAE - UC Davis), University of California [Davis] (UC Davis), University of California (UC)-University of California (UC), Tongji University, Laboratory for Measles and Rubella, Laboratoire National de Santé [Luxembourg] (LNS), Department of Human Genetics, Radboud University Medical Center [Nijmegen], INSERM U1012, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), School of biosciences and biotechnology, University of Camerino, Università degli Studi di Camerino = University of Camerino (UNICAM), Division of Rheumatology, Immunology and Allergy and Partners Asthma Center, Brigham and Women's Hospital [Boston], Department of Health Education and Promotion, Maastricht University [Maastricht], University of Amsterdam [Amsterdam] (UvA), Department of rheumatology, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Rheumatology Unit, Department of Medicine, University of California [San Francisco] (UC San Francisco), University of California (UC), Rheumatology Unit, Karolinska Institutet [Stockholm], Merck & Co. Inc, Structural Bioinformatics Group (GRIB), Barcelona Research Park of Biomedicine (PRBB), Universitat Pompeu Fabra [Barcelona] (UPF), Capital Normal University [Beijing], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), MINES ParisTech - École nationale supérieure des mines de Paris, California Institute of Technology (CALTECH)-NASA, Department of Mechanical and Aerospace Engineering [Davis], University of California-University of California, Università degli Studi di Camerino (UNICAM), University of California [San Francisco] (UCSF), University of California, Sage Bionetworks, University of Michigan, Ann Arbor, Pompeu Fabra University, Icahn School of Medicine at Mount Sinai, Corrona LLC, Northeastern University, Harvard University, University of Lisbon, IBM, INSERM U900, University of Helsinki, University of Toronto, Scripps Research Institute, Medical University of Vienna, University of Texas at Dallas, New York University, Albany Medical College, Arthritis Research Center Foundation, Radboud University Nijmegen, INSERM U1184, University of Amsterdam, Glaxo Smith Kline, Leiden University, University of Alabama at Birmingham, University of California San Francisco, University of Pittsburgh, Karolinska Institutet, North Shore-Long Island Jewish Health System, Merck, Aalto-yliopisto, and Aalto University
Subjects: Male, 0301 basic medicine, General Physics and Astronomy, Arthritis, Genome-wide association study, Bioinformatics, DISEASE, Arthritis, Rheumatoid, Cohort Studies, Missing heritability problem, MISSING HERITABILITY, Medicine, Certolizumab pegol, RISK, Multidisciplinary, Antibodies, Monoclonal, Middle Aged, Prognosis, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, STACKED GENERALIZATION, Treatment Outcome, Antirheumatic Agents, Crowdsourcing, Biomarker (medicine), Female, Erratum, medicine.drug, Adult, Science, Context (language use), Antibodies, Monoclonal, Humanized, Polymorphism, Single Nucleotide, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, INFLIXIMAB, Journal Article, Humans, SNP, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, METAANALYSIS, Aged, ta113, Tumor Necrosis Factor-alpha, business.industry, NETWORK INFERENCE, COMPLEX TRAITS, Artritis reumatoide -- Tractament, CLINICAL-RESPONSE, General Chemistry, 113 Computer and information sciences, medicine.disease, Infliximab, 030104 developmental biology, 3121 General medicine, internal medicine and other clinical medicine, Certolizumab Pegol, business, RC
Abstract: Rheumatoid arthritis (RA) affects millions world-wide. While anti-TNF treatment is widely used to reduce disease progression, treatment fails in ∼one-third of patients. No biomarker currently exists that identifies non-responders before treatment. A rigorous community-based assessment of the utility of SNP data for predicting anti-TNF treatment efficacy in RA patients was performed in the context of a DREAM Challenge (http://www.synapse.org/RA_Challenge). An open challenge framework enabled the comparative evaluation of predictions developed by 73 research groups using the most comprehensive available data and covering a wide range of state-of-the-art modelling methodologies. Despite a significant genetic heritability estimate of treatment non-response trait (h2=0.18, P value=0.02), no significant genetic contribution to prediction accuracy is observed. Results formally confirm the expectations of the rheumatology community that SNP information does not significantly improve predictive performance relative to standard clinical traits, thereby justifying a refocusing of future efforts on collection of other data., Rheumatoid arthritis patients respond differently to anti-TNF treatment. Using community-based challenge, the authors show that currently available data does not reveal meaningful genetic predictors of response to anti-TNF therapy, thus confirming clinical observations.
Published: 2016

30. Phenolic Metabolites Modulate Cardiomyocyte Beating in Response to Isoproterenol

Author: Andreia Gomes, Cláudia N. Santos, Helena L. A. Vieira, Joel Guerra, Daniela Dias-Pedroso, Catherine Brenner, Carole Oudot, Centro de Estudos de Doenças Crónicas (CEDOC), NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Centre de pharmacologie et innovation dans le diabète (CPID), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre National de la Recherche Scientifique (CNRS), INSERM, UMR-S1180, Human Language Technology Interest Group (HULTIG), Universidade de Beira Interior, and Instituto de Biologia Experimental e Tecnológica (IBET)
Subjects: Agonist, Programmed cell death, Cardiotonic Agents, Time Factors, medicine.drug_class, [SDV]Life Sciences [q-bio], Population, Catechols, Stimulation, 030204 cardiovascular system & hematology, Pharmacology, Pyrogallol, Toxicology, medicine.disease_cause, Mitochondria, Heart, Cell Line, Contractility, 03 medical and health sciences, 0302 clinical medicine, medicine, Cyclic AMP, Animals, Myocytes, Cardiac, Calcium Signaling, Rats, Wistar, education, Receptor, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Biotransformation, 2. Zero hunger, Cardioprotection, education.field_of_study, Chemistry, Isoproterenol, Cyclic AMP-Dependent Protein Kinases, Myocardial Contraction, 3. Good health, Oxidative Stress, Animals, Newborn, 030220 oncology & carcinogenesis, Cardiology and Cardiovascular Medicine, Reactive Oxygen Species, Oxidative stress
Abstract: Cardiovascular disease (CVD) is a public health concern, and the third cause of death worldwide. Several epidemiological studies and experimental approaches have demonstrated that consumption of polyphenol-enriched fruits and vegetables can promote cardioprotection. Thus, diet plays a key role in CVD development and/or prevention. Physiological β-adrenergic stimulation promotes beneficial inotropic effects by increasing heart rate, contractility and relaxation speed of cardiomyocytes. Nevertheless, chronic activation of β-adrenergic receptors can cause arrhythmias, oxidative stress and cell death. Herein the cardioprotective effect of human metabolites derived from polyphenols present in berries was assessed in cardiomyocytes, in response to chronic β-adrenergic stimulation, to disclose some of the underlying molecular mechanisms. Ventricular cardiomyocytes derived from neonate rats were treated with three human bioavailable phenolic metabolites found in circulating human plasma, following berries’ ingestion (catechol-O-sulphate, pyrogallol-O-sulphate, and 1-methylpyrogallol-O-sulphate). The experimental conditions mimic the physiological concentrations and circulating time of these metabolites in the human plasma (2 h). Cardiomyocytes were then challenged with the β-adrenergic agonist isoproterenol (ISO) for 24 h. The presence of phenolic metabolites limited ISO-induced mitochondrial oxidative stress. Likewise, phenolic metabolites increased cell beating rate and synchronized cardiomyocyte beating population, following prolonged β-adrenergic receptor activation. Finally, phenolic metabolites also prevented ISO-increased activation of PKA–cAMP pathway, modulating Ca2+ signalling and rescuing cells from an arrhythmogenic Ca2+ transients’ phenotype. Unexpected cardioprotective properties of the recently identified human-circulating berry-derived polyphenol metabolites were identified. These metabolites modulate cardiomyocyte beating and Ca2+ transients following β-adrenergic prolonged stimulation.
Published: 2018

31. Ligand Access Channels in Cytochrome P450 Enzymes: A Review

Author: Esteves, Francisco, Campelo, Diana, Bozonnet, Sophie, Rueff, Jose, Kranendonk, Michel, Urban, Philippe, Lautier, Thomas, Pompon, Denis, Truan, Gilles, Center for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Dept Genet, Fac Med Sci, Centre de génétique moléculaire (CGM), Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Universidade Nova de Lisboa (NOVA)-Universidade Nova de Lisboa (NOVA), and Urban, Philippe
Subjects: 0301 basic medicine, CAVER, Hydrolases, substrate specificity, [SDV]Life Sciences [q-bio], channel, Review, haloalkane dehalogenase, Computing Cavities, lcsh:Chemistry, Cytochrome P-450 Enzyme System, lcsh:QH301-705.5, Spectroscopy, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, biology, Chemistry, QSAR, General Medicine, Pores and Pockets (CCCPP), Computer Science Applications, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], polycyclic, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], P450, Channels, Random acceleration molecular dynamics (RAMD), structure, In silico, Molecular Dynamics Simulation, Catalysis, Inorganic Chemistry, 03 medical and health sciences, Animals, Humans, Computing Cavities, Channels, Pores and Pockets (CCCPP), [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, P450 Enzymes, Physical and Theoretical Chemistry, Amino acid residue, Molecular Biology, Binding Sites, 030102 biochemistry & molecular biology, Ligand, Organic Chemistry, Cytochrome P450, Active site, 030104 developmental biology, Enzyme, lcsh:Biology (General), lcsh:QD1-999, biology.protein, Biophysics, Substrate specificity
Abstract: International audience; Quantitative structure-activity relationships may bring invaluable information on structural elements of both enzymes and substrates that, together, govern substrate specificity. Buried active sites in cytochrome P450 enzymes are connected to the solvent by a network of channels exiting at the distal surface of the protein. This review presents different in silico tools that were developed to uncover such channels in P450 crystal structures. It also lists some of the experimental evidence that actually suggest that these predicted channels might indeed play a critical role in modulating P450 functions. Amino acid residues at the entrance of the channels may participate to a first global ligand recognition of ligands by P450 enzymes before they reach the buried active site. Moreover, different P450 enzymes show different networks of predicted channels. The plasticity of P450 structures is also important to take into account when looking at how channels might play their role.
Published: 2018

32. Target highlights from the first post-PSI CASP experiment (CASP12, May-August 2016)

Author: Shabir Najmudin, Johan C. Hill, Guido Pintacuda, Kinlin L. Chao, John Moult, Arnaud Baslé, T.H. Nguyen, Kaspars Tars, Harry J. Gilbert, Krzysztof Fidelis, Christopher S. Hayes, Marco Nardini, Reinhard Albrecht, Mark J. van Raaij, Valentina Nardone, Roman I. Koning, Celia W. Goulding, Pedro Bule, A.K. Singh, Nicole Zitzmann, Andrzej Joachimiak, Osnat Herzberg, Leila Lo Leggio, Carlos M. G. A. Fontes, Eric J. Sundberg, Pietro Roversi, Didier Ndeh, Andriy Kryshtafovych, Amir Shimon, Gert Wieland Kohring, Folmer Fredslund, Alessandro T. Caputo, Ana Luísa Carvalho, Marco Mangiagalli, Karolina Michalska, Sandra Postel, Marcus D. Hartmann, Torsten Schwede, Ron Diskin, Genome Center [UC Davis], University of California [Davis] (UC Davis), University of California-University of California, Abteilung Membranbiochemie [Martinsried], Max-Planck-Institut für Biochemie (MPIB), Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Institute for Cell and Molecular Biosciences, Newcastle University [Newcastle], Interdisciplinary Centre of Research in Animal Health, Faculdade de Medicina Veterinária, Pólo Universitário do Alto da Ajuda, Universidade de Lisboa, Oxford Glycobiol Inst, Dept Biochem, University of Oxford [Oxford], Unidade de Ciencias Biomoleculares Aplicadas (UCIBIO), Requimte, Departamento de Química (DQ), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto, Dept Mol Cellular & Dev Biol, University of California [Santa Barbara] (UCSB), Structural Biology Center, Biosciences Division, Universität des Saarlandes [Saarbrücken], Department of Chemistry, University of Copenhagenn, Department of Cell Biology and Molecular Genetics, University of Maryland [College Park], University of Maryland System-University of Maryland System, Department of Biomolecular Sciences and Biotechnology, University of Milano, Biological Solid-State NMR Methods - Méthodes de RMN à l'état solide en biologie, Institut des Sciences Analytiques (ISA), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Biomedical Research & Study Centre, Department of Biochemistry [Oxford], Biozentrum [Basel, Suisse], University of Basel (Unibas), Kryshtafovych, A, Albrecht, R, Baslé, A, Bule, P, Caputo, A, Carvalho, A, Chao, K, Diskin, R, Fidelis, K, Fontes, C, Fredslund, F, Gilbert, H, Goulding, C, Hartmann, M, Hayes, C, Herzberg, O, Hill, J, Joachimiak, A, Kohring, G, Koning, R, Lo Leggio, L, Mangiagalli, M, Michalska, K, Moult, J, Najmudin, S, Nardini, M, Nardone, V, Ndeh, D, Nguyen, T, Pintacuda, G, Postel, S, Van Raaij, M, Roversi, P, Shimon, A, Singh, A, Sundberg, E, Tars, K, Zitzmann, N, and Schwede, T
Subjects: 0301 basic medicine, Models, Molecular, Protein Folding, Protein Conformation, Bioinformatics, FIS/07 - FISICA APPLICATA (A BENI CULTURALI, AMBIENTALI, BIOLOGIA E MEDICINA), Computational biology, computer.software_genre, Crystallography, X-Ray, Biochemistry, Article, Mathematical Sciences, 03 medical and health sciences, Structural Biology, Models, Information and Computing Sciences, [CHIM]Chemical Sciences, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, CASP, Molecular Biology, X-ray crystallography, Physics, Crystallography, Bacteria, Proteins, Computational Biology, Molecular, Protein structure prediction, Biological Sciences, BIO/10 - BIOCHIMICA, NMR, protein structure prediction, 030104 developmental biology, Biological significance, X-Ray, Data mining, computer, Software
Abstract: International audience; The functional and biological significance of the selected CASP12 targets are described by the authors of the structures. The crystallographers discuss the most interesting structural features of the target proteins and assess whether these features were correctly reproduced in the predictions submitted to the CASP12 experiment.
Published: 2018

33. Evaluation of oxfendazole in the treatment of zoonotic Onchocerca lupi infection in dogs

Author: Nuno Gonçalves, Luís Cardoso, Lenea Campino, Vito Colella, Carla Maia, Domenico Otranto, André Pereira, Marta Caruso, Ivan Scandale, Coralie Martin, Dipartimento di Medicina Veterinaria, Università degli studi di Bari Aldo Moro (UNIBA), Global Health and Tropical Medicine (GHTM), Global Health and Tropical Medicine [Lisbonne, Portugal] (GHTM), Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Molécules de Communication et Adaptation des Micro-organismes (MCAM), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), University of Trás-os-Montes e Alto Douro (UTAD), Vila Real, Portugal, Drugs for Neglected Diseases initiative [Geneva, Switzerland], Global Antibiotic Research and Development Partnership [Geneva, Switzerland] (GARDP), and Vector borne diseases and pathogens (VBD)
Subjects: 0301 basic medicine, Eye Diseases, Nematoda, Physiology, [SDV]Life Sciences [q-bio], Onchocerciasis, Parasite load, Gastroenterology, Parasite Load, Diagnostic Radiology, 0302 clinical medicine, Ultrasound Imaging, Medicine and Health Sciences, Onchocerca, Dog Diseases, Nematode Infections, ComputingMilieux_MISCELLANEOUS, Ultrasonography, Mammals, CATS, biology, Pharmaceutics, lcsh:Public aspects of medicine, Antinematodal Agents, Radiology and Imaging, Eukaryota, 3. Good health, Body Fluids, Infectious Diseases, Treatment Outcome, Blood, Vertebrates, Anatomy, Research Article, medicine.medical_specialty, Oxfendazole, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, Imaging Techniques, 030231 tropical medicine, Research and Analysis Methods, 03 medical and health sciences, Pharmacotherapy, Dogs, SDG 3 - Good Health and Well-being, Drug Therapy, Diagnostic Medicine, Internal medicine, Helminths, medicine, Parasitic Diseases, Animals, business.industry, Public Health, Environmental and Occupational Health, Organisms, Biology and Life Sciences, lcsh:RA1-1270, medicine.disease, biology.organism_classification, Onchocerca volvulus, Invertebrates, Ophthalmology, 030104 developmental biology, Onchocerca Volvulus, Amniotes, Parasitology, Benzimidazoles, business, Follow-Up Studies
Abstract: The genus Onchocerca encompasses parasitic nematodes including Onchocerca volvulus, causative agent of river blindness in humans, and the zoonotic Onchocerca lupi infecting dogs and cats. In dogs, O. lupi adult worms cause ocular lesions of various degrees while humans may bear the brunt of zoonotic onchocercosis with patients requiring neurosurgical intervention because of central nervous system localization of nematodes. Though the zoonotic potential of O. lupi has been well recognized from human cases in Europe, the United States and the Middle East, a proper therapy for curing this parasitic infection in dogs is lacking. To evaluate the efficacy of oxfendazole, 11 out of the 21 client-owned dogs (21/123; 17.1%) positive for skin-dwelling O. lupi microfilariae (mfs), were enrolled in the efficacy study and were treated with oxfendazole (50 mg/kg) per OS once a day for 5 (G2) or 10 (G3) consecutive days or were left untreated (G1). The efficacy of oxfendazole in the reduction of O. lupi mfs was evaluated by microfilarial count and by assessing the percentage of mfs reduction and mean microfilaricidal efficacy, whereas the efficacy in the reduction of ocular lesions was evaluated by ultrasound imaging. All dogs where subjected to follow-ups at 30 (D30), 90 (D90) and 180 (D180) days post-treatment. The percentage of reduction of mfs was 78% for G2 and 12.5% for G3 at D180. The mean microfilaricidal efficacy of oxfendazole in the treatment of canine onchocercosis by O. lupi at D30, D90 and D180 was 41%, 81% and 90%, in G2 and 40%, 65% and 70%, in G3, respectively. Retrobulbar lesions did not reduce from D0 to D180 in control group (dogs in G1), whereas all treated dogs (in G2 and G3) had slightly decreased ocular lesions. Percentage of reduction of ocular lesions by ultrasound examination was 50% and 47.5% in G2 and G3 at D180, respectively. Despite the decrease in ocular lesions in all treated dogs (G2 and G3), oxfendazole was ineffective in reducing ocular lesions and skin-dwelling O. lupi mfs in treated dogs (G2 and G3) in a six-month follow-up period. Here we discuss the need for more reliable diagnostic techniques and efficient treatment protocols to better plan future intervention strategies., Author summary The genus Onchocerca (Spirurida, Onchocercidae) includes Onchocerca volvulus, which is estimated to infect at least 37 million people globally, and zoonotic Onchocerca lupi in carnivores. Infection by O. lupi has been reported in dogs and cats from several European countries and recently also in the U.S. and Canada, causing mainly ocular lesions. In humans, O. lupi displays a marked neurotropism with nematodes embedded in nodules localized in the cervical spine of infant, children and adults. Though the reported severity of infection in humans and the high prevalence detected in dogs are now well-recognized, a proper treatment regime for curing this parasitic infection is lacking, being the surgical removal of the parasitic nodule the therapy of choice in canine patients. Hence, there is an unmet medical need for treatment of this zoonotic disease in both humans and animals. In this study we evaluated the efficacy of oxfendazole under two treatment regimes in the reduction of ocular lesions and skin-dwelling microfilariae of O. lupi in naturally infected dogs.
Published: 2018

34. Correction: The hinge segment of human NADPH-cytochrome P450 reductase in conformational switching: the critical role of ionic strength

Author: Diana Campelo, Thomas Lautier, Philippe Urban, Francisco Esteves, Sophie Bozonnet, Gilles Truan, Michel Kranendonk, Center for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa (NOVA)-Universidade Nova de Lisboa (NOVA), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Truan, Gilles, and Kranendonk, Michel
Subjects: Pharmacology, diflavin reductase, protein dynamics, multidomain proteins, conformational exchange, electron transfer, protein-protein interaction, 0303 health sciences, lcsh:RM1-950, Pharmacologie, 03 medical and health sciences, lcsh:Therapeutics. Pharmacology, protein–protein interaction, 0302 clinical medicine, protéine, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Pharmacology (medical), protein, Original Research, 030304 developmental biology
Abstract: NADPH-cytochrome P450 reductase (CPR) is a redox partner of microsomal cytochromes P450 and is a prototype of the diflavin reductase family. CPR contains 3 distinct functional domains: a FMN-binding domain (acceptor reduction), a linker (hinge), and a connecting/FAD domain (NADPH oxidation). It has been demonstrated that the mechanism of CPR exhibits an important step in which it switches from a compact, closed conformation (locked state) to an ensemble of open conformations (unlocked state), the latter enabling electron transfer to redox partners. The conformational equilibrium between the locked and unlocked states has been shown to be highly dependent on ionic strength, reinforcing the hypothesis of the presence of critical salt interactions at the interface between the FMN and connecting FAD domains. Here we show that specific residues of the hinge segment are important in the control of the conformational equilibrium of CPR. We constructed six single mutants and two double mutants of the human CPR, targeting residues G240, S243, I245 and R246 of the hinge segment, with the aim of modifying the flexibility or the potential ionic interactions of the hinge segment. We measured the reduction of cytochrome c at various salt concentrations of these 8 mutants, either in the soluble or membrane-bound form of human CPR. All mutants were found capable of reducing cytochrome c yet with different efficiency and their maximal rates of cytochrome c reduction were shifted to lower salt concentration. In particular, residue R246 seems to play a key role in a salt bridge network present at the interface of the hinge and the connecting domain. Interestingly, the effects of mutations, although similar, demonstrated specific differences when present in the soluble or membrane-bound context. Our results demonstrate that the electrostatic and flexibility properties of the hinge segment are critical for electron transfer from CPR to its redox partners.
Published: 2018

35. Framework support for Usability evaluation of Domain- Specific Languages

Author: Ankica Barisic, NOVA Laboratory for Computer Science and Informatics (NOVA-LINCS), Departamento de Informática (DI), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), and Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)
Subjects: 0301 basic medicine, Iterative and incremental development, Agile usability engineering, Pluralistic walkthrough, Cognitive walkthrough, Computer science, business.industry, domain-specific language, usability evaluation, Usability inspection, [SCCO.COMP]Cognitive science/Computer science, 020207 software engineering, Usability, 02 engineering and technology, [INFO.INFO-SE]Computer Science [cs]/Software Engineering [cs.SE], Usability lab, 03 medical and health sciences, Usability goals, 030104 developmental biology, Human–computer interaction, Heuristic evaluation, Usability engineering, 0202 electrical engineering, electronic engineering, information engineering, business, Web usability, Component-based usability testing
Abstract: International audience; In this paper we propose a conceptual framework that supports the iterative development process of DSLs concerning the issue of their Usability evaluation. A multiple-case studies were conducted in order validate the proposed method. CCS Concepts • Software and its engineering → Software usability; Domain specific languages
Published: 2018

36. Human cytochrome P450 expression in bacteria: Whole-cell high-throughput activity assay for CYP1A2, 2A6 and 3A4

Author: Francisco de Assis Esteves, Sophie Bozonnet, Gilles Truan, Thomas Lautier, Diana Campelo, Philippe Urban, José Rueff, Michel Kranendonk, Center for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Portuguese Fundacao para a Ciencia e a Tecnologia [FCT-ANR/BEXBCM/0002/2013, SFRH/BPD/110633/2015], Portuguese Fundacao para a Ciencia e a Tecnologia [Research Center for Toxicogenomics and Human Health (ToxOmics)] [UID/BIM/0009/2016], ANR-13-ISV5-0001,DODYCOEL,Dynamique de domaines dans le contrôle du flux d'électrons(2013), Universidade Nova de Lisboa (NOVA)-Universidade Nova de Lisboa (NOVA), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), and ANR-13-ISV5-0001
Subjects: 0301 basic medicine, cytochrome, médicament, medicine, Cytochrome, microsomal cytochrome P450 monooxygenases (CYP), Metabolite, xénobiotique, medicine.disease_cause, 030226 pharmacology & pharmacy, Biochemistry, Gene Expression Regulation, Enzymologic, Cytochrome P-450 CYP2A6, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cytochrome P-450 CYP1A2, Cytochrome b5, Escherichia coli, Cytochrome P-450 CYP3A, Humans, xenobiotics, Enzyme kinetics, cytochrome b(5) (CYB5), Pharmacology, chemistry.chemical_classification, biology, Chemistry, CYP1A2, real-time fluorometric measurement, 3. Good health, High-Throughput Screening Assays, NADPH cytochrome P450 oxidoreductase (CPR), whole-cell high-throughput biocatalysis, enzymes and coenzymes (carbohydrates), enzyme, 030104 developmental biology, Enzyme, biology.protein, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Drug metabolism
Abstract: Cytochrome P450s (CYPs) are key enzymes involved in drug and xenobiotic metabolism. A wide array of in vitro methodologies, including recombinant sources, are currently been used to assess CYP catalysis, to identify the metabolic profile of compounds, potential drug-drug interactions, protein-protein interactions in the CYP enzyme complex and the role of polymorphic enzymes. We report here on a bacterial whole-cells high-throughput method for the activity evaluation of human CYP1A2, 2A6, and 3A4, when sustained by NADPH cytochrome P450 oxidoreductase (CPR), in the absence or presence of cytochrome b(5) (CYB5). This new assay consists of a microplate real-time fluorometric method, with direct measurement of metabolite formation, in a suspension of Escherichia coli BTC-CYP bacteria, a human CYP competent tester strain when incubated with specific fluorogenic substrates. Overall, the maximum turnover (k(cat)) velocities of the three human CYPs resulting from the whole-BTC cells assays were similar to those obtained when applying the corresponding standard reference membrane fractions assays. CYP activity screening with co-expression of CYB5 suggests an enhancing effect of CYB5 on the k(cat) of specific isoforms, when using the whole-BTC cells assay. Our results demonstrate that this new approach can offer an efficient high-throughput method for screening of CYP1A2, 2A6 and 3A4 activity and can be potentially applicable for other human CYPs. This can be of particular use for timely and efficient screening of chemical libraries or mutant libraries of CYP enzyme complex proteins, without the necessity for labor intensive isolation of subcellular fractions.
Published: 2018

37. Mouse Tracking Measures and Movement Patterns with Application for Online Surveys

Author: João Rodrigues, Marcus Cheetham, Hugo Gamboa, Dina Rindlisbacher, Cátia Cepeda, Maria Camila Dias, Diogo Oliveira, Department of Internal Medicine [Zürich], University hospital of Zurich [Zurich], Laboratorio de Instrumentaçao, Engenharia Biomédica e Fisica da Radiaçao (LIBPhys-UNL), Departamento de Fìsica [Lisboa] (DF), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Universität Zürich [Zürich] = University of Zurich (UZH), Andreas Holzinger, Peter Kieseberg, A Min Tjoa, Edgar Weippl, TC 5, TC 8, TC 12, WG 8.4, WG 8.9, and WG 12.9
Subjects: Data collection, Mouse behavior patterns, Computer science, Movement (music), [SHS.INFO]Humanities and Social Sciences/Library and information sciences, Context (language use), 02 engineering and technology, Mouse tracking, Human-computer interaction, User, Field (computer science), Likert scale, 03 medical and health sciences, Knowledge extraction, 0302 clinical medicine, Human–computer interaction, 020204 information systems, 0202 electrical engineering, electronic engineering, information engineering, [INFO]Computer Science [cs], Survey, Scale (map), 030217 neurology & neurosurgery
Abstract: Part 1: MAKE-Main Track; International audience; There is growing interest in the field of human-computer interaction in the use of mouse movement data to infer e.g. user’s interests, preferences and personality. Previous work has defined various patterns of mouse movement behavior. However, there is a paucity of mouse tracking measures and defined movement patterns for use in the specific context of data collection with online surveys. The present study aimed to define and visualize patterns of mouse movements while the user provided responses in a survey (with questions to be answered using a 5-point Likert response scale). The study produced a wide range of different patterns, including new patterns, and showed that these can easily be distinguished. The identified patterns may - in conjunction with machine learning algorithms - be used for further investigation toward e.g. the recognition of the user’s state of mind or for user studies.
Published: 2018

38. Challenges in Antibody Development against Tn and Sialyl-Tn Antigens

Author: Ana Barbas, Carlos Novo, Mylène A. Carrascal, Liliana R. Loureiro, José S. Ramalho, Philippe Delannoy, Paula A. Videira, Centro de Estudos de Doenças Crónicas (CEDOC), Instituto de Higiene e Medicina Tropical (IHMT), DCV - Departamento de Ciências da Vida, UCIBIO - Applied Molecular Biosciences Unit, NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), Instituto de Biologia Experimental e Tecnológica (IBET), NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa (NOVA)-Universidade Nova de Lisboa (NOVA), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Centro de Recursos Microbiológicos (CREM), Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université de Lille-Centre National de la Recherche Scientifique (CNRS), CNRS, Université de Lille, Instituto de Biologia Experimental e Tecnológica [IBET], Universidade Nova de Lisboa = NOVA University Lisbon [NOVA], Centro de Estudos de Doenças Crónicas [CEDOC], and Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Subjects: Phage display, medicine.drug_class, medicine.medical_treatment, Tn antigen, lcsh:QR1-502, Sialyl Tn antigen, therapeutic antibodies, Review, Monoclonal antibody, Biochemistry, lcsh:Microbiology, immune response, Antibodies, 03 medical and health sciences, 0302 clinical medicine, Immune system, Antigen, SDG 3 - Good Health and Well-being, Neoplasms, medicine, Journal Article, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Antigens, Tumor-Associated, Carbohydrate, Molecular Biology, 030304 developmental biology, antibody production, 0303 health sciences, biology, Research Support, Non-U.S. Gov't, Immunotherapy, 3. Good health, 030220 oncology & carcinogenesis, Immunology, biology.protein, Hybridoma technology, Antibody, Genetic Engineering
Abstract: PMID: 26270678 PMCID:4598775 The carbohydrate antigens Tn and sialyl-Tn (STn) are expressed in most carcinomas and usually absent in healthy tissues. These antigens have been correlated with cancer progression and poor prognosis, and associated with immunosuppressive microenvironment. Presently they are used in clinical trials as therapeutic vaccination, but with limited success due to their low immunogenicity. Alternatively, anti-Tn and/or STn antibodies may be used to harness the immune system against tumor cells. Whilst the development of antibodies against these antigens had a boost two decades ago for diagnostic use, so far no such antibody entered into clinical trials. Possible limitations are the low specificity and efficiency of existing antibodies and that novel antibodies are still necessary. The vast array of methodologies available today will allow rapid antibody development and novel formats. Following the advent of hybridoma technology, the immortalization of human B cells became a methodology to obtain human monoclonal antibodies with better specificity. Advances in molecular biology including phage display technology for high throughput screening, transgenic mice and more recently molecularly engineered antibodies enhanced the field of antibody production. The development of novel antibodies against Tn and STn taking advantage of innovative technologies and engineering techniques may result in innovative therapeutic antibodies for cancer treatment. publishersversion published
Published: 2015

39. Subproteomic signature comparison of in vitro selected fluoroquinolone resistance and ciprofloxacin stress in Salmonella Typhimurium DT104B

Author: Patrícia Poeta, Gilberto Igrejas, Carmen Torres, Manuela Caniça, Ingrid Chafsey, José Luis Capelo, Susana Correia, Christophe Chambon, Didier Viala, Michel Hébraud, department of neurology, clinical dementia center and DZNE, University Medical Centre Goettingen, Microbiologie Environnement Digestif Santé - Clermont Auvergne ( MEDIS ), INRA Clermont-Ferrand-Theix-Université Clermont Auvergne ( UCA ), Qualité des Produits Animaux ( QUAPA ), Institut National de la Recherche Agronomique ( INRA ), Unité Mixte de Recherches sur les Herbivores ( UMR 1213 Herbivores ), VetAgro Sup ( VAS ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique ( INRA ), Universidad de La Rioja ( UR ), National Reference Laboratory of Antibiotic Resistances and Healthcare Associated Infections (NRL-AMR-HAI), Department of Infectious Diseases, National Institute of Health Doutor Ricardo Jorge, I.P, UCIBIO-REQUIMTE, Faculty of Science and Technology, Universidade Nova de Lisboa, Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro, Department of Genetics and Biotechnology, Department of Genetics and Biotechnology, Functional Genomics and Proteomics Unit, University of Trás-os-Montes and Alto Douro (Portugal), Veterinary Science Department, Unidade de Ciencias Biomoleculares Aplicadas (UCIBIO), Requimte, Universidade do Porto [Porto]-Departamento de Química (DQ), Faculdade de Ciências e Tecnologia (FCT NOVA), Universidade Nova de Lisboa (NOVA)-Universidade Nova de Lisboa (NOVA)-Faculdade de Ciências e Tecnologia (FCT NOVA), Universidade Nova de Lisboa (NOVA)-Universidade Nova de Lisboa (NOVA)-Universidade do Porto [Porto]-Departamento de Química (DQ), Universidade Nova de Lisboa (NOVA)-Universidade Nova de Lisboa (NOVA), Microbiologie Environnement Digestif Santé - Clermont Auvergne (MEDIS), Université Clermont Auvergne (UCA)-INRA Clermont-Ferrand-Theix, Qualité des Produits Animaux (QuaPA), Institut National de la Recherche Agronomique (INRA), Unité Mixte de Recherches sur les Herbivores - UMR 1213 (UMRH), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA), Área de Bioquímica y Biología Molecular, Universidad de La Rioja (UR), Faculty of Sciences and Technology (FCT NOVA), Universidade Nova de Lisboa (NOVA), Departamento de Química (DQ), Universidade Nova de Lisboa (NOVA)-Universidade Nova de Lisboa (NOVA)-Universidade do Porto [Porto], Faculty of Sciences and Technology, ProteoMass Scientific Society, Universidade do Porto = University of Porto-Departamento de Química (DQ), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto = University of Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Microbiologie Environnement Digestif Santé (MEDIS), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Unité Mixte de Recherche sur les Herbivores - UMR 1213 (UMRH), Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Portuguese Foundation for Science and Technology (FCT) SFRH/BD/75160/2010, European Social Fund Ministry of Education and Science (MEC), national funds from FCT/MEC UID/Multi/04378/2013, ERDF under the PT Partnership Agreement POCI-01-0145-FEDER-007728, Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto, INRA Clermont-Ferrand-Theix-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de la Recherche Agronomique (INRA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Universidade do Porto-Departamento de Química (DQ), and Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement
Subjects: 0301 basic medicine, Salmonella, Proteome, [SDV]Life Sciences [q-bio], [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, education, Shotgun Proteomics, Salmonella Typhimurium DT104B, Biology, [ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, medicine.disease_cause, fluoroquinolone, Biochemistry, Microbiology, ciprofloxacine, 03 medical and health sciences, stress, Antibiotic resistance, Stress, Physiological, ciprofloxacin, Lc ms ms, Drug Resistance, Bacterial, medicine, antimicrobial resistance, Selection, Genetic, LC-MS/MS, Shotgun proteomics, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Comparative Subproteomics, [ SDV ] Life Sciences [q-bio], Resistência aos Antimicrobianos, comparative subproteomics, in vitro, 2-DE, salmonella Typhimurium DT104B, In vitro, Fluoroquinolone resistance, 3. Good health, Anti-Bacterial Agents, Ciprofloxacin, 030104 developmental biology, shotgun proteomics, Antimicrobial Resistance, salmonella typhimurium, medicine.drug, Fluoroquinolones
Abstract: Background: Fluoroquinolone resistance in nontyphoidal Salmonella is a situation of serious and international concern, particularly in S. Typhimurium DT104B multiresistant strains. Although known to be multifactorial, fluoroquinolone resistance is still far from a complete understanding. Methods: Subproteome changes between an experimentally selected fluoroquinolone-resistant strain (Se6-M) and its parent strain (Se6), and also in Se6-M under ciprofloxacin (CIP) stress, were evaluated in order to give new insights into the mechanisms involved. Proteomes were compared at the intracellular and membrane levels by a 2-DE~LC-MS/MS and a shotgun LC-MS/MS approach, respectively. Results: In total, 35 differentially abundant proteins were identified when comparing Se6 with Se6-M (25 more abundant in Se6 and 10 more abundant in Se6-M) and 82 were identified between Se6-M and Se6-M+CIP (51 more abundant in Se6-M and 31 more abundant under ciprofloxacin stress). Conclusion: Several proteins with known and possible roles in quinolone resistance were identified which provide important information about mechanism-related differential protein expression, supporting the current knowledge and also leading to new testable hypotheses on the mechanism of action of fluoroquinolone drugs. info:eu-repo/semantics/publishedVersion
Published: 2017

40. FUNGAL SEX: THE BASIDIOMYCOTA

Author: Tatiana Giraud, Guus Bakkeren, Sheng Sun, Michael E. Hood, Marco A. Coelho, Departamento de Ciencias da Vida (DCV), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Pacific Agri-Food Research Centre, Agriculture and Agri-Food [Ottawa] (AAFC), Duke University Medical Center, Department of Biology, Amherst College, Ecologie Systématique et Evolution (ESE), and Université Paris-Sud - Paris 11 (UP11)-AgroParisTech-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0106 biological sciences, 0301 basic medicine, Microbiology (medical), Mating type, Genotype, Physiology, 030106 microbiology, Genes, Fungal, Biology, Haploidy, 010603 evolutionary biology, 01 natural sciences, Genome, Article, Pheromones, [SDV.BDLR.RS]Life Sciences [q-bio]/Reproductive Biology/Sexual reproduction, Evolution, Molecular, Fungal Proteins, 03 medical and health sciences, Meiosis, Genetic linkage, Genetics, 10. No inequality, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, reproductive and urinary physiology, Alleles, Phylogeny, Ploidies, General Immunology and Microbiology, Ecology, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Basidiomycota, Reproduction, Cell Cycle, Fungal genetics, Fungi, Cell Biology, Genes, Mating Type, Fungal, Sexual reproduction, 030104 developmental biology, Infectious Diseases, Mating of yeast, behavior and behavior mechanisms, Sex, Ploidy, Genome, Fungal, Transcription Factors
Abstract: Fungi of the Basidiomycota, representing major pathogen lineages and mushroom-forming species, exhibit diverse means to achieve sexual reproduction, with particularly varied mechanisms to determine compatibilities of haploid mating partners. For species that require mating between distinct genotypes, discrimination is usually based on both the reciprocal exchange of diffusible mating pheromones, rather than sexes, and the interactions of homeodomain protein signals after cell fusion. Both compatibility factors must be heterozygous in the product of mating, and genetic linkage relationships of the mating pheromone/receptor and homeodomain genes largely determine the complex patterns of mating-type variation. Independent segregation of the two compatibility factors can create four haploid mating genotypes from meiosis, referred to as tetrapolarity. This condition is thought to be ancestral to the basidiomycetes. Alternatively, cosegregation by linkage of the two mating factors, or in some cases the absence of the pheromone-based discrimination, yields only two mating types from meiosis, referred to as bipolarity. Several species are now known to have large and highly rearranged chromosomal regions linked to mating-type genes. At the population level, polymorphism of the mating-type genes is an exceptional aspect of some basidiomycete fungi, where selection under outcrossing for rare, intercompatible allelic variants is thought to be responsible for numbers of mating types that may reach several thousand. Advances in genome sequencing and assembly are yielding new insights by comparative approaches among and within basidiomycete species, with the promise to resolve the evolutionary origins and dynamics of mating compatibility genetics in this major eukaryotic lineage.
Published: 2017

41. Resveratrol and Grape Extract-loaded Solid Lipid Nanoparticles for the Treatment of Alzheimer’s Disease

Author: Maria do Carmo Pereira, Ana Rita C. Duarte, Emmanuel Sevin, Manuel A. N. Coelho, Stephanie Andrade, Cláudia Nunes, Fabien Gosselet, Joana Fontes Queiroz, Ana Rute Neves, Joana A. Loureiro, Laurence Fenart, Faculdade de Engenharia, Laboratory for Process Engineering, Environment, Biotechnology and Energy (LEPABE), Universidade do Porto, Unidade de Ciencias Biomoleculares Aplicadas (UCIBIO), Requimte, Universidade do Porto-Departamento de Química (DQ), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Laboratoire de la Barrière Hémato-Encéphalique (LBHE), and Université d'Artois (UA)
Subjects: 0301 basic medicine, Immunoconjugates, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Pharmaceutical Science, 02 engineering and technology, Resveratrol, resveratrol, Analytical Chemistry, chemistry.chemical_compound, drug delivery systems, Drug Discovery, Stilbenes, antibodies, Vitis, Senile plaques, Receptor, food and beverages, 021001 nanoscience & nanotechnology, Lipids, 3. Good health, Transcytosis, Biochemistry, Chemistry (miscellaneous), Molecular Medicine, 0210 nano-technology, Alzheimer’s disease, medicine.drug_class, Drug Compounding, Monoclonal antibody, Neuroprotection, Protein Aggregation, Pathological, Article, Permeability, lcsh:QD241-441, 03 medical and health sciences, Protein Aggregates, lcsh:Organic chemistry, Alzheimer Disease, Solid lipid nanoparticle, medicine, Animals, Physical and Theoretical Chemistry, Particle Size, Amyloid beta-Peptides, Grape Seed Extract, Plant Extracts, grape extracts, Organic Chemistry, blood-brain barrier, Glucuronic acid, body regions, Drug Liberation, 030104 developmental biology, chemistry, immuno SLN, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Nanoparticles
Abstract: International audience; The aggregation of amyloid-β peptide (Aβ) has been linked to the formation of neuritic plaques, which are pathological hallmarks of Alzheimer's disease (AD). Various natural compounds have been suggested as therapeutics for AD. Among these compounds, resveratrol has aroused great interest due to its neuroprotective characteristics. Here, we provide evidence that grape skin and grape seed extracts increase the inhibition effect on Aβ aggregation. However, after intravenous injection, resveratrol is rapidly metabolized into both glucuronic acid and sulfate conjugations of the phenolic groups in the liver and intestinal epithelial cells (within less than 2 h), which are then eliminated. In the present study, we show that solid lipid nanoparticles (SLNs) functionalized with an antibody, the anti-transferrin receptor monoclonal antibody (OX26 mAb), can work as a possible carrier to transport the extract to target the brain. Experiments on human brain-like endothelial cells show that the cellular uptake of the OX26 SLNs is substantially more efficient than that of normal SLNs and SLNs functionalized with an unspecific antibody. As a consequence, the transcytosis ability of these different SLNs is higher when functionalized with OX-26.
Published: 2017

42. Wheat glutenin: the 'tail' of the 1By protein subunits

Author: Emmanuelle Bancel, Gilberto Igrejas, Gérard Branlard, José Luis Capelo, J. D. Nunes-Miranda, Christophe Chambon, Didier Viala, Catherine Ravel, Functional Genomics and Proteomics Unit, Department of Genetics and Biotechnology, University of Trás-os-Montes and Alto Douro (Portugal), UCIBIO-REQUIMTE, Faculty of Science and Technology, Universidade Nova de Lisboa, Génétique Diversité et Ecophysiologie des Céréales ( GDEC ), Institut National de la Recherche Agronomique ( INRA ) -Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ), Unité Mixte de Recherches sur les Herbivores ( UMR 1213 Herbivores ), VetAgro Sup ( VAS ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique ( INRA ), Qualité des Produits Animaux ( QUAPA ), Institut National de la Recherche Agronomique ( INRA ), Faculty of Sciences and Technology, Universidade Nova de Lisboa ( UNINOVA ), Unidade de Ciencias Biomoleculares Aplicadas (UCIBIO), Requimte, Universidade do Porto-Departamento de Química (DQ), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Génétique Diversité et Ecophysiologie des Céréales (GDEC), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Unité Mixte de Recherche sur les Herbivores - UMR 1213 (UMRH), Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Qualité des Produits Animaux (QuaPA), Institut National de la Recherche Agronomique (INRA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Portuguese Foundation for Science and Technology (FCT) SFRH/BD/80496/2011, European Social Fund, Ministry of Education and Science (MEC), FCT/MEC UID/Multi/04378/2013, ERDF POCI-01-0145-FEDER-007728, Departamento de Química (DQ), Faculdade de Ciências e Tecnologia (FCT NOVA), Universidade Nova de Lisboa (NOVA)-Universidade Nova de Lisboa (NOVA)-Faculdade de Ciências e Tecnologia (FCT NOVA), Universidade Nova de Lisboa (NOVA)-Universidade Nova de Lisboa (NOVA)-Universidade do Porto [Porto]-Departamento de Química (DQ), Universidade Nova de Lisboa (NOVA)-Universidade Nova de Lisboa (NOVA)-Universidade do Porto [Porto], Institut National de la Recherche Agronomique (INRA)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP), Unité Mixte de Recherches sur les Herbivores - UMR 1213 (UMRH), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA), Faculty of Sciences and Technology (FCT NOVA), Universidade Nova de Lisboa (NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto, Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Recherche Agronomique (INRA), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de la Recherche Agronomique (INRA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Universidade do Porto = University of Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto = University of Porto-Departamento de Química (DQ), Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Universidade do Porto [Porto]-Departamento de Química (DQ), and Universidade Nova de Lisboa (NOVA)-Universidade Nova de Lisboa (NOVA)
Subjects: 0106 biological sciences, 0301 basic medicine, gluténine, Glutens, [SDV]Life Sciences [q-bio], Protein subunit, Biophysics, proteolytic cleavage, 01 natural sciences, Biochemistry, 1By HMW-GS, Polymerization, 03 medical and health sciences, Glutenin, clivage proteolytique, blé, wheat, Immunochemistry, Food Quality, Storage protein, Asparagine, Cysteine, Triticum, wheat glutenin, 2. Zero hunger, chemistry.chemical_classification, C-terminal domain maturation, biology, [ SDV ] Life Sciences [q-bio], asparaginyl endopeptidase, Seed Storage Proteins, food and beverages, asparagine, Gluten, Molecular Weight, Protein Subunits, 030104 developmental biology, Enzyme, chemistry, protéine, biology.protein, protein, Protein Processing, Post-Translational, 010606 plant biology & botany, glutenin
Abstract: Epub ahead of print; Gluten-forming storage proteins play a major role in the viscoelastic properties of wheat dough through the formation of a continuous proteinaceous network. The high-molecular-weight glutenin subunits represent a functionally important subgroup of gluten proteins by promoting the formation of large glutenin polymers through interchain disulphide bonds between glutenin subunits. Here, we present evidences that y-type glutenin subunits encoded at the Glu-B1 locus are prone to proteolytic processing at the C-terminus tail, leading to the loss of the unique cysteine residue present at the C-terminal domain. Results obtained by intact mass measurement and immunochemistry for each proteoform indicate that the proteolytic cleavage appears to occur at the carboxyl-side of two conserved asparagine residues at the C-terminal domain start. Hence, we hypothesize that the responsible enzymes are a class of cysteine endopeptidases - asparaginyl endopeptidases - described in post-translational processing of other storage proteins in wheat. Biological significance The reported study provides new insights into wheat storage protein maturation. In view of the importance of gluten proteins on dough viscoelastic properties and end-product quality, the reported C-terminal domain cleavage of high-molecular-weight glutenin subunits is of particular interest, since this domain possesses a unique conserved cysteine residue which is assumed to participate in gluten polymerization.
Published: 2017

43. Comparative subproteomic analysis of clinically acquired fluoroquinolone resistance and ciprofloxacin stress in Salmonella Typhimurium DT104B

Author: José Luis Capelo, Susana Correia, Christophe Chambon, Michel Hébraud, Yolanda Sáenz, Gilberto Igrejas, Didier Viala, Ingrid Chafsey, Patrícia Poeta, Functional Genomics and Proteomics Unit, Universidade de Trás-os-Montes e Alto Douro, Department of Genetics and Biotechnology, University of Tras-os-Montes and Alto Douro, Veterinary Science Department, University of Trás-os-Montes and Alto Douro (Portugal), Unidade de Ciencias Biomoleculares Aplicadas (UCIBIO), Requimte, Departamento de Química (DQ), Faculdade de Ciências e Tecnologia (FCT NOVA), Universidade Nova de Lisboa (NOVA)-Universidade Nova de Lisboa (NOVA)-Faculdade de Ciências e Tecnologia (FCT NOVA), Universidade Nova de Lisboa (NOVA)-Universidade Nova de Lisboa (NOVA)-Universidade do Porto [Porto]-Departamento de Química (DQ), Universidade Nova de Lisboa (NOVA)-Universidade Nova de Lisboa (NOVA)-Universidade do Porto [Porto], Microbiologie Environnement Digestif Santé - Clermont Auvergne (MEDIS), Université Clermont Auvergne (UCA)-INRA Clermont-Ferrand-Theix, Qualité des Produits Animaux (QuaPA), Institut National de la Recherche Agronomique (INRA), Unité Mixte de Recherches sur les Herbivores - UMR 1213 (UMRH), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA), Área de Microbiología Molecular, Centro de Investigación Biomédica de La Rioja (CIBIR), Faculty of Sciences and Technology (FCT NOVA), Universidade Nova de Lisboa (NOVA), Portuguese Foundation for Science and Technology (FCT) SFRH/BD/75160/2010, European Social Fund, Ministry of Education and Science (MEC), FCT/MEC UID/Multi/04378/2013, ERDF POCI-01-0145-FEDER-007728, Universidade do Porto = University of Porto-Departamento de Química (DQ), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto = University of Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Microbiologie Environnement Digestif Santé (MEDIS), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Unité Mixte de Recherche sur les Herbivores - UMR 1213 (UMRH), Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), department of neurology, clinical dementia center and DZNE, University Medical Centre Goettingen, Microbiologie Environnement Digestif Santé - Clermont Auvergne ( MEDIS ), Université Clermont Auvergne ( UCA ) -INRA Clermont-Ferrand-Theix, Qualité des Produits Animaux ( QUAPA ), Institut National de la Recherche Agronomique ( INRA ), Unité Mixte de Recherches sur les Herbivores ( UMR 1213 Herbivores ), VetAgro Sup ( VAS ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique ( INRA ), Centro de Investigación Biomédica de La Rioja, UCIBIO-REQUIMTE, Faculty of Science and Technology, Universidade Nova de Lisboa, Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro, Universidade do Porto [Porto]-Departamento de Química (DQ), Universidade Nova de Lisboa (NOVA)-Universidade Nova de Lisboa (NOVA), INRA Clermont-Ferrand-Theix-Université Clermont Auvergne ( UCA ), Faculty of Sciences and Technology, Universidade Nova de Lisboa ( UNINOVA ), Universidade do Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto-Departamento de Química (DQ), INRA Clermont-Ferrand-Theix-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto, and VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de la Recherche Agronomique (INRA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement
Subjects: 0301 basic medicine, Serotype, Salmonella, fluoroquinolone resistance, salmonella typhimurium DT104B, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, [SDV]Life Sciences [q-bio], Clinical Biochemistry, [ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, medicine.disease_cause, fluoroquinolone, Microbiology, ciprofloxacine, 03 medical and health sciences, Antibiotic resistance, Stress, Physiological, ciprofloxacin, Drug Resistance, Bacterial, medicine, Humans, antimicrobial resistance, ciprofloxacin stress, ComputingMilieux_MISCELLANEOUS, résistance antimicrobienne, biology, Strain (chemistry), [ SDV ] Life Sciences [q-bio], comparative subproteomics, biology.organism_classification, 3. Good health, Ciprofloxacin, 030104 developmental biology, Mechanism of action, Salmonella enterica, Proteome, medicine.symptom, salmonella typhimurium, medicine.drug
Abstract: PURPOSE Antimicrobial resistance is a worldwide public health threat and Salmonella enterica subsp. enterica serotype Typhimurium phage type DT104B multiresistant strains with additional quinolone resistance have been responsible for global outbreaks and high mortality. Quinolone resistance is known to be multifactorial but is still far from a complete understanding. To give new insights about the resistance mechanisms involved, this work aimed to evaluate subproteome changes between an S. Typhimurium DT104B clinical strain that acquired fluoroquinolone resistance after treatment (Se20) and its pretreatment parental strain (Se6), and also subproteome variations in Se20 under ciprofloxacin (CIP) stress (Se20+CIP). EXPERIMENTAL DESIGN The proteomes were compared at the intracellular and membrane levels by a 2-DE∼LC-MS/MS and a shotgun LC-MS/MS approach, respectively. RESULTS In total, 14 differentially abundant proteins were identified when comparing Se6 with Se20 and 91 were identified between Se20 and Se20+CIP. Several proteins with known and possible roles in quinolone resistance (AAC(6')-Ib-cr4, OmpD, OmpX, GlmS, GlmU, H-NS, etc.) were identified and discussed. CONCLUSIONS AND CLINICAL RELEVANCE The great number of proteins identified in this study provides important information about mechanism-related differential protein expression which supports the current knowledge and might lead to new testable hypotheses on the mechanism of action of fluoroquinolone drugs.
Published: 2017

44. The Hinge Segment of Human NADPH-Cytochrome P450 Reductase in Conformational Switching: The Critical Role of Ionic Strength

Author: Michel Kranendonk, Sophie Bozonnet, Thomas Lautier, Diana Campelo, Gilles Truan, Francisco de Assis Esteves, Philippe Urban, Center for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Portuguese national funds, through the Fundacao para a Ciencia e a Tecnologia [FCT-ANR/BEX-BCM/0002/2013], ANR-13-ISV5-0001,DODYCOEL,Dynamique de domaines dans le contrôle du flux d'électrons(2013), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Kranendonk, Michel, Universidade Nova de Lisboa (NOVA)-Universidade Nova de Lisboa (NOVA), ANR/FCT program [ANR-13-ISV5-0001], NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), and Centre for Toxicogenomics and Human Health (ToxOmics)
Subjects: 0301 basic medicine, cytochrome, conformational exchange, Context (language use), nadph, Protein dynamics, Reductase, diflavin reductase, Redox, Protein–protein interaction, Electron transfer, protein-protein interaction, 03 medical and health sciences, Protein-protein interaction, Pharmaceutical sciences, Multidomain proteins, force ionique, Pharmacology (medical), mutant, électrostatique, Pharmacology, biology, Chemistry, Cytochrome c, lcsh:RM1-950, Correction, static electricity, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, electron transfer, conformattional exchange, Diflavin reductase, diflavine réductase, lcsh:Therapeutics. Pharmacology, 030104 developmental biology, protein–protein interaction, Biochemistry, Conformational exchange, protein dynamics, biology.protein, Biophysics, multidomain proteins, Salt bridge, Sciences pharmaceutiques, ionic strength
Abstract: This work was in part funded by a joint ANR/FCT program; France: ANR-13-ISV5-0001 (DODYCOEL), and Portuguese national funds, through the Fundacao para a Ciencia e a Tecnologia (Project FCT-ANR/BEX-BCM/0002/2013). NADPH-cytochrome P450 reductase (CPR) is a redox partner of microsomal cytochromes P450 and is a prototype of the diflavin reductase family. CPR contains 3 distinct functional domains: a FMN-binding domain (acceptor reduction), a linker (hinge), and a connecting/FAD domain (NADPH oxidation). It has been demonstrated that the mechanism of CPR exhibits an important step in which it switches from a compact, closed conformation (locked state) to an ensemble of open conformations (unlocked state), the latter enabling electron transfer to redox partners. The conformational equilibrium between the locked and unlocked states has been shown to be highly dependent on ionic strength, reinforcing the hypothesis of the presence of critical salt interactions at the interface between the FMN and connecting FAD domains. Here we show that specific residues of the hinge segment are important in the control of the conformational equilibrium of CPR. We constructed six single mutants and two double mutants of the human CPR, targeting residues G240, S243, I245 and R246 of the hinge segment, with the aim of modifying the flexibility or the potential ionic interactions of the hinge segment. We measured the reduction of cytochrome c at various salt concentrations of these 8 mutants, either in the soluble or membrane-bound form of human CPR. All mutants were found capable of reducing cytochrome c yet with different efficiency and their maximal rates of cytochrome c reduction were shifted to lower salt concentration. In particular, residue R246 seems to play a key role in a salt bridge network present at the interface of the hinge and the connecting domain. Interestingly, the effects of mutations, although similar, demonstrated specific differences when present in the soluble or membrane-bound context. Our results demonstrate that the electrostatic and flexibility properties of the hinge segment are critical for electron transfer from CPR to its redox partners. publishersversion published
Published: 2017

45. The role of calcium supplementation in healthy musculoskeletal ageing: An expert consensus meeting of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Foundation for Osteoporosis (IOF)

Author: Jürgen M. Bauer, Francesco Landi, Véronique Coxam, Maria Luisa Brandi, H. P. Dimai, Olivier Bruyère, Nicholas C. Harvey, Jean-Marc Kaufman, Emmanuel Biver, John A. Kanis, Jaime Branco, Edward Czerwiński, Patrice Fardellone, René Rizzoli, Bess Dawson-Hughes, Cyrus Cooper, Alfonso J. Cruz-Jentoft, Jean-Yves Reginster, MRC Lifecourse Epidemiology Unit, University of Southampton, NIHR Southampton Biomedical Research Centre, Southampton University Hospitals NHS Foundation Trust, Service of Bone Diseases, Université de Genève = University of Geneva (UNIGE)-Geneva University Hospital (HUG), Department of Internal Medicine, section Endocrinology, Ghent University Hospital, Universitätsklinik für Geriatrie, Kinikum Oldenburg, University of Oldenburg, CEDOC - Department of Rheumatology, Centro de Estudos de Doenças Crónicas (CEDOC), NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), CHLO/Hospital Egas Moniz, Department of Surgery and Translational Medicine, Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Department of Public Health, Epidemiology and Health Economics, Université de Liège, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), Department of Bone and Joint Diseases, Faculty of Medicine and Health Sciences, Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University Graz, U 1088, CHU Amiens-Picardie, Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Picardie Jules Verne (UPJV), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Geriatric Department, Catholic University of the Sacred Heart, Jean Meyer USDA Human Nutrition Research Centeron Aging, Tufts University [Medford], Centre for Metabolic Bone Diseases, University of Sheffield [Sheffield], Institute for Health and Ageing, Catholic University of Australia, NIHR Oxford Musculoskeletal Biomedical Research Unit, Botnar Research Centre, University of Oxford, and European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO)
Subjects: medicine.medical_specialty, Gastrointestinal Diseases, Endocrinology, Diabetes and Metabolism, Osteoporosis, Calcium supplementation, Fracture reduction, Myocardial infarction, Vitamin D supplementation, Placebo-controlled study, vitamine D, chemistry.chemical_element, 030209 endocrinology & metabolism, supplement, Osteoarthritis, Calcium, Article, law.invention, 03 medical and health sciences, Kidney Calculi, 0302 clinical medicine, Randomized controlled trial, Meta-Analysis as Topic, law, fracture ostéoporotique, Internal medicine, medicine, Vitamin D and neurology, Humans, 030212 general & internal medicine, Vitamin D, Muscle, Skeletal, calcium, Bone Density Conservation Agents, business.industry, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, Rheumatology, 3. Good health, chemistry, Orthopedic surgery, Dietary Supplements, Physical therapy, complement alimentaire, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Osteoporotic Fractures
Abstract: The place of calcium supplementation, with or without concomitant vitamin D supplementation, has been much debated in terms of both efficacy and safety. There have been numerous trials and meta-analyses of supplementation for fracture reduction, and associations with risk of myocardial infarction have been suggested in recent years. In this report, the product of an expert consensus meeting of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Foundation for Osteoporosis (IOF), we review the evidence for the value of calcium supplementation, with or without vitamin D supplementation, for healthy musculoskeletal ageing. We conclude that (1) calcium and vitamin D supplementation leads to a modest reduction in fracture risk, although population-level intervention has not been shown to be an effective public health strategy; (2) supplementation with calcium alone for fracture reduction is not supported by the literature; (3) side effects of calcium supplementation include renal stones and gastrointestinal symptoms; (4) vitamin D supplementation, rather than calcium supplementation, may reduce falls risk; and (5) assertions of increased cardiovascular risk consequent to calcium supplementation are not convincingly supported by current evidence. In conclusion, we recommend, on the basis of the current evidence, that calcium supplementation, with concomitant vitamin D supplementation, is supported for patients at high risk of calcium and vitamin D insufficiency, and in those who are receiving treatment for osteoporosis.
Published: 2017

46. Coordinated waves of actomyosin flow and apical cell constriction immediately after wounding

Author: João V. Cordeiro, Telmo Pereira, Luis Almeida, António Jacinto, Marco Antunes, Chronic Diseases Research Center (CEDOC), NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Laboratoire Jacques-Louis Lions (LJLL), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), ANR-11-BSV5-0021,REGENR,Modélisation Mathématique et Physique de la Réparation Régénérative(2011), Centro de Estudos de Doenças Crónicas (CEDOC), and Repositório da Universidade de Lisboa
Subjects: Microfilament, Polymerization, PATHWAY, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Drosophila Proteins, Cytoskeleton, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Research Articles, ComputingMilieux_MISCELLANEOUS, GENE-EXPRESSION, rho-Associated Kinases, 0303 health sciences, integumentary system, 030302 biochemistry & molecular biology, Pupa, ACTIN CYTOSKELETON, Actomyosin, Biomechanical Phenomena, Cell biology, Actin Cytoskeleton, cardiovascular system, Drosophila, circulatory and respiratory physiology, POLARITY, Formins, TRPM Cation Channels, macromolecular substances, Biology, Article, Adherens junction, 03 medical and health sciences, TISSUE REGENERATION, Animals, Calcium Signaling, DROSOPHILA EMBRYOS, Gelsolin, Actin, 030304 developmental biology, Wound Healing, Calcium channel, ADHERENS JUNCTIONS, MYOSIN-II, Biological Transport, Epithelial Cells, Cell Biology, Actin cytoskeleton, Luminescent Proteins, MORPHOGENESIS, CLOSURE, Anisotropy, Calcium, Stress, Mechanical, Carrier Proteins, Wound healing
Abstract: Epithelial wounding causes waves of actomyosin flow and apical cell constriction that are dependent on calcium signaling and actin filament severing., Epithelial wound healing relies on tissue movements and cell shape changes. Our work shows that, immediately after wounding, there was a dramatic cytoskeleton remodeling consisting of a pulse of actomyosin filaments that assembled in cells around the wound edge and flowed from cell to cell toward the margin of the wound. We show that this actomyosin flow was regulated by Diaphanous and ROCK and that it elicited a wave of apical cell constriction that culminated in the formation of the leading edge actomyosin cable, a structure that is essential for wound closure. Calcium signaling played an important role in this process, as its intracellular concentration increased dramatically immediately after wounding, and down-regulation of transient receptor potential channel M, a stress-activated calcium channel, also impaired the actomyosin flow. Lowering the activity of Gelsolin, a known calcium-activated actin filament–severing protein, also impaired the wound response, indicating that cleaving the existing actin filament network is an important part of the cytoskeleton remodeling process.
Published: 2013

47. Zika Virus, a New Threat for Europe?

Author: Carla A. Sousa, Gonçalo Seixas, Laurence Mousson, Anna-Bella Failloux, Henri Jupille, Vector borne diseases and pathogens (VBD), Global Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical (IHMT), Arbovirus et Insectes Vecteurs - Arboviruses and Insect Vectors, Institut Pasteur [Paris] (IP), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Global Health and Tropical Medicine [Lisboa], Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), The work was supported by a grant FP7-HEALTH HEALTH.2011.2.3.3-2 (grant number: 282378) 'Dengue research Framework for resisting epidemics in Europe' (DENFREE) and the Institut Pasteur (ACIP grant A15-2014)., European Project: 282378,EC:FP7:HEALTH,FP7-HEALTH-2011-single-stage,DENFREE(2012), and Institut Pasteur [Paris]
Subjects: 0301 basic medicine, RNA viruses, Viral Diseases, Epidemiology, Physiology, viruses, Dengue virus, Disease Vectors, medicine.disease_cause, Pathology and Laboratory Medicine, Mosquitoes, Zika virus, Geographical Locations, 0302 clinical medicine, Aedes, Medicine and Health Sciences, 030212 general & internal medicine, Chikungunya, education.field_of_study, Chikungunya Virus, Transmission (medicine), Zika Virus Infection, lcsh:Public aspects of medicine, virus diseases, 3. Good health, Body Fluids, Insects, Europe, Flavivirus, Infectious Diseases, Medical Microbiology, Viral Pathogens, Viruses, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, France, Pathogens, Anatomy, Brazil, Research Article, Neglected Tropical Diseases, Aedes albopictus, lcsh:Arctic medicine. Tropical medicine, Arthropoda, Genotype, lcsh:RC955-962, Alphaviruses, 030231 tropical medicine, Population, Aedes aegypti, Mosquito Vectors, Biology, Microbiology, Togaviruses, 03 medical and health sciences, New Caledonia, SDG 3 - Good Health and Well-being, medicine, Animals, Humans, Viremia, education, Saliva, Microbial Pathogens, Flaviviruses, fungi, Organisms, Public Health, Environmental and Occupational Health, Outbreak, Biology and Life Sciences, Chikungunya Infection, Humidity, lcsh:RA1-1270, Zika Virus, South America, biology.organism_classification, Tropical Diseases, Virology, Invertebrates, Insect Vectors, 030104 developmental biology, People and Places
Abstract: Background Since its emergence in 2007 in Micronesia and Polynesia, the arthropod-borne flavivirus Zika virus (ZIKV) has spread in the Americas and the Caribbean, following first detection in Brazil in May 2015. The risk of ZIKV emergence in Europe increases as imported cases are repeatedly reported. Together with chikungunya virus (CHIKV) and dengue virus (DENV), ZIKV is transmitted by Aedes mosquitoes. Any countries where these mosquitoes are present could be potential sites for future ZIKV outbreak. We assessed the vector competence of European Aedes mosquitoes (Aedes aegypti and Aedes albopictus) for the currently circulating Asian genotype of ZIKV. Methodology/Principal Findings Two populations of Ae. aegypti from the island of Madeira (Funchal and Paul do Mar) and two populations of Ae. albopictus from France (Nice and Bar-sur-Loup) were challenged with an Asian genotype of ZIKV isolated from a patient in April 2014 in New Caledonia. Fully engorged mosquitoes were then maintained in insectary conditions (28°±1°C, 16h:8h light:dark cycle and 80% humidity). 16–24 mosquitoes from each population were examined at 3, 6, 9 and 14 days post-infection to estimate the infection rate, disseminated infection rate and transmission efficiency. Based on these experimental infections, we demonstrated that Ae. albopictus from France were not very susceptible to ZIKV. Conclusions/Significance In combination with the restricted distribution of European Ae. albopictus, our results on vector competence corroborate the low risk for ZIKV to expand into most parts of Europe with the possible exception of the warmest regions bordering the Mediterranean coastline., Author Summary In May 2015, local transmission of Zika virus (ZIKV) was reported in Brazil and since then, more than 1.5 million human cases have been reported in Latin America and the Caribbean. This arbovirus, primarily found in Africa and Asia, is mainly transmitted by Aedes mosquitoes, Aedes aegypti and Aedes albopictus. Viremic travelers returning from America to European countries where Ae. albopictus is established could become the source for local transmission of ZIKV. In order to estimate the risk of seeding ZIKV into local mosquito populations, the susceptibility of European Ae. aegypti and Ae. albopictus to ZIKV was measured using experimental infections. We demonstrated that Ae. albopictus and Ae. aegypti from Europe were not very susceptible to ZIKV. The threat for a Zika outbreak in Europe should be limited.
Published: 2016

48. Automatic EOG and EMG Artifact Removal Method for Sleep Stage Classification

Author: José Fonseca, Shirin Najdi, Tohid Yousefi Rezaii, Ali Abdollahi Gharbali, Computational Intelligence Research Group (CA3), Centre of Technology and Systems (CTS), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), University of Tabriz [Tabriz], Luis M. Camarinha-Matos, António J. Falcão, Nazanin Vafaei, Shirin Najdi, TC 5, and WG 5.5
Subjects: Channel (digital image), Computer science, 02 engineering and technology, Electroencephalography, Adaptive filtering, Artifact detection, 03 medical and health sciences, 0302 clinical medicine, Wavelet, 0202 electrical engineering, electronic engineering, information engineering, medicine, Computer vision, [INFO]Computer Science [cs], Artifact (error), Sleep Stages, medicine.diagnostic_test, Artificial neural network, business.industry, Artifact removing, 020206 networking & telecommunications, Pattern recognition, Sleep stage classification, Wavelet packet, Thresholding, Adaptive filter, Artificial intelligence, business, 030217 neurology & neurosurgery
Abstract: Part 5: Biomedical Applications; International audience; In this paper, a new algorithm is proposed for artifact removing of sleep electroencephalogram (EEG) with application in sleep stage classification. Rather than other works which used artificial noise, in this study real EEG data contaminated with electro-oculogram (EOG) and electromyogram (EMG) are used for evaluating the proposed artifact removal algorithm’s efficiency using classification accuracy. The artifact detection is performed by thresholding the EEG-EOG and EEG-EMG cross correlation coefficients. Then, the segments considered contaminated are denoised by normalized least-mean squares (NLMS) adaptive filtering technique. Using a single EEG channel, four sleep stages consisting of Awake, Stage1 + REM, Stage 2 and Slow Wave Stage (SWS) are classified. A wavelet packet (WP) based feature set together with artificial neural network (ANN) are deployed for sleep stage classification purpose. Simulation results show that artifact removed EEG allows a classification accuracy improvement of around 14 %.
Published: 2016

49. Structure of a truncated form of leucine zipper II of JIP3 reveals an unexpected antiparallel coiled-coil arrangement

Author: Julie Ménétrey, Paola Llinas, Annélie de Régibus, Mélanie Chenon, Cátia Moreira, Pedro A. Fernandes, T. Quyen Nguyen, Maria J. Ramos, Raphael Guerois, Aline Coquard, Laboratoire d'Enzymologie et Biochimie Structurales (LEBS), Centre National de la Recherche Scientifique (CNRS), Faculty of Science and Technology, BIOSCOPE Group, UCIBIO-REQUIMTE, Universidade de Lisboa (ULISBOA), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Requimte, Departamento de Química (DQ), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto, Laboratoire d'Enzymologie et Biochimie Structurales ( LEBS ), Centre National de la Recherche Scientifique ( CNRS ), Universidade de Lisboa ( ULISBOA ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), Requimente, Departamento de Química, Faculdade de Ciências, Universidade do Porto [Porto], Universidade de Lisboa = University of Lisbon (ULISBOA), Universidade do Porto = University of Porto-Departamento de Química (DQ), and Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)
Subjects: 0301 basic medicine, Leucine zipper, crystal structure, buried asparagine, Stereochemistry, [SDV]Life Sciences [q-bio], Biophysics, Nerve Tissue Proteins, Small G Protein, Plasma protein binding, Molecular Dynamics Simulation, Crystallography, X-Ray, Antiparallel (biochemistry), Biochemistry, Protein Structure, Secondary, Research Communications, 03 medical and health sciences, Structural Biology, leucine zipper II, Genetics, Molecular motor, Humans, JIP4, Protein Interaction Domains and Motifs, Amino Acid Sequence, Binding site, Structural motif, Adaptor Proteins, Signal Transducing, JIP3, antiparallel coiled coil, Coiled coil, Leucine Zippers, 030102 biochemistry & molecular biology, [ SDV ] Life Sciences [q-bio], Chemistry, Condensed Matter Physics, Peptide Fragments, molecular dynamics, Protein Structure, Tertiary, Crystallography, 030104 developmental biology, Crystallization
Abstract: International audience; JIP3 and JIP4, two highly related scaffolding proteins for MAP kinases, are binding partners for two molecular motors as well as for the small G protein ARF6. The leucine zipper II (LZII) region of JIP3/4 is the binding site for these three partners. Previously, the crystal structure of ARF6 bound to JIP4 revealed LZII in a parallel coiled-coil arrangement. Here, the crystal structure of an N-terminally truncated form of LZII of JIP3 alone shows an unexpected antiparallel arrangement. Using molecular dynamics and modelling, the stability of this antiparallel LZII arrangement, as well as its specificity for ARF6, were investigated. This study highlights that N-terminal truncation of LZII can change its coiled-coil orientation without affecting its overall stability. Further, a conserved buried asparagine residue was pinpointed as a possible structural determinant for this dramatic structural rearrangement. Thus, LZII of JIP3/4 is a versatile structural motif, modifications of which can impact partner recognition and thus biological function.
Published: 2016

50. New insights into wheat toxicity: Breeding did not seem to contribute to a prevalence of potential celiac disease's immunostimulatory epitopes

Author: Gilberto Igrejas, Gérard Branlard, Fernando M. Nunes, Miguel Ribeiro, José A. Carrillo, Marta Rodríguez-Quijano, Functional Genomics and Proteomics Unit, University of Trás-os-Montes and Alto Douro (Portugal), Department of Genetics and Biotechnology, CQ-VR, Chemistry Research Centre, Chemistry Department, Unidad de Genética y Mejora de plantas Departamento de Biotecnología-Biología Vegetal, E.T.S. Ingenieros Agrónomos, Universidad Politécnica de Madrid (UPM), Génétique Diversité et Ecophysiologie des Céréales (GDEC), Institut National de la Recherche Agronomique (INRA)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP), Unidade de Ciencias Biomoleculares Aplicadas (UCIBIO), Requimte, Universidade do Porto-Departamento de Química (DQ), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Foundation for Science and Technology (FCT) - Portugal and European Social Fund (ESF) [SFRH/BD/82334/2011], Unidade de Ciencias Biomoleculares Aplicadas-UCIBIO - national funds from FCT/MEC [UID/Multi/04378/2013], ERDF under the PT2020 Partnership [POCI-01-0145-FEDER-007728], FCT [PTDC/QUI-QUI/100044/2008, PEst-OE/QUI/UI0616/2014], COMPETE, Universidade do Porto = University of Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto = University of Porto-Departamento de Química (DQ), Departamento de Química (DQ), Faculdade de Ciências e Tecnologia (FCT NOVA), Universidade Nova de Lisboa (NOVA)-Universidade Nova de Lisboa (NOVA)-Faculdade de Ciências e Tecnologia (FCT NOVA), Universidade Nova de Lisboa (NOVA)-Universidade Nova de Lisboa (NOVA)-Universidade do Porto [Porto]-Departamento de Química (DQ), Universidade Nova de Lisboa (NOVA)-Universidade Nova de Lisboa (NOVA)-Universidade do Porto [Porto], Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Institut National de la Recherche Agronomique (INRA), Universidade do Porto [Porto]-Departamento de Química (DQ), and Universidade Nova de Lisboa (NOVA)-Universidade Nova de Lisboa (NOVA)
Subjects: 0301 basic medicine, Hot Temperature, Glutens, [SDV]Life Sciences [q-bio], Prevalence, Gliadins, Enzyme-Linked Immunosorbent Assay, Disease, Epitope, Gliadin, Analytical Chemistry, 03 medical and health sciences, Epitopes, Immune system, Toxic epitopes, Humans, Chromatography, High Pressure Liquid, Triticum, 2. Zero hunger, Genetics, chemistry.chemical_classification, 030109 nutrition & dietetics, biology, business.industry, nutritional and metabolic diseases, food and beverages, General Medicine, Gluten Proteins, Gluten, digestive system diseases, Biotechnology, Tetraploidy, Celiac Disease, Plant Breeding, 030104 developmental biology, chemistry, RP-HPLC, Toxicity, biology.protein, Food Technology, business, Food Science
Abstract: Gluten proteins, namely gliadins, are the primary trigger of the abnormal immune response in celiac disease. It has been hypothesised that modern wheat breeding practices may have contributed to the increase in celiac disease prevalence during the latter half of the 20th century. Our results do not support this hypothesis as Triticum aestivum spp. vulgare landraces, which were not subjected to breeding practices, presented higher amounts of potential celiac disease's immunostimulatory epitopes when compared to modern varieties. Furthermore, high variation between wheat varieties concerning the toxic epitopes amount was observed. We carried out quantitative analysis of gliadin types by RP-HPLC to verify its correlation with the amount of toxic epitopes: x-type gliadins content explain about 40% of the variation of toxic epitopes in tetraploid wheat varieties. This research provides new insights regarding wheat toxicity and into the controversial idea that human practices may have conducted to an increased exposure to toxic epitopes.
Published: 2016

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