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19 results on '"University of Barcelona-Barcelona Institute of Science and Technology (BIST)"'

1. Democratizing knowledge representation with BioCypher

Author

Lobentanzer, Sebastian, Aloy, Patrick, Baumbach, Jan, Bohar, Balazs, Charoentong, Pornpimol, Danhauser, Katharina, Doğan, Tunca, Dreo, Johann, Dunham, Ian, Fernandez-Torras, Adrià, Gyori, Benjamin, Hartung, Michael, Hoyt, Charles Tapley, Klein, Christoph, Korcsmaros, Tamas, Maier, Andreas, Mann, Matthias, Ochoa, David, Pareja-Lorente, Elena, Preusse, Martin, Probul, Niklas, Schwikowski, Benno, Sen, Bünyamin, Strauss, Maximilian, Turei, Denes, Ulusoy, Erva, Wodke, Judith, Waltemath, Dagmar, Saez-Rodriguez, Julio, Carey, Vincent, Farr, Elias, Popp, Ferdinand, Universität Heidelberg [Heidelberg] = Heidelberg University, Institute for Research in Biomedicine [Barcelona, Spain] (IRB), University of Barcelona-Barcelona Institute of Science and Technology (BIST), University of Hamburg, Earlham Institute [Norwich], Biological Research Centre [Szeged] (BRC), Dr von Hauner Children's Hospital [Munich, Germany], Ludwig-Maximilians-Universität München (LMU), Hacettepe University = Hacettepe Üniversitesi, Biomédecine computationelle des systèmes / Computational systems biomedicine, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Harvard Medical School [Boston] (HMS), Dr Von Hauner Children's Hospital, Partenaires INRAE, Quadram Institute Bioscience [Norwich, U.K.] (QIB), Biotechnology and Biological Sciences Research Council (BBSRC), Imperial College London, Universität zu Köln = University of Cologne, Max-Planck-Institut für Biochemie = Max Planck Institute of Biochemistry (MPIB), Max-Planck-Gesellschaft, German Center for Diabetes Research - Deutsches Zentrum für Diabetesforschung [Neuherberg] (DZD), University of Medicine Greifswald, Brigham & Women’s Hospital [Boston] (BWH), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), European Project: 965193, H2020-EU.3.1. - SOCIETAL CHALLENGES - Health, demographic change and well-being H2020-EU.3.1.5. - Methods and data ,DECIDER(2021), European Project: 066490,WT::(2003), European Project: 031L0181B,LaMarck, European Project: 031L0212A,SMART-CARE, European Project: W911NF-20-1-0255, and European Project: 01ZZ2019,MIRACUM

Subjects
prior knowledge, knowledge graph, federated learning, harmonisation, FAIRness, ontology, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], database
Abstract

International audience; Standardising the representation of biomedical knowledge among allresearchers is an insurmountable task, hindering the effectiveness of manycomputational methods. To facilitate harmonisation and interoperability despitethis fundamental challenge, we propose to standardise the framework ofknowledge graph creation instead. We implement this standardisation inBioCypher, a FAIR (findable, accessible, interoperable, reusable) framework totransparently build biomedical knowledge graphs while preserving provenances ofthe source data. Mapping the knowledge onto biomedical ontologies helps tobalance the needs for harmonisation, human and machine readability, and ease ofuse and accessibility to non-specialist researchers. We demonstrate the usefulnessof the framework on a variety of use cases, from maintenance of task-specificknowledge stores, to interoperability between biomedical domains, to on-demandbuilding of task-specific knowledge graphs for federated learning. BioCypher(https://biocypher.org) thus facilitates automating knowledge-based biomedicalresearch, and we encourage the community to further develop and use it.

Published
2023

2. Binary Interactome Models of Inner- Versus Outer-Complexome Organization

Author

Thomas Rolland, Atina G. Cote, Marc Vidal, Michael E. Cusick, Alice Desbuleux, István Kovács, Michael A. Calderwood, Kerstin Spirohn, Sadie Schlabach, Jan Tavernier, Jüri Reimand, Irma Lemmens, Jean-Claude Twizere, Patrick Aloy, Pascal Falter-Braun, David E. Hill, Jennifer K. Knapp, Carles Pons, Noor Jailkhani, Yang Wang, Luke Lambourne, Yves Jacob, Tiziana M. Cafarelli, Marinella Gebbia, Nishka Kishore, Tong Hao, David De Ridder, Quan Zhong, Wenting Bian, Benoit Charloteaux, Mohamed Helmy, Katja Luck, Joseph C. Mellor, Dae-Kyum Kim, Frederick P. Roth, Anupama Yadav, Miles W. Mee, Yun Shen, Dana-Farber Cancer Institute [Boston], Université de Liège, University of Toronto, Institute for Research in Biomedicine [Barcelona, Spain] (IRB), University of Barcelona-Barcelona Institute of Science and Technology (BIST), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)

Subjects
Physics, 0303 health sciences, 03 medical and health sciences, 0302 clinical medicine, Homogeneous, Structural plasticity, Binary number, Computational biology, Interactome, Functional similarity, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

SummaryHundreds of different protein complexes that perform important functions across all cellular processes, collectively comprising the “complexome” of an organism, have been identified1. However, less is known about the fraction of the interactome that exists outside the complexome, in the “outer-complexome”. To investigate features of “inner”- versus outer-complexome organisation in yeast, we generated a high-quality atlas of binary protein-protein interactions (PPIs), combining three previous maps2–4 and a new reference all-by-all binary interactome map. A greater proportion of interactions in our map are in the outer-complexome, in comparison to those found by affinity purification followed by mass spectrometry5–7 or in literature curated datasets8–11. In addition, recent advances in deep learning predictions of PPI structures12 mirror the existing experimentally resolved structures in being largely focused on the inner complexome and missing most interactions in the outer-complexome. Our new PPI network suggests that the outer-complexome contains considerably more PPIs than the inner-complexome, and integration with functional similarity networks13–15 reveals that interactions in the inner-complexome are highly detectable and correspond to pairs of proteins with high functional similarity, while proteins connected by more transient, harder-to-detect interactions in the outer-complexome, exhibit higher functional heterogeneity.

Published
2021

3. ELIXIR-CONVERGE: Connect and align ELIXIR Nodes to deliver sustainable FAIR life-science data management services (871075)

Author

Adam-Blondon, Anne-Françoise, Alper, Pinar, Capella-Guttierez, Salvador, Faria, Daniel, Portell Silva, Laura, Hospital, Adam, Willassen, Nils-Peder, Unité de Recherche Génomique Info (URGI), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université du Luxembourg (UNI.LU), Barcelona Supercomputing Center - Centro Nacional de Supercomputacion (BSC - CNS), Instituto de Engenharia de Sistemas e Computadores (INESC), Institute for Research in Biomedicine [Barcelona, Spain] (IRB), University of Barcelona-Barcelona Institute of Science and Technology (BIST), The Arctic University of Norway (UiT), This project has received funding from the European Union’s Horizon 2020 Research and Innovation programme under grant agreement No 871075., INRAE, European Project: 871075,ELIXIR-CONVERGE, and The Arctic University of Norway [Tromsø, Norway] (UiT)

Subjects
Use Cases, Data management tools, Data management plan, Persona development, [SDV]Life Sciences [q-bio]
Abstract

Task 5.1 aims to analyse the different demonstrators in light of the process necessary to implement their DMPs and to propose a categorization based on users’ needs. This effort will provide input to WP1 with respect to needs in terms of experts and resources across ELIXIR Nodes (Task 1.3, Business plans). It is expected that some of them will be generic whereas others will be very specific to projects, which is an important factor for establishing a strategy towards the sustainability of such a service in all its diversity.D5.1 therefore describes the needs in terms of DMP of the demonstrator use-cases and proposes a project categorization from the point of view of :- Area of expertise- The resources they use / toolkit- Training needsThe first challenge was to develop a method to describe the needs of the users and their current practices in terms of data management as a prerequisite to the development of an adequate toolkit. The method adopted with the guidance of WP2 and WP3 relied on the description of users stories, and scenarios for different types of personas. In addition, a table was also developed to collect knowledge on the current practices and existing resources in terms of data management with guidance from WP1 and WP3. The six demonstrator use-cases are divided into two waves to facilitate having a broad diversity of data types, potential users and variable expertise and, at the same time, have first mature demonstrator use-cases that can start providing input to other WPs in the projects. The Plant and the Marine Metagenomics demonstrator use-cases were used as testers for the method developed as they are the two selected ones for the first wave. Federated access to human genomics data belongs to the second wave of demonstrator use-cases. However, considering its broad reach, it has been partially developed for this deliverable. User stories and scenarios with personas were developed by WP5 partners on the Plant, Marine metagenomics and Federated access to human genomics data: GDPR use-cases. The table on existing tools and resources was also filled in by WP5 partners and target interviews of researchers for some of the demonstrator use-cases. Additional input was sought from the ELIXIR communities for the demonstrator use-cases mentioned before.This method implemented to describe the demonstrator use-cases in detail has beenefficient to isolate the specific context of each case, and to identify specific tools/resources in relation with the use-cases that can be used for data management.The main aspect used to classify a new use-case is the type of biological material linked to the data that links to many specific requirements, e.g. legal and scientific metadata. The second is the relation of the personas with the data, e.g. consumers/producers, and the type of data, including workflows, models, and the various types of experimental data. The landscape analysis of the resources already available in relation with the demonstrator use-cases and the different stages of a data management plan, showed that the guidelines developed by WP1 are very useful to clarify the scope of these stages before filling such a survey.The personas/users related to the use-cases are very diverse but always include the researchers in various positions, e.g. data consumer, data producer, data owner, PI writing a proposal, and the data curators. This will be further developed in collaboration with WP2. Finally, the work achieved to deliver D5.1 facilitated the development of pages dedicated to the “domains” in the RDMKit website (https://rdmkit.elixir-europe.org/) for demonstrator use-case 1, 3, 4 and 6. In these pages, specific challenges linked with the demonstrator use-cases are highlighted, and dedicated resources to solve them are listed. These tools have also been flagged in bio.tools with the domain name.

Published
2021

4. Altered Mitochondrial Opa1-Related Fusion in Mouse Promotes Endothelial Cell Dysfunction and Atherosclerosis

Author

Ahmad Chehaitly, Anne-Laure Guihot, Coralyne Proux, Linda Grimaud, Jade Aurrière, Benoit Legouriellec, Jordan Rivron, Emilie Vessieres, Clément Tétaud, Antonio Zorzano, Vincent Procaccio, Françoise Joubaud, Pascal Reynier, Guy Lenaers, Laurent Loufrani, Daniel Henrion, MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III [Madrid] (ISC), Institute for Research in Biomedicine [Barcelona, Spain] (IRB), University of Barcelona-Barcelona Institute of Science and Technology (BIST), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), and Henrion, Daniel

Subjects
endocrine system, Artèries, Malalties cardiovasculars, Physiology, Clinical Biochemistry, mitochondrial fusion, blood flow, shear stress, arteries, endothelial cell, atherosclerosis, Arteries, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Cell Biology, Atherosclerosis, Biochemistry, eye diseases, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Cardiovascular diseases, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Molecular Biology, Aterosclerosi
Abstract

Flow (shear stress)-mediated dilation (FMD) of resistance arteries is a rapid endothelial response involved in tissue perfusion. FMD is reduced early in cardiovascular diseases, generating a major risk factor for atherosclerosis. As alteration of mitochondrial fusion reduces endothelial cells’ (ECs) sprouting and angiogenesis, we investigated its role in ECs responses to flow. Opa1 silencing reduced ECs (HUVECs) migration and flow-mediated elongation. In isolated perfused resistance arteries, FMD was reduced in Opa1+/− mice, a model of the human disease due to Opa1 haplo-insufficiency, and in mice with an EC specific Opa1 knock-out (EC-Opa1). Reducing mitochondrial oxidative stress restored FMD in EC-Opa1 mice. In isolated perfused kidneys from EC-Opa1 mice, flow induced a greater pressure, less ATP, and more H2O2 production, compared to control mice. Opa1 expression and mitochondrial length were reduced in ECs submitted in vitro to disturbed flow and in vivo in the atheroprone zone of the mouse aortic cross. Aortic lipid deposition was greater in Ldlr−/--Opa1+/- and in Ldlr−/--EC-Opa1 mice than in control mice fed with a high-fat diet. In conclusion, we found that reduction in mitochondrial fusion in mouse ECs altered the dilator response to shear stress due to excessive superoxide production and induced greater atherosclerosis development.

Published
2022

5. Natural variants suppress mutations in hundreds of essential genes

Author

Gianni Liti, Bryan-Joseph San Luis, Jolanda van Leeuwen, Leopold Parts, Meredith Laver, Michael W Yuen, Carles Pons, Elise Eray, Amandine Batté, Patrick Aloy, Maykel Lopes, Jia-Xing Yue, University of Toronto, Université de Lausanne (UNIL), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institute for Research in Biomedicine [Barcelona, Spain] (IRB), University of Barcelona-Barcelona Institute of Science and Technology (BIST), Université de Lausanne = University of Lausanne (UNIL), Université Nice Sophia Antipolis (1965 - 2019) (UNS), and Liti, Gianni

Subjects
genetic interactions, Medicine (General), Saccharomyces cerevisiae Proteins, QH301-705.5, Mutant, Context (language use), Saccharomyces cerevisiae, [SDV.GEN] Life Sciences [q-bio]/Genetics, Biology, medicine.disease_cause, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, 0302 clinical medicine, R5-920, Gene Expression Regulation, Fungal, Genetic variation, medicine, [SDV.BID.EVO] Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], natural variation, Allele, Biology (General), Gene, 030304 developmental biology, Genetics, 0303 health sciences, Mutation, [SDV.GEN]Life Sciences [q-bio]/Genetics, Genes, Essential, Genes, Modifier, General Immunology and Microbiology, Applied Mathematics, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], compensatory evolution, Genetic Variation, Articles, genetic modifiers, Phenotype, Computational Theory and Mathematics, Gain of Function Mutation, genetic suppression, Genetics, Gene Therapy & Genetic Disease, General Agricultural and Biological Sciences, 030217 neurology & neurosurgery, Function (biology), Information Systems
Abstract

The consequence of a mutation can be influenced by the context in which it operates. For example, loss of gene function may be tolerated in one genetic background, and lethal in another. The extent to which mutant phenotypes are malleable, the architecture of modifiers and the identities of causal genes remain largely unknown. Here, we measure the fitness effects of ~ 1,100 temperature‐sensitive alleles of yeast essential genes in the context of variation from ten different natural genetic backgrounds and map the modifiers for 19 combinations. Altogether, fitness defects for 149 of the 580 tested genes (26%) could be suppressed by genetic variation in at least one yeast strain. Suppression was generally driven by gain‐of‐function of a single, strong modifier gene, and involved both genes encoding complex or pathway partners suppressing specific temperature‐sensitive alleles, as well as general modifiers altering the effect of many alleles. The emerging frequency of suppression and range of possible mechanisms suggest that a substantial fraction of monogenic diseases could be managed by modulating other gene products., A survey of ~ 1,100 temperature‐sensitive alleles of yeast essential genes in ten diverse strains shows that natural genetic variants frequently suppress deleterious mutations. Genetic mapping and allele replacement identify causal suppressor genes.

Published
2021

6. Bioimage analysis workflows: community resources to navigate through a complex ecosystem

Author

Chong Zhang, Volker Baecker, Julien Colombelli, Jean-Karim Hériché, Kota Miura, Alban Gaignard, Sébastien Tosi, Matúš Kalaš, Raphaël Marée, Anna H. Klemm, Hervé Ménager, Perrine Paul-Gilloteaux, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Structure fédérative de recherche François Bonamy (SFR François Bonamy), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Santé de l'Université de Nantes (IRS-UN), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), ANR-11-INBS-0013,IFB (ex Renabi-IFB),Institut français de bioinformatique(2011), European Project: CA15124,NEUBIAS, Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institute for Research in Biomedicine [Barcelona, Spain] (IRB), University of Barcelona-Barcelona Institute of Science and Technology (BIST), European Molecular Biology Laboratory [Heidelberg] (EMBL), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics, Institut Pasteur [Paris] (IP), Institut Français de Bioinformatique (IFB-CORE), Institut National de Recherche en Informatique et en Automatique (Inria)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Liège, Université de Montpellier (UM), University of Bergen (UiB), Universitat Pompeu Fabra [Barcelona] (UPF), Universität Heidelberg [Heidelberg] = Heidelberg University, and PPG and VB acknowledge France-BioImaging infrastructure supported by the French National Research Agency (ANR-10-INBS-04). AG and HM acknowledge l’Institut Français de Bioinformatique supported by the French National Research Agency (ANR-11-INBS-0013).

Subjects
0301 basic medicine, Computer science, Big data, Interoperability, Information Storage and Retrieval, Cloud computing, MESH: Algorithms, scientific workflow management systems, remote computing, NEUBIAS, General Biochemistry, Genetics and Molecular Biology, Field (computer science), Workflow, components, MESH: Workflow, 03 medical and health sciences, 0302 clinical medicine, MESH: Ecosystem, [INFO]Computer Science [cs], collections, General Pharmacology, Toxicology and Pharmaceutics, Ecosystem, General Immunology and Microbiology, FAIR principles, business.industry, Computational Biology, MESH: Information Storage and Retrieval, General Medicine, Gateway (computer program), Articles, Opinion Article, Data science, knowledge database, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Data sharing, 030104 developmental biology, Knowledge base, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], workflows, business, 030217 neurology & neurosurgery, Algorithms, Bioimage analysis, MESH: Computational Biology
Abstract

Workflows are the keystone of bioimage analysis, and the NEUBIAS (Network of European BioImage AnalystS) community is trying to gather the actors of this field and organize the information around them. One of its most recent outputs is the opening of the F1000Research NEUBIAS gateway, whose main objective is to offer a channel of publication for bioimage analysis workflows and associated resources. In this paper we want to express some personal opinions and recommendations related to finding, handling and developing bioimage analysis workflows. The emergence of "big data” in bioimaging and resource-intensive analysis algorithms make local data storage and computing solutions a limiting factor. At the same time, the need for data sharing with collaborators and a general shift towards remote work, have created new challenges and avenues for the execution and sharing of bioimage analysis workflows. These challenges are to reproducibly run workflows in remote environments, in particular when their components come from different software packages, but also to document them and link their parameters and results by following the FAIR principles (Findable, Accessible, Interoperable, Reusable) to foster open and reproducible science. In this opinion paper, we focus on giving some directions to the reader to tackle these challenges and navigate through this complex ecosystem, in order to find and use workflows, and to compare workflows addressing the same problem. We also discuss tools to run workflows in the cloud and on High Performance Computing resources, and suggest ways to make these workflows FAIR.

Published
2021

7. Aβ(1-42) tetramer and octamer structures reveal edge conductivity pores as a mechanism for membrane damage

Author

Emad Tajkhorshid, Eduard Puig, Sonia Ciudad, Thomas Botzanowski, Mariam Bayoumi, Vladislav Yu. Orekhov, Benjamin Bardiaux, Giovanni Maglia, Sarah Cianférani, Andres S. Arango, Stéphane Chaignepain, Jimmy Do, Moeen Meigooni, Natàlia Carulla, Maxim Mayzel, Chemical Biology 1, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institute for Research in Biomedicine [Barcelona, Spain] (IRB), University of Barcelona-Barcelona Institute of Science and Technology (BIST), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), University of Illinois at Urbana-Champaign [Urbana], University of Illinois System, University of Gothenburg (GU), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Groningen [Groningen], Laboratoire de Spectrométrie de Masse BioOrganique [Strasbourg] (LSMBO), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Bioinformatique structurale - Structural Bioinformatics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institute for Research in Biomedicine (IRB Barcelona) (IRB), Institute for Research in Biomedicine, This study was supported by MINECO (SAF2015-68789), the Fondation Recherche Médicale (AJE20151234751) and the Counseil Régional d’Aquitaine Limousin Poitou-Charentes (1R30117-00007559) to N.C. The authors G.M and N.C. acknowledge funds from Fundació La Marató de TV3 (20140730). B.B research was supported by the INCEPTION project (ANR-16-CONV-0005). E.T. was supported by the National Institutes of Health (P41-GM104601 and R01-GM123455) and also acknowledges computing resources provided by Blue Waters at National Center for Supercomputing Applications, and Extreme Science and Engineering Discovery Environment XSEDE (grant MCA06N060). V.O. research was supported by the Swedish Research Council Formas (2015-04614). S. Cianferani research was supported by Agence Nationale de la Recherche and the French Proteomic Infrastructure (ANR-10-INBS-08-03). N.C., S. Cianferani, T.B. and E.P. acknowledge the support of COST Action (BM1403). E.P. was a PhD fellow funded by MINECO (FPI). T.B. was a PhD fellow funded by Institut de Recherche Servier., ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), ANR-10-INBS-0008,ProFI,Infrastructure Française de Protéomique(2010), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, AMYLOID-BETA-PEPTIDE, PROTEINS, Science, General Physics and Astronomy, COLLISION CROSS-SECTIONS, Conductivity, Oligomer, General Biochemistry, Genetics and Molecular Biology, Article, ATOMIC-RESOLUTION STRUCTURE, 03 medical and health sciences, Molecular dynamics, chemistry.chemical_compound, CONFORMATIONS, 0302 clinical medicine, Tetramer, Alzheimer Disease, Humans, Histone octamer, Lipid bilayer, lcsh:Science, A-BETA, Multidisciplinary, Amyloid beta-Peptides, CHANNELS, PURIFICATION, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Brain, Membrane structure and assembly, General Chemistry, Permeation, Peptide Fragments, NMR, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, ALZHEIMERS-DISEASE, 030104 developmental biology, Membrane, chemistry, Biophysics, lcsh:Q, Solution-state NMR, 030217 neurology & neurosurgery
Abstract

Formation of amyloid-beta (Aβ) oligomer pores in the membrane of neurons has been proposed to explain neurotoxicity in Alzheimerʼs disease (AD). Here, we present the three-dimensional structure of an Aβ oligomer formed in a membrane mimicking environment, namely an Aβ(1-42) tetramer, which comprises a six stranded β-sheet core. The two faces of the β-sheet core are hydrophobic and surrounded by the membrane-mimicking environment while the edges are hydrophilic and solvent-exposed. By increasing the concentration of Aβ(1-42) in the sample, Aβ(1-42) octamers are also formed, made by two Aβ(1-42) tetramers facing each other forming a β-sandwich structure. Notably, Aβ(1-42) tetramers and octamers inserted into lipid bilayers as well-defined pores. To establish oligomer structure-membrane activity relationships, molecular dynamics simulations were carried out. These studies revealed a mechanism of membrane disruption in which water permeation occurred through lipid-stabilized pores mediated by the hydrophilic residues located on the core β-sheets edges of the oligomers., Formation of amyloid-beta (Aβ) oligomer pores in the membrane of neurons has been proposed to explain neurotoxicity in Alzheimer´s disease. Here authors present the 3D- structure of an Aβ oligomer formed in a membrane mimicking environment and observe that Aβ tetramers and octamers inserted into lipid bilayers as well-defined pores.

Published
2020

8. Polyglucosan body structure in Lafora disease

Author

Annette Uittenbogaard, Mitchell A. Sullivan, Jean-Luc Putaux, M. Kathryn Brewer, Matthew S. Gentry, Alberto Rondon, Department of Molecular and Cellular Biochemistry, University of Kentucky, Institute for Research in Biomedicine [Barcelona, Spain] (IRB), University of Barcelona-Barcelona Institute of Science and Technology (BIST), Centre de Recherches sur les Macromolécules Végétales (CERMAV), Institut de Chimie du CNRS (INC)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), and University of Southern Queensland (USQ)

Subjects
Childhood epilepsy, medicine.medical_specialty, Polymers and Plastics, 02 engineering and technology, Biology, 010402 general chemistry, 01 natural sciences, Lafora disease, Article, Epilepsy, chemistry.chemical_compound, Mice, Internal medicine, Materials Chemistry, medicine, Glycogen storage disease, Animals, Glucans, Lafora body, ComputingMilieux_MISCELLANEOUS, Inclusion Bodies, Mice, Knockout, Glycogen, Organic Chemistry, Glycogen metabolism, Disease progression, 021001 nanoscience & nanotechnology, medicine.disease, 0104 chemical sciences, Disease Models, Animal, Endocrinology, [CHIM.POLY]Chemical Sciences/Polymers, chemistry, Lafora Disease, 0210 nano-technology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Abnormal carbohydrate structures known as polyglucosan bodies (PGBs) are associated with neurodegenerative disorders, glycogen storage diseases (GSDs), and aging. A hallmark of the GSD Lafora disease (LD), a fatal childhood epilepsy caused by recessive mutations in the EPM2A or EPM2B genes, are cytoplasmic PGBs known as Lafora bodies (LBs). LBs result from aberrant glycogen metabolism and drive disease progression. They are abundant in brain, muscle and heart of LD patients and Epm2a(−/−) and Epm2b(−/−) mice. LBs and PGBs are histologically reminiscent of starch, semicrystalline carbohydrates synthesized for glucose storage in plants. In this study, we define LB architecture, tissue-specific differences, and dynamics. We propose a model for how small polyglucosans aggregate to form LBs. LBs are very similar to PGBs of aging and other neurological disorders, and so these studies have direct relevance to the general understanding of PGB structure and formation.

Published
2020

9. Guidelines and definitions for research on epithelial-mesenchymal transition

Author

Yang, Jing, Antin, Parker, Berx, Geert, Blanpain, Cédric, Brabletz, Thomas, Bronner, Marianne, Campbell, Kyra, Cano, Amparo, Casanova, Jordi, Christofori, Gerhard, Dedhar, Shoukat, Derynck, Rik, Ford, Heide, Fuxe, Jonas, García De Herreros, Antonio, Goodall, Gregory, Hadjantonakis, Anna-Katerina, Huang, Ruby, Kalcheim, Chaya, Kalluri, Raghu, Kang, Yibin, Khew-Goodall, Yeesim, Levine, Herbert, Liu, Jinsong, Longmore, Gregory, Mani, Sendurai, Massagué, Joan, Mayor, Roberto, McClay, David, Mostov, Keith, Newgreen, Donald, Nieto, M, Puisieux, Alain, Runyan, Raymond, Savagner, Pierre, Stanger, Ben, Stemmler, Marc, Takahashi, Yoshiko, Takeichi, Masatoshi, Théveneau, Eric, Thiery, Jean, Thompson, Erik, Weinberg, Robert, Williams, Elizabeth, Xing, Jianhua, Zhou, Binhua, Sheng, Guojun, Department of Biomedical Molecular Biology [Ghent], Universiteit Gent = Ghent University [Belgium] (UGENT), Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles (ULB), Brussels 1070, Belgium., Instituto de Investigaciones Biomedicas, Universidad Nacional Autónoma de México (UNAM), Institute for Research in Biomedicine [Barcelona, Spain] (IRB), University of Barcelona-Barcelona Institute of Science and Technology (BIST), and Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
[SDV]Life Sciences [q-bio], embryonic structures
Abstract

Epithelial–mesenchymal transition (EMT) encompasses dynamic changes in cellular organization from epithelial to mesenchymal phenotypes, which leads to functional changes in cell migration and invasion. EMT occurs in a diverse range of physiological and pathological conditions and is driven by a conserved set of inducing signals, transcriptional regulators and downstream effectors. With over 5,700 publications indexed by Web of Science in 2019 alone, research on EMT is expanding rapidly. This growing interest warrants the need for a consensus among researchers when referring to and undertaking research on EMT. This Consensus Statement, mediated by ‘the EMT International Association’ (TEMTIA), is the outcome of a 2-year-long discussion among EMT researchers and aims to both clarify the nomenclature and provide definitions and guidelines for EMT research in future publications. We trust that these guidelines will help to reduce misunderstanding and misinterpretation of research data generated in various experimental models and to promote cross-disciplinary collaboration to identify and address key open questions in this research field. While recognizing the importance of maintaining diversity in experimental approaches and conceptual frameworks, we emphasize that lasting contributions of EMT research to increasing our understanding of developmental processes and combatting cancer and other diseases depend on the adoption of a unified terminology to describe EMT.

Published
2020

10. A synthesis of bacterial and archaeal phenotypic trait data

Author

Ross Corkrey, David Danko, Joshua S. Madin, T. B. K. Reddy, Mark Westoby, Sara Vieira-Silva, Thomas M. Schmidt, Eduardo P. C. Rocha, Martin K. M. Engqvist, Matthew A. Richards, Noah Fierer, Lisa R. Moore, Alice R. Wattam, Fran Supek, Maria Brbic, Heba Shaaban, Michael R. Gillings, Christopher E. Mason, David A. Westfall, Nikos C. Kyrpides, Daniel A. Nielsen, Maulik Shukla, Elena Litchman, Kyle F. Edwards, Jemma L. Geoghegan, Sasha G. Tetu, Søren Laurentius Nielsen, Nathan D. Price, Ian T. Paulsen, University of Hawai‘i [Mānoa] (UHM), Macquarie University [Sydney], Rudjer Boskovic Institute [Zagreb], University of Tasmania [Hobart, Australia] (UTAS), Weill Cornell Medicine [New York], Chalmers University of Technology [Gothenburg, Sweden], University of Colorado [Boulder], Lawrence Berkeley National Laboratory [Berkeley] (LBNL), Michigan State University [East Lansing], Michigan State University System, Roskilde University, Institute for Systems Biology [Seattle] (ISB), Génomique évolutive des Microbes / Microbial Evolutionary Genomics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), University of Michigan [Ann Arbor], University of Michigan System, Argonne National Laboratory [Lemont] (ANL), Institute for Research in Biomedicine [Barcelona, Spain] (IRB), University of Barcelona-Barcelona Institute of Science and Technology (BIST), Rega Institute for Medical Research [Leuven, België], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Virginia [Charlottesville], Weill Cornell Medicine [Cornell University], Cornell University [New York], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and University of Virginia

Subjects
Statistics and Probability, Data Descriptor, MESH: Genome, Archaeal, Library and Information Sciences, MESH: Genome, Bacterial, MESH: Phenotype, Genome, Education, Microbial ecology, 03 medical and health sciences, Genome, Archaeal, Abundance (ecology), [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, Ecosystem, MESH: Ecosystem, lcsh:Science, 030304 developmental biology, 0303 health sciences, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], biology, Bacteria, 030306 microbiology, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Human Genome, Bacterial, Phenotypic trait, biology.organism_classification, Phenotype, Archaea, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Computer Science Applications, MESH: Bacteria, Habitat, Evolutionary biology, Archaeal, MESH: Archaea, Trait, lcsh:Q, Statistics, Probability and Uncertainty, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Genome, Bacterial, Information Systems, Biotechnology
Abstract

A synthesis of phenotypic and quantitative genomic traits is provided for bacteria and archaea, in the form of a scripted, reproducible workflow that standardizes and merges 26 sources. The resulting unified dataset covers 14 phenotypic traits, 5 quantitative genomic traits, and 4 environmental characteristics for approximately 170,000 strain-level and 15,000 species-aggregated records. It spans all habitats including soils, marine and fresh waters and sediments, host-associated and thermal. Trait data can find use in clarifying major dimensions of ecological strategy variation across species. They can also be used in conjunction with species and abundance sampling to characterize trait mixtures in communities and responses of traits along environmental gradients., Measurement(s)Trait • phenotypic trait • quantitative genomic traitTechnology Type(s)digital curationFactor Type(s)habitat • speciesSample Characteristic - OrganismArchaea • BacteriaSample Characteristic - Locationglobal Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.12221732

Published
2020

11. Soybean aphid biotype 1 genome: Insights into the invasive biology and adaptive evolution of a major agricultural pest

Author

Nick Miller, Richard Hall, Jose A.P. Marcelino, Chiun-Cheng Ko, Deirdre Prischmann-Voldseth, Michela Panini, Ravi Kiran Donthu, Giulia Melchiori, Christina D. DiFonzo, Minh Nguyen, Everett Weber, Curt B. Hill, Brian W. Diers, Anthony Bretaudeau, Alejandra Flores, George E. Heimpel, Toni Gabaldon, John F. Tooker, Jonathan H. Badger, Andrew Aschwanden, Ana Micijevic, Anitha Chirumamilla, Tugrul Giray, Peter Desborough, Rosanna Giordano, Massimo Pessino, Brad S. Coates, Fabrice Legeai, Janet Knodel, David J. Voegtlin, Matthew E. O'Neal, Manuella van Munster, Bruce D Potter, Glen L. Hartman, Christopher J. Fields, Doris Lagos-Kutz, Brian A. Nault, Joon-Ho Lee, Hojun Song, Giuseppe E. Massimino Cocuzza, Aleksey V. Zimin, Felipe N. Soto-Adames, Olga Chiesa, Hugh M. Robertson, Genevieve Labrie, Sijun Liu, Arian Avalos, Eileen Cullen, Bryony C. Bonning, Seunghwan Lee, Mauro Mandrioli, Emanuele Mazzoni, Mark Band, Yongping Huanga, Irene Consuelo Julca Chavez, Kelley J. Tilmon, Kongming Wu, Theresa K. Herman, Lawrence Hon, Andi Nasuddin, Tatsiana Akraiko, Gian Carlo Manicardi, Shuai Zhan, Puerto Rico Science, Know Your Bee Inc, Johns Hopkins University (JHU), Barcelona Institute of Science and Technology (BIST), Barcelona Supercomputing Center - Centro Nacional de Supercomputacion (BSC - CNS), Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Institute for Research in Biomedicine [Barcelona, Spain] (IRB), University of Barcelona-Barcelona Institute of Science and Technology (BIST), Plant Health Institute of Montpellier (UMR PHIM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Université de Montpellier (UM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Color Genomics, Pacific Biosciences [Menlo Park], Pacific Biosciences of California, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Columbia University Irving Medical Center (CUIMC), University of Illinois at Urbana-Champaign [Urbana], University of Illinois System, Southwest Research and Outreach Center [Lamberton], University of Minnesota [Twin Cities] (UMN), University of Minnesota System-University of Minnesota System, University of Puerto Rico (UPR), University of Florida [Gainesville] (UF), Agricen Sciences, USDA-ARS : Agricultural Research Service, Pennsylvania State University (Penn State), Penn State System, Institut de Génétique, Environnement et Protection des Plantes (IGEPP), Université de Rennes (UR)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-INSTITUT AGRO Agrocampus Ouest, Università cattolica del Sacro Cuore [Piacenza e Cremona] (Unicatt), North Dakota State University (NDSU), Iowa State University (ISU), University of Catania [Italy], University of Wisconsin - Milwaukee, New South Wales Department of Primary Industries (NSW DPI), Michigan State University [East Lansing], Michigan State University System, University of Minnesota [Morris], University of Minnesota System, Chinese Academy of Sciences [Beijing] (CAS), National Taiwan University [Taiwan] (NTU), Centre de Recherche sur les Grains [Québec] (CEROM), United States Department of Agriculture (USDA), Seoul National University [Seoul] (SNU), University of Haifa [Haifa], Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Università cattolica del Sacro Cuore [Milano] (Unicatt), South Dakota State University (SDSTATE), Illinois Institute of Technology (IIT), Hasanuddin University (Unhas), Cornell AgriTech, College of Agriculture and Life Sciences [Cornell University] (CALS), Cornell University [New York]-Cornell University [New York], Department of Entomology [CALS], Texas A&M University [College Station], Ohio State University [Columbus] (OSU), Chinese Academy of Agricultural Sciences (CAAS), United Soybean Board, Agricultural Research Service, 432114, Integrated Management of Soybean Pathogens and Pests, 2018-67015-28199, USDA NIFA, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Innovation et Développement dans l'Agriculture et l'Alimentation (UMR Innovation), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-AGROCAMPUS OUEST, Scalable, Optimized and Parallel Algorithms for Genomics (GenScale), Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-GESTION DES DONNÉES ET DE LA CONNAISSANCE (IRISA-D7), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Università degli Studi di Modena e Reggio Emilia, and Cornell University [New York]

Subjects
0106 biological sciences, Pesticide resistance, Population genetics, [SDV]Life Sciences [q-bio], Genome, Insect, Adaptation, Biological, Zoology, SNP, Phylome, Polymorphism, Single Nucleotide, 01 natural sciences, Biochemistry, 03 medical and health sciences, Animals, Polymorphism, Adaptation, Soybean aphid, Biotype 1, Molecular Biology, Rhamnus cathartica, Aphid, Alleles, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Ecotype, 0303 health sciences, Genome, biology, food and beverages, Aphididae, Single Nucleotide, Biological, biology.organism_classification, Biological Evolution, Hemiptera, United States, 010602 entomology, Settore AGR/11 - ENTOMOLOGIA GENERALE E APPLICATA, Aphids, Insect Science, PEST analysis, Aphis glycines, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Introduced Species, Insect
Abstract

International audience; The soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae) is a serious pest of the soybean plant, Glycine max, a major world-wide agricultural crop. We assembled a de novo genome sequence of Ap. glycines Biotype 1, from a culture established shortly after this species invaded North America. 20.4% of the Ap. glycines proteome is duplicated. These in-paralogs are enriched with Gene Ontology (GO) categories mostly related to apoptosis, a possible adaptation to plant chemistry and other environmental stressors. Approximately one-third of these genes show parallel duplication in other aphids. But Ap. gossypii, its closest related species, has the lowest number of these duplicated genes. An Illumina GoldenGate assay of 2380 SNPs was used to determine the world-wide population structure of Ap. Glycines. China and South Korean aphids are the closest to those in North America. China is the likely origin of other Asian aphid populations. The most distantly related aphids to those in North America are from Australia. The diversity of Ap. glycines in North America has decreased over time since its arrival. The genetic diversity of Ap. glycines North American population sampled shortly after its first detection in 2001 up to 2012 does not appear to correlate with geography. However, aphids collected on soybean Rag experimental varieties in Minnesota (MN), Iowa (IA), and Wisconsin (WI), closer to high density Rhamnus cathartica stands, appear to have higher capacity to colonize resistant soybean plants than aphids sampled in Ohio (OH), North Dakota (ND), and South Dakota (SD). Samples from the former states have SNP alleles with high FST values and frequencies, that overlap with genes involved in iron metabolism, a crucial metabolic pathway that may be affected by the Rag-associated soybean plant response. The Ap. glycines Biotype 1 genome will provide needed information for future analyses of mechanisms of aphid virulence and pesticide resistance as well as facilitate comparative analyses between aphids with differing natural history and host plant range.

Published
2020

12. Reverse-transcribing viruses of the families Belpaoviridae, Metaviridae and Pseudoviridae (order Ortervirales)

Author

Llorens, Carlos, Soriano, Beatriz, Navarrete-Muñoz, Maria, Hafez, Ahmed, Arnau, Vicente, Benito, Jose Miguel, Gabaldon, Toni, Rallón, Norma, Pérez-Sánchez, Jaume, Krupovic, Mart, Biotechvana [Valencia, Spain], Institute for Integrative Systems Biology [Valencia] (i2sysbio), Spanish National Research Council (CSIC)-Universitat de València (UV), Hospital Universitario Rey Juan Carlos [Spain], Instituto de Investigación Sanitaria Fundación Jiménez Diaz [Madrid] (IIS-FJD), Universidad Autonoma de Madrid (UAM)-Fundacion Jimenez Diaz [Madrid] (FJD), Universitat Pompeu Fabra [Barcelona] (UPF), Minia University, Barcelona Supercomputing Center - Centro Nacional de Supercomputacion (BSC - CNS), Institute for Research in Biomedicine [Barcelona, Spain] (IRB), University of Barcelona-Barcelona Institute of Science and Technology (BIST), Institució Catalana de Recerca i Estudis Avançats (ICREA), Instituto de Acuicultura de Torre de la Sal, Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Virologie des archées - Archaeal Virology, Institut Pasteur [Paris], Universidad Autónoma de Madrid (UAM)-Fundacion Jimenez Diaz [Madrid] (FJD), Institut Pasteur [Paris] (IP), Bamford DH, and Zuckerman M

Subjects
Gag and pol, Diversity, Host environment, Retrovirus, Eukaryotes, Evolution, Life cycle, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, LTR retrotransposon, Ortervirales, Proto-retrovirus
Abstract

International audience; The Metaviridae, Pseudoviridae, and Belpaoviridae are the three families of eukaryotic reverse-transcribing viruses with Long Terminal Repeats (LTRs), popularly known as Ty3/Gypsy, Ty1/Copia, and Bel/Pao LTR retrotransposons, respectively. The three families are unified into the order Ortervirales together with members of the families Retroviridae and Caulimoviridae which infect vertebrates and plants, respectively. Here, we review the molecular biology and diversity of metaviruses, pseudoviruses and belpaoviruses. We explore the similarities and evolutionary relationships among them as well as with other members of the Ortervirales based on life cycle, sequence, architecture of genes and other features. Their host range and impact on the biology and evolution of eukaryotes is also discussed.

Published
2020

13. Trimeric heptad repeat synthetic peptides HR1 and HR2 efficiently inhibit HIV-1 entry

Author

Mzoughi, Olfa, Teixido, Meritxell, Planès, Rémi, Serrero, Manutea, Hamimed, Ibtissem, Zurita, Esther, Moreno, Miguel, Granados, Giovana, Lakhdar-Ghazal, Faouzi, BenMohamed, Lbachir, Giralt, Ernest, Bahraoui, Elmostafa, CARBILLET, Véronique, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institute for Research in Biomedicine [Barcelona, Spain] (IRB), University of Barcelona-Barcelona Institute of Science and Technology (BIST), Laboratory of Cellular and Molecular Immunology, University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), and University of Barcelona

Subjects
Protein Conformation, alpha-Helical, Protein Conformation, HIV Infections, MESH: Peptide Fragments / pharmacology, MESH: Drug Design, Membrane Fusion, MESH: Membrane Fusion / drug effects, MESH: Circular Dichroism, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, inhibitors, Research Articles, MESH: HIV Envelope Protein gp41 / chemistry, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Circular Dichroism, N36, HIV Envelope Protein gp41, AIDS, trimers, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, HIV/AIDS, Infection, Research Article, Biochemistry & Molecular Biology, MESH: HIV Infections / drug therapy, MESH: HIV-1 / pathogenicity, MESH: HIV-1 / drug effects, Vaccine Related, MESH: HIV Infections / genetics, MESH: HIV Envelope Protein gp41 / pharmacology, Humans, MESH: HIV Infections / virology, Amino Acid Sequence, Vaccine Related (AIDS), C34, MESH: Protein Conformation, alpha-Helical, MESH: Humans, Prevention, alpha-Helical, MESH: Amino Acid Sequence / genetics, Peptide Fragments, Good Health and Well Being, Drug Design, MESH: Peptide Fragments / chemical synthesis, HIV-1, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Immunization, Biochemistry and Cell Biology, MESH: Peptide Fragments / chemistry, MESH: HIV Envelope Protein gp41 / chemical synthesis
Abstract

International audience; The trimeric heptad repeat domains HR1 and HR2 of the human immunodeficiency virus 1 (HIV-1) gp41 play a key role in HIV-1-entry by membrane fusion. To develop efficient inhibitors against this step, the corresponding trimeric-N36 and C34 peptides were designed and synthesized. Analysis by circular dichroism of monomeric and trimeric N36 and C34 peptides showed their capacities to adopt α-helical structures and to establish physical interactions. At the virological level, while trimeric-C34 conserves the same high anti-fusion activity as monomeric-C34, trimerization of N36-peptide induced a significant increase, reaching 500-times higher in anti-fusion activity, against R5-tropic virus-mediated fusion. This result was associated with increased stability of the N36 trimer peptide with respect to the monomeric form, as demonstrated by the comparative kinetics of their antiviral activities during 6-day incubation in a physiological medium. Collectively, our findings demonstrate that while the trimerization of C34 peptide had no beneficial effect on its stability and antiviral activity, the trimerization of N36 peptide strengthened both stability and antiviral activity. This approach, promotes trimers as new promising HIV-1 inhibitors and point to future development aimed toward innovative peptide fusion inhibitors, microbicides or as immunogens.

Published
2019

14. Cellular Senescence: Defining a Path Forward

Author

John M. Sedivy, Paul D. Robbins, Cleo L. Bishop, Vassilis G. Gorgoulis, Konstantinos Vougas, Konstantinos Evangelou, Valery Krizhanovsky, Dorothy C. Bennett, Eiji Hara, Diana Jurk, Gerardo Ferbeyre, Judith Campisi, Masashi Narita, Laura J. Niedernhofer, Manuel Serrano, Clemens A. Schmitt, Peter D. Adams, Oliver Bischof, Andrea Alimonti, Marco Demaria, Jesús Gil, Daohong Zhou, Manuel Collado, Thomas von Zglinicki, Andrea B. Maier, João F. Passos, Institut Pasteur [Paris], National and Kapodistrian University of Athens (NKUA), University of Manchester [Manchester], Biomedical Research Foundation of the Academy of Athens (BRFAA), Institute of Cancer Sciences [Glasgow, UK] (CR-UK Beatson Institute), University of Glasgow, Sanford Burnham Prebys Medical Discovery Institute, Oncology Institute of Southern Switzerland (IOSI), Università della Svizzera italiana = University of Italian Switzerland (USI), Universita degli Studi di Padova, Veneto Institute of Molecular Medicine [Padova, Italy] (VIMM), University of London [London], Organisation Nucléaire et Oncogenèse / Nuclear Organization and Oncogenesis, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Bart's and The London School of Medicine and Dentistry, Queen Mary University of London (QMUL), Buck Institute for Research on Aging, Universidade de Santiago de Compostela [Spain] (USC ), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Université de Montréal (UdeM), MRC London Institute of Medical Sciences (LMC), Imperial College London, Research Institute for Microbial Diseases [Osaka, Japan] (RIMD), Osaka University [Osaka], Department of Molecular Cell Biology [Rehovot], Weizmann Institute of Science [Rehovot, Israël], Robert and Arlene Kogod Center on Aging [Rochester, MN, USA], Mayo Clinic, Vrije Universiteit Amsterdam [Amsterdam] (VU), University of Melbourne, University of Cambridge [UK] (CAM), University of Minnesota [Twin Cities] (UMN), University of Minnesota System, Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Kepler University Hospital, Brown University, Newcastle University [Newcastle], University of Florida [Gainesville] (UF), Institute for Research in Biomedicine [Barcelona, Spain] (IRB), University of Barcelona-Barcelona Institute of Science and Technology (BIST), Institució Catalana de Recerca i Estudis Avançats (ICREA), University of Groningen [Groningen], European Research Institute for the Biology of Ageing [Groningen] (ERIBA), University Medical Center Groningen [Groningen] (UMCG), M.D. is funded by the Dutch Cancer Foundation, Netherlands (grant ID 10989). V.G., K.E., and K.V. were financially supported by the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grants agreement no. 722729 (SYNTRAIN), the Welfare Foundation for Social & Cultural Sciences (KIKPE), Greece, the KIKPE Foundation, Athens, Greece, Pentagon Biotechnology, UK, DeepMed IO, UK, grant no. 775 from the Hellenic Foundation for Research and Innovation (HFRI), and NKUA-SARG grants 70/3/9816, 70/3/12128, and 70/3/15603. M.S.: is funded by the IRB and by grants from the Spanish Ministry of Economy co-funded by the European Regional Development Fund (ERDF) (SAF2013-48256-R), the European Research Council (ERC-2014-AdG/669622), and 'laCaixa' Foundation., We would like to thank Nikolaos Kastrinakis, Panagiotis V.S. Vasileiou, Gkikas Magiorkinis, Eleni Fitsiou, and Michela Borghesan for their valuable support to this work. We apologize in advance that, for reason of space, we have omitted the citations of relevant papers and reviews., National and Kapodistrian University of Athens = University of Athens (NKUA | UoA), Organisation Nucléaire et Oncogenèse - Nuclear Organization and Oncogenesis, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], University of Santiago de Compostela [Spain] (USC), Centre de recherche du Chum [Montréal] (CRCHUM), Université de Montréal [Montréal], Research Institute for Microbial Diseases, Weizmann Institute of Science, University of Minnesota [Twin Cities], Max Delbrück Center for Molecular Medicine [Berlin], Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, University of Florida [Gainesville], University of Barcelona, Università degli Studi di Padova = University of Padua (Unipd), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Narita, Masashi [0000-0001-7764-577X], and Apollo - University of Cambridge Repository

Subjects
Senescence, EXPRESSION, Aging, Cell cycle checkpoint, [SDV]Life Sciences [q-bio], Cell, DNA-DAMAGE RESPONSE, [SDV.CAN]Life Sciences [q-bio]/Cancer, Computational biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Mitochondrion, Biology, General Biochemistry, Genetics and Molecular Biology, CHROMATIN LANDSCAPE, 03 medical and health sciences, 0302 clinical medicine, MITOCHONDRIA, ONCOGENE-INDUCED SENESCENCE, medicine, Humans, OXIDATIVE STRESS, Senolytic, Cellular Senescence, 11 Medical and Health Sciences, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Regulation of gene expression, 0303 health sciences, P53, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Genetic Diseases, Inborn, DARK SIDE, Cell Cycle Checkpoints, 06 Biological Sciences, CANCER, Chromatin, medicine.anatomical_structure, Gene Expression Regulation, CELLS, Developmental biology, 030217 neurology & neurosurgery, Biomarkers, Developmental Biology
Abstract

International audience; Cellular senescence is a cell state implicated in various physiological processes and a wide spectrum of age-related diseases. Recently, interest in therapeutically targeting senescence to improve healthy aging and age-related disease, otherwise known as senotherapy, has been growing rapidly. Thus, the accurate detection of senescent cells, especially in vivo, is essential. Here, we present a consensus from the International Cell Senescence Association (ICSA), defining and discussing key cellular and molecular features of senescence and offering recommendations on how to use them as biomarkers. We also present a resource tool to facilitate the identification of genes linked with senescence, SeneQuest (available at http://Senequest.net). Lastly, we propose an algorithm to accurately assess and quantify senescence, both in cultured cells and in vivo.

Published
2019
Full Text
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15. GATA6 regulates EMT and tumour dissemination, and is a marker of response to adjuvant chemotherapy in pancreatic cancer

Author

Martinelli, Paola, Carrillo-de Santa Pau, Enrique, Cox, Trevor, Sainz, Bruno, Dusetti, Nelson, Greenhalf, William, Rinaldi, Lorenzo, Costello, Eithne, Ghaneh, Paula, Malats, Núria, Büchler, Markus, Pajic, Marina, Biankin, Andrew V., Iovanna, Juan, Neoptolemos, John, Real, Francisco X., Epithelial Carcinogenesis Group [Madrid, Spain], Spanish National Cancer Research Center (CNIO), Cancer Progression and Metastasis Group [Vienna, Austria], Medizinische Universität Wien = Medical University of Vienna, Cancer Research UK Liverpool Clinical Trials Unit [Liverpool, UK], University of Liverpool, NIHR Liverpool Pancreas Biomedical Research Unit [Liverpool, UK], University of Liverpool-Department of Molecular and Clinical Cancer Medicine [Liverpool, UK], Department of Preventive Medicine, Public Health and Microbiology [Madrid, Spain], Universidad Autónoma de Madrid (UAM), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institute for Research in Biomedicine [Barcelona, Spain] (IRB), University of Barcelona-Barcelona Institute of Science and Technology (BIST), Genetic & Molecular Epidemiology Group [Madrid, Spain] (Human Cancer Genetics Program), Department for General, Visceral and Transplantation Surgery [Heidelberg, Germany], Heidelberg University Hospital [Heidelberg], Cancer Division [Sydney, Australia] (The Kinghorn Cancer Centre), Garvan Institute of medical research, Wolfson Wohl Cancer Research Centre [Glasgow, UK], University of Glasgow-Institute of Cancer Sciences [Glasgow, UK], West of Scotland Pancreatic Unit [Glasgow, UK], Glasgow Royal Infirmary, South Western Sydney Clinical School [Liverpool, Australia] (Faculty of Medicine), University of New South Wales [Sydney] (UNSW), Departament de Ciències Experimentals i de la Salut [Barcelona, Spain], Universitat Pompeu Fabra [Barcelona] (UPF), MITOYAN, Louciné, Universidad Autonoma de Madrid (UAM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), and Garvan Institute of Medical Research [Sydney, Australia]

Subjects
Antimetabolites, Antineoplastic, endocrine system, Epithelial-Mesenchymal Transition, [SDV]Life Sciences [q-bio], Statistics as Topic, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.GEN] Life Sciences [q-bio]/Genetics, Mice, GENE REGULATION, [SDV.CAN] Life Sciences [q-bio]/Cancer, Epithelial differentiation, Cell Movement, Cell Line, Tumor, GATA6 Transcription Factor, Animals, Humans, Cancer genetics, Pancreas, [SDV.GEN]Life Sciences [q-bio]/Genetics, Pancreatic cancer, Adjuvant treatment, PANCREATIC CANCER, Gene regulation, CANCER GENETICS, Gene Expression Regulation, Neoplastic, Pancreatic Neoplasms, [SDV] Life Sciences [q-bio], Chemotherapy, Adjuvant, EPITHELIAL DIFFERENTIATION, ADJUVANT TREATMENT, Fluorouracil, Carcinoma, Pancreatic Ductal
Abstract

BACKGROUND AND AIMS: The role of GATA factors in cancer has gained increasing attention recently, but the function of GATA6 in pancreatic ductal adenocarcinoma (PDAC) is controversial. GATA6 is amplified in a subset of tumours and was proposed to be oncogenic, but high GATA6 levels are found in well-differentiated tumours and are associated with better patient outcome. By contrast, a tumour-suppressive function of GATA6 was demonstrated using genetic mouse models. We aimed at clarifying GATA6 function in PDAC. DESIGN: We combined GATA6 silencing and overexpression in PDAC cell lines with GATA6 ChIP-Seq and RNA-Seq data, in order to understand the mechanism of GATA6 functions. We then confirmed some of our observations in primary patient samples, some of which were included in the ESPAC-3 randomised clinical trial for adjuvant therapy. RESULTS: GATA6 inhibits the epithelial-mesenchymal transition (EMT) in vitro and cell dissemination in vivo. GATA6 has a unique proepithelial and antimesenchymal function, and its transcriptional regulation is direct and implies, indirectly, the regulation of other transcription factors involved in EMT. GATA6 is lost in tumours, in association with altered differentiation and the acquisition of a basal-like molecular phenotype, consistent with an epithelial-to-epithelial (ET2) transition. Patients with basal-like GATA6low tumours have a shorter survival and have a distinctly poor response to adjuvant 5-fluorouracil (5-FU)/leucovorin. However, modulation of GATA6 expression in cultured cells does not directly regulate response to 5-FU. CONCLUSIONS: We provide mechanistic insight into GATA6 tumour-suppressive function, its role as a regulator of canonical epithelial differentiation, and propose that loss of GATA6 expression is both prognostic and predictive of response to adjuvant therapy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/. This work was supported, in part, by grants SAF2007-60860, SAF2011-29530 and ONCOBIO Consolider from Ministerio de Economía y Competitividad (Madrid, Spain), RTICC from Instituto de Salud Carlos III, grants 256974 and 289737 from European Union Seventh Framework Program to FXR and by grant P27361-B23 from the Austrian Science Fund (FWF) to PM. AB receives support from the Wellcome Trust, Cancer Research UK, the Medical Research Council (MRC), The Engineering and Physical Sciences Research Council (EPSRC), Pancreatic Cancer UK, the Chief Scientists Office (Scottish Government) and Pancreatic Cancer Action Network (USA). The Cancer Research UK Liverpool Clinical Trials Unit, the ESPAC trials, and the ESPAC tissue collections, storage and analyses are all funded by Cancer Research UK. PM was recipient of a Juan de la Cierva grant from Spanish Ministry of Science and Innovation. BSJr is recipient of a Ramón y Cajal Merit Award from the Spanish Ministry of Science and Innovation and a Clinic and Laboratory Integration Program (CLIP) grant from the Cancer Research Institute, NY.

Published
2017

16. HepatoDyn: A Dynamic Model of Hepatocyte Metabolism That Integrates 13C Isotopomer Data

Author

Foguet, Carles, Marín Martínez, Silvia, Selivanov, Vitaly A., Fanchon, Eric, Lee, Paul W. N., Guinovart, Joan J. (Joan Josep), 1947, Atauri Carulla, Ramón de, Cascante i Serratosa, Marta, Department of Biochemistry and Molecular Biology [Barcelona, Spain], Universitat de Barcelona (UB), Institute of Biomedicine of University of Barcelona, Biologie Computationnelle et Mathématique (TIMC-IMAG-BCM), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019]), Department of Pediatrics [Los Angeles, CA, USA], University of Southern California (USC), Institute for Research in Biomedicine [Barcelona, Spain] (IRB), University of Barcelona-Barcelona Institute of Science and Technology (BIST), and Universitat de Barcelona

Subjects
Male, Glycogens, [SDV]Life Sciences [q-bio], Glycobiology, Fructoses, Biochemistry, Isotopes, Animal Cells, Medicine and Health Sciences, Metabolites, Biology (General), Carbon Isotopes, Organic Compounds, Monosaccharides, Metabolisme, Chemistry, Liver, Physical Sciences, Metabolic Labeling, Cellular Types, Anatomy, Metabolic Networks and Pathways, Network Analysis, Research Article, Computer and Information Sciences, Isòtops, QH301-705.5, Carbohydrates, Fructose, In Vitro Techniques, Research and Analysis Methods, Models, Biological, Phosphates, Metabolic Networks, Animals, Computer Simulation, Rats, Wistar, Molecular Biology Techniques, Molecular Biology, Hepatology, Organic Chemistry, Chemical Compounds, Computational Biology, Biology and Life Sciences, Cell Biology, Hepatologia, Rats, Kinetics, Glucose, Metabolism, Cell Labeling, Hepatocytes
Abstract

The liver performs many essential metabolic functions, which can be studied using computational models of hepatocytes. Here we present HepatoDyn, a highly detailed dynamic model of hepatocyte metabolism. HepatoDyn includes a large metabolic network, highly detailed kinetic laws, and is capable of dynamically simulating the redox and energy metabolism of hepatocytes. Furthermore, the model was coupled to the module for isotopic label propagation of the software package IsoDyn, allowing HepatoDyn to integrate data derived from 13C based experiments. As an example of dynamical simulations applied to hepatocytes, we studied the effects of high fructose concentrations on hepatocyte metabolism by integrating data from experiments in which rat hepatocytes were incubated with 20 mM glucose supplemented with either 3 mM or 20 mM fructose. These experiments showed that glycogen accumulation was significantly lower in hepatocytes incubated with medium supplemented with 20 mM fructose than in hepatocytes incubated with medium supplemented with 3 mM fructose. Through the integration of extracellular fluxes and 13C enrichment measurements, HepatoDyn predicted that this phenomenon can be attributed to a depletion of cytosolic ATP and phosphate induced by high fructose concentrations in the medium., Author Summary Despite the key role of hepatocytes in carbohydrate and lipid homeostasis, available dynamic models of hepatocyte metabolism tend to be limited to a single pathway and/or are based on assumptions of constant concentrations of key metabolites involved in redox and energy metabolism (ATP, NAD, NADPH etc.). Furthermore, most dynamic models are unable to integrate information from 13C based experiments. 13C based experiments allow us to infer the relative activity of alternative pathways and hence are highly useful for indicating flux distributions. To overcome these limitations, we developed HepatoDyn, a dynamic model of hepatic metabolism. HepatoDyn uses a large metabolic network including key pathways such as glycolysis, the Krebs cycle, the pentose phosphate pathway and fatty acid metabolism, and dynamically models the concentrations of metabolites involved in the redox and energy metabolism of hepatocytes. In addition, the model was coupled to the label propagation module of the package IsoDyn, allowing it to integrate data from 13C based experiments to assist in the parametrization process. These features make HepatoDyn a powerful tool for studying the dynamics of hepatocyte metabolism.

Published
2016

17. MiniAp-4: A Venom-Inspired Peptidomimetic for Brain Delivery

Author

Roméo Cecchelli, Meritxell Teixidó, Pol Arranz-Gibert, Sonia Ciudad, Ernest Giralt, Benjamí Oller-Salvia, Roger R. Gomis, Jesús García, Cristina Quintana García, Macarena Sánchez-Navarro, Marc Guiu, Institute for Research in Biomedicine [Barcelona, Spain] (IRB), University of Barcelona-Barcelona Institute of Science and Technology (BIST), Institute for Research in Biomedicine (IRB Barcelona) (IRB), Institute for Research in Biomedicine, Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique (LBHE), Université d'Artois (UA), and University of Barcelona

Subjects
0301 basic medicine, Proteases, Peptidomimetic, [SDV]Life Sciences [q-bio], Molecular Sequence Data, Peptide, Venom, Malalties cerebrals, 010402 general chemistry, Blood–brain barrier, Apamin, blood–brain barrier, 01 natural sciences, Models, Biological, Catalysis, 03 medical and health sciences, chemistry.chemical_compound, medicine, Neurotoxin, Humans, Drug Delivery | Hot Paper, Amino Acid Sequence, chemistry.chemical_classification, 010405 organic chemistry, Venoms, Communication, Verins animals, General Medicine, General Chemistry, blood-brain barrier, Síntesi de pèptids, Communications, 0104 chemical sciences, 3. Good health, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Peptide synthesis, chemistry, Biochemistry, Drug delivery, drug delivery, peptides, Brain diseases, Peptidomimetics, apamin
Abstract

International audience; Drug delivery across the blood-brain barrier (BBB) is a formidable challenge for therapies targeting the central nervous system. Although BBB shuttle peptides enhance transport into the brain non-invasively, their application is partly limited by lability to proteases. The present study proposes the use of cyclic peptides derived from venoms as an affordable way to circumvent this drawback. Apamin, a neurotoxin from bee venom, was minimized by reducing its complexity, toxicity, and immunogenicity, while preserving brain targeting, active transport, and protease resistance. Among the analogues designed, the monocyclic lactam-bridged peptidomimetic MiniAp-4 was the most permeable. This molecule is capable of translocating proteins and nanoparticles in a human-cell-based BBB model. Furthermore, MiniAp-4 can efficiently deliver a cargo across the BBB into the brain parenchyma of mice.

Published
2016

18. The making of a fusion branch in the Drosophila trachea

Author

Gervais, Louis, Casanova, Jordi, Institut de Biologia Molecular de Barcelona, Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Institute for Research in Biomedicine [Barcelona, Spain] (IRB), University of Barcelona-Barcelona Institute of Science and Technology (BIST), and Gervais, Louis

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

International audience

Published
2012

19. The Drosophila homologue of SRF acts as a boosting mechanism to sustain FGF-induced terminal branching in the tracheal system

Author

Louis Gervais, Jordi Casanova, Institute for Research in Biomedicine [Barcelona, Spain] (IRB), University of Barcelona-Barcelona Institute of Science and Technology (BIST), Institut de Biologia Molecular de Barcelona, and Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)

Subjects
Serum Response Factor, Organogenesis, [SDV]Life Sciences [q-bio], Morphogenesis, Biology, Fibroblast growth factor, Animals, Genetically Modified, 03 medical and health sciences, 0302 clinical medicine, Branching morphogenesis, Transcription (biology), Serum response factor, Animals, Drosophila Proteins, FGF, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Sprouting angiogenesis, 0303 health sciences, Gene Expression Regulation, Developmental, SRF (BS), Anatomy, Immunohistochemistry, 3. Good health, Cell biology, Fibroblast Growth Factors, Trachea, Signalling, Axonal branching, Drosophila, 030217 neurology & neurosurgery, Developmental Biology
Abstract

Recent data have demonstrated a crucial role for the transcription factor SRF (serum response factor) downstream of VEGF and FGF signalling during branching morphogenesis. This is the case for sprouting angiogenesis in vertebrates, axonal branching in mammals and terminal branching of the Drosophila tracheal system. However, the specific functions of SRF in these processes remain unclear. Here, we establish the relative contributions of the Drosophila homologues of FGF [Branchless (BNL)] and SRF [Blistered (BS)] in terminal tracheal branching. Conversely to an extended view, we show that BNL triggers terminal branching initiation in a DSRF-independent mechanism and that DSRF transcription induced by BNL signalling is required to maintain terminal branch elongation. Moreover, we report that increased and continuous FGF signalling can trigger tracheal cells to develop full-length terminal branches in the absence of DSRF transcription. Our results indicate that DSRF acts as an amplifying step to sustain the progression of terminal branch elongation even in the wild-type conditions of FGF signalling. © 2011. Published by The Company of Biologists Ltd., L.G. was supported by FRM (“Fondation pour la Recherche Médicale”), EMBO and JAE-Doc (CSIC) fellowships. This work was supported by the ‘Generalitat de Catalunya’, the Spanish ‘Ministerio de Ciencia e Innovación’ and its Consolider-Ingenio 2010 programme.

Published
2011

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