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5,202 results on '"Institute of Biochemistry and Biophysics"'

1. Building Machine-Learning Scoring Functions for Structure-Based Prediction of Intermolecular Binding Affinity

Author: Maciej Wójcikowski, Pawel Siedlecki, Pedro J. Ballester, Institute of Biochemistry and Biophysics PAS, Ul. Pawinskiego 5A, 02-106 Warsaw, Institute of Biochemistry and Biophysics [Warsaw] (IBB), 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 of Biochemistry and Biophysics, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU)
Subjects: 0303 health sciences, 010304 chemical physics, Computer science, business.industry, [SDV]Life Sciences [q-bio], Intermolecular force, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Ligand (biochemistry), Machine learning, computer.software_genre, 01 natural sciences, Small molecule, Docking, 03 medical and health sciences, Binding affinity, Docking (molecular), 0103 physical sciences, Structure based, Artificial intelligence, Scoring function, business, computer, 030304 developmental biology, Macromolecule
Abstract: International audience; Molecular docking enables large-scale prediction of whether and how small molecules bind to a macromolecular target. Machine-learning scoring functions are particularly well suited to predict the strength of this interaction. Here we describe how to build RF-Score, a scoring function utilizing the machine-learning technique known as Random Forest (RF). We also point out how to use different data, features, and regression models using either R or Python programming languages.
Published: 2019
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2. Performance of machine-learning scoring functions in structure-based virtual screening

Author: Pedro J. Ballester, Maciej Wójcikowski, Pawel Siedlecki, Institute of Biochemistry and Biophysics PAS, Ul. Pawinskiego 5A, 02-106 Warsaw, Institute of Biochemistry and Biophysics [Warsaw] (IBB), 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), MITOYAN, Louciné, Institute of Biochemistry and Biophysics, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU)
Subjects: 0301 basic medicine, Computer science, [SDV]Life Sciences [q-bio], Overfitting, Machine learning, computer.software_genre, 01 natural sciences, Article, Set (abstract data type), 03 medical and health sciences, Virtual screening, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Multidisciplinary, business.industry, Ligand (biochemistry), [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 0104 chemical sciences, [SDV] Life Sciences [q-bio], 010404 medicinal & biomolecular chemistry, 030104 developmental biology, Docking (molecular), Test set, Benchmark (computing), Artificial intelligence, business, computer
Abstract: Classical scoring functions have reached a plateau in their performance in virtual screening and binding affinity prediction. Recently, machine-learning scoring functions trained on protein-ligand complexes have shown great promise in small tailored studies. They have also raised controversy, specifically concerning model overfitting and applicability to novel targets. Here we provide a new ready-to-use scoring function (RF-Score-VS) trained on 15 426 active and 893 897 inactive molecules docked to a set of 102 targets. We use the full DUD-E data sets along with three docking tools, five classical and three machine-learning scoring functions for model building and performance assessment. Our results show RF-Score-VS can substantially improve virtual screening performance: RF-Score-VS top 1% provides 55.6% hit rate, whereas that of Vina only 16.2% (for smaller percent the difference is even more encouraging: RF-Score-VS top 0.1% achieves 88.6% hit rate for 27.5% using Vina). In addition, RF-Score-VS provides much better prediction of measured binding affinity than Vina (Pearson correlation of 0.56 and −0.18, respectively). Lastly, we test RF-Score-VS on an independent test set from the DEKOIS benchmark and observed comparable results. We provide full data sets to facilitate further research in this area (http://github.com/oddt/rfscorevs) as well as ready-to-use RF-Score-VS (http://github.com/oddt/rfscorevs_binary).
Published: 2017
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3. TFIIS-Dependent Non-coding Transcription Regulates Developmental Genome Rearrangements

Author: Olivier Arnaiz, Jacek K. Nowak, Cyril Denby Wilkes, Robert Gromadka, Nathalie Mathy, Kamila Maliszewska-Olejniczak, Julita Gruchota, Sandra Duharcourt, Mireille Bétermier, Institute of Biochemistry and Biophysics PAS, Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ), Institut Jacques Monod ( IJM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Polish National Science Centre (#N N303 808840), Polish Ministry of Science and Higher Education (#IP2010 028470), ARC Foundation for Cancer Research (#SFI20121205487), Centre National de la Recherche Scientifique (CNRS, an ATIP Plus grant), CNRS, Polish Academy of Sciences, CNRS GDRE 'Paramecium Genome Dynamics and Evolution', School of Molecular Biology—Institute of Biochemistry and Biophysics, PAS, European Science Foundation 'Frontiers of Functional Genomics' program), ANR-10-BLAN-1603,GENOMAC,Analyse à grande échelle du positionnement des nucléosomes dans les noyaux de Paramecium tetraurelia ( 2010 ), ANR-12-BSV6-0017,INFERNO,Hérédité épigénétique transgénérationnelle chez les ciliés : mécanismes et conséquences évolutives ( 2012 ), 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), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), ANR-10-BLAN-1603,GENOMAC,Analyse à grande échelle du positionnement des nucléosomes dans les noyaux de Paramecium tetraurelia(2010), ANR-12-BSV6-0017,INFERNO,Hérédité épigénétique transgénérationnelle chez les ciliés : mécanismes et conséquences évolutives(2012), and Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay
Subjects: Cancer Research, Genome evolution, lcsh:QH426-470, Transcription, Genetic, Somatic cell, RNA polymerase II, Genomics, Biology, Genome, 03 medical and health sciences, 0302 clinical medicine, Transcription (biology), Genetics, Nuclear dimorphism, Cell Lineage, Molecular Biology, Genetics (clinical), Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, High-Throughput Nucleotide Sequencing, Non-coding RNA, lcsh:Genetics, Germ Cells, biology.protein, RNA, Long Noncoding, RNA Polymerase II, Paramecium tetraurelia, Transcriptional Elongation Factors, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, 030217 neurology & neurosurgery, Research Article
Abstract: Because of their nuclear dimorphism, ciliates provide a unique opportunity to study the role of non-coding RNAs (ncRNAs) in the communication between germline and somatic lineages. In these unicellular eukaryotes, a new somatic nucleus develops at each sexual cycle from a copy of the zygotic (germline) nucleus, while the old somatic nucleus degenerates. In the ciliate Paramecium tetraurelia, the genome is massively rearranged during this process through the reproducible elimination of repeated sequences and the precise excision of over 45,000 short, single-copy Internal Eliminated Sequences (IESs). Different types of ncRNAs resulting from genome-wide transcription were shown to be involved in the epigenetic regulation of genome rearrangements. To understand how ncRNAs are produced from the entire genome, we have focused on a homolog of the TFIIS elongation factor, which regulates RNA polymerase II transcriptional pausing. Six TFIIS-paralogs, representing four distinct families, can be found in P. tetraurelia genome. Using RNA interference, we showed that TFIIS4, which encodes a development-specific TFIIS protein, is essential for the formation of a functional somatic genome. Molecular analyses and high-throughput DNA sequencing upon TFIIS4 RNAi demonstrated that TFIIS4 is involved in all kinds of genome rearrangements, including excision of ~48% of IESs. Localization of a GFP-TFIIS4 fusion revealed that TFIIS4 appears specifically in the new somatic nucleus at an early developmental stage, before IES excision. RT-PCR experiments showed that TFIIS4 is necessary for the synthesis of IES-containing non-coding transcripts. We propose that these IES+ transcripts originate from the developing somatic nucleus and serve as pairing substrates for germline-specific short RNAs that target elimination of their homologous sequences. Our study, therefore, connects the onset of zygotic non coding transcription to the control of genome plasticity in Paramecium, and establishes for the first time a specific role of TFIIS in non-coding transcription in eukaryotes., Author Summary Paramecium tetraurelia provides an excellent model for studying the mechanisms involved in the production of non-coding transcripts and their mode of action. Different types of non-coding RNAs (ncRNAs) were shown to be implicated in the programmed DNA elimination process that occurs in this organism. At each sexual cycle, during development of the somatic nucleus from the germline nucleus, the genome is massively rearranged through the reproducible elimination of germline-specific sequences including thousands of short, single copy, non-coding Internal Eliminated Sequences (IES). Here, we demonstrate, using RNA interference, that the TFIIS4 gene encoding a development-specific homolog of RNA polymerase II elongation factor TFIIS, is indispensable for ncRNA synthesis in the new somatic nucleus. TFIIS4 depletion impairs the assembly of a functional somatic genome and affects excision of a large fraction of IESs, which leads to strong lethality in the sexual progeny. We propose that TFIIS4-dependent ncRNAs provide an important component of the molecular machinery that is responsible for developmental genome remodeling in Paramecium.
Published: 2015
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4. Abolishment of morphology-based taxa and change to binomial species names: 2022 taxonomy update of the ICTV bacterial viruses subcommittee

Author: Dann Turner, Andrey N. Shkoporov, Cédric Lood, Andrew D. Millard, Bas E. Dutilh, Poliane Alfenas-Zerbini, Leonardo J. van Zyl, Ramy K. Aziz, Hanna M. Oksanen, Minna M. Poranen, Andrew M. Kropinski, Jakub Barylski, J Rodney Brister, Nina Chanisvili, Rob A. Edwards, François Enault, Annika Gillis, Petar Knezevic, Mart Krupovic, Ipek Kurtböke, Alla Kushkina, Rob Lavigne, Susan Lehman, Malgorzata Lobocka, Cristina Moraru, Andrea Moreno Switt, Vera Morozova, Jesca Nakavuma, Alejandro Reyes Muñoz, Jānis Rūmnieks, BL Sarkar, Matthew B. Sullivan, Jumpei Uchiyama, Johannes Wittmann, Tong Yigang, Evelien M. Adriaenssens, UCL - SST/ELI/ELIM - Applied Microbiology, University of the West of England [Bristol] (UWE Bristol), University College Cork (UCC), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Leicester, Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Utrecht University [Utrecht], Universidade Federal de Viçosa = Federal University of Viçosa (UFV), University of the Western Cape (UWC), Cairo University, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, University of Guelph, Adam Mickiewicz University in Poznań (UAM), National Center for Biotechnology Information (NCBI), George Eliava Institute of Bacteriophages, Microbiology and Virology [Tbilisi, Georgia], Flinders Accelerator for Microbiome Exploration [Adelaide, Australia], Laboratoire Microorganismes : Génome et Environnement (LMGE), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Université Catholique de Louvain = Catholic University of Louvain (UCL), University of Novi Sad, Virologie des archées - Archaeal Virology, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of the Sunshine Coast (USC), D.K. Zabolotny Institute of Microbiology and Virology [Kyiv, Ukraine], National Academy of Sciences of Ukraine (NASU), University of Gdańsk (UG), Center for Biologics Evaluation and Research, U.S. Food and Drug Administration (FDA), Institute of Biochemistry and Biophysics [Warsaw] (IBB), University of Oldenburg, Pontificia Universidad Católica de Chile (UC), Institute of Chemical Biology and Fundamental Medicine [Novosibirsk, Russia] (ICBFM SB RAS), Siberian Branch of the Russian Academy of Sciences (SB RAS), Makerere University [Kampala, Ouganda] (MAK), Universidad de los Andes [Bogota] (UNIANDES), Latvian Biomedical Research and Study Center (BMC), National Institute of Cholera and Enteric Diseases, Ohio State University [Columbus] (OSU), Okayama University, Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH / Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures (DSMZ), Beijing University of Chemical Technology, Quadram Institute Bioscience [Norwich, U.K.] (QIB), Biotechnology and Biological Sciences Research Council (BBSRC), B.E.D. was supported by the European Research Council (ERC) Consolidator Grant 865694: DiversiPHI, the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy – EXC 2051 – Project-ID 390713860, the Alexander von Humboldt Foundation in the context of an Alexander von Humboldt Professorship funded by the German Federal Ministry of Education and Research, and the European Union’s Horizon 2020 Research and Innovation Program, under the Marie Skłodowska-Curie Actions Innovative Training Networks grant agreement no. 955974 (VIROINF). Work by J.R.B. was supported by the National Center for Biotechnology Information of the National Library of Medicine (NLM), National Institutes of Health. R.A.E was supported by an award from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institute of Health RC2DK116713 and an award from the Australian Research Council, DP220102915. R.L. is supported by the research grant PHAGEFORCE from the KU Leuven. C.L. is supported by the Research Foundation - Flanders (FWO Grant 12D8623N) and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy – EXC 2051 – Project-ID 390713860. V.M. is supported by the Russian state-funded project For ICBFM SB RAS, Grant 121031300043-8. H.M.O. was supported by the University of Helsinki and Academy of Finland by funding for FINStruct and Instruct Centre Finland, Instruct-ERIC. M.M.P. acknowledges funding from the Sigrid Jusélius Foundation and the Academy of Finland (grant 331627). A.N.S is supported by a Wellcome Trust Research Career Development Fellowship [220646/Z/20/Z] and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Grant agreement No 101001684). E.M.A. gratefully acknowledges funding by the Biotechnology and Biological Sciences Research Council (BBSRC), this research was funded by the BBSRC Institute Strategic Programme Gut Microbes and Health BB/R012490/1 and its constituent projects BBS/E/F/000PR10353 and BBS/E/F/000PR10356., European Project: 865694,H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC),DiversiPHI(2020), and European Project: 101001684,ERC-2020-COG,PHAGENET(2021)
Subjects: Science & Technology, [SDV]Life Sciences [q-bio], Virology, General Medicine, Life Sciences & Biomedicine
Abstract: This article summarises the activities of the Bacterial Viruses Subcommittee of the International Committee on Taxonomy of Viruses for the period of March 2021−March 2022. We provide an overview of the new taxa proposed in 2021, approved by the Executive Committee, and ratified by vote in 2022. Significant changes to the taxonomy of bacterial viruses were introduced: the paraphyletic morphological families Podoviridae, Siphoviridae, and Myoviridae as well as the order Caudovirales were abolished, and a binomial system of nomenclature for species was established. In addition, one order, 22 families, 30 subfamilies, 321 genera, and 862 species were newly created, promoted, or moved.
Published: 2023
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5. Zinc finger oxidation of Fpg/Nei DNA glycosylases by 2-thioxanthine: biochemical and X-ray structural characterization

Author: Alicja Winczura, Didier Gasparutto, Artur Biela, Thomas Carell, Zygmunt Kazimierczuk, Barbara Tudek, Jarosław M. Cieśla, Franck Coste, Martine Guérin, Karola L. Gasteiger, Stéphane Goffinont, Bertrand Castaing, Françoise Culard, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Ludwig-Maximilians-Universität München, Department of Chemistry and Biochemistry, Institute of Biochemistry and Biophysics PAS, Ul. Pawinskiego 5A, 02-106 Warsaw, Institute of Biochemistry and Biophysics, Warsaw University of Life Sciences (SGGW), Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), Institute of Genetics and Biotechnology, University of Warsaw (UW), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Institute of Biochemistry and Biophysics [Warsaw] (IBB)
Subjects: Models, Molecular, endocrine system diseases, [SDV]Life Sciences [q-bio], Biology, Crystallography, X-Ray, DNA-formamidopyrimidine glycosylase, DNA Glycosylases, chemistry.chemical_compound, Structural Biology, Genetics, Enzyme Inhibitors, chemistry.chemical_classification, Zinc finger, Zinc Fingers, DNA-binding domain, Base excision repair, DNA, Molecular biology, 3. Good health, Zinc, Enzyme, chemistry, Biochemistry, DNA-Formamidopyrimidine Glycosylase, DNA glycosylase, Thioxanthenes, Uncompetitive inhibitor, Oxidation-Reduction
Abstract: International audience; DNA glycosylases from the Fpg/Nei structural superfamily are base excision repair enzymes involved in the removal of a wide variety of mutagen and potentially lethal oxidized purines and pyrimidines. Although involved in genome stability, the recent discovery of synthetic lethal relationships between DNA glycosylases and other pathways highlights the potential of DNA glycosylase inhibitors for future medicinal chemistry development in cancer therapy. By combining biochemical and structural approaches, the physical target of 2-thioxanthine (2TX), an uncompetitive inhibitor of Fpg, was identified. 2TX interacts with the zinc finger (ZnF) DNA binding domain of the enzyme. This explains why the zincless hNEIL1 enzyme is resistant to 2TX. Crystal structures of the enzyme bound to DNA in the presence of 2TX demonstrate that the inhibitor chemically reacts with cysteine thiolates of ZnF and induces the loss of zinc. The molecular mechanism by which 2TX inhibits Fpg may be generalized to all prokaryote and eukaryote ZnF-containing Fpg/Nei-DNA glycosylases. Cell experiments show that 2TX can operate in cellulo on the human Fpg/Nei DNA glycosylases. The atomic elucidation of the determinants for the interaction of 2TX to Fpg provides the foundation for the future design and synthesis of new inhibitors with high efficiency and selectivity.
Published: 2014
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6. Discovery of novel potent ΔF508-CFTR correctors that target the nucleotide binding domain

Author: Sara Bitam, Krzysztof Tarnowski, Mario Ollero, Julien Colas, Ariel Roldan, Melanie Faria da Cunha, Nathalie Servel, Janine Fritsch, Grazyna Faure, Danielle Tondelier, Norbert Odolczyk, Patricia Melin-Heschel, Anna Kupniewska, Michal Dadlez, Aleksander Edelman, Harald Herrmann, Piotr Zielenkiewicz, Frédéric Becq, Ludovic Wiszniewski, Gergely L. Lukacs, Emilie L. Saussereau, Grzegorz Wieczorek, Caroline Norez, Department of Bioinformatics Institute of Biochemistry and Biophysics, Medical University of Warsaw - Poland, Centre de recherche Croissance et signalisation (UMR_S 845), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), sans affiliation, U845, Institut National de la Santé et de la Recherche Médicale (INSERM), Epithelix SARL, University of Geneva [Switzerland], Laboratory of Mass Spectrometry Institute of Biochemistry and Biophysics, Laboratoire de physique des interfaces et des couches minces [Palaiseau] (LPICM), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Biologie Moléculaire du Gène chez les Extrêmophiles (BMGE), Institut Pasteur [Paris], Cellule Pasteur UPMC, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris], Institut de physiologie et biologie cellulaires (IPBC), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Hungarian Academy of Sciences (MTA), Récepteurs Canaux - Channel Receptors, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Angewandte Physik, Universität Paderborn (UPB), Inserm U955, équipe 21, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Signalisation et Transports Ioniques Membranaires (STIM), Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Laboratory of Plant Molecular Biology, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), European Commission, FP6‐2003‐Lifescihealth‐I program, Université de Poitiers-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Centre de recherche Croissance et signalisation ( UMR_S 845 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale, Laboratoire de physique des interfaces et des couches minces [Palaiseau] ( LPICM ), École polytechnique ( X ) -Centre National de la Recherche Scientifique ( CNRS ), Biologie Moléculaire du Gène chez les Extrêmophiles ( BMGE ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut Pasteur [Paris], Institut de physiologie et biologie cellulaires ( IPBC ), Université de Poitiers-Centre National de la Recherche Scientifique ( CNRS ), Hungarian Academy of Sciences [Budapest], Récepteurs Canaux, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Universität Paderborn ( UPB ), Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Signalisation et Transports Ioniques Membranaires ( STIM ), Institut Necker Enfants-Malades (INEM) ( INEM - UM 111 (UMR 8253 / U1151) ), Sans affiliation, Université de Genève = University of Geneva (UNIGE), Institut Pasteur [Paris] (IP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Morillon, Christelle, and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: lung disease, Patch-Clamp Techniques, Cystic Fibrosis, [SDV]Life Sciences [q-bio], Closeups, Drug Evaluation, Preclinical, Cystic Fibrosis Transmembrane Conductance Regulator, Plasma protein binding, medicine.disease_cause, Mice, Protein Interaction Maps, Cells, Cultured, 0303 health sciences, Mutation, biology, Drug discovery, Homozygote, 030302 biochemistry & molecular biology, Transfection, respiratory system, Cystic fibrosis transmembrane conductance regulator, 3. Good health, Cell biology, [SDV] Life Sciences [q-bio], Cyclic nucleotide-binding domain, Molecular Medicine, Protein Binding, congenital, hereditary, and neonatal diseases and abnormalities, Bronchi, drug discovery, Small Molecule Libraries, 03 medical and health sciences, Chloride Channels, medicine, Animals, Humans, Binding site, ΔF508, 030304 developmental biology, therapy, Binding Sites, proteostasis, [ SDV ] Life Sciences [q-bio], Keratin-8, Epithelial Cells, Molecular biology, Protein Structure, Tertiary, respiratory tract diseases, ion channel, biology.protein, HeLa Cells
Abstract: International audience; The deletion of Phe508 (ΔF508) in the first nucleotide binding domain (NBD1) of CFTR is the most common mutation associated with cystic fibrosis. The ΔF508-CFTR mutant is recognized as improperly folded and targeted for proteasomal degradation. Based on molecular dynamics simulation results, we hypothesized that interaction between ΔF508-NBD1 and housekeeping proteins prevents ΔF508-CFTR delivery to the plasma membrane. Based on this assumption we applied structure-based virtual screening to identify new low-molecular-weight compounds that should bind to ΔF508-NBD1 and act as protein-protein interaction inhibitors. Using different functional assays for CFTR activity, we demonstrated that in silico-selected compounds induced functional expression of ΔF508-CFTR in transfected HeLa cells, human bronchial CF cells in primary culture, and in the nasal epithelium of homozygous ΔF508-CFTR mice. The proposed compounds disrupt keratin8-ΔF508-CFTR interaction in ΔF508-CFTR HeLa cells. Structural analysis of ΔF508-NBD1 in the presence of these compounds suggests their binding to NBD1. We conclude that our strategy leads to the discovery of new compounds that are among the most potent correctors of ΔF508-CFTR trafficking defect known to date.
Published: 2013
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7. Aberrant repair of etheno-DNA adducts in leukocytes and colon tissue of colon cancer patients

Author: Paweł Kowalczyk, Jean Cadet, Beata Janowska, Zbigniew Banaszkiewicz, Maja Swoboda, Arkadiusz Jawień, Daniel Gackowski, Elżbieta Speina, Ryszard Olinski, Andrzej Chaber, Helmut Bartsch, Alicja Winczura, Jarosław M. Cieśla, Barbara Tudek, Ireneusz W. Krasnodębski, Jagadesaan Nair, Thierry Douki, Tomasz Obtułowicz, Justyna Janik, Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-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), Institute of Biochemistry and Biophysics PAS, Ul. Pawinskiego 5A, 02-106 Warsaw, Institute of Biochemistry and Biophysics [Warsaw] (IBB), Institute of Genetics and Biotechnology, University of Warsaw (UW), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-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)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-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)-Centre National de la Recherche Scientifique (CNRS), and Institute of Biochemistry and Biophysics
Subjects: Adult, DNA Repair, DNA damage, Colorectal cancer, Colon, medicine.disease_cause, Biochemistry, Deoxycytidine, DNA Glycosylases, Endonuclease, chemistry.chemical_compound, DNA Adducts, Deoxyadenosine, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Physiology (medical), medicine, DNA-(Apurinic or Apyrimidinic Site) Lyase, Humans, AP site, Aged, biology, Deoxyadenosines, Chemistry, Carcinoma, Base excision repair, Middle Aged, medicine.disease, Molecular biology, Thymine DNA Glycosylase, DNA glycosylase, Case-Control Studies, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Colonic Neoplasms, Mutation, biology.protein, Leukocytes, Mononuclear, Female, Lipid Peroxidation, Carcinogenesis
Abstract: International audience; To assess the role of lipid peroxidation-induced DNA damage and repair in colon carcinogenesis, the excision rates and levels of 1,N-6-etheno-2'-deoxyadenosine (epsilon dA), 3,N-4-etheno-2'-deoxycytidine (epsilon dC), and 1,N-2-etheno-2'-deoxyguanosine (1,N-2-epsilon dG) were analyzed in polymorphic blood leukocytes (PBL) and resected colon tissues of 54 colorectal carcinoma (CRC) patients and PBL of 56 healthy individuals. In PBL the excision rates of 1,N-6-ethenoadenine (epsilon Ade) and 3,N-4-ethenocytosine (epsilon Cyt), measured by the nicking of oligodeoxynucleotide duplexes with single lesions, and unexpectedly also the levels of epsilon dA and 1,N-2-epsilon dG, measured by LC/MS/MS, were lower in CRC patients than in controls. In contrast the mRNA levels of repair enzymes, alkylpurine- and thymine-DNA glycosylases and abasic site endonuclease (APE1), were higher in PBL of CRC patients than in those of controls, as measured by QPCR. In the target colon tissues epsilon Ade and epsilon Cyt excision rates were higher, whereas the epsilon dA and epsilon dC levels in DNA, measured by P-32-postlabeling, were lower in tumor than in adjacent colon tissue, although a higher mRNA level was observed only for APE1. This suggests that during the onset of carcinogenesis, etheno adduct repair in the colon seems to be under a complex transcriptional and posttranscriptional control, whereby deregulation may act as a driving force for malignancy.
Published: 2010
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8. Reproducibility and accuracy of microscale thermophoresis in the NanoTemper Monolith: a multi laboratory benchmark study

Author: Caroline Mas, Grzegorz Piszczek, Marjetka Podobnik, Kathryn Perez, Timothy Sharpe, Stephen H. McLaughlin, Roland Montserret, Stefan H. Knauer, Bruno Baron, Christopher M. Johnson, Quyen Nguyen, Mark A. Williams, Katja Pirc, Arthur Sedivy, Celeste Abreu, Tina Daviter, David Ortega-Alarcon, Daumantas Matulis, Rouba Nasreddine, Carlo Carolis, Thomas A. Jowitt, Stephan Uebel, David Staunton, Andrew P. Leech, Maria Garcia-Alai, June Southall, Alexander Fish, Jitka Holková, Alexander K. Buell, Michael Weyand, Jasmina Rokov-Plavec, Blanca López-Méndez, Sylvie Berger, Josef Houser, Natalia Rodrigo, Wojciech Bal, Chad A. Brautigam, Josef Hamacek, Reine Nehmé, Olga Abian, Christian Guenther, Ondrej Vanek, Susanne Schaefer, Sharon M. Kelly, Malgorzata Adamczyk, Di Wu, Pedro Tavares, University of Copenhagen = Københavns Universitet (KU), Biophysique Moléculaire (plateforme) - Molecular Biophysics (platform), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), University of Texas Southwestern Medical Center [Dallas], University of Manchester [Manchester], Universität Bayreuth, Max Planck Institute of Biochemistry (MPIB), Max-Planck-Gesellschaft, University of London [London], Vienna Biocenter Core Facilities, Partenaires INRAE, University of Zaragoza - Universidad de Zaragoza [Zaragoza], Charles University [Prague] (CU), Warsaw University of Technology [Warsaw], Institute of Biochemistry and Biophysics, Polish Academy of Sciences (PAN), Institut de Recherches SERVIER (IRS), Technical University of Denmark [Lyngby] (DTU), Centre for Genomic Regulation [Barcelona] (CRG), Universitat Pompeu Fabra [Barcelona] (UPF)-Centro Nacional de Analisis Genomico [Barcelona] (CNAG), The institute of cancer research [London], Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, EMBL Hamburg, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Central European Institute of Technology [Brno] (CEITEC MU), Brno University of Technology [Brno] (BUT), MRC Laboratory of Molecular Biology [Cambridge, UK] (LMB), University of Cambridge [UK] (CAM)-Medical Research Council, University of Glasgow, University of York [York, UK], Integrated Structural Biology Grenoble (ISBG - UMS 3518 ), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Vilnius University [Vilnius], Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie Organique et Analytique (ICOA), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Institut National de la Santé et de la Recherche Médicale (INSERM), EMBL Heidelberg, National Institute of Chemistry, National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), University of Zagreb, University of Bayreuth, University of Basel (Unibas), University of Oxford [Oxford], Faculdade de Ciências e Tecnologia [Faro] (FCT), Universidade do Algarve (UAlg), This research was funded by Fondo de Investigaciones Sanitarias from Instituto de Salud Carlos III and European Union (ERDF/ESF, 'Investing in your future' PI18/00349 and Diputación General de Aragón Digestive Pathology Group B25_17R to O.A. Spanish Ministry of Science, Innovation and Universities, FPI Predoctoral Research Contract BES-2017-080739 to D.O.A. This research was funded by project no 2015/17/B/NZ2/01160 (granted to MA), we also acknowledge financial support, from the Faculty of Chemistry at Warsaw University of Technology. As part of the Federal FTI strategy, this work was generously supported by the City of Vienna and the Austrian Ministry for Education, Science and Research., Frapart, Isabelle, University of Copenhagen = Københavns Universitet (UCPH), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Max-Planck-Institut für Biochemie = Max Planck Institute of Biochemistry (MPIB), Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Integrated Structural Biology Grenoble (ISBG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and University of Oxford
Subjects: 0301 basic medicine, 030103 biophysics, Materials science, Thermophoresis, Interaction, Biophysics, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Calorimetry, Benchmark, 03 medical and health sciences, Biomolècules, MST, TRIC, KD, [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], Surface plasmon resonance, Monolith, Reliability (statistics), Reproducibility, geography, geography.geographical_feature_category, K D, Microscale thermophoresis, Intensity change, Temperature, Reproducibility of Results, Correction, General Medicine, Biofísica, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Benchmarking, 030104 developmental biology, [PHYS.PHYS.PHYS-INS-DET] Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], Benchmark (computing), Original Article, Biological system, Laboratories
Abstract: Microscale thermophoresis (MST), and the closely related Temperature Related Intensity Change (TRIC), are synonyms for a recently developed measurement technique in the field of biophysics to quantify biomolecular interactions, using the (capillary-based) NanoTemper Monolith and (multiwell plate-based) Dianthus instruments. Although this technique has been extensively used within the scientific community due to its low sample consumption, ease of use, and ubiquitous applicability, MST/TRIC has not enjoyed the unambiguous acceptance from biophysicists afforded to other biophysical techniques like isothermal titration calorimetry (ITC) or surface plasmon resonance (SPR). This might be attributed to several facts, e.g., that various (not fully understood) effects are contributing to the signal, that the technique is licensed to only a single instrument developer, NanoTemper Technology, and that its reliability and reproducibility have never been tested independently and systematically. Thus, a working group of ARBRE-MOBIEU has set up a benchmark study on MST/TRIC to assess this technique as a method to characterize biomolecular interactions. Here we present the results of this study involving 32 scientific groups within Europe and two groups from the US, carrying out experiments on 40 Monolith instruments, employing a standard operation procedure and centrally prepared samples. A protein-small molecule interaction, a newly developed protein-protein interaction system and a pure dye were used as test systems. We characterized the instrument properties and evaluated instrument performance, reproducibility, the effect of different analysis tools, the influence of the experimenter during data analysis, and thus the overall reliability of this method. All authors acknowledge the COST Action project ARBRE-MOBIEU CA15126 under the auspices of whose Working Group 4 this study was carried out. ARBRE-MOBIEU COST Action CA15126 funded meetings in the Center for Protein Research, University of Copenhagen (ECOST-MEETING-CA15126-280618-098884) to organize this study and in the Vienna Biocenter Core Facilities GmbH (ECOST-MEETING-CA15126-121119-111544) to discuss the results of the benchmark. Ondřej Vaněk acknowledges support from the Ministry of Education, Youth and Sports of the Czech Republic (LTC17065 in frame of the COST Action CA15126). Jitka Holková and Josef Houser acknowledge CF Biomolecular Interactions and Crystallization of CIISB, Instruct-CZ Centre, supported by MEYS CR (LM2018127). Jasmina Rokov-Plavec acknowledges support from the Croatian Science Foundation (IP-2016-06-6272). Alexander K. Buell thanks the Novo Nordisk Foundation (grant number NNFSA170028392) for funding. Li Peng Lundgren acknowledges for preliminary MST/TRIC experiments (STMS 37745 in the frame of the COST Action CA15126) and the COST Action (CA15126) for a STMS (STMS 44783) for the data analysis. The Novo Nordisk Foundation Center for Protein Research is supported financially by the Novo Nordisk Foundation (Grant agreement NNF14CC0001). Katja Pirc and Marjetka Podobnik acknowledge the grant by the Slovenian Research Agency P1-0391 (Title: Molecular Interactions). This research was funded by Fondo de Investigaciones Sanitarias from Instituto de Salud Carlos III and European Union (ERDF/ESF, “Investing in your future” PI18/00349 and Diputación General de Aragón Digestive Pathology Group B25_17R to O.A. Spanish Ministry of Science, Innovation and Universities, FPI Predoctoral Research Contract BES-2017-080739 to D.O.A. This research was funded by project no 2015/17/B/NZ2/01160 (granted to MA)
Published: 2021
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9. Rsp5p ubiquitin ligase and the transcriptional activators Spt23p and Mga2p are involved in co-regulation of biosynthesis of end products of the mevalonate pathway and triacylglycerol in yeast Saccharomyces cerevisiae

Author: Thierry Ferreira, Thierry Bergès, Teresa Zołądek, Anna Szkopinska, Pawel Kaliszewski, Ewa Świeżewska, Department of lipid Biochemistry, Polska Akademia Nauk = Polish Academy of Sciences (PAN)-Institute of Biochemistry and Biophysics, Physiologie Moléculaire du Transport des Sucres chez les Végétaux (PhyMoTS), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Institute of Biochemistry and Biophysics, and Polska Akademia Nauk = Polish Academy of Sciences (PAN)
Subjects: MESH: Dimethylallyltranstransferase, Ubiquinone, MESH: Ergosterol, MESH: Endosomal Sorting Complexes Required for Transport, chemistry.chemical_compound, MESH: Saccharomyces cerevisiae Proteins, Dolichols, Ergosterol, MESH: Ubiquinone, Overproduction, MESH: Dolichol, MESH: Lipid Metabolism, 0303 health sciences, biology, 030302 biochemistry & molecular biology, Ubiquitin-Protein Ligase Complexes, MESH: Transcription Factors, MESH: Mevalonic Acid, MESH: Saccharomyces cerevisiae, Ubiquitin ligase, Sterols, Biochemistry, lipids (amino acids, peptides, and proteins), MESH: Biosynthetic Pathways, Mevalonate pathway, MESH: Membrane Proteins, MESH: Triglycerides, Saccharomyces cerevisiae Proteins, MESH: Mutation, MESH: Trans-Activators, Saccharomyces cerevisiae, Mevalonic Acid, MESH: Cytoplasmic Granules, MESH: Transformation, Genetic, MESH: Alkyl and Aryl Transferases, Cytoplasmic Granules, 03 medical and health sciences, Transformation, Genetic, Biosynthesis, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Molecular Biology, Triglycerides, 030304 developmental biology, Alkyl and Aryl Transferases, Endosomal Sorting Complexes Required for Transport, Membrane Proteins, Lipid metabolism, MESH: Ubiquitin-Protein Ligase Complexes, Cell Biology, biology.organism_classification, Dimethylallyltranstransferase, Lipid Metabolism, Yeast, Biosynthetic Pathways, chemistry, MESH: Sterols, Mutation, biology.protein, Trans-Activators, Transcription Factors
Abstract: International audience; Rsp5p, a yeast S. cerevisiae ubiquitin ligase, is essential for regulation of unsaturated fatty acid synthesis via activation of the transcriptional activators Spt23p and Mga2p. Here we show that the conditional mutant rsp5-19 produces decreased levels of the end products of mevalonate pathway, such as ergosterol, ubiquinone and of dolichols, especially those with 19-24 isoprene units. The mechanism of Rsp5p involvement in the control of these lipid synthesis pathways was addressed by overproduction of Rsp5p-independent Spt23p or Mga2p. Expression of constitutively active forms of these transactivators resulted in excess production of ergosterol, but did not restore a wild-type level of dolichols. Moreover, synthesis of long chain dolichols was decreased in the wild-type and a rsp5-19 background. Finally, overproduction of active Spt23p or Mga2p was accompanied by the appearance of large lipid particles in the wild-type and rsp5-19 strains as observed by Nile Red staining, due to accumulation of unsaturated triacylglycerol. Thus, we conclude that Rsp5p, Spt23p and Mga2p may participate in the control of the homeostasis of lipids and lipid particles.
Published: 2008
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10. Nedd4, a human ubiquitin ligase, affects actin cytoskeleton in yeast cells

Author: Dale S. Haines, Marta Stawiecka-Mirota, Joanna Kaminska, Teresa Zoladek, Danièle Urban-Grimal, department of genetics - Institute of biochemistry and biophysics, institute of biochemistry an biophysics-polish academic of sciences, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, and Ministry of Science and Higher Education, Poland
Subjects: Saccharomyces cerevisiae Proteins, Nedd4 Ubiquitin Protein Ligases, Ubiquitin-Protein Ligases, Arp2/3 complex, Fluorescent Antibody Technique, Saccharomyces cerevisiae, macromolecular substances, Actin cytoskeleton organization, Latrunculin A, 03 medical and health sciences, 0302 clinical medicine, Gene Expression Regulation, Fungal, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Humans, Actin-binding protein, Cytoskeleton, 030304 developmental biology, 0303 health sciences, biology, Endosomal Sorting Complexes Required for Transport, Gene Transfer Techniques, Temperature, Actin remodeling, Cell Biology, 16. Peace & justice, Actin cytoskeleton, Bridged Bicyclo Compounds, Heterocyclic, Actins, Yeast, Cell biology, Ubiquitin ligase, Profilin, Mutation, biology.protein, Thiazolidines, MDia1, 030217 neurology & neurosurgery, Wiskott-Aldrich Syndrome Protein
Abstract: International audience; Human Nedd4 ubiquitin ligase is involved in protein trafficking, signal transduction and oncogenesis. Nedd4 with an inactive WW4 domain is toxic to yeast cells. We report here that actin cytoskeleton is abnormal in yeast cells expressing the NEDD4 or NEDD4w4 gene and these cells are more sensitive to Latrunculin A, an actin-depolymerizing drug. These phenotypes are less pronounced when a mutation inactivating the catalytic domain of the ligase has been introduced. In contrast, overexpression of the LAS17 gene, encoding an activator of the Arp2/3 actin nucleating complex, is detrimental to NEDD4w4-expressing cells. The level of Las17p is increased in cells overproducing Nedd4w4 and this depends partially on its catalytic domain. Expression of genes encoding Nedd4 variants, like overexpression of LAS17, suppresses the growth defect of the arp2-1 strain. Our results suggest that human Nedd4 ligase inhibits yeast cell growth by disturbing the actin cytoskeleton, in part by increasing Las17p level, and that Nedd4 ubiquitination targets may include actin cytoskeleton-associated proteins conserved in evolution.
Published: 2008
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11. Targeting of Sna3p to the endosomal pathway depends on its interaction with Rsp5p and multivesicular body sorting on its ubiquitylation

Author: Pierre Morsomme, Teresa Zoladek, Marta Stawiecka-Mirota, Danièle Urban-Grimal, Wojciech Pokrzywa, Rosine Haguenauer-Tsapis, Joëlle Morvan, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), department of genetics - Institute of biochemistry and biophysics, institute of biochemistry an biophysics-polish academic of sciences, unite de biochimie physiologie, Université Catholique de Louvain (UCL)-Institut des Sciences de la Vie, Centre National de la Recherche Scientifique, the Universities Paris 6 and Paris 7, Association pour la recherche sur le Cancer, Ministère de l‘Enseignement et de la Recherche , Action Concertée Incitative, Belgian National Fund for Scientific Research, Interuniversity Attraction Poles Programme Belgian Science Policy, Communauté française de Belgique-Actions de Recherches Concertées, Career Development Award (CDA), Human Frontier Science Program Organization, and Université Catholique de Louvain = Catholic University of Louvain (UCL)-Institut des Sciences de la Vie
Subjects: Saccharomyces cerevisiae Proteins, Endosome, Endocytic cycle, Endosomes, Saccharomyces cerevisiae, macromolecular substances, yeast, Biochemistry, ubiquitin ligase, multivesicular body, Sna3, 03 medical and health sciences, Ubiquitin, Structural Biology, Rsp5, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Genetics, Immunoprecipitation, Multivesicular Body, Transport Vesicles, Molecular Biology, 030304 developmental biology, 0303 health sciences, Binding Sites, biology, Endosomal Sorting Complexes Required for Transport, Vacuolar lumen, Lysine, 030302 biochemistry & molecular biology, Membrane Proteins, Ubiquitin-Protein Ligase Complexes, Cell Biology, Original Articles, Ubiquitin ligase, Transport protein, Cell biology, Lys63, Protein Transport, Membrane protein, Mutation, biology.protein, Nedd4, Protein Processing, Post-Translational, Protein Binding
Abstract: Rsp5p is an ubiquitin (Ub)-protein ligase of the Nedd4 family that carries WW domains involved in interaction with PPXY-containing proteins. It plays a key role at several stages of intracellular trafficking, such as Ub-mediated internalization of endocytic cargoes and Ub-mediated sorting of membrane proteins to internal vesicles of multivesicular bodies (MVBs), a process that is crucial for their subsequent targeting to the vacuolar lumen. Sna3p is a membrane protein previously described as an Ub-independent MVB cargo, but proteomic studies have since shown it to be an ubiquitylated protein. Sna3p carries a PPXY motif. We observed that this motif mediates its interaction with Rsp5p WW domains. Mutation of either the Sna3p PPXY motif or the Rsp5p WW3 domain or reduction in the amounts of Rsp5 results in the mistargeting of Sna3p to multiple mobile vesicles and prevents its sorting to the endosomal pathway. This sorting defect appears to occur prior to the defect displayed in rsp5 mutants by other MVB cargoes, which are correctly sorted to the endosomal pathway but missorted to the vacuolar membrane instead of the vacuolar lumen. Sna3p is polyubiquitylated on one target lysine, and a mutant Sna3p lacking its target lysine displays defective MVB sorting. Sna3p undergoes Rsp5-dependent polyubiquitylation, with K63-linked Ub chains.
Published: 2007
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12. Dinucleotide TpT and Its 2'-O-Me Analogue Possess Different Backbone Conformations and Flexibilities but Similar Stacked Geometries

Author: Jean A. H. Cognet, Alain Favre, Pascal Auffinger, Pascale Clivio, Céline Moriou, Christophe Pakleza, Guillaume Santini, Laboratoire de Biophysique Moléculaire Cellulaire et Tissulaire (BIOMOCETI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris 13 (UP13)-Centre National de la Recherche Scientifique (CNRS), Institute of Biochemistry and Biophysics, Architecture et réactivité de l'ARN (ARN), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Isolement, structure, transformations et synthèse de substances naturelles (ISTSSN), Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Université Paris 13 (UP13)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Institute of Biochemistry and Biophysics [Warsaw] (IBB), and Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Models, Molecular, Circular dichroism, Magnetic Resonance Spectroscopy, Photochemistry, Stereochemistry, Quantum dynamics, Stacking, 010402 general chemistry, Methylation, 01 natural sciences, 03 medical and health sciences, Molecular dynamics, chemistry.chemical_compound, Materials Chemistry, Molecule, Computer Simulation, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Physical and Theoretical Chemistry, Pliability, Chromatography, High Pressure Liquid, 030304 developmental biology, 0303 health sciences, Photolysis, Molecular Structure, Chemistry, Photodissociation, Nuclear magnetic resonance spectroscopy, 0104 chemical sciences, Surfaces, Coatings and Films, Thymine, Kinetics, Crystallography, Dinucleoside Phosphates, Thymidine
Abstract: International audience; UV irradiation at 254 nm of 2'-O,5-dimethyluridylyl(3'-5')-2'-O,5-dimethyluridine (1a) and of natural thymidylyl(3'-5')thymidine (1b) generates the same photoproducts (CPD and (6-4)PP; responsible for cell death and skin cancer). The ratios of quantum yields of photoproducts obtained from 1a (determined herein) to that from 1b are in a proportion close to the approximately threefold increase of stacked dinucleotides for 1a compared with those of 1b (from previous circular dichroism results). 1a and 1b however are endowed with different predominant sugar conformations, C3'-endo (1a) and C2'-endo (1b). The present investigation of the stacked conformation of these molecules, by unrestrained state-of-the-art molecular simulation in explicit solvent and salt, resolves this apparent paradox and suggests the following main conclusions. Stacked dinucleotides 1a and 1b adopt the main characteristic features of a single-stranded A and B form, respectively, where the relative positions of the backbone and the bases are very different. Unexpectedly, the geometry of the stacking of two thymine bases, within each dinucleotide, is very similar and is in excellent agreement with photochemical and circular dichroism results. Analyses of molecular dynamics trajectories with conformational adiabatic mapping show that 1a and 1b explore two different regions of conformational space and possess very different flexibilities. Therefore, even though their base stacking is very similar, these molecules possess different geometrical, mechanical, and dynamical properties that may account for the discrepancy observed between increased stacking and increased photoproduct formations. The computed average stacked conformations of 1a and 1b are well-defined and could serve as starting models to investigate photochemical reactions with quantum dynamics simulations.
Published: 2007
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13. Enterolactone: A novel radiosensitizer for human breast cancer cell lines through impaired DNA repair and increased apoptosis

Author: Mamashli, Fatemeh [Department of Biophysics, Institute of Biochemistry and Biophysics, University of Tehran, 16th Azar St., Enghelab Sq., Tehran (Iran, Islamic Republic of)]
Published: 2016
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14. Investigating the caffeine effects in the yeast Saccharomyces cerevisiae brings new insights into the connection between TOR, PKC and Ras/cAMP signalling pathways

Author: Véronique Anton Leberre, Klaudia Kuranda, Grazyna Palamarczyk, Jean Marie François, Serguei Sokol, Centre de recherche en myologie, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Université Pierre et Marie Curie - Paris 6 (UPMC), Department of Bioinformatics Institute of Biochemistry and Biophysics, Medical University of Warsaw - Poland, 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), Institute of Biochemistry and Biophysics, Polska Akademia Nauk (PAN), ITAV, Université Fédérale Toulouse Midi-Pyrénées, Université Pierre et Marie Curie - Paris 6 (UPMC)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Polska Akademia Nauk = Polish Academy of Sciences (PAN), Institut des Technologies Avancées en sciences du Vivant (ITAV), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)
Subjects: Saccharomyces cerevisiae Proteins, Transcription, Genetic, Hydrolases, [SDV]Life Sciences [q-bio], Mutant, Saccharomyces cerevisiae, Protein Serine-Threonine Kinases, Biology, Microbiology, Inhibitory Concentration 50, 03 medical and health sciences, Cell Wall, Caffeine, Cyclic AMP, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Phosphorylation, Molecular Biology, Transcription factor, Cell wall modification, Protein Kinase C, Protein kinase C, ComputingMilieux_MISCELLANEOUS, Oligonucleotide Array Sequence Analysis, 030304 developmental biology, Sirolimus, 0303 health sciences, 030306 microbiology, Kinase, Benzenesulfonates, Biological Transport, Congo Red, Enzyme Activation, Biochemistry, ras Proteins, cAMP-dependent pathway, Mitogen-Activated Protein Kinases, Intracellular, Signal Transduction
Abstract: Caffeine is a natural purine analogue that elicits pleiotropic effects leading ultimately to cell's death by a largely uncharacterized mechanism. Previous works have shown that this drug induces a rapid phosphorylation of the Mpk1p, the final mitogen-activated protein (MAP) kinase of the Pkc1p-mediated cell integrity pathway. In this work, we showed that this phosphorylation did not necessitate the main cell wall sensors Wsc1p and Mid2p, but was abolished upon deletion of ROM2 encoding a GDP/GTP exchange factor of Rho1p. We also showed that the caffeine-induced phosphorylation of Mpk1p was accompanied by a negligible activation of its main downstream target, the Rlm1p transcription factor. This result was consolidated by the finding that the loss of RLM1 had no consequence on the increased resistance of caffeine-treated cells to zymolyase, indicating that the cell wall modification caused by this drug is largely independent of transcriptional activation of Rlm1p-regulated genes. Additionally, the transcriptional programme elicited by caffeine resembled that of rapamycin, a potent inhibitor of the TOR1/2 kinases. Consistent with this analysis, we found that the caffeine-induced phosphorylation of Mpk1p was lost in a tor1Delta mutant. Moreover, a tor1Delta mutant was, like mutants defective in components of the Pkc1p-Mpk1p cascade, highly sensitive to caffeine. However, the hypersensitivity of a tor1 null mutant to this drug was rescued neither by sorbitol nor by adenine, which was found to outcompete caffeine effects specially on mutants in the PKC pathway. Altogether, these data indicated that Tor1 kinase is a target of caffeine, whose inhibition incidentally activates the Pkc1p-Mpk1p cascade, and that the caffeine-dependent phenotypes are largely dependent on inhibition of Tor1p-regulated cellular functions. Finally, we found that caffeine provoked, in a Rom2p-dependent manner, a transient drop in intracellular levels of cAMP, that was followed by change in expression of genes implicated in Ras/cAMP pathway. This result may pose Rom2p as a mediator in the interplay between Tor1p and the Ras/cAMP pathway.
Published: 2006
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15. Nuclear translocation of silver ions and hepatocyte nuclear receptor impairment upon exposure to silver nanoparticles

Author: Mireille Chevallet, Christine Moriscot, Isabelle Michaud-Soret, Benoit Gallet, Giulia Veronesi, Peggy Charbonnier, Wojciech Bal, Cécile Cottet-Rousselle, Aurélien Deniaud, Rémi Tucoulou, Vanessa Tardillo Suárez, Elizaveta Karepina, Alexandra Fuchs, Pierre-Henri Jouneau, European Synchrotron Radiation Facility (ESRF), Biologie des Métaux (BioMet ), 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), Groupe Microscopie Electronique et Méthodes (IBS-MEM), Institut de biologie structurale (IBS - UMR 5075), 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)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), 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), Integrated Structural Biology Grenoble (ISBG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institute of Biochemistry and Biophysics, Polish Academy of Sciences, INSERM, U1160, Département de Gastroentérologie, Université Paris Diderot - Paris 7 (UPD7), Groupe modélisation et chimie théorique (MCT ), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), and Integrated Structural Biology Grenoble (ISBG - UMS 3518 )
Subjects: [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, 0303 health sciences, Chemistry, Nucleolus, Materials Science (miscellaneous), 02 engineering and technology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 021001 nanoscience & nanotechnology, Silver nanoparticle, Nuclear translocation, 03 medical and health sciences, Subcellular distribution, Human health, medicine.anatomical_structure, Nuclear receptor, Hepatocyte, [SDE]Environmental Sciences, medicine, Biophysics, 0210 nano-technology, Intracellular, 030304 developmental biology, General Environmental Science
Abstract: International audience; The impact on human health of long-term exposure to low doses of silver nanoparticles (AgNPs) remainsunderstudied. Cellular studies have shown the intracellular dissolution of AgNPs within endolysosomesfollowed by Ag(I) binding to biomolecular thiolate-containing molecules. However, the precise subcellulardistribution of Ag(I) and the nature of the disrupted physiological pathways remained unknown. Novelimaging approaches enabled us to visualize the trafficking of AgNP-containing lysosomes towards aperinuclear location and a nuclear transfer of Ag(I) species with accumulation in the nucleoli. These Ag(I)species impaired nuclear receptor activity, disrupting critical mechanisms of liver physiology in low doseexposure scenarios, thus justifying further research into defining a framework for the safe use of AgNPs.
Published: 2020
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16. Differentiating between viruses and virus species by writing their names correctly

Author: Zerbini, Francisco Murilo, Siddell, Stuart G, Mushegian, Arcady R, Walker, Peter J, Lefkowitz, Elliot J, Adriaenssens, Evelien M, Alfenas-Zerbini, Poliane, Dutilh, Bas E, García, María Laura, Junglen, Sandra, Krupovic, Mart, Kuhn, Jens H, Lambert, Amy J, Łobocka, Małgorzata, Oksanen, Hanna M, Robertson, David L, Rubino, Luisa, Sabanadzovic, Sead, Simmonds, Peter, Suzuki, Nobuhiro, Van Doorslaer, Koenraad, Vandamme, Anne-Mieke, Varsani, Arvind, Theoretical Biology and Bioinformatics, Sub Bioinformatics, Universidade Federal de Viçosa = Federal University of Viçosa (UFV), University of Bristol [Bristol], National Science Foundation [Arlington] (NSF), University of Queensland [Brisbane], University of Alabama at Birmingham [ Birmingham] (UAB), Quadram Institute Bioscience [Norwich, U.K.] (QIB), Biotechnology and Biological Sciences Research Council (BBSRC), Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Utrecht University [Utrecht], Instituto de Biotecnología y Biología Molecular [La Plata] (IBBM), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Facultad de Ciencias Exactas [La Plata], Universidad Nacional de la Plata [Argentine] (UNLP)-Universidad Nacional de la Plata [Argentine] (UNLP), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Virologie des archées - Archaeal Virology, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Integrated Research Facility at Fort Detrick (IRF-Frederick), National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Centers for Disease Control and Prevention [Fort Collins, Colorado, USA], Institute of Biochemistry and Biophysics, Polska Akademia Nauk = Polish Academy of Sciences (PAN), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, MRC - University of Glasgow Centre for Virus Research, CNR Istituto per la Protezione Sostenibile delle Piante [Torino, Italia] (IPSP), National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), Mississippi State University [Mississippi], University of Oxford, Okayama University, BIO5 Institute, University of Arizona, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Arizona State University [Tempe] (ASU), Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number U24AI162625 to E.J.L. This work was supported in part through Laulima Government Solutions, LLC prime contract with the US National Institute of Allergy and Infectious Diseases (NIAID) under Contract No. HHSN272201800013C. J.H.K. performed this work as an employee of Tunnell Government Services (TGS), a subcontractor of Laulima Government Solutions, LLC under Contract No. HHSN272201800013C. B.E.D. is supported by the European Research Council (ERC) Consolidator Grant 865694: DiversiPHI, and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy—EXC 2051—Project-ID 390713860. E.M.A. gratefully acknowledges the support of the Biotechnology and Biological Sciences Research Council (BBSRC), this research was funded by the BBSRC Institute Strategic Program Gut Microbes and Health BB/R012490/1 and its constituent projects BBS/E/F/000PR10353 and BBS/E/F/000PR10356. H.M.O. was supported by University of Helsinki funding for FINStruct and Instruct-ERIC research infrastructure. S.S. acknowledges partial support from the Special Research Initiative (MAFES), Mississippi State University, and from the National Institute of Food and Agriculture, US Department of Agriculture, Hatch Project 1021494. A.R.M. is a Program Director at the U.S. National Science Foundation (NSF), the statements and opinions expressed herein are made in a personal capacity and do not constitute endorsement by NSF or the government of the United States. D.L.R. is supported by the U.K. Medical Research Council (MC_UU_1201412). F.M.Z. is supported by grants from Capes (Finance code 01), CNPq and Fapemig. P.A.Z. is supported by Suzano Papel e Celulose, Capes (Finance code 01), Conselho Nacional de Desenvolvimento Científico e Tecnológico and Fundação de Amparo à Pesquisa do Estado de Minas Gerais., European Project: 865694,H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC),DiversiPHI(2020), Theoretical Biology and Bioinformatics, Sub Bioinformatics, Molecular and Integrative Biosciences Research Programme, and Molecular Principles of Viruses
Subjects: 11832 Microbiology and virology, Writing, viruses, virus species, education, DNA Viruses, Coronacrisis-Taverne, virus nomenclature, General Medicine, Article, taxonomy, ICTV, classification, Virology, Viruses, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Viruses, Unclassified, Unclassified, Viruses/genetics, health care economics and organizations
Abstract: Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly. Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly. Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.
Published: 2022
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17. Thermodynamic parameters for binding of some halogenated inhibitors of human protein kinase CK2

Author: Shugar, David [Institute of Biochemistry and Biophysics PAS, Warszawa (Poland)]
Published: 2015
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18. Static Curvature and Flexibility Measurements of DNA with Microscopy. A Simple Renormalization Method, its Assessment by Experiment and Simulation

Author: Eric Le Cam, Christophe Pakleza, Jean A.H. Cognet, Dmitry I. Cherny, Etienne Delain, Le Cam, Eric, Laboratoire Jean Perrin (LJP), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-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), Institute of Biochemistry and Biophysics, Institute of Biochemistry and Biophysics [Warsaw] (IBB), Institut Gustave Roussy (IGR), and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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)
Subjects: Models, Molecular, Computation, [SDV]Life Sciences [q-bio], 030303 biophysics, Analytical chemistry, Electron, Curvature, Molecular physics, Standard deviation, Rod, Renormalization, 03 medical and health sciences, Structural Biology, Microscopy, Image Processing, Computer-Assisted, Base Pairing, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Persistence length, Physics, 0303 health sciences, DNA, [SDV] Life Sciences [q-bio], Microscopy, Electron, Oligodeoxyribonucleotides, Nucleic Acid Conformation
Abstract: We present the derivation of equations based on statistical polymer chain analysis and a method to quantify the average angle value of intrinsic bends and the local flexibility at a given locus on DNA fragments imaged by electron microscopy. DNA fragments of n base-pairs are considered as stiff chains of n jointed unit rigid rods. If the DNA fragments are composed of two branches A0Am and A0Bn, with, respectively, m and n base-pairs, where the standard deviations of the angle formed by two consecutive base-pairs are uniform over each branch, respectively, σθA and σθB, we show that the standard deviation of the angle AmA0Bn is: {\sigma^2_{{\rm A}_m{\rm A}_0{\rm B}_n}={(m-1)(2m-1)\over 6m}\sigma^2_{\theta_{\rm A}}+{(n-1)(2n-1)\over 6n}\sigma^2_{\theta_{\rm B}}+\sigma^2_{\theta_0}}where σθ0 is the standard deviation of the angle at locus A0. This equation is established for small angular deviations by analysis of DNA at different scales and the validity of the methodology is controlled with the computation of the reduced χ2 statistical test. The length of the DNA fragments must be of the order of, or below, the persistence length, as determined by sets of statistics from computer simulations of DNA fragments. This is verified experimentally by a detailed analysis of the digitized contours of homogeneous linear 139 base-pair DNA fragments observed by electron microscopy. The images are compared to the reconstruction of DNA fragments from the measurements. The value found, σ0=4.6 °/bp, is consistent with the well-accepted value for DNA in a plane. We discuss the relationship between the standard deviation of the measured angles and the flexibility at the base-pair level. This method is useful to quantify directly from microscopy techniques, such as electron or scanning force microscopy, the true bending angle, either intrinsic or induced by a ligand, and its associated flexibility at a given locus in any small DNA fragment.
Published: 1999
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19. Bacterial Viruses Subcommittee and Archaeal Viruses Subcommittee of the ICTV: Update of taxonomy changes in 2021

Author: Krupovic, Mart, Turner, Dann, Morozova, Vera, Dyall-Smith, Mike, Oksanen, Hanna M., Edwards, Rob, Dutilh, Bas E., Lehman, Susan M., Reyes, Alejandro, Baquero, Diana P., Sullivan, Matthew B., Uchiyama, Jumpei, Nakavuma, Jesca, Barylski, Jakub, Young, Mark J., Du, Shishen, Alfenas-Zerbini, Poliane, Kushkina, Alla, Kropinski, Andrew M., Kurtboke, Ipek, Brister, J. Rodney, Lood, Cedric, Sarkar, B. L., Yigang, Tong, Liu, Ying, Huang, Li, Wittmann, Johannes, Chanishvili, Nina, van Zyl, Leonardo J., Rumnieks, Janis, Mochizuki, Tomohiro, Jalasvuori, Matti, Aziz, Ramy K., Lobocka, Malgorzata, Stedman, Kenneth M., Shkoporov, Andrey N., Gillis, Annika, Peng, Xu, Enault, Francois, Knezevic, Petar, Lavigne, Rob, Rhee, Sung-Keun, Cvirkaite-Krupovic, Virginija, Moraru, Cristina, Moreno Switt, Andrea I., Poranen, Minna M., Millard, Andrew, Prangishvili, David, Adriaenssens, Evelien M., Sub Bioinformatics, Theoretical Biology and Bioinformatics, UCL - SST/ELI/ELIM - Applied Microbiology, Sub Bioinformatics, Theoretical Biology and Bioinformatics, Virologie des archées - Archaeal Virology, Institut Pasteur [Paris], University of the West of England [Bristol] (UWE Bristol), Institute of Chemical Biology and Fundamental Medicine [Novosibirsk, Russia] (ICBFM SB RAS), Siberian Branch of the Russian Academy of Sciences (SB RAS), University of Melbourne, University of Helsinki, Flinders Accelerator for Microbiome Exploration [Adelaide, Australia], Utrecht University [Utrecht], U.S. Food and Drug Administration (FDA), Universidad de los Andes [Bogota] (UNIANDES), Ohio State University [Columbus] (OSU), Azabu University, Makerere University [Kampala, Ouganda] (MAK), Adam Mickiewicz University in Poznań (UAM), Montana State University (MSU), Wuhan University [China], Universidade Federal de Vicosa (UFV), National Academy of Sciences of Ukraine (NASU), University of Guelph, University of the Sunshine Coast (USC), National Institutes of Health [Bethesda] (NIH), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Indian Council of Medical Research [New Dehli] (ICMR), Beijing University of Chemical Technology, Chinese Academy of Sciences [Beijing] (CAS), Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH / Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures (DSMZ), George Eliava Institute of Bacteriophages, Microbiology and Virology [Tbilisi, Georgia], University of the Western Cape, Latvian Biomedical Research and Study Centre [Rīga], Tokyo Institute of Technology [Tokyo] (TITECH), University of Jyväskylä (JYU), Cairo University, Polish Academy of Sciences (PAN), Portland State University [Portland] (PSU), University College Cork (UCC), Université Catholique de Louvain = Catholic University of Louvain (UCL), University of Copenhagen = Københavns Universitet (KU), Laboratoire Microorganismes : Génome et Environnement (LMGE), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), University of Novi Sad, Chungbuk National University, University of Oldenburg, Pontificia Universidad Católica de Chile (UC), University of Leicester, Ivane Javakhishvili Tbilisi State University (TSU), Quadram Institute, V.M. was supported by Russian Ministry of Education and Science Project No. 0245-2021-0008, H.M.O. was supported by University of Helsinki funding for FINStruct and Instruct-ERIC research infrastructure, R.A.E. was supported by the National Institute Of Diabetes And Digestive And Kidney Diseases of the National Institutes of Health under Award Number RC2DK116713, B.E.D. was supported by the European Research Council (ERC) Consolidator grant 865694: DiversiPHI, M.B.S. was supported by National Science Foundation Advances in Biological Infrastructure award #1758974, M.Y. acknowledges funding by the Gordon and Betty Moore Foundation grant GBMF9195, S.D. was supported by National Natural Science Foundation of of China grant 32070032, C.L. is supported by the Fonds Wetenschappelijk Onderzoek (1S64718N), L.H. was funded by the Strategic Priority Research Program of the Chinese Academy of Sciences Award XDB42000000,National Natural Science Foundation of China (NSFC) grant 31970170, T.M. was supported by JSPS KAKENHI Grant Numbers 21H02100, 19H04827, 18K14372, and JST JPMJJR2005, and SUMITOMO Fund 200673, MJ is supported by Academy of Finland grants #336518 and #297049 and Jane and Aatos Erkko Foundation, R.K.A. is supported by the Egyptian Academy of Scientific Research and Technology (ASRT) project #3046 (JESOR), M.L. is supported by the statutory funds for the Institute of Biochemistry and Biophysics of the Polish Academy of Sciences, K.M.S. is supported by the US. National Science Foundation (MCB1929273 and MCB2025305), A.N.S. is supported by Wellcome Trust Research Career Development Fellowship (220646/Z/20/Z) and by European Research Council (ERC) grant under the European Union’s Horizon 2020 research and innovation programme (grant agreement 101001684), X.P. is supported by Novo Nordisk Foundation/Hallas-Møller Ascending Investigator Grant (grant number NNF17OC0031154) and the Danish Council for Independent Research/FNU (grant number DFF–0135-00402), S.K.R. was supported by the National Research Foundation of Korea (NRF) grants funded by the Ministry of Science, ICT & Future Planning (2021R1A2C3004015), C.M. acknowledges funding by the Deutsche Forschungsgemeinschaft within the Collaborative Research Center TRR51 Roseobacter (INST 184/170-1), M.M.P. acknowledges funding from the Academy of Finland (grant 331627) and the Sigrid Juselius Foundation, E.M.A. gratefully acknowledges funding by the Biotechnology and Biological Sciences Research Council (BBSRC), this research was funded by the BBSRC Institute Strategic Programme Gut Microbes and Health BB/R012490/1 and its constituent projects BBS/E/F/000PR10353 and BBS/E/F/000PR10356., European Project: 865694,H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC),DiversiPHI(2020), European Project: 101001684,ERC-2020-COG,PHAGENET(2021), Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Universidade Federal de Viçosa = Federal University of Viçosa (UFV), University of the Western Cape (UWC), University of Copenhagen = Københavns Universitet (UCPH), Biotechnology and Biological Sciences Research Council (BBSRC), Molecular and Integrative Biosciences Research Programme, and Molecular and Translational Virology
Subjects: Archaeal Viruses, Societies, Scientific, virukset, Library science, Biology, bakteriofagit, Executive committee, 03 medical and health sciences, Virology Division News, Virology, viruses, Bacteriophages, 030304 developmental biology, Taxonomy, 11832 Microbiology and virology, 0303 health sciences, Science & Technology, Bacteria, 030306 microbiology, systematiikka (biologia), General Medicine, Archaea, virologia, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Taxonomy (biology), Bacterial virus, Life Sciences & Biomedicine
Abstract: In this article, we – the Bacterial Viruses Subcommittee and the Archaeal Viruses Subcommittee of the International Committee on Taxonomy of Viruses (ICTV) – summarise the results of our activities for the period March 2020 – March 2021. We report the division of the former Bacterial and Archaeal Viruses Subcommittee in two separate Subcommittees, welcome new members, a new Subcommittee Chair and Vice Chair, and give an overview of the new taxa that were proposed in 2020, approved by the Executive Committee and ratified by vote in 2021. In particular, a new realm, three orders, 15 families, 31 subfamilies, 734 genera and 1845 species were newly created or redefined (moved/promoted). Supplementary Information The online version contains supplementary material available at 10.1007/s00705-021-05205-9.
Published: 2021
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20. Effects of activated fibroblasts on phenotype modulation, EGFR signalling and cell cycle regulation in OSCC cells

Author: Liebmann, Claus [Institute of Biochemistry and Biophysics, Friedrich Schiller University Jena, 07740 Jena (Germany)]
Published: 2014
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21. The Aggregation Pattern of Aβ 1–40 is Altered by the Presence of N ‐Truncated Aβ 4–40 and/or Cu II in a Similar Way through Ionic Interactions

Author: Stefaniak, Ewelina, Atrián-Blasco, Elena, Goch, Wojciech, Sabater, Laurent, Hureau, Christelle, Bal, Wojciech, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 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), Medical University of Warsaw - Poland, European Regional Development Fund and Innovative Economy, National Cohesion Strategy of Poland, National Science Centre of Poland (grants: Preludium, no. 2016/21/N/NZ1/02785 - Opus, no. 2016/23/B/ST5/02253), European Project: 638712,H2020,ERC-2014-STG,aLzINK(2015), 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), and Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Aggregation, Amyloid beta-peptides, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Peptides, Copper, Fluorescence
Abstract: International audience; Alzheimer's disease (AD) is one of the most common of the multifactorial diseases and is characterized by a range of abnormal molecular processes, such as the accumulation of extracellular plaques containing the amyloid‐β (Aβ) peptides and dyshomeostasis of copper in the brain. In this study, we have investigated the effect of CuII on the aggregation of Aβ1–40 and Aβ4–40, representing the two most prevalent families of Aβ peptides, that is, the full length and N‐truncated peptides. Both families are similarly abundant in healthy and AD brains. For either of the studied peptides, substoichiometric CuII concentrations accelerated aggregation, whereas superstoichiometric CuII inhibited fibril formation, likely by stabilizing the oligomers. The addition of either Aβ4–40 or substoichiometric CuII affected the aggregation profile of Aβ1–40, by yielding shorter and thicker fibrils; amorphous aggregates were formed in the presence of a molar excess of CuII. The similarity of these two effects can be attributed to the increase in the positive charge on the Aβ N terminus, caused both by CuII complexation and N truncation at position 4. Our findings provide a better understanding of the biological Aβ aggregation process as these two Aβ species and CuII coexist and interact under physiological conditions.
Published: 2021
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22. Unusual spiral structures formed by glycated β-casein in the presence of thioflavin T: amyloid transformation?

Author: Aleksandra K. Melnikova, Ali Akbar Moosavi-Movahedi, Ivan A. Zanyatkin, Ali Akbar Saboury, Yulia Yu. Stroylova, Vladimir I. Muronetz, Thomas Haertlé, Moscow MV Lomonosov State Univ, Fac Chem, Moscow 119991, Russia, Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University (MSU), Faculty of Bioengineering and Bioinformatics, Moscow State University, Institute of Biochemistry and Biophysics, Pawinskiego 5a, Univ Tehran, Inst Biochem & Biophys, POB 13145-1384, Tehran, Iran, Partenaires INRAE, Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Russian Science Foundation (RSF) : 16-14-10027.
Subjects: 0303 health sciences, Amyloid, thioflavin T, Sodium cyanoborohydride, aggregation, General Chemistry, beta-casein, amyloid structure, protein glycation, 03 medical and health sciences, chemistry.chemical_compound, Transformation (genetics), 0302 clinical medicine, advanced glycation end-products, chemistry, β casein, Glycation, Biophysics, [CHIM]Chemical Sciences, Thioflavin, Glycated protein, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: International audience; Unusual spiral-like structures in aggregates formed by beta-casein glycated in a special way in the presence of thioflavin T are reported. Different glycation agents, temperature, pH, incubation time, and concentrations of protein and modifier were characterized, but only glycated by 200 mM glucose for 48 h at 37 degrees C without sodium cyanoborohydride beta-casein forms spiral structures in the presence of thioflavin T. Thioflavin T affects the size of particles formed by glycated beta-casein and also stimulates heat-induced aggregation, indicating that the formation of unusual spiral structures is determined both by the structure of the advanced glycation end products and by the properties of the glycated protein.
Published: 2021
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23. GAG-DB, the New Interface of the Three-Dimensional Landscape of Glycosaminoglycans

Author: Frédérique Lisacek, Serge Pérez, François Bonnardel, Anne Imberty, Sylvie Ricard Blum, Olga Makshakova, Centre de Recherches sur les Macromolécules Végétales (CERMAV), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Swiss Institute of Bioinformatics [Genève] (SIB), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), and Kazan Institute of Biochemistry and Biophysics
Subjects: Glycan, Keratan sulfate, lcsh:QR1-502, Molecular Conformation, Protein Data Bank (RCSB PDB), polysaccharide conformation, Computational biology, Biochemistry, lcsh:Microbiology, Article, Dermatan sulfate, User-Computer Interface, 03 medical and health sciences, chemistry.chemical_compound, Imaging, Three-Dimensional, [CHIM]Chemical Sciences, Chondroitin sulfate, Molecular Biology, database, 030304 developmental biology, 0303 health sciences, biology, Chemistry, 030302 biochemistry & molecular biology, Heparan sulfate, computer.file_format, Protein Data Bank, three-dimensional structure, Solutions, Databases as Topic, glycosaminoglycans, protein-carbohydrate interactions, biology.protein, computer, Protein ligand
Abstract: International audience; Glycosaminoglycans (GAGs) are complex linear polysaccharides. GAG-DB is a curated database that classifies the three-dimensional features of the six mammalian GAGs (chondroitin sulfate, dermatan sulfate, heparin, heparan sulfate, hyaluronan, and keratan sulfate) and their oligosaccharides complexed with proteins. The entries are structures of GAG and GAG-protein complexes determined by X-ray single-crystal diffraction methods, X-ray fiber diffractometry, solution NMR spectroscopy, and scattering data often associated with molecular modeling. We designed the database architecture and the navigation tools to query the database with the Protein Data Bank (PDB), UniProtKB, and GlyTouCan (universal glycan repository) identifiers. Special attention was devoted to the description of the bound glycan ligands using simple graphical representation and numerical format for cross-referencing to other databases in glycoscience and functional data. GAG-DB provides detailed information on GAGs, their bound protein ligands, and features their interactions using several open access applications. Binding covers interactions between monosaccharides and protein monosaccharide units and the evaluation of quaternary structure. GAG-DB is freely available.
Published: 2020
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24. Environmental science

Author: Tardillo Suarez, Vanessa, Karepina, Elizaveta, Chevallet, Mireille, Gallet, Benoit, Cottet-Rousselle, Cécile, Charbonnier, Peggy, Moriscot, Christine, Michaud-Soret, Isabelle, Bal, Wojciech, Fuchs, Alexandra, Tucoulou, Remi, Jouneau, Pierre-Henri, Veronesi, Giulia, Deniaud, Aurélien, European Synchrotron Radiation Facility (ESRF), Biologie des Métaux (BioMet ), 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), Groupe Microscopie Electronique et Méthodes (IBS-MEM), Institut de biologie structurale (IBS - UMR 5075), 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)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), 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), Integrated Structural Biology Grenoble (ISBG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institute of Biochemistry and Biophysics, Polish Academy of Sciences, INSERM, U1160, Département de Gastroentérologie, Université Paris Diderot - Paris 7 (UPD7), Groupe modélisation et chimie théorique (MCT ), GON, Nathalie, and Integrated Structural Biology Grenoble (ISBG - UMS 3518 )
Subjects: [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, [SDE] Environmental Sciences, [SDE]Environmental Sciences, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology
Abstract: International audience; The impact on human health of long-term exposure to low doses of silver nanoparticles (AgNPs) remainsunderstudied. Cellular studies have shown the intracellular dissolution of AgNPs within endolysosomesfollowed by Ag(I) binding to biomolecular thiolate-containing molecules. However, the precise subcellulardistribution of Ag(I) and the nature of the disrupted physiological pathways remained unknown. Novelimaging approaches enabled us to visualize the trafficking of AgNP-containing lysosomes towards aperinuclear location and a nuclear transfer of Ag(I) species with accumulation in the nucleoli. These Ag(I)species impaired nuclear receptor activity, disrupting critical mechanisms of liver physiology in low doseexposure scenarios, thus justifying further research into defining a framework for the safe use of AgNPs.
Published: 2020
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25. Clarity analysis of the Cl/pH sensor expression in the brain of transgenic mice

Author: Diuba, V, Artem, Samigullin, Dmitry, Kaszas, Attila, Zonfrillo, Francesca, Malkov, Anton, Petukhova, Elena, Casini, Antonio, Arosio, Daniele, Esclapez, Monique, Gross, Cornelius T., Bregestovski, Piotr, Otten, Lisa, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University (MSU), Kazan Institute of Biochemistry and Biophysics, Kazan National Research Technical University (KNRTU-KAI), Kazan Federal University (KFU), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), European Molecular Biology Laboratory [Rome] (EMBL), Institute Of Theoretical And Experimental Biophysics, Kazan State Medical University (KSMU), Centre for Integrative Biology (CIBIO), University of Trento (CIBIO), University of Trento [Trento], and National Research Council of Italy [Trento]
Subjects: 0301 basic medicine, Genetically modified mouse, Transgene, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Green Fluorescent Proteins, PROTEIN, Mice, Transgenic, COLOCALIZATION, MOUSE, Cell morphology, Green fluorescent protein, Protein–protein interaction, 03 medical and health sciences, Mice, 0302 clinical medicine, fluorescence imaging, Organelle, TOOL, Animals, genetically encoded biosensors, RECEPTOR, Chemistry, General Neuroscience, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Colocalization, Brain, Hydrogen-Ion Concentration, Axons, Cell biology, 030104 developmental biology, Microscopy, Fluorescence, TISSUE, transparent brain, intracellular ions monitoring, CHLORIDE INDICATOR, 030217 neurology & neurosurgery, Intracellular
Abstract: Genetically encoded biosensors are widely used in cell biology for the non-invasive imaging of concentrations of ions or the activity of enzymes, to evaluate the distribution of small molecules, proteins and organelles, and to image protein interactions in living cells. These fluorescent molecules can be used either by transient expression in cultured cells or in entire organisms or through stable expression by producing transgenic animals characterized by genetically encoded and heritable biosensors. Using the mouse Thy1 mini-promoter, we generated a line of transgenic mice expressing a genetically encoded sensor for the simultaneous measurements of intracellular Cl- and pH. This construct, called ClopHensor, consists of a H+- and Cl--sensitive variant of the enhanced green fluorescent protein (E(2)GFP) fused with a red fluorescent protein (DsRedm). Stimulation of hippocampal Schaffer collaterals proved that the sensor is functionally active. To reveal the expression pattern of ClopHensor across the brain of Thy1 ::ClopHensor mice, we obtained transparent brain samples using the CLARITY method and imaged them with confocal and light-sheet microscopy. We then developed a semi-quantitative approach to identify brain structures with high intrinsic sensor fluorescence. This approach allowed us to assess cell mor- phology and track axonal projection, as well as to confirm E(2)GFP and DsRedm fluorescence colocalization. This analysis also provides a map of the brain areas suitable for non-invasive monitoring of intracellular Cl-/pH in normal and pathological conditions. This article is part of a Special Issue entitled: Honoring Ricardo Miledi- outstanding neuroscientist of XX-XXI centuries. (c) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.
Published: 2020
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26. Evidence and quantitative evaluation of tensile maturation strain in flax phloem through longitudinal splitting

Author: Liudmila Kozlova, Joseph Gril, Tatyana Gorshkova, Tancrède Alméras, Anna A. Petrova, Bois (BOIS), Laboratoire de Mécanique et Génie Civil (LMGC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Kazan Institute of Biochemistry and Biophysics, RAS, Laboratoire de Physique et Physiologie Intégratives de l’Arbre en environnement Fluctuant - Clermont Auvergne (PIAF), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Institut Pascal - Clermont Auvergne (IP), Sigma CLERMONT (Sigma CLERMONT)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique et Physiologie Intégratives de l’Arbre en environnement Fluctuant (PIAF), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
Subjects: 0106 biological sciences, 0301 basic medicine, roots, flax, bast fibers, gelatinous fibers, tension, stem splitting, maturation strain, stress generation, cellulose microfibrils, mechanical-properties, aerial, fibers, wood, seedlings, behavior, trees, Linum, Plant Science, 01 natural sciences, lin, 03 medical and health sciences, tige, Botany, Ultimate tensile strength, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, stem, Ecology, Evolution, Behavior and Systematics, Longitudinal splitting, Vegetal Biology, Ecology, Strain (chemistry), biology, Tension (physics), maturation, fungi, food and beverages, biology.organism_classification, 030104 developmental biology, Mechanical stability, Bast fibre, Phloem, Biologie végétale, 010606 plant biology & botany
Abstract: International audience; The stems of flax (Linum usitatissimum L. cv. 'Mogilevsky') contain many gelatinous fibers in their phloem. These fibers are important for the mechanical stability of the plant as well as for industrial applications. Gelatinous fibers are known to have a motor function in the xylem of trees and in many plant organs. This function arises from the so-called maturation strain, i.e., the tendency of the gelatinous layer to shrink during fiber maturation, resulting in a state of residual tensile stress. However, the occurrence of tensile maturation strain in flax phloem fibers remains to be demonstrated, and its magnitude has never been evaluated. Here we present a novel method to highlight and quantify this strain. The method consists in splitting a stem segment longitudinally, and measuring the curvature of the half segments through their opening distance. By using a mechanical model, the maturation strain can be calculated from the curvature, the dimensions of the component tissues, and their elastic properties. The model is validated by the agreement between model predictions and observations. The splitting experiment provides qualitative evidence that flax phloem develops tensile stress during maturation, just as xylem gelatinous fibers do. Calculations enable quantitative estimation of the maturation strain. The magnitude of this strain for the material studied is, on average, -1.5%.
Published: 2020
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27. Distinct MAPK signaling pathways, p21 up-regulation and caspase-mediated p21 cleavage establishes the fate of U937 cells exposed to 3-hydrogenkwadaphnin: Differentiation versus apoptosis

Author: Yazdanparast, Razieh [Institute of Biochemistry and Biophysics, P. O. Box 13145-1384 University of Tehran, Tehran (Iran, Islamic Republic of)]
Published: 2008
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28. Multiple functions of the vacuolar sorting protein Ccz1p in Saccharomyces cerevisiae

Author: Kucharczyk, Roza [Institute of Biochemistry and Biophysics PAS, Pawinskiego 5A, 02-106 Warsaw (Poland)]
Published: 2005
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29. Quantitative Conformational Analysis of Functionally Important Electrostatic Interactions in the Intrinsically Disordered Region of Delta Subunit of Bacterial RNA Polymerase

Author: Milan Zachrdla, Aleksandra Gruca, Petr Padrta, Malene Ringkjøbing Jensen, Vojtěch Kubáň, Libor Krásný, Hana Šanderová, Martin Blackledge, Marcin Grynberg, Zuzana Jaseňáková, Patryk Jarnot, Tomáš Koval, Lukáš Žídek, Dragana Vítovská, Hana Stegnerova, Pavel Srb, Joanna Ziemska-Legiecka, Jan Dohnálek, Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB / CAS), Czech Academy of Sciences [Prague] (CAS), Laboratory of Microbial Genetics and Gene Expression, Institute of Microbiology of the Czech Academy of Sciences [Prague, Czech Republic] (MBU / CAS), Czech Academy of Sciences [Prague] (CAS)-Czech Academy of Sciences [Prague] (CAS), Laboratory of Structure and Function of Biomolecules, Institute of Biotechnology of the Czech Academy of Sciences (IBT / CAS), Institute of Biochemistry and Biophysics PAS, Silesian University of Technology, Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-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), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), Institute of Microbiology of the Czech Academy of Sciences (MBU / CAS), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Models, Molecular, Protein Conformation, Protein subunit, Static Electricity, 010402 general chemistry, Intrinsically disordered proteins, 01 natural sciences, Biochemistry, Catalysis, chemistry.chemical_compound, Colloid and Surface Chemistry, Protein structure, Transcription (biology), RNA polymerase, Static electricity, Amino Acid Sequence, Polymerase, chemistry.chemical_classification, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], DNA-Directed RNA Polymerases, General Chemistry, 0104 chemical sciences, Amino acid, Protein Subunits, chemistry, Biophysics, biology.protein, Bacillus subtilis
Abstract: International audience; Electrostatic interactions play important roles in the functional mechanisms exploited by intrinsically disordered proteins (IDPs). The atomic resolution description of long-range and local structural propensities that can both be crucial for the function of highly charged IDPs presents significant experimental challenges. Here, we investigate the conformational behavior of the δ subunit of RNA polymerase from Bacillus subtilis whose unfolded domain is highly charged, with 7 positively charged amino acids followed by 51 acidic amino acids. Using a specifically designed analytical strategy, we identify transient contacts between the two regions using a combination of NMR paramagnetic relaxation enhancements, residual dipolar couplings (RDCs), chemical shifts, and small-angle scattering. This strategy allows the resolution of long-range and local ensemble averaged structural contributions to the experimental RDCs, and reveals that the negatively charged segment folds back onto the positively charged strand, compacting the conformational sampling of the protein while remaining highly flexible in solution. Mutation of the positively charged region abrogates the long-range contact, leaving the disordered domain in an extended conformation, possibly due to local repulsion of like-charges along the chain. Remarkably, in vitro studies show that this mutation also has a significant effect on transcription activity, and results in diminished cell fitness of the mutated bacteria in vivo. This study highlights the importance of accurately describing electrostatic interactions for understanding the functional mechanisms of IDPs.
Published: 2019
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30. Mécanisme de stimulation de la liaison à l'ADN des facteurs de transcription par l'endonucléase apurinique/apyrimidinique humaine 1, APE1

Author: Eric Le Cam, Murat Saparbaev, Anton V. Endutkin, Milena Bazlekowa-Karaban, Paulina Prorok, Zhiger Akishev, Alexander V. Popov, Amangeldy K. Bissenbaev, Bakhyt T. Matkarimov, Sabira Taipakova, Regina Groisman, Sonia Baconnais, Barbara Tudek, Dmitry O. Zharkov, Dominika Zembrzuska, Alexander A. Ishchenko, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Maintenance des génomes, Microscopies Moléculaire et Bionanosciences, Centre National de la Recherche Scientifique-Université Paris Sud, Maintenance des génomes, Department of Molecular Biology and Genetics, Al-Farabi Kazakh National University, European Synchrotron Radiation Facility (ESRF), Laboratoire Epigenetique et Cancer, Centre National de la Recherche Scientifique (CNRS), Stabilité Génétique et Oncogenèse (UMR 8200), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), National Laboratory Astana, Nazarbayev University [Kazakhstan], Signalisation, noyaux et innovations en cancérologie (UMR8126), Novosibirsk State University (NSU), Institute of Biochemistry and Biophysics, and Polska Akademia Nauk = Polish Academy of Sciences (PAN)
Subjects: Models, Molecular, DNA damage, [SDV]Life Sciences [q-bio], oxidative damage, Biochemistry, base excision repair, AP endonuclease, redox regulation, 03 medical and health sciences, Endonuclease, chemistry.chemical_compound, 0302 clinical medicine, transcription factors, DNA-(Apurinic or Apyrimidinic Site) Lyase, Humans, oxidative stress, AP site, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, Protein Structure, Quaternary, Molecular Biology, Transcription factor, nucleotide incision repair, 030304 developmental biology, 0303 health sciences, biology, Cooperative binding, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, DNA, Cell Biology, Base excision repair, Dna damage, chemistry, 030220 oncology & carcinogenesis, Biocatalysis, biology.protein, Biophysics, Protein Multimerization, Protein Binding
Abstract: International audience; Aerobic respiration generates reactive oxygen species (ROS), which can damage nucleic acids, proteins and lipids. A number of transcription factors (TFs) contain redox-sensitive cysteine residues at their DNA-binding sites, hence ROS-induced thiol oxidation strongly inhibits their recognition of the cognate DNA sequences. Major human apurinic/apyrimidinic (AP) endonuclease 1 (APE1/APEX1/HAP-1), referred also as a redox factor 1 (Ref-1), stimulates the DNA binding activities of the oxidized TFs such as AP-1 and NF-κB. Also, APE1 participates in the base excision repair (BER) and nucleotide incision repair (NIR) pathways to remove oxidative DNA base damage. At present, the molecular mechanism underlying the TF-stimulating/redox function of APE1 and its biological role remains disputed. Here, we provide evidence that, instead of direct cysteine reduction in TFs by APE1, APE1-catalyzed NIR and TF-stimulating activities may be based on transient cooperative binding of APE1 to DNA and induction of conformational changes in the helix. The structure of DNA duplex strongly influences NIR and TF-stimulating activities. Homologous plant AP endonucleases lacking conserved cysteine residues stimulate DNA binding of the p50 subunit of NF-κB. APE1 acts synergistically with low-molecular-weight reducing agents on TFs. Finally, APE1 stimulates DNA binding of the redox-insensitive p50-C62S mutant protein. Electron microscopy imaging of APE1 complexes with DNA revealed preferential polymerization of APE1 on the gapped and intrinsically curved DNA duplexes. Molecular modeling offers a structural explanation how full-length APE1 can oligomerize on DNA. In conclusion, we propose that DNA-directed APE1 oligomerization can be regarded as a substitute for diffusion of APE1 along the DNA contour to probe for anisotropic flexibility. APE1 oligomers exacerbate pre-existing distortions in DNA and enable both NIR activity and DNA binding by TFs regardless of their oxidation state.; La respiration aérobie génère des espèces réactives de l'oxygène (ERO), qui peuvent endommager les acides nucléiques, les protéines et les lipides. Un certain nombre de facteurs de transcription (TF) contiennent des résidus de cystéine sensibles à l'oxydoréduction sur leurs sites de liaison à l'ADN, c'est pourquoi l'oxydation des thiols induite par les ROS inhibe fortement leur reconnaissance des séquences d'ADN apparentées. L'endonucléase 1 apurinique /apyrimidinique (AP) humaine majeure (APE1/APEX1/HAP-1), également appelée facteur redox 1 (Ref-1), stimule les activités de liaison à l'ADN des TF oxydés tels que AP-1 et NF-κB. De plus, l'APE1 participe aux voies de réparation par excision des bases (BER) et de réparation par incision des nucléotides (NIR) pour éliminer les dommages oxydatifs des bases de l'ADN. À l'heure actuelle, le mécanisme moléculaire qui sous-tend la fonction de stimulation des TF/redox de l'APE1 et son rôle biologique restent contestés. Ici, nous apportons la preuve qu'au lieu d'une réduction directe de la cystéine dans les TF par l'APE1, les activités NIR et de stimulation des TF catalysées par l'APE1 peuvent être basées sur une liaison coopérative transitoire de l'APE1 à l'ADN et l'induction de changements conformationnels dans l'hélice. La structure du duplex de l'ADN influence fortement les activités de stimulation de la RNI et de la TF. Les endonucléases AP des plantes homologues dépourvues de résidus de cystéine conservés stimulent la liaison de l'ADN de la sous-unité p50 de NF-κB. L'APE1 agit en synergie avec des agents réducteurs de faible poids moléculaire sur les TF. Enfin, APE1 stimule la liaison de l'ADN de la protéine mutante p50-C62S insensible à l'oxydoréduction. L'imagerie au microscope électronique des complexes APE1 avec l'ADN a révélé une polymérisation préférentielle de l'APE1 sur les duplex d'ADN à espacement et à courbure intrinsèque. La modélisation moléculaire offre une explication structurelle de la façon dont l'APE1 peut s'oligomériser sur l'ADN. En conclusion, nous proposons que l'oligomérisation de l'APE1 dirigée par l'ADN peut être considérée comme un substitut à la diffusion de l'APE1 le long du contour de l'ADN pour sonder la flexibilité anisotrope. Les oligomères de l'APE1 exacerbent les distorsions préexistantes de l'ADN et permettent à la fois une activité NIR et une liaison de l'ADN par les TF, quel que soit leur état d'oxydation. Traduit avec www.DeepL.com/Translator (version gratuite)
Published: 2019
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31. Mechanism of stimulation of DNA binding of the transcription factors by human apurinic/apyrimidinic endonuclease 1, APE1

Author: Bazlekowa-Karaban, Milena, Prorok, Paulina, Baconnais, Sonia, Taipakova, Sabira, Akishev, Zhiger, Zembrzuska, Dominika, Popov, Alexander, Endutkin, Anton, Groisman, Regina, Ishchenko, Alexander, Matkarimov, Bakhyt, Bissenbaev, Amangeldy, Le Cam, Eric, Zharkov, Dmitry, Tudek, Barbara, Saparbaev, Murat, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Maintenance des génomes, Microscopies Moléculaire et Bionanosciences, Centre National de la Recherche Scientifique-Université Paris Sud, Maintenance des génomes, Department of Molecular Biology and Genetics, Al-Farabi Kazakh National University, European Synchrotron Radiation Facility (ESRF), Laboratoire Epigenetique et Cancer, Centre National de la Recherche Scientifique (CNRS), Stabilité Génétique et Oncogenèse (UMR 8200), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), National Laboratory Astana, Nazarbayev University [Kazakhstan], Signalisation, noyaux et innovations en cancérologie (UMR8126), Novosibirsk State University (NSU), Institute of Biochemistry and Biophysics, and Polska Akademia Nauk = Polish Academy of Sciences (PAN)
Subjects: redox regulation, AP endonuclease, transcription factors, [SDV]Life Sciences [q-bio], oxidative stress, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, oxidative damage, Dna damage, base excision repair, nucleotide incision repair
Abstract: International audience; Aerobic respiration generates reactive oxygen species (ROS), which can damage nucleic acids, proteins and lipids. A number of transcription factors (TFs) contain redox-sensitive cysteine residues at their DNA-binding sites, hence ROS-induced thiol oxidation strongly inhibits their recognition of the cognate DNA sequences. Major human apurinic/apyrimidinic (AP) endonuclease 1 (APE1/APEX1/HAP-1), referred also as a redox factor 1 (Ref-1), stimulates the DNA binding activities of the oxidized TFs such as AP-1 and NF-κB. Also, APE1 participates in the base excision repair (BER) and nucleotide incision repair (NIR) pathways to remove oxidative DNA base damage. At present, the molecular mechanism underlying the TF-stimulating/redox function of APE1 and its biological role remains disputed. Here, we provide evidence that, instead of direct cysteine reduction in TFs by APE1, APE1-catalyzed NIR and TF-stimulating activities may be based on transient cooperative binding of APE1 to DNA and induction of conformational changes in the helix. The structure of DNA duplex strongly influences NIR and TF-stimulating activities. Homologous plant AP endonucleases lacking conserved cysteine residues stimulate DNA binding of the p50 subunit of NF-κB. APE1 acts synergistically with low-molecular-weight reducing agents on TFs. Finally, APE1 stimulates DNA binding of the redox-insensitive p50-C62S mutant protein. Electron microscopy imaging of APE1 complexes with DNA revealed preferential polymerization of APE1 on the gapped and intrinsically curved DNA duplexes. Molecular modeling offers a structural explanation how full-length APE1 can oligomerize on DNA. In conclusion, we propose that DNA-directed APE1 oligomerization can be regarded as a substitute for diffusion of APE1 along the DNA contour to probe for anisotropic flexibility. APE1 oligomers exacerbate pre-existing distortions in DNA and enable both NIR activity and DNA binding by TFs regardless of their oxidation state.; La respiration aérobie génère des espèces réactives de l'oxygène (ERO), qui peuvent endommager les acides nucléiques, les protéines et les lipides. Un certain nombre de facteurs de transcription (TF) contiennent des résidus de cystéine sensibles à l'oxydoréduction sur leurs sites de liaison à l'ADN, c'est pourquoi l'oxydation des thiols induite par les ROS inhibe fortement leur reconnaissance des séquences d'ADN apparentées. L'endonucléase 1 apurinique /apyrimidinique (AP) humaine majeure (APE1/APEX1/HAP-1), également appelée facteur redox 1 (Ref-1), stimule les activités de liaison à l'ADN des TF oxydés tels que AP-1 et NF-κB. De plus, l'APE1 participe aux voies de réparation par excision des bases (BER) et de réparation par incision des nucléotides (NIR) pour éliminer les dommages oxydatifs des bases de l'ADN. À l'heure actuelle, le mécanisme moléculaire qui sous-tend la fonction de stimulation des TF/redox de l'APE1 et son rôle biologique restent contestés. Ici, nous apportons la preuve qu'au lieu d'une réduction directe de la cystéine dans les TF par l'APE1, les activités NIR et de stimulation des TF catalysées par l'APE1 peuvent être basées sur une liaison coopérative transitoire de l'APE1 à l'ADN et l'induction de changements conformationnels dans l'hélice. La structure du duplex de l'ADN influence fortement les activités de stimulation de la RNI et de la TF. Les endonucléases AP des plantes homologues dépourvues de résidus de cystéine conservés stimulent la liaison de l'ADN de la sous-unité p50 de NF-κB. L'APE1 agit en synergie avec des agents réducteurs de faible poids moléculaire sur les TF. Enfin, APE1 stimule la liaison de l'ADN de la protéine mutante p50-C62S insensible à l'oxydoréduction. L'imagerie au microscope électronique des complexes APE1 avec l'ADN a révélé une polymérisation préférentielle de l'APE1 sur les duplex d'ADN à espacement et à courbure intrinsèque. La modélisation moléculaire offre une explication structurelle de la façon dont l'APE1 peut s'oligomériser sur l'ADN. En conclusion, nous proposons que l'oligomérisation de l'APE1 dirigée par l'ADN peut être considérée comme un substitut à la diffusion de l'APE1 le long du contour de l'ADN pour sonder la flexibilité anisotrope. Les oligomères de l'APE1 exacerbent les distorsions préexistantes de l'ADN et permettent à la fois une activité NIR et une liaison de l'ADN par les TF, quel que soit leur état d'oxydation. Traduit avec www.DeepL.com/Translator (version gratuite)
Published: 2019
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32. Helicobacter pylori and Its Antibiotic Heteroresistance: A Neglected Issue in Published Guidelines

Author: Albert A. Rizvanov, Thomas Haertlé, Lydia Bogomolnaya, Amin Talebi Bezmin Abadi, Kazan (Volga region) Federal University, Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Department of Animal Nutrition and Feed Management, University of Life Sciences in Poznan, Institute of Biochemistry and Biophysics, Pawinskiego 5a, University of Texas Health Science Center, The University of Texas Health Science Center at Houston (UTHealth), Tarbiat Modares University, Partenaires INRAE, Ministry of Science and Higher Education of the Russian Federation [17.9783.2017/8.9], and Rizvanov, Albert A.
Subjects: Microbiology (medical), antibiotic resistance, medicine.drug_class, Antibiotics, lcsh:QR1-502, Helicobacter pylori, heteroresistance, guidelines, antibiotic therapy, Clinical settings, Review, Microbiology, lcsh:Microbiology, 03 medical and health sciences, Antibiotic resistance, Antibiotic therapy, [SDV.IDA]Life Sciences [q-bio]/Food engineering, Medicine, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, 030304 developmental biology, 0303 health sciences, biology, 030306 microbiology, business.industry, biology.organism_classification, 3. Good health, Immunology, Standard protocol, business
Abstract: International audience; "Heteroresistance" is a widely applied term that characterizes most of the multidrug-resistant microorganisms. In microbiological practice, the word "heteroresistance" indicates diverse responses to specific antibiotics by bacterial subpopulations in the same patient. These resistant subpopulations of heteroresistant strains do not respond to antibiotic therapy in vitro or in vivo. Presently, there is no standard protocol available for the treatment of infections caused by heteroresistant Helicobacter pylori in clinical settings, at least according to recent guidelines. Thus, there is a definite need to open a new discussion on how to recognize, how to screen, and how to eliminate those problematic strains in clinical and environmental samples. Since there is great interest in developing new strategies to improve the eradication rate of anti-H. pylon treatments, the presence of heteroresistant strains/clones among clinical isolates of the bacteria should be taken into account. Indeed, increased knowledge of gastroenterologists about the existence of heteroresistance phenomena is highly required. Moreover, the accurate breakpoints should be examined/determined in order to have a solid statement of heteroresistance among the H. pylori isolates. The primary definition of heteroresistance was about coexistence of both resistant and susceptible isolates at the similar gastric microniche at once, while we think that it can be happened subsequently as well. The new guidelines should include a personalized aspect in the standard protocol to select a precise, effective antibiotic therapy for infected patients and also address the problems of regional antibiotic susceptibility profiles.
Published: 2019
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33. Expression and purification of recombinant extracellular sulfatase HSulf-2 allows deciphering of enzyme sub-domain coordinated role for the binding and 6-O-desulfation of heparan sulfate

Author: Amal Seffouh, Hugues Lortat-Jacob, Zahra el Oula Hassoun, Rana El Masri, Jean-Pierre Andrieu, Romain R. Vivès, Evelyne Gout, Olga Makshakova, Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-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)-Centre National de la Recherche Scientifique (CNRS), Kazan Institute of Biochemistry and Biophysics, Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-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), and ANR-17-CE11-0040,SULFatAS,Structure et activités des sulfatases extracellulaires SULF(2017)
Subjects: Models, Molecular, Mutant, MESH: Catalytic Domain, Substrate Specificity, law.invention, MESH: Recombinant Proteins, chemistry.chemical_compound, MESH: Structure-Activity Relationship, law, Catalytic Domain, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, 0303 health sciences, Sulfatase, MESH: Hydrophobic and Hydrophilic Interactions, 030302 biochemistry & molecular biology, Extracellular matrix, Heparan sulfate, Recombinant Proteins, Cell biology, Structure–function relationships, MESH: HEK293 Cells, Recombinant DNA, Molecular Medicine, Sulfatases, Sulfotransferases, Hydrophobic and Hydrophilic Interactions, MESH: Models, Molecular, Protein Binding, Glycocalyx, Cell Line, Structure-Activity Relationship, 03 medical and health sciences, Cellular and Molecular Neuroscience, MESH: Heparitin Sulfate, Extracellular, Humans, MESH: Protein Binding, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Binding site, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Molecular Biology, Pharmacology, Binding Sites, MESH: Humans, Heparin, HEK 293 cells, Cell Biology, MESH: Sulfotransferases, MESH: Cell Line, HEK293 Cells, Enzyme, Glycosaminoglycan, MESH: Binding Sites, chemistry, MESH: Substrate Specificity, Heparitin Sulfate
Abstract: International audience; Through their ability to edit 6-O-sulfation pattern of Heparan sulfate (HS) polysaccharides, Sulf extracellular endosulfatases have emerged as critical regulators of many biological processes, including tumor progression. However, study of Sulfs remains extremely intricate and progress in characterizing their functional and structural features has been hampered by limited access to recombinant enzyme. In this study, we unlock this critical bottleneck, by reporting an efficient expression and purification system of recombinant HSulf-2 in mammalian HEK293 cells. This novel source of enzyme enabled us to investigate the way the enzyme domain organization dictates its functional properties. By generating mutants, we confirmed previous studies that HSulf-2 catalytic (CAT) domain was sufficient to elicit arylsulfatase activity and that its hydrophilic (HD) domain was necessary for the enzyme 6-O-endosulfatase activity. However, we demonstrated for the first time that high-affinity binding of HS substrates occurred through the coordinated action of both domains, and we identified and characterized 2 novel HS binding sites within the CAT domain. Altogether, our findings contribute to better understand the molecular mechanism governing HSulf-2 substrate recognition and processing. Furthermore, access to purified recombinant protein opens new perspectives for the resolution of HSulf structure and molecular features, as well as for the development of Sulf-specific inhibitors.
Published: 2019
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34. Polymyxins interaction to the human serum albumin: A thermodynamic and computational study

Author: Vladimir I. Muronetz, Z. Zolmajd-Haghighi, G. Rezaei Behbehani, Mohammad Hossein Karimi-Jafari, Yulia Yu. Stroylova, Mojtaba Bagheri, Atiyeh Ghasemi, Atefeh Poursoleiman, Ali Akbar Saboury, Thomas Haertlé, Institute of Biochemistry and Biophysics, Pawinskiego 5a, Univ Tehran, Inst Biochem & Biophys, POB 13145-1384, Tehran, Iran, Partenaires INRAE, Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Poznan University of Life Sciences, Imam Khomeini International University (IKIU), Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University (MSU), Lomonosov Moscow State Univ, Belozersky Inst Physicochem Biol, Moscow, Russia, Research Council of University of TehranUniversity of Tehran, and Iran National Science Foundation (INSF)Iran National Science Foundation (INSF)
Subjects: Circular dichroism, Protein Conformation, medicine.drug_class, Polymyxin, Serum Albumin, Human, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Fluorescence, Analytical Chemistry, Protein structure, [SDV.IDA]Life Sciences [q-bio]/Food engineering, medicine, Humans, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Polymyxins, Instrumentation, Protein secondary structure, Spectroscopy, Polymyxin B, Binding Sites, Simulated-annealing, Chemistry, Colistin, Isothermal titration calorimetry, Isothermal titration calorimetry (ITC), 021001 nanoscience & nanotechnology, Human serum albumin, Atomic and Molecular Physics, and Optics, 0104 chemical sciences, 3. Good health, Molecular Docking Simulation, body regions, Biophysics, Thermodynamics, 0210 nano-technology, Hydrophobic and Hydrophilic Interactions, Protein Binding, medicine.drug, Fluorescence anisotropy
Abstract: International audience; Polymyxin B and E (colistin), are a group of cationic charged cyclic antibiotic lipopeptides that are frequently used in the clinics to treat infections caused by the multidrug-resistant gram-negative bacteria. Since the interactions with the blood plasma drug-transport proteins may play a critical role in determining their pharmacological and pharmacokinetic profiles, we studied the binding properties of polymyxins to the human serum albumin (HSA) under simulated physiological conditions by the combination of biophysical approaches, such as isothermal titration calorimetry (ITC), fluorescence anisotropy, circular dichroism (CD) buttressed by computational studies. The HSA binding to the polymyxins was relatively strong (K-a approximate to 1.0 x 10(7) M-1). Molecular docking indicated that polymyxins bind to the cleft of HSA between domains I and III via the electrostatic interactions. This evidence was further confirmed by the entropy-driven interaction for the polymyxins bound HSA. Far UV-CD experiments showed that the secondary structure of HSA doesn't alter and its stable structure is preserved. Collectively, these investigations revealed that the polymyxins bind preferentially to the partially unfolded intermediate forms of the protein structure; however, HSA molecule does not undergo any significant conformational changes upon binding. This is promising as it may limit the unfavorable side effects of the medicine. On the whole, the results provide quantitative and qualitative insight of the binding interaction between HSA and polymyxins, which is important in understanding their effect as therapeutic agents.
Published: 2019
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35. Characterization of Mucus-Related Properties of Streptococcus thermophilus:From Adhesion to Induction

Author: Neïké Fernandez, Laura Wrzosek, Joanna M. Radziwill-Bienkowska, Belinda Ringot-Destrez, Marie-Pierre Duviau, Marie-Louise Noordine, Valérie Laroute, Véronique Robert, Claire Cherbuy, Marie-Line Daveran-Mingot, Muriel Cocaign-Bousquet, Renaud Léonard, Catherine Robbe-Masselot, Françoise Rul, Eric Ogier-Denis, Muriel Thomas, Muriel Mercier-Bonin, CNRS, Université de Lille, MICrobiologie de l'ALImentation au Service de la Santé [MICALIS], Polska Akademia Nauk = Polish Academy of Sciences [PAN], Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF], Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés [LISBP], Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF], Centre de recherche sur l'Inflammation [CRI (UMR_S_1149 / ERL_8252 / U1149)], Thomas, Muriel, Mercier Bonin, Muriel, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Université Paris-Saclay, Institute of Biochemistry and Biophysics, Pawinskiego 5a, Centre National de la Recherche Scientifique (CNRS), 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), Université Fédérale Toulouse Midi-Pyrénées, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7), Sorbonne Universités, Syndifrais-CNIEL (Paris, France), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), 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), Université de Toulouse (UT), and Sorbonne Université (SU)
Subjects: 0301 basic medicine, Streptococcus thermophilus, Physiology, [SDV]Life Sciences [q-bio], 030106 microbiology, lcsh:Physiology, law.invention, Microbiology, 03 medical and health sciences, Probiotic, gnotobiotic rodent, fluids and secretions, mucin, law, mucus, Physiology (medical), microbiota, gut, lactic acid bacteria, lactate, Feces, Original Research, biology, lcsh:QP1-981, Chemistry, Mucus, Lactococcus lactis, Mucin, biology.organism_classification, In vitro, Bacteria
Abstract: Mucus is a major component of the intestinal barrier involved both in the protection of the host and the fitness of commensals of the gut. Streptococcus thermophilus is consumed world-wide in fermented dairy products and is also recognized as a probiotic, as its consumption is associated with improved lactose digestion. We determined the overall effect of S. thermophilus on the mucus by evaluating its ability to adhere, degrade, modify, or induce the production of mucus and/or mucins. Adhesion was analyzed in vitro using two types of mucins (from pig or human biopsies) and mucus-producing intestinal HT29-MTX cells. The induction of mucus was characterized in two different rodent models, in which S. thermophilus is the unique bacterial species in the digestive tract or transited as a sub-dominant bacterium through a complex microbiota. S. thermophilus LMD-9 and LMG18311 strains did not grow in sugars used to form mucins as the sole carbon source and displayed weak binding to mucus/mucins relative to the highly adhesive TIL448 Lactococcus lactis. The presence of S. thermophilus as the unique bacteria in the digestive tract of gnotobiotic rats led to accumulation of lactate and increased the number of Alcian-Blue positive goblet cells and the amount of the mucus-inducer KLF4 transcription factor. Lactate significantly increased KLF4 protein levels in HT29-MTX cells. Introduction of S. thermophilusvia transit as a sub-dominant bacterium (103 CFU/g feces) in a complex endogenous microbiota resulted in a slight increase in lactate levels in the digestive tract, no induction of overall mucus production, and moderate induction of sulfated mucin production. We thus show that although S. thermophilus is a poor mucus-adhesive bacterium, it can promote mucus pathway at least in part by producing lactate in the digestive tract. 9
Published: 2018
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36. Food-grade TiO2 is trapped by intestinal mucus in vitro but does not impair mucin O-glycosylation and short-chain fatty acid synthesis in vivo:implications for gut barrier protection

Author: Pauline Talbot, Joanna M. Radziwill-Bienkowska, Jasper B. J. Kamphuis, Karine Steenkeste, Sarah Bettini, Véronique Robert, Marie-Louise Noordine, Camille Mayeur, Eric Gaultier, Philippe Langella, Catherine Robbe-Masselot, Eric Houdeau, Muriel Thomas, Muriel Mercier-Bonin, CNRS, Université de Lille, MICrobiologie de l'ALImentation au Service de la Santé [MICALIS], Polska Akademia Nauk = Polish Academy of Sciences [PAN], ToxAlim [ToxAlim], Institut des Sciences Moléculaires d'Orsay [ISMO], Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF], MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Institute of Biochemistry and Biophysics, Pawinskiego 5a, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Institut des Sciences Moléculaires d’Orsay (ISMO), Centre National de la Recherche Scientifique (CNRS), Endocrinologie & Toxicologie de la Barrière Intestinale (ToxAlim-ENTeRisk), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), and This work was funded by INRA in the frame of the 'Nutrition, Chemical Food Safety, and Consumer Behaviour' division (AlimH priority program 2013)
Subjects: Short-chain fatty acids, Mucus, lcsh:Medical technology, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, lcsh:R855-855.5, lcsh:Biotechnology, lcsh:TP248.13-248.65, Gut barrier, Food-grade TiO2, Mucin O-glycans
Abstract: Background Titanium dioxide (TiO2) particles are commonly used as a food additive (E171 in the EU) for its whitening and opacifying properties. However, the risk of gut barrier disruption is an increasing concern because of the presence of a nano-sized fraction. Food-grade E171 may interact with mucus, a gut barrier protagonist still poorly explored in food nanotoxicology. To test this hypothesis, a comprehensive approach was performed to evaluate in vitro and in vivo interactions between TiO2 and intestinal mucus, by comparing food-grade E171 with NM-105 (Aeroxyde P25) OECD reference nanomaterial. Results We tested E171-trapping properties of mucus in vitro using HT29-MTX intestinal epithelial cells. Time-lapse confocal laser scanning microscopy was performed without labeling to avoid modification of the particle surface. Near-UV irradiation of E171 TiO2 particles at 364 nm resulted in fluorescence emission in the visible range, with a maximum at 510 nm. The penetration of E171 TiO2 into the mucoid area of HT29-MTX cells was visualized in situ. One hour after exposure, TiO2 particles accumulated inside “patchy” regions 20 µm above the substratum. The structure of mucus produced by HT29-MTX cells was characterized by MUC5AC immunofluorescence staining. The mucus layer was thin and organized into regular “islands” located approximately 20 µm above the substratum. The region-specific trapping of food-grade TiO2 particles was attributed to this mucus patchy structure. We compared TiO2-mediated effects in vivo in rats after acute or sub-chronic oral daily administration of food-grade E171 and NM-105 at relevant exposure levels for humans. Cecal short-chain fatty acid profiles and gut mucin O-glycosylation patterns remained unchanged, irrespective of treatment. Conclusions Food-grade TiO2 is trapped by intestinal mucus in vitro but does not affect mucin O-glycosylation and short-chain fatty acid synthesis in vivo, suggesting the absence of a mucus barrier impairment under “healthy gut” conditions.
Published: 2018
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37. Toxicity of Food-Grade TiO2 to Commensal Intestinal and Transient Food-Borne Bacteria: New Insights Using Nano-SIMS and Synchrotron UV Fluorescence Imaging

Author: Isabelle Fourquaux, Jacek Bardowski, Jean-Nicolas Audinot, Matthieu Réfrégiers, Frédéric Jamme, Eric Houdeau, Jasper B. J. Kamphuis, Muriel Thomas, Philippe Langella, Muriel Mercier-Bonin, Esther Lentzen, Christel Cartier, Véronique Robert, Magdalena Kowalczyk, Pauline Talbot, Joanna M. Radziwill-Bienkowska, Institute of Biochemistry and Biophysics, Polish Academy of Science, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Luxembourg Institute of Science and Technology (LIST), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), Institute of Biochemistry & Biophysics, Polish Academy of Sciences (PAN), Mercier-Bonin, Muriel, Endocrinologie & Toxicologie de la Barrière Intestinale (ToxAlim-ENTeRisk), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), INRA of the 'Nutrition, Chemical Food Safety and Consumer Behaviour' Division (AlimH priority program), Polska Akademia Nauk = Polish Academy of Sciences (PAN), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
Subjects: 0301 basic medicine, Microbiology (medical), Streptococcus thermophilus, lcsh:QR1-502, [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain, 010501 environmental sciences, Gut flora, medicine.disease_cause, bacterial toxicity, 01 natural sciences, Microbiology, lcsh:Microbiology, 03 medical and health sciences, Lactobacillus rhamnosus, medicine, media_common.cataloged_instance, European union, food-grade TiO2, Escherichia coli, 0105 earth and related environmental sciences, media_common, cellular and subcellular bioimaging, biology, Chemistry, Lactococcus lactis, technology, industry, and agriculture, biology.organism_classification, medicine.disease, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, 030104 developmental biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, 13. Climate action, food-borne bacteria, intestinal bacteria, Dysbiosis, Bacteria
Abstract: Titanium dioxide (TiO2) is commonly used as a food additive (E171 in the EU) for its whitening and opacifying properties. However, a risk of intestinal barrier disruption, including dysbiosis of the gut microbiota, is increasingly suspected because of the presence of a nano-sized fraction in this additive. We hypothesized that food-grade E171 and Aeroxyde P25 (identical to the NM-105 OECD reference nanomaterial in the European Union Joint Research Centre) interact with both commensal intestinal bacteria and transient food-borne bacteria under non-UV-irradiated conditions. Based on differences in their physicochemical properties, we expect a difference in their respective effects. To test these hypotheses, we chose a panel of eight Gram-positive/Gram-negative bacterial strains, isolated from different biotopes and belonging to the species Escherichia coli, Lactobacillus rhamnosus, Lactococcus lactis (subsp. lactis and cremoris), Streptococcus thermophilus, and Lactobacillus sakei. Bacterial cells were exposed to food-grade E171 vs. P25 in vitro and the interactions were explored with innovative (nano)imaging methods. The ability of bacteria to trap TiO2 was demonstrated using synchrotron UV fluorescence imaging with single cell resolution. Subsequent alterations in the growth profiles were shown, notably for the transient food-borne L. lactis and the commensal intestinal E. coli in contact with food-grade TiO2. However, for both species, the reduction in cell cultivability remained moderate, and the morphological and ultrastructural damages, observed with electron microscopy, were restricted to a small number of cells. E. coli exposed to food-grade TiO2 showed some internalization of TiO2 (7% of cells), observed with high-resolution nano-secondary ion mass spectrometry (Nano-SIMS) chemical imaging. Taken together, these data show that E171 may be trapped by commensal and transient food-borne bacteria within the gut. In return, it may induce some physiological alterations in the most sensitive species, with a putative impact on gut microbiota composition and functioning, especially after chronic exposure.
Published: 2018
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38. ATP Synthase Diseases of Mitochondrial Genetic Origin

Author: Alain Dautant, Thomas Meier, Alexander Hahn, Déborah Tribouillard-Tanvier, Jean-Paul di Rago, Roza Kucharczyk, Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Department of Structural Biology, Max-Planck-Institute of Biophysics, Frankfurt, Germany, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland (IBB), and Wellcome Trust
Subjects: mitochondrial diseases, lcsh:QP1-981, Physiology, [SDV]Life Sciences [q-bio], MT-ATP6, MT-ATP8, F 1 F o ATP synthase structure, Review, F1Fo ATP synthase structure, mitochondrial DNA (mtDNA), lcsh:Physiology
Abstract: International audience; Devastating human neuromuscular disorders have been associated to defects in the ATP synthase. This enzyme is found in the inner mitochondrial membrane and catalyzes the last step in oxidative phosphorylation, which provides aerobic eukaryotes with ATP. With the advent of structures of complete ATP synthases, and the availability of genetically approachable systems such as the yeast Saccharomyces cerevisiae, we can begin to understand these molecular machines and their associated defects at the molecular level. In this review, we describe what is known about the clinical syndromes induced by 58 different mutations found in the mitochondrial genes encoding membrane subunits 8 and a of ATP synthase, and evaluate their functional consequences with respect to recently described cryo-EM structures.
Published: 2018
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39. The role of the N-terminal domain of human apurinic/apyrimidinic endonuclease 1, APE1, in DNA glycosylase stimulation

Author: Alexander A. Ishchenko, Andrey S. Vasenko, Danila A. Iakovlev, Milena Bazlekowa-Karaban, Murat Saparbaev, Olivier Piétrement, Olga A. Kladova, Olga S. Fedorova, Nikita A. Kuznetsov, Bakhyt T. Matkarimov, Sonia Baconnais, Eric Le Cam, Barbara Tudek, Signalisation, noyaux et innovations en cancérologie (UMR8126), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Stabilité Génétique et Oncogenèse (UMR 8200), National Laboratory Astana, Nazarbayev University [Kazakhstan], Lomonosov Moscow State University (MSU), Institute of Biochemistry and Biophysics, Polska Akademia Nauk = Polish Academy of Sciences (PAN), Maintenance des génomes, Microscopies Moléculaire et Bionanosciences, Centre National de la Recherche Scientifique-Université Paris Sud, Maintenance des génomes, Institut Gustave Roussy (IGR), Réparation de l’ADN (CNRS UMR 8200), and Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, DNA Repair, DNA repair, [SDV]Life Sciences [q-bio], Biochemistry, DNA Glycosylases, MBD4, AP endonuclease, 03 medical and health sciences, Endonuclease, chemistry.chemical_compound, DNA-(Apurinic or Apyrimidinic Site) Lyase, Humans, Protein Interaction Domains and Motifs, AP site, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Endodeoxyribonucleases, 030102 biochemistry & molecular biology, biology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, DNA, Cell Biology, Base excision repair, 030104 developmental biology, chemistry, DNA glycosylase, Biophysics, biology.protein, Nucleic Acid Conformation, DNA Damage
Abstract: The base excision repair (BER) pathway consists of sequential action of DNA glycosylase and apurinic/apyrimidinic (AP) endonuclease necessary to remove a damaged base and generate a single-strand break in duplex DNA. Human multifunctional AP endonuclease 1 (APE1, a.k.a. APEX1, HAP-1, or Ref-1) plays essential roles in BER by acting downstream of DNA glycosylases to incise a DNA duplex at AP sites and remove 3′-blocking sugar moieties at DNA strand breaks. Human 8-oxoguanine-DNA glycosylase (OGG1), methyl-CpG-binding domain 4 (MBD4, a.k.a. MED1), and alkyl-N-purine-DNA glycosylase (ANPG, a.k.a. Aag or MPG) excise a variety of damaged bases from DNA. Here we demonstrated that the redox-deficient truncated APE1 protein lacking the first N-terminal 61 amino acid residues (APE1-NΔ61) cannot stimulate DNA glycosylase activities of OGG1, MBD4, and ANPG on duplex DNA substrates. Electron microscopy imaging of APE1–DNA complexes revealed oligomerization of APE1 along the DNA duplex and APE1-mediated DNA bridging followed by DNA aggregation. APE1 polymerizes on both undamaged and damaged DNA in cooperative mode. Association of APE1 with undamaged DNA may enable scanning for damage; however, this event reduces effective concentration of the enzyme and subsequently decreases APE1-catalyzed cleavage rates on long DNA substrates. We propose that APE1 oligomers on DNA induce helix distortions thereby enhancing molecular recognition of DNA lesions by DNA glycosylases via a conformational proofreading/selection mechanism. Thus, APE1-mediated structural deformations of the DNA helix stabilize the enzyme–substrate complex and promote dissociation of human DNA glycosylases from the AP site with a subsequent increase in their turnover rate. Significance Statement The major human apurinic/apyrimidinic (AP) endonuclease, APE1, stimulates DNA glycosylases by increasing their turnover rate on duplex DNA substrates. At present, the mechanism of the stimulation remains unclear. We report that the redox domain of APE1 is necessary for the active mode of stimulation of DNA glycosylases. Electron microscopy revealed that full-length APE1 oligomerizes on DNA possibly via cooperative binding to DNA. Consequently, APE1 shows DNA length dependence with preferential repair of short DNA duplexes. We propose that APE1-catalyzed oligomerization along DNA induces helix distortions, which in turn enable conformational selection and stimulation of DNA glycosylases. This new biochemical property of APE1 sheds light on the mechanism of redox function and its role in DNA repair.
Published: 2018
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40. Crystal Structures of Fungal Tectonin in Complex with O-Methylated Glycans Suggest Key Role in Innate Immune Defense

Author: Therese Wohlschlager, Alexander Titz, Annabelle Varrot, Roman Sommer, Olga N. Makshakova, Stephanie Hutin, Markus Künzler, May Marsh, HIPS, Helmholtz-Institut für pharmazeutische Forschung Saarland, Universitätscampus 8.1, 66123 Saarbrücken, Germany., Chemical Biology of Carbohydrates, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Kazan Institute of Biochemistry and Biophysics, Institute of Microbiology [Zurich], Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-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), The Swiss Light Source (SLS) (SLS-PSI), Paul Scherrer Institute (PSI), Institute of Medical Microbiology [Zurich], Universität Zürich [Zürich] = University of Zurich (UZH), Centre de Recherches sur les Macromolécules Végétales (CERMAV ), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Helmholtz Association (to AT, grant no VH-NG-934)the Swiss National Science Foundation (to MK, grant no 31003A-130671), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Models, Molecular, 0301 basic medicine, Glycan, Crystallography, X-Ray, Methylation, Epitope, Fungal Proteins, Laccaria, 03 medical and health sciences, Tetramer, Polysaccharides, Structural Biology, Lectins, Scattering, Small Angle, [CHIM.CRIS]Chemical Sciences/Cristallography, Animals, Humans, Binding site, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Molecular Biology, Binding Sites, Innate immune system, 030102 biochemistry & molecular biology, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Effector, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Immunity, Innate, Protein Structure, Tertiary, Cell biology, 030104 developmental biology, Capsid, biology.protein, Protein Multimerization
Abstract: International audience; Innate immunity is the first line of defense against pathogens and predators. To initiate a response, it relies on the detection of invaders, where lectin-carbohydrate interactions play a major role. O-methylated glycans were previously identified as non-self epitopes and conserved targets for defense effector proteins belonging to the tectonin superfamily. Here, we present two crystal structures of Tectonin 2 from the mushroom Laccaria bicolor (Lb-Tec2) in complex with methylated ligands, unraveling the molecular basis for this original specificity. Furthermore, they revealed the formation of a ball-shaped tetramer with 24 binding sites distributed at its surface, resembling a small virus capsid. Based on the crystal structures, a methylation recognition motif was identified and found in the sequence of many tectonins from bacteria to human. Our results support a key role of tectonins in innate defense based on a distinctive and conserved type of lectin-glycan interaction.
Published: 2018
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41. Role of Copper in the Onset of Alzheimer’s Disease Compared to Other Metals

Author: Soghra Bagheri, Rosanna Squitti, Thomas Haertlé, Mariacristina Siotto, Ali A. Saboury, Saboury, Ali A., Iran University of Medical Sciences, Istituto Centro San Giovanni di Dio Fatebenefratelli, Partenaires INRAE, Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Institute of Biochemistry and Biophysics, Pawinskiego 5a, Department of Animal Nutrition and Feed Management, University of Life Sciences in Poznan, and Fondazione Don Carlo Gnocchi
Subjects: 0301 basic medicine, Aging, medicine.medical_specialty, amyloid plaques, Cognitive Neuroscience, chemistry.chemical_element, Brain tissue, Disease, Review, lcsh:RC321-571, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, [SDV.IDA]Life Sciences [q-bio]/Food engineering, medicine, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, In patient, Copper levels, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, calcium, zinc, cholesterol, Alzheimer's disease, medicine.disease, Copper, 030104 developmental biology, Endocrinology, chemistry, copper, neurodegenerative disorder, Copper deficiency, Alzheimer’s disease, 030217 neurology & neurosurgery, Neuroscience
Abstract: Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by amyloid plaques in patients' brain tissue. The plaques are mainly made of beta-amyloid peptides and trace elements including Zn2+, Cu2+, and Fe2+. Some studies have shown that AD can be considered a type of metal dyshomeostasis. Among metal ions involved in plaques, numerous studies have focused on copper ions, which seem to be one of the main cationic elements in plaque formation. The involvement of copper in AD is controversial, as some studies show a copper deficiency in AD, and consequently a need to enhance copper levels, while other data point to copper overload and therefore a need to reduce copper levels. In this paper, the role of copper ions in AD and some contradictory reports are reviewed and discussed.
Published: 2018
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42. Synthesized CuFe2O4/SiO2 nanocomposites added to water/EG: Evaluation of the thermophysical properties beside sensitivity analysis & EANN

Author: Mehdi Bahiraei, Mohammad Reza Safaei, Marjan Goodarzi, Mostafa Safdari Shadloo, Arash Karimipour, Seyed Amin Bagherzadeh, Abdulwahab A. Alnaqi, Islamic Azad University, Najafabad (IAU, Najafabad), West Tehran Islamic Azad University [Tehran] (WTIAU), Institute of Biochemistry and Biophysics, Pawinskiego 5a, Ton Duc Thang University [Hô-Chi-Minh-City], Complexe de recherche interprofessionnel en aérothermochimie (CORIA), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)
Subjects: Materials science, Relative viscosity, Nanoparticle, Thermo-physical property, 02 engineering and technology, Iron compounds, 01 natural sciences, 010305 fluids & plasmas, Nanocomposites, Thermodynamic properties, Copper alloys, Nanofluid, Electric conductivity, Settling, Electrical resistivity and conductivity, Curve fitting methods, 0103 physical sciences, Curve fitting, Electrical conductivity, [PHYS.MECA.MEFL]Physics [physics]/Mechanics [physics]/Fluid mechanics [physics.class-ph], Magnetic materials, Fluid Flow and Transfer Processes, Nanocomposite, Viscosity, Mechanical Engineering, Copper compounds, Nanofluidics, Ferrite, Silica, Empirical correlations, Copper ferrites, 021001 nanoscience & nanotechnology, Condensed Matter Physics, Relative electrical conductivities, Chemical engineering, Synthesis (chemical), Ferrite (magnet), Nanoparticles, 0210 nano-technology, Optimization procedures, Sensitivity analysis, Neural networks
Abstract: cited By 24; The new nanocomposite material of CuFe2O4 (copper ferrite) nanoparticles coated by SiO2 is synthesized. Then, this newly generated nanocomposite is dispersed in water/ethylene glycol (60:40) to make a new homogeneous nanofluid in order to avoid settling and agglomeration. Through suitable accurate experiments, density, viscosity and electrical conductivity of the mixture are measured at various temperatures and nanoparticles concentrations. Besides we empirical correlations for the same parameters developed via the curve fitting method. To have a better statistical view, the optimization procedure based on the enhanced artificial neural network (EANN), developed at present study, is performed. Furthermore, according to the obtained empirical results, the sensitivity analysis is provided and the margin of deviations is represented for each proposed correlation. Generation, stabilization and measuring the density, viscosity and electrical conductivity of the newly mentioned nanofluid, make present work different from the previous ones in this field. The highest amount of relative electrical conductivity is observed at T = 75 °C and φ = 0.02 (g/mL); however, the case of T = 30 °C and φ = 0.02 (g/mL) represents the maximum value of relative viscosity. Moreover, density is decreased by temperature augmentation, through all cases. © 2018 Elsevier Ltd
Published: 2018
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43. Decreasing cytosolic translation is beneficial to yeast and human tafazzin-deficient cells

Author: Maxence, de Taffin de Tilques, Jean-Paul, Lasserre, François, Godard, Elodie, Sardin, Marine, Bouhier, Marina, Le Guedard, Roza, Kucharczyk, Patrice X, Petit, Eric, Testet, Jean-Paul, di Rago, Déborah, Tribouillard-Tanvier, Université de Bordeaux (UB), Laboratoire de biogenèse membranaire (LBM), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), ADERA, Institute of Biochemistry and Biophysics, and Université Paris Descartes - Paris 5 (UPD5)
Subjects: Applied Microbiology, [SDV]Life Sciences [q-bio], oxidative phosphorylation, cytosolic protein synthesis, Microbiology, mitochondrial disease, lcsh:Biology (General), cardiolipin remodeling, Genetics, barth syndrome, cycloheximide, Molecular Biology, lcsh:QH301-705.5
Abstract: International audience; Cardiolipin (CL) optimizes diverse mitochondrial processes, including oxidative phosphorylation (OXPHOS). To function properly, CL needs to be unsaturated, which requires the acyltransferase Tafazzin (TAZ). Loss-offunction mutations in the TAZ gene are responsible for the Barth syndrome (BTHS), a rare X-linked cardiomyopathy, presumably because of a diminished OXPHOS capacity. Herein we show that a partial inhibition of cytosolic protein synthesis, either chemically with the use of cycloheximide or by specific genetic mutations, fully restores biogenesis and the activity of the oxidative phosphorylation system in a yeast BTHS model (taz1 Delta). Interestingly, the defaults in CL were not suppressed, indicating that they are not primarily responsible for the OXPHOS deficiency in taz1 Delta yeast. Low concentrations of cycloheximide in the picomolar range were beneficial to TAZ-deficient HeLa cells, as evidenced by the recovery of a good proliferative capacity. These findings reveal that a diminished capacity of CL remodeling deficient cells to preserve protein homeostasis is likely an important factor contributing to the pathogenesis of BTHS. This in turn, identifies cytosolic translation as a potential therapeutic target for the treatment of this disease.
Published: 2018
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44. Investigation of the Mechanical Properties of Flax Cell Walls during Plant Development: The Relation between Performance and Cell Wall Structure

Author: Christophe Baley, David Siniscalco, Tatyana Gorshkova, Camille Goudenhooft, Olivier Arnould, Alain Bourmaud, Olivier Sire, Institut de Recherche Dupuy de Lôme (IRDL), Université de Bretagne Sud (UBS)-Université de Brest (UBO)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Centre National de la Recherche Scientifique (CNRS), Bois (BOIS), Laboratoire de Mécanique et Génie Civil (LMGC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Kazan Institute of Biochemistry and Biophysics, ANR-12-BS09-0004,StressInTrees,Approche couplée physiologique et micro-mécanique de la génération des contraintes de maturation dans le bois de tension(2012), Institut de Recherche Dupuy de Lôme ( IRDL ), Université de Bretagne Sud ( UBS ) -Université de Brest ( UBO ) -ENSTA Bretagne-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Mécanique et Génie Civil ( LMGC ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Bois ( BOIS ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), and ANR-12-BS09-0004,StressInTrees,Approche couplée physiologique et micro-mécanique de la génération des contraintes de maturation dans le bois de tension ( 2012 )
Subjects: 0106 biological sciences, Materials science, Modulus, 02 engineering and technology, 01 natural sciences, fiber crops, Biomaterials, Cell wall, lcsh:TP890-933, Indentation, lcsh:TP200-248, Ultimate tensile strength, [SPI.MECA.MEMA]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Mechanics of materials [physics.class-ph], Fiber, Composite material, lcsh:QH301-705.5, Civil and Structural Engineering, Tensile testing, thickening, tensile test, [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], lcsh:Chemicals: Manufacture, use, etc, 021001 nanoscience & nanotechnology, lcsh:QC1-999, Fiber cell, lcsh:Biology (General), Mechanics of Materials, [ SPI.MECA.MEMA ] Engineering Sciences [physics]/Mechanics [physics.med-ph]/Mechanics of materials [physics.class-ph], flax fibers, Raman spectroscopy, Ceramics and Composites, cell wall, AFM (Atomic Force Microscopy), lcsh:Textile bleaching, dyeing, printing, etc, [ SPI.MECA.BIOM ] Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], 0210 nano-technology, lcsh:Physics, 010606 plant biology & botany, Cell wall thickening
Abstract: International audience; The development of flax (Linum usitatissimum L.) fibers was studied to obtain better insight on the progression of their high mechanical performances during plant growth. Fibers at two steps of plant development were studied, namely the end of the fast growth period and at plant maturity, each time at three plant heights. The indentation modulus of the fiber cell wall was characterized by atomic force microscopy (AFM) using peak-force quantitative nano-mechanical property mapping (PF-QNM). Changes in the cell wall modulus with the cell wall thickening were highlighted. For growing plants, fibers from top and middle heights show a loose inner Gn layer with a lower indentation modulus than mature fibers, which exhibit thickened homogeneous cell walls made only of a G layer. The influence of these changes in the fiber cell wall on the mechanical performances of extracted elementary fibers was also emphasized by tensile tests. In addition, Raman spectra were recorded on samples from both growing and mature plants. The results suggest that, for the fiber cell wall, the cellulose contribution increases with fiber maturity, leading to a greater cell wall modulus of flax fibers.
Published: 2018
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45. ( beta-Cyclodextrin-Modified Magnetic Nanoparticles Immobilized on Sepharose Surface Provide an Effective Matrix for Protein Refolding)

Author: Faizan Ahmad, Ali Akbar Saboury, Marziyeh Ghaeidamini, Ali Nemati Kharat, Thomas Haertlé, University of Tehran, Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Poznan University of Life Sciences, Institute of Biochemistry and Biophysics, Pawinskiego 5a, Jamia Millia Islamia, and Partenaires INRAE
Subjects: 0301 basic medicine, facile, column, 02 engineering and technology, Protein Refolding, Matrix (chemical analysis), Sepharose, 03 medical and health sciences, Phase (matter), Spectroscopy, Fourier Transform Infrared, artificial chaperone, [SDV.IDA]Life Sciences [q-bio]/Food engineering, Materials Chemistry, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Physical and Theoretical Chemistry, Magnetite Nanoparticles, Nuclear Magnetic Resonance, Biomolecular, chemistry.chemical_classification, Cyclodextrin, Propylamines, beta-Cyclodextrins, Proteins, Spectrometry, X-Ray Emission, Silanes, molecular chaperone, 021001 nanoscience & nanotechnology, Combinatorial chemistry, Ferrosoferric Oxide, Surfaces, Coatings and Films, secondary structure analyses, size-exclusion chromatography, 030104 developmental biology, inclusion-body proteins, chemistry, Protein refolding, high loading concentrations, Magnetic nanoparticles, solid-state nanopores, alpha-Amylases, 0210 nano-technology, solubilization
Abstract: In this article, we propose an impressive and facile strategy to improve protein refolding using solid phase artificial molecular chaperones consisting of the surface-functionalized magnetic nanoparticles. Specifically, monotosyl-beta-cyclodextrin connected to the surface of 3-aminopropyltriethoxysilane (APES)-modified magnetic nanoparticles is immobilized on the sepharose surface to promote interaction with exposed hydrophobic surfaces of partially folded (intermediates) and unfolded states of proteins. Their efficiencies were investigated by circular dichroism spectroscopy and photoluminescence spectroscopy of the protein. Although the mechanism of this method is based on principles of hydrophobic chromatography, this system is not only purging the native protein from inactive inclusion bodies but also improving the protein refolding process. We chose beta-cyclodextrin (beta-CD) considering multiple reports in the literature about its efficiency in protein refolding and its biocompatibility. To increase the surface area/volume ratio of the sepharose surface by nanoparticles, more beta-CD molecules are connected to the sepharose surface to make a better interaction with proteins. We suppose that proteins are isolated in the nanospace created by bound cyclodextrins on the resin surface so intermolecular interactions are reduced. The architecture of nanoparticles was characterized by Fourier transform infrared spectra, X-ray diffraction, scanning electron microscopy images, energy dispersive X-ray spectroscopy, nuclear magnetic resonance H-1 NMR and C-13 NMR), and dynamic light scattering.
Published: 2018
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46. Yeast as a system for modeling mitochondrial disease mechanisms and discovering therapies

Author: Laras Pitayu, Vincent Procaccio, Agnès Rötig, Jean-Paul Lasserre, Pascal Reynier, Annie Glatigny, Déborah Tribouillard-Tanvier, Natalia Skoczen, Joanna Rytka, Alain Dautant, Roza Kucharczyk, Lars M. Steinmetz, Jean-Paul di Rago, Raeka S. Aiyar, Marc Blondel, Geneviève Dujardin, Agnès Delahodde, Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), European Molecular Biology Laboratory [Heidelberg] (EMBL), Institute of Biochemistry and Biophysics, Polska Akademia Nauk = Polish Academy of Sciences (PAN)-Sciences, BioInformatique Moléculaire (BIM), Département Biologie des Génomes (DBG), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Fonctions et dysfonctions de la mitochondrie (FDMITO), Département Biologie Cellulaire (BioCell), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Stanford Genome Technology Center, Biogenèse et fonctionnement des complexes OXPHOS mitochondriaux (BIOMIT), Polska Akademia Nauk (PAN)-Sciences, Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Institut de Biologie Intégrative de la Cellule (I2BC), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Institut de biochimie et génétique cellulaires ( IBGC ), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique ( CNRS ), European Molecular Biology Laboratory [Heidelberg] ( EMBL ), Polska Akademia Nauk ( PAN ) -Sciences, BioInformatique Moléculaire ( BIM ), Département Biologie des Génomes ( DBG ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ) -Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078), EFS-Université de Brest ( UBO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Biologie Neurovasculaire et Mitochondriale Intégrée, Université d'Angers ( UA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Fonctions et dysfonctions de la mitochondrie ( FDMITO ), Département Biologie Cellulaire ( BioCell ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Biogenèse et fonctionnement des complexes OXPHOS mitochondriaux ( BIOMIT ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Brest ( UBO ) -EFS-Institut Brestois Santé Agro Matière ( IBSAM ), Université de Brest ( UBO ), and Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: [SDV]Life Sciences [q-bio], ved/biology.organism_classification_rank.species, Medicine (miscellaneous), lcsh:Medicine, Review, Mitochondrion, Genome, Translational Research, Biomedical, 0302 clinical medicine, Immunology and Microbiology (miscellaneous), Models, DNA, Fungal, Translational Medical Research, Genetics, 0303 health sciences, OXPHOS, 3. Good health, mitochondria, Fungal, mitochondrial fusion, Drug screening, lcsh:RB1-214, Mitochondrial DNA, Mitochondrial disease, Saccharomyces cerevisiae, Neuroscience (miscellaneous), Mitochondrial diseases, Biology, Models, Biological, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, medicine, lcsh:Pathology, Animals, Humans, Model organism, 030304 developmental biology, [ SDV ] Life Sciences [q-bio], Genetic suppressors, ved/biology, lcsh:R, DNA, biology.organism_classification, medicine.disease, Biological, Yeast, DNAJA3, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Mitochondrial diseases are severe and largely untreatable. Owing to the many essential processes carried out by mitochondria and the complex cellular systems that support these processes, these diseases are diverse, pleiotropic, and challenging to study. Much of our current understanding of mitochondrial function and dysfunction comes from studies in the baker's yeast Saccharomyces cerevisiae. Because of its good fermenting capacity, S. cerevisiae can survive mutations that inactivate oxidative phosphorylation, has the ability to tolerate the complete loss of mitochondrial DNA (a property referred to as ‘petite-positivity’), and is amenable to mitochondrial and nuclear genome manipulation. These attributes make it an excellent model system for studying and resolving the molecular basis of numerous mitochondrial diseases. Here, we review the invaluable insights this model organism has yielded about diseases caused by mitochondrial dysfunction, which ranges from primary defects in oxidative phosphorylation to metabolic disorders, as well as dysfunctions in maintaining the genome or in the dynamics of mitochondria. Owing to the high level of functional conservation between yeast and human mitochondrial genes, several yeast species have been instrumental in revealing the molecular mechanisms of pathogenic human mitochondrial gene mutations. Importantly, such insights have pointed to potential therapeutic targets, as have genetic and chemical screens using yeast., Summary: In this Review, we discuss the use of budding yeast to understand mitochondrial diseases and help in the search for their treatments.
Published: 2015
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47. Soymilk fermentation by Enterococcus faecalis VB43 leads to reduction in the immunoreactivity of allergenic proteins β-conglycinin (7S) and glycinin (11S)

Author: Bernadette Dora Gombossy de Melo Franco, Marisa S. Garro, Yvan Choiset, A. Rodriguez de Olmos, Fernanda Mozzi, Jean-Marc Chobert, Martine Drouet, Thomas Haertlé, Hanitra Rabesona, Vanessa Biscola, Universidade de São Paulo (USP), UR 1268 Biopolymères Interactions Assemblages, Institut National de la Recherche Agronomique (INRA), Centro de Referencia para Lactobacilos [Tucumán] (CERELA), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Unité d'Allergologie Générale et de Pneumologie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Department of Animal Nutrition and Feed Management, University of Life Sciences in Poznan, Institute of Biochemistry and Biophysics, Pawinskiego 5a, Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior and Comite Francais d 'Evaluation de la Cooperation Universitaire avec le Bresil (CAPES-COFECUB / USP-COFECUB), Brazilian Research Council (CNPq), Sao Paulo Research Foundation (FAPESP) [2013/07914-8, 2013/11168-0, 2014/22097-9], and ECOS-Sud Argentina [A14B04]
Subjects: 0301 basic medicine, glycinin, chemistry.chemical_compound, LACTIC ACID BACTERIA, [SDV.IDA]Life Sciences [q-bio]/Food engineering, Enterococcus faecalis, soymilk fermentation, Food science, Polyacrylamide gel electrophoresis, Chromatography, High Pressure Liquid, 2. Zero hunger, CONGLYCININ, biology, Chemistry, Seed Storage Proteins, Proteolytic enzymes, 04 agricultural and veterinary sciences, 040401 food science, Soy allergy, Lactic acid, Biochemistry, Soybean Proteins, Electrophoresis, Polyacrylamide Gel, Lactic acid fermentation, SOYMILK FERMENTATION, SOY ALLERGY, Microbiology (medical), beta-conglycinin, Otras Ingenierías y Tecnologías, Enzyme-Linked Immunosorbent Assay, INGENIERÍAS Y TECNOLOGÍAS, Microbiology, Hydrolysate, Alimentos y Bebidas, 03 medical and health sciences, 0404 agricultural biotechnology, medicine, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, 030109 nutrition & dietetics, soy allergy, Globulins, Antigens, Plant, medicine.disease, biology.organism_classification, Soy Milk, lactic acid bacteria, GLYCININ, Fermentation, Soybeans
Abstract: Food allergies represent a serious problem affecting human health and soy proteins rank among the most allergenic proteins from food origin. The proteolytic enzymes produced by lactic acid bacteria (LAB) can hydrolyse the major allergens present in soybean, reducing their immunoreactivity. Many studies have reported the ability of LAB to ferment soy-based products; while the majority of them focus on the improvement of the sensory characteristics and functionality of soy proteins, a lack of information about the role of lactic fermentation in the reduction of immunoreactivity of these proteins exists. The aim of the present study was to evaluate the capability of the proteolytic strain Enterococcus faecalis VB43 to hydrolyse the main allergenic proteins present in soymilk and to determine the immunoreactivity of the obtained hydrolysates. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) results of fermented soymilk demonstrated complete hydrolysis of the β-subunit from β-conglycinin and the acidic polypeptide from glycinin. Reversed phase high performance liquid chromatography (RP-HPLC) analysis of the peptides released after hydrolysis revealed the appearance of new peptides and the disappearance of non-hydrolysed proteins, indicating extensive hydrolysis of the substrate. Results from competitive enzyme-linked immunosorbent assay (ELISA) tests clearly indicated a reduction in the immunoreactivity (more than one logarithmic unit) in the fermented sample as compared to the non-fermented control. Our results suggest that the soymilk fermented by E. faecalis VB43 may induce lower allergic responses in sensitive individuals. The strain E. faecalis VB43 may be considered as an excellent candidate to efficiently reduce the immunoreactivity of soymilk proteins. Fil: Biscola, V.. Universidade de Sao Paulo; Brasil. Centre de Recherche de Nantes. Institut National de la Recherche Agronomique; Francia Fil: Rodríguez de Olmos, Antonieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina. Centre de Recherche de Nantes. Institut National de la Recherche Agronomique; Francia Fil: Choiset, Y.. Centre de Recherche de Nantes. Institut National de la Recherche Agronomique; Francia Fil: Rabesona, H.. Centre de Recherche de Nantes. Institut National de la Recherche Agronomique; Francia Fil: Garro, Marisa Selva. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina Fil: Mozzi, Fernanda Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina Fil: Chobert, J. M.. Centre de Recherche de Nantes. Institut National de la Recherche Agronomique; Francia Fil: Drouet, M.. Centre hospitalier universitaire d'Angers; Francia Fil: Haertlé, T.. Centre de Recherche de Nantes. Institut National de la Recherche Agronomique; Francia. University Of Tehran; Irán Fil: Franco, B. D. G. M.. Universidade de Sao Paulo; Brasil
Published: 2017
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48. Stress-Related Gene Expression Reflects Morphophysiological Responses to Water Deficit

Author: Alexis Bédiée, Dominika Kamrowska, Nathalie Luchaire, Myriam Dauzat, Wojciech Rymaszewski, Christine Granier, Denis Vile, Jacek Hennig, Institute of Biochemistry and Biophysics, Pawinskiego 5a, Écophysiologie des Plantes sous Stress environnementaux (LEPSE), Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), National Science Centre, Poland (PRELUDIUM grant no. 2012/05/N/NZ9/01396), European Project: 284443,EC:FP7:INFRA,FP7-INFRASTRUCTURES-2011-1,EPPN(2012), 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), and European Project: 284443
Subjects: 0106 biological sciences, 0301 basic medicine, Chalcone synthase, expression génique, Physiology, Arabidopsis, Plant Science, 01 natural sciences, Acclimatization, Soil, 03 medical and health sciences, Gene Expression Regulation, Plant, Stress, Physiological, phénotypage, Botany, Genetics, tolérance au stress abiotique, Arabidopsis thaliana, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, MYB, Transpiration, water deficit, Ecotype, 2. Zero hunger, Regulation of gene expression, Principal Component Analysis, biology, déficit hydrique, arabidopsis thaliana, Water, Plant Transpiration, Articles, 15. Life on land, biology.organism_classification, Phenotype, 030104 developmental biology, caractère morphophysiologique, biology.protein, gene expression, 010606 plant biology & botany
Abstract: Acclimation to water deficit (WD) enables plants to maintain growth under unfavorable environmental conditions, although the mechanisms are not completely understood. In this study, the natural variation of long-term acclimation to moderate and severe soil WD was investigated in 18 Arabidopsis (Arabidopsis thaliana) accessions using PHENOPSIS, an automated phenotyping platform. Soil water content was adjusted at an early stage of plant development and maintained at a constant level until reproductive age was achieved. The accessions were selected based on the expression levels of ANNEXIN1, a drought-related marker. Severe WD conditions had a greater effect on most of the measured morphophysiological traits than moderate WD conditions. Multivariate analyses indicated that trait responses associated with plant size and water management drove most of the variation. Accessions with similar responses at these two levels were grouped in clusters that displayed different response strategies to WD. The expression levels of selected stress-response genes revealed large natural variation under WD conditions. Responses of morphophysiological traits, such as projected rosette area, transpiration rate, and rosette water content, were correlated with changes in the expression of stress-related genes, such as NINE-CIS-EPOXYCAROTENOID DIOXYGENASE3 and N-MYC DOWNREGULATED-LIKE1 (NDL1), in response to WD. Interestingly, the morphophysiological acclimation response to WD also was reflected in the gene expression levels (most notably those of NDL1, CHALCONE SYNTHASE, and MYB DOMAIN PROTEIN44) in plants cultivated under well-watered conditions. Our results may lead to the development of biomarkers and predictors of plant morphophysiological responses based on gene expression patterns.
Published: 2017
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49. Inhibition of food-spoilage and foodborne pathogenic bacteria by a nisin Z-producing Lactococcus lactis subsp. lactis KT2W2L

Author: Xavier Dousset, Thomas Haertlé, Noraphat Hwanhlem, Emmanuel Jaffrès, Teodora Ivanova, Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Faculty of Agriculture, Natural Resources and Environment, Naresuan University, Department of General and Industrial Microbiology, Faculty of Biology, University of Sofia, Department of Animal Nutrition and Feed Management, University of Life Sciences in Poznan, Institute of Biochemistry and Biophysics, Pawinskiego 5a, UMR 1014 SECurité des ALIments et Microbiologie, Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), PRES Université Nantes Angers Le Mans (UNAM), Institut National de la Recherche Agronomique (INRA)-Département Microbiologie et Chaîne Alimentaire (MICA), and Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-SECurité des ALIments et Microbiologie (SECALIM)
Subjects: 0301 basic medicine, food.ingredient, Bacteriocin, Nisin Z, [SDV]Life Sciences [q-bio], 030106 microbiology, Food spoilage, medicine.disease_cause, Microbiology, 03 medical and health sciences, chemistry.chemical_compound, 0404 agricultural biotechnology, food, medicine, Agar, Food science, Escherichia coli, Nisin, biology, Lactococcus lactis, Foodborne pathogen, Pathogenic bacteria, 04 agricultural and veterinary sciences, biology.organism_classification, 040401 food science, chemistry, Staphylococcus aureus, bacteria, Food Science
Abstract: The growth of food-spoilage and foodborne pathogenic bacteria was inhibited by a nisin Z-producing Lactococcus lactis subsp. lactis KT2W2L as determined by the agar spot test and agar well diffusion assay. The growth of Brochothrix thermosphacta DSMZ 20171T and Staphylococcus aureus CIP 76.25 was inhibited when co-cultivated with L. lactis subsp. lactis KT2W2L whereas the growth of Escherichia coli CIP 76.24 and Salmonella Enteritidis CIP 81.3 was not. However, the growth level of E. coli CIP 76.24 and S. Enteritidis CIP 81.3 co-cultivated with L. lactis subsp. lactis KT2W2L was diminished compared to cultivation without L. lactis subsp. lactis KT2W2L. The neutralized cell-free supernatant (NCFS) collected from the culture of L. lactis subsp. lactis KT2W2L, cultivated with and without indicator strain, exhibited inhibition zones against the indicator strains as determined by the agar well diffusion assay. The results reported in this study indicate that a nisin Z-producing L. lactis subsp. lactis KT2W2L may find application as a bio-preservative for reducing food-spoilage and foodborne pathogens in food products.
Published: 2017
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50. Viability and genetic stability of potato spindle tuber viroid mutants with indels in specific loops of the rod-like secondary structure

Author: Włodzimierz Zagórski-Ostoja, Anna Góra-Sochacka, Aneta Więsyk, Thierry Candresse, Institute of Biochemistry and Biophysics, Pawinskiego 5a, Biologie du fruit et pathologie (BFP), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1, and Université Sciences et Technologies - Bordeaux 1-Institut National de la Recherche Agronomique (INRA)-Université Bordeaux Segalen - Bordeaux 2
Subjects: 0301 basic medicine, Cancer Research, Agroinfiltration, Viroid, Mutant, agroinfiltration, medicine.disease_cause, 03 medical and health sciences, Solanum lycopersicum, viroide phytopathogène, Virology, santé des plantes, genetic stability, indel mutants, medicine, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Indel, pathologie végétale, Potato spindle tuber viroid, Plant Diseases, Sequence Deletion, Solanum tuberosum, 2. Zero hunger, Genetics, Mutation, biology, infectivity, viroid, Inverted Repeat Sequences, Wild type, biology.organism_classification, Viroids, maladie des plantes, [SDV.BV.PEP]Life Sciences [q-bio]/Vegetal Biology/Phytopathology and phytopharmacy, Restriction site, 030104 developmental biology, Infectious Diseases, potato spindle tuber viroid, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Nucleic Acid Conformation, RNA, Viral, plant health
Abstract: UMR BFP - Equipe Virologie; Maintenance of the rod-like structure of potato spindle tuber viroid (PSTVd), which contains over 20 loops and bulges between double-stranded helices, is important for viroid biology. To study tolerance to modifications of the stem-loop structures and PSTVd capacity for mutation repair, we have created 6 mutants carrying 3-4 nucleotides deletions or insertions at three unique restriction sites, EagI, StyI and AvaII. Differences in the infectivity of these in vitro generated PSTVd mutants can result from where the mutations map, as well as from the extent to which the secondary structure of the molecule is affected. Deletion or insertion of 4 nucleotides at the EagI and StyI sites led to loss of infectivity. However, mutants with deletion (PSTVd-Ava-del) or insertion (PSTVd-Ava-in) of 3 nucleotides (221GAC223), at the AvaII site (loop 20) were viable but not genetically stable. In all analyzed plants, reversion to the wild type PSTVd-S23 sequence was observed for the PSTVd-Ava-in mutant a few weeks after agroinfiltration. Analysis of PSTVd-Ava-del progeny allowed the identification of 10 new sequence variants carrying various modifications, some of them having retained the original three nucleotide deletion at the AvaII site. Interestingly, other variants gained three nucleotides in the deletion site but did not revert to the original wild type sequence. The genetic stability of the progeny PSTVd-Ava-del sequence variants was evaluated in tomato leaves (early infection) and in both leaves and roots (late infection), respectively.
Published: 2017
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