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1. Behavior of XLPE for HVDC Cables under Thermo-Electrical Stress: Experimental Study and Ageing Kinetics Proposal

Author

Hanen Yahyaoui, Jerome Castellon, Serge Agnel, Aurelien Hascoat, Wilfried Frelin, Christophe Moreau, Pierre Hondaa, Dominique le Roux, Virginie Eriksson, and Carl Johan Andersson

Subjects
HVDC, XLPE cable, ageing, space charge, electric field, dielectric spectroscopy, Technology
Abstract

The present work deals with the study of the electrical behavior of cross-linked polyethylene (XLPE) used for HVDC cable insulation. The aim is to better understand the influences of electrical and thermal stresses on the insulating material in order to provide useful information for designing HVDC cables. This study was carried out on Rogowski samples made of XLPE insulation with semiconductive electrodes, aged for more than 3 years (1220 days) at three different temperatures (70, 80 and 90 °C) under two DC electric fields (30 and 60 kV/mm). Dielectric loss factor, volume resistivity and space charge accumulation were measured. Results are analyzed and cross-correlated, in order to propose possible ageing kinetics.

Published
2021
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2. Structures of parasite calreticulins provide insights into their flexibility and dual carbohydrate/peptide-binding properties

Author

Christophe Moreau, Gianluca Cioci, Marina Iannello, Emmanuelle Laffly, Anne Chouquet, Arturo Ferreira, Nicole M. Thielens, and Christine Gaboriaud

Subjects
protein structure, molecular recognition, X-ray crystallography, solution scattering, calreticulin, parasites, Crystallography, QD901-999
Abstract

Calreticulin (CRT) is a multifaceted protein, initially discovered as an endoplasmic reticulum (ER) chaperone protein, that is essential in calcium metabolism. Various implications in cancer, early development and immunology have been discovered more recently for CRT, as well as its role as a dominant `eat-me' prophagocytic signal. Intriguingly, cell-surface exposure/secretion of CRT is among the infective strategies used by parasites such as Trypanosoma cruzi, Entamoeba histolytica, Taenia solium, Leishmania donovani and Schistosoma mansoni. Because of the inherent flexibility of CRTs, their analysis by X-ray crystallography requires the design of recombinant constructs suitable for crystallization, and thus only the structures of two very similar mammalian CRT lectin domains are known. With the X-ray structures of two distant parasite CRTs, insights into species structural determinants that might be harnessed to fight against the parasites without affecting the functions of the host CRT are now provided. Moreover, although the hypothesis that CRT can exhibit both open and closed conformations has been proposed in relation to its chaperone function, only the open conformation has so far been observed in crystal structures. The first evidence is now provided of a complex conformational transition with the junction reoriented towards P-domain closure. SAXS experiments also provided additional information about the flexibility of T. cruzi CRT in solution, thus complementing crystallographic data on the open conformation. Finally, regarding the conserved lectin-domain structure and chaperone function, evidence is provided of its dual carbohydrate/protein specificity and a new scheme is proposed to interpret such unusual substrate-binding properties. These fascinating features are fully consistent with previous experimental observations, as discussed considering the broad spectrum of CRT sequence conservations and differences.

Published
2016
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3. Les séjours de rupture

Author

Cinderella Bernard, Jacques Trémintin, Claire Sotto-Jeauneau, Stéphanie Le Bouffos, Hervé Stephant, Xavier Velly, Grégoire Millet, David Le Breton, Thierry Trontin, Mylène Stephan, and Christophe Moreau

Published
2022
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4. Total synthesis of the natural (-)-205B alkaloid and its activity toward α7 nAChRs

Author

Sara Mazeh, M. Dolores Garcia-Fernandez, Barbara Pelletier, Christophe Moreau, Philippe Delair, Département de pharmacochimie moléculaire (DPM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut de biologie structurale (IBS - UMR 5075), 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), Labex Arcane CBH-EUR-GS, Mass spectrometry, Animal facility, ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), and ANR-15-IDEX-0002,UGA,IDEX UGA(2015)

Subjects
[SDV]Life Sciences [q-bio], Organic Chemistry, Physical and Theoretical Chemistry, Biochemistry
Abstract

A new approach to the synthesis of the (-)-205B alkaloid is described in this paper. This work is characterised by the development of an efficient chirality transfer through a silyl tethered intramolecular alkylation reaction, an unprecedented tandem highly selective iridium catalyzed partial reduction of lactam coupled with an acid promoted aza-Prins reaction, and an almost complete stereochemical control in Shenvi's radical hydrogen atom transfer on an exocyclic methylene. The second part of this work demonstrates the positive allosteric behavior of this natural alkaloid toward α7 nAChRs, in contrast to the reported inhibitory effect of the unnatural enantiomer.

Published
2023
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5. MARINE RESERVOIR EFFECT OF SPERMACETI, A WAX OBTAINED FROM THE HEAD OF THE SPERM WHALE: A FIRST ESTIMATION FROM MUSEUM SPECIMENS

Author

Lucile Beck, Ingrid Caffy, Emmanuelle Delqué-Količ, Jean-Pascal Dumoulin, Stéphane Hain, Christophe Moreau, Marion Perron, Marc Sieudat, Bruno Thellier, Charlotte Van Hove, Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire de mesure du carbone 14 (LMC14 - UMS 2572), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDU.OCEAN]Sciences of the Universe [physics]/Ocean, Atmosphere, Archeology, General Earth and Planetary Sciences, [SDU.ENVI]Sciences of the Universe [physics]/Continental interfaces, environment
Abstract

Spermaceti is a waxy substance found in the head cavities of sperm whales (Physeter macrocephalus and P. catodon). This substance had a variety of commercial applications from the end of the 18th to the beginning of the 20th century, such as candles, soap, cosmetics and other compounds. Spermaceti was also occasionally used as wax for modeling sculptures. In order to date such artworks the marine reservoir effect (MRE) has to be considered. The chemical library of the Muséum national d’Histoire naturelle (Paris, France) contains samples of spermaceti studied by the French chemist M. E. Chevreul (1786–1889) at the beginning of the 19th century. Eight samples of substances preserved in their original containers were 14C dated. According to the whaling practices and the publications of Chevreul, we estimated that the spermaceti samples came from whales caught between 1805 and 1815. AMS 14C dating results are from 550 to 1180 ± 30 BP, R values between 393 and 1023 (± 34) 14C yr and ΔR between –168 and 504 (± 60) 14C yr. The values presented here are the first ever obtained for spermaceti. However, being based on museum specimens, further measurements on crude material would be necessary to refine these results.

Published
2022
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6. Distinct classes of potassium channels fused to GPCRs as electrical signaling biosensors

Author

Hugues Nury, M. Dolores García-Fernández, Franck C. Chatelain, Anna Moroni, Christophe Moreau, Institut de biologie structurale (IBS - UMR 5075), 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 pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Dipartimento di Biologia, Milano University, ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), ANR-11-LABX-0015,ICST,Canaux ioniques d'intérêt thérapeutique(2011), European Project: 682286,H2020,ERC-2015-CoG,NANOZ-ONIC(2016), Université Nice Sophia Antipolis (1965 - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)

Subjects
Allosteric regulation, 010402 general chemistry, 01 natural sciences, Biochemistry, Genetics and Molecular Biology (miscellaneous), Biochemistry, Article, 03 medical and health sciences, G protein-coupled receptors, viral channels, Genetics, Radiology, Nuclear Medicine and imaging, Receptor, Ion channel, K2P channels, 030304 developmental biology, G protein-coupled receptor, 0303 health sciences, man-made ligand-gated ion channels, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Chemistry, ion channels, protein engineering, Protein engineering, biosensors, Potassium channel, allosteric regulation, 0104 chemical sciences, Computer Science Applications, Biophysics, electrical signal, Biosensor, Linker, Biotechnology
Abstract

Summary Ligand-gated ion channels (LGICs) are natural biosensors generating electrical signals in response to the binding of specific ligands. Creating de novo LGICs for biosensing applications is technically challenging. We have previously designed modified LGICs by linking G protein-coupled receptors (GPCRs) to the Kir6.2 channel. In this article, we extrapolate these design concepts to other channels with different structures and oligomeric states, namely a tetrameric viral Kcv channel and the dimeric mouse TREK-1 channel. After precise engineering of the linker regions, the two ion channels were successfully regulated by a GPCR fused to their N-terminal domain. Two-electrode voltage-clamp recordings showed that Kcv and mTREK-1 fusions were inhibited and activated by GPCR agonists, respectively, and antagonists abolished both effects. Thus, dissimilar ion channels can be allosterically regulated through their N-terminal domains, suggesting that this is a generalizable approach for ion channel engineering., Graphical abstract, Highlights • GPCR regulation of diverse potassium channels through N-terminal fusions • Fusion to the viral PBCV-1 Kcv channel requires a specific linker and receptor • Tetrameric Kcv and dimeric mTREK-1 channels fusions respond to GPCR ligands • The engineered fusions broaden the properties of the channels' electrical signals, Motivation For biosensing applications, electrical signals are attractive since they can be recorded by micro- or nano-electronic systems for developing miniaturized detection devices in biomedical or environmental fields. One of the main limiting steps is the design of sensing elements that specifically recognize ligands such as biomarkers or chemical compounds. Ligand-gated ion channels are natural biosensors that specifically recognize ligands and generate an electrical signal. They have naturally evolved to be finely tuned by regulatory domains or proteins resulting in an appropriate electrical signal. The objective of this work is to leverage these natural biosensors by engineering diverse artificial ion channels that have the desired properties for biosensing or basic research applications. The main challenge is to design de novo allosteric regulations between ion channels and physiologically unrelated membrane proteins. Previously, different G protein-coupled receptors were successfully coupled to a specific ion channel, Kir6.2. In this work, we demonstrate that other ion channels (viral and murine) with distinct oligomerization properties can also be fused to GPCRs via their N-terminal domains. These results open avenues for diversifying engineered ligand-gated ion channels., Ligand-gated ion channels are natural biosensors that generate highly sensitive and fast electrical signals. García-Fernández et al. broaden the regulatory properties of electrical signal output by fusing different potassium channels to GPCRs. Functional fusion to tetrameric and dimeric channels demonstrates the versatility of this approach.

Published
2021
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7. Elicitation of potent SARS-CoV-2 neutralizing antibody responses through immunization using a versatile adenovirus-inspired multimerization platform

Author

Isabelle Bally, Pascal Fender, Daphna Fenel, Evelyne Gout, Solene Besson, Christopher Chevillard, M. Buisson, Axelle Amen, Dalil Hannani, Guy Schoehn, Christophe Moreau, Pascal Poignard, Salome Gallet, Marie-Claire Dagher, Valentin Dettling, Emilie Vassal-Stermann, Institut de biologie structurale (IBS - UMR 5075), 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), Translational microbial Evolution and Engineering (TIMC-TrEE), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), GEFLUC Dauphiné-Savoie, Ligue contre le Cancer Comité Isère, Université Grenoble, Alpes IDEX Initiatives de Recherche Stratégiques and Fondation du Souffle-Fonds de recherche en santé respiratoire (FdS-FRSR), Région Auvergne Rhône-Alpes, AuRA, MEM, ISBG, and ANR-20-COVI-0000,Flash Covid Cov Mime

Subjects
Infectivity, 0303 health sciences, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], biology, viruses, [SDV]Life Sciences [q-bio], biochemical phenomena, metabolism, and nutrition, Virology, Neutralization, 3. Good health, Herd immunity, 03 medical and health sciences, Titer, 0302 clinical medicine, Antigen, Immunization, Immunity, biology.protein, Neutralizing antibody, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has shown that vaccine preparedness is critical to anticipate a fast response to emergent pathogens with high infectivity. To rapidly reach herd immunity, an affordable, easy to store and versatile vaccine platform is thus desirable. We previously designed a non-infectious adenovirus-inspired nanoparticle (ADDomer), and in the present work, we efficiently decorated this original vaccine platform with glycosylated receptor binding domain (RBD) of SARS-CoV-2. Cryo-Electron Microscopy structure revealed that up to 60 copies of this antigenic domain were bound on a single ADDomer particle with the symmetrical arrangements of a dodecahedron. Mouse immunization with the RBD decorated particles showed as early as the first immunization a significant anti-coronavirus humoral response, which was boosted after a second immunization. Neutralization assays with spike pseudo-typed-virus demonstrated the elicitation of strong neutralization titers. Remarkably, the existence of pre-existing immunity against adenoviral-derived particles enhanced the humoral response against SARS-CoV-2. This plug and play vaccine platform revisits the way of using adenovirus to combat emergent pathogens while potentially taking advantage of the adenovirus pre-immunity.

Published
2021

9. An IoT-based Precision Agriculture Project for Education in Circuits and Systems

Author

Francois Rivet, Guillaume Ferre, Ryan Raimond, Christophe Moreau, Corentin Gaury, Eric Kerherve, Laboratoire de l'intégration, du matériau au système (IMS), Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS), École Nationale Supérieure d’Électronique, Informatique, Télécommunications, MATMECA de Bordeaux (Institut Polytechnique de Bordeaux (INP Bordeaux)) (ENSEIRB-MATMECA), and Equipe, Circuits and Systems

Subjects
General Medicine, [SPI.TRON] Engineering Sciences [physics]/Electronics, [SPI.TRON]Engineering Sciences [physics]/Electronics
Abstract

National audience; In this paper, we present how education can be involved in innovative CAS-based solutions and precision agriculture. We focus on a student project dedicated to plant growth monitoring using the Internet of Things (IoT). The objective was to make the students aware of the need for electronic solutions to sustain food production. They were proposed to design and deploy a network of connected devices using LoRa technology to monitor plants in our engineering school, ENSEIRB-MATMECA. We choose a deployment in LoRa technology in order to master the deployment of the network from the beginning to the end. Their work was divided into 3 parts: sensors, radiofrequency circuitry and data management.

Published
2021

10. L'arbre, un levier d'adaptation face au changement climatique

Author

Camille Béral, Donato Andueza, Cécile Ginane, Mickaël Bernard, Fabien Liagre, Sandra NOVAK, Jean-Claude Emile, Véronique Deiss, Jean-Christophe Moreau, Agroof SCOP, Unité Mixte de Recherche sur les Herbivores - UMR 1213 (UMRH), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité Expérimentale Systèmes d'Elevage de Ruminants de Moyenne Montagne (Herbipôle), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Fourrages Environnement Ruminants Lusignan (FERLUS), and Institut de l'élevage (IDELE)

Subjects
[SDV.SA.AGRO]Life Sciences [q-bio]/Agricultural sciences/Agronomy
Abstract

9èmes Journées techniques Ovines; National audience

Published
2020

11. Espaces de vie et climat scolaire : l’appropriation des espaces et la place des adolescents au collège

Author

Christophe Moreau and Coline Poupeau

Subjects
Global and Planetary Change, School climate, bien-être, Geography, Planning and Development, appropriation, climat scolaire, espaces de vie, junior high schools’ students, Urban Studies, collégiens, experimentation, living spaces, well-being, Sociology, expérimentation, Humanities, school climate
Abstract

EnglishThrough this article, we present the first elements of knowledge resulting from an experiment on the school climate that takes place in 10 junior high schools of the Nantes agglomeration, from 2017 to 2021. We present the experimentation which is currently in course in Loire-Atlantique (1). We present our questions about the school climate under the particular prism of the living spaces in the schools and the well-being of the students (2). Then we present the findings that emerge in terms of the layout of reception and living spaces for schoolchildren, and the educational experience of adolescents in these spaces (3). An analysis addresses the various issues (educational, pedagogical and social) to which it refers, and describes some tools, approaches and inspiring practices in the direction of improving the quality of school climate and the well-being of junior high schools students (4). francaisA travers cet article, nous presentons les premiers elements de connaissance issus d’une experimentation sur le climat scolaire qui a lieu dans 10 colleges de l’agglomeration nantaise, de 2017 a 2021. Nous revenons en introduction sur l’experimentation qui est actuellement en cours en Loire-Atlantique (1). Nous presentons nos questionnements autour du climat scolaire sous le prisme particulier des espaces de vie dans les etablissements et du bien-etre des eleves (2). Sont ensuite presentes les constats qui ressortent en termes d’amenagement des espaces d’accueil et de vie des collegiens, et concernant le vecu scolaire des adolescents au sein de ces espaces (3). Une analyse sur l’appropriation des lieux d’accueil et de vie par les adolescents aborde les differents enjeux (educatifs, pedagogiques et sociaux) auquel elle fait reference, et decrit quelques outils, demarches et pratiques inspirantes dans le sens d’une amelioration du climat scolaire et du bien-etre des collegiens (4).

Published
2020

12. Behavior of XLPE for HVDC Cables under Thermo-Electrical Stress: Experimental Study and Ageing Kinetics Proposal

Author

Virginie Eriksson, Jerome Castellon, H. Yahyaoui, Dominique le Roux, Aurelien Hascoat, Serge Agnel, Wilfried Frelin, Pierre Hondaa, Christophe Moreau, and Carl Johan Andersson

Subjects
Technology, Control and Optimization, Materials science, Energy Engineering and Power Technology, Stress (mechanics), chemistry.chemical_compound, Electrical resistivity and conductivity, Electric field, Electrical and Electronic Engineering, Composite material, dielectric spectroscopy, Engineering (miscellaneous), HVDC, Renewable Energy, Sustainability and the Environment, Polyethylene, Space charge, electric field, Dielectric spectroscopy, chemistry, ageing, Electrode, space charge, XLPE cable, Rogowski coil, Energy (miscellaneous)
Abstract

The present work deals with the study of the electrical behavior of cross-linked polyethylene (XLPE) used for HVDC cable insulation. The aim is to better understand the influences of electrical and thermal stresses on the insulating material in order to provide useful information for designing HVDC cables. This study was carried out on Rogowski samples made of XLPE insulation with semiconductive electrodes, aged for more than 3 years (1220 days) at three different temperatures (70, 80 and 90 °C) under two DC electric fields (30 and 60 kV/mm). Dielectric loss factor, volume resistivity and space charge accumulation were measured. Results are analyzed and cross-correlated, in order to propose possible ageing kinetics.

Published
2021
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13. Unexpected presence of

Author

Lucile, Beck, Cyrielle, Messager, Ingrid, Caffy, Emmanuelle, Delqué-Količ, Marion, Perron, Jean-Pascal, Dumoulin, Christophe, Moreau, Christian, Degrigny, and Vincent, Serneels

Subjects
Chemistry, Mass spectrometry, Archaeology, Article
Abstract

The absolute dating of paintings is crucial for tackling the problem of fake art. Investigations to authenticate paintings rely on an advanced knowledge of art history and a collection of scientific techniques. Radiocarbon dating is the only technique that gives access to an absolute time scale, but its application is limited to organic materials such as wood, canvas or natural binder. Extending absolute dating to inorganic pigments would make it possible to overcome the lack of available materials for dating easel and mural paintings. Here, we present a novel technique permitting paintings that contain inorganic pigment to be radiocarbon dated. We report results obtained on lead white that was the major white pigment used from Antiquity to the 20th century. We demonstrate that its manufacture is the key point for an absolute and reliable dating. We report an unprecedented use of 14C to date 14th to 16th century wall paintings. Since lead white was extensively used by the greatest artists, we anticipate that this study will open new avenues for detecting forgeries on the art market and for museums.

Published
2019

14. A Unified Description of Intrinsically Disordered Protein Dynamics under Physiological Conditions Using NMR Spectroscopy

Author

Anton Abyzov, Christophe Moreau, Nicola Salvi, Martin Blackledge, Wiktor Adamski, Malene Ringkjøbing Jensen, Justine Magnat, Damien Maurin, Sigrid Milles, 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), 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-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017)

Subjects
MAP Kinase Kinase 4, Protein Conformation, 010402 general chemistry, Intrinsically disordered proteins, 01 natural sciences, Biochemistry, Sendai virus, Catalysis, Viral Proteins, Xenopus laevis, Colloid and Surface Chemistry, Protein structure, Protein Domains, Animals, Spectroscopy, Nuclear Magnetic Resonance, Biomolecular, chemistry.chemical_classification, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Nitrogen Isotopes, Biomolecule, Protein dynamics, Relaxation (NMR), General Chemistry, Nuclear magnetic resonance spectroscopy, 0104 chemical sciences, Intrinsically Disordered Proteins, Range (mathematics), Nucleoproteins, chemistry, Chemical physics, Oocytes
Abstract

International audience; Intrinsically disordered proteins (IDPs) are flexible biomolecules whose essential functions are defined by their dynamic nature. Nuclear magnetic resonance (NMR) spectroscopy is ideally suited to the investigation of this behavior at atomic resolution. NMR relaxation is increasingly used to detect conformational dynamics in free and bound forms of IDPs under conditions approaching physiological, although a general framework providing a quantitative interpretation of these exquisitely sensitive probes as a function of experimental conditions is still lacking. Here, measuring an extensive set of relaxation rates sampling multiple-time-scale dynamics over a broad range of crowding conditions, we develop and test an integrated analytical description that accurately portrays the motion of IDPs as a function of the intrinsic properties of the crowded molecular environment. In particular we observe a strong dependence of both short-range and long-range motional time scales of the protein on the friction of the solvent. This tight coupling between the dynamic behavior of the IDP and its environment allows us to develop analytical expressions for protein motions and NMR relaxation properties that can be accurately applied over a vast range of experimental conditions. This unified dynamic description provides new insight into the physical behavior of IDPs, extending our ability to quantitatively investigate their conformational dynamics under complex environmental conditions, and accurately predicting relaxation rates reporting on motions on time scales up to tens of nanoseconds, both in vitro and in cellulo.

Published
2019
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15. Assessment of the impact of the electrical stress on the ageing for a HVDC model cable

Author

Julien Cenes, Gilbert Teyssedre, Séverine Le Roy, Laurent Berquez, Virginie Eriksson, Wendy Loyens, Marc Bailleul, Pierre Hondâa, Christophe Moreau, Diélectriques Solides et Fiabilité (LAPLACE-DSF), LAboratoire PLasma et Conversion d'Energie (LAPLACE), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, and le roy, severine

Subjects
[SPI]Engineering Sciences [physics], [SPI] Engineering Sciences [physics], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2019

20. Expression, Biochemistry, and Stabilization with Camel Antibodies of Membrane Proteins: Case Study of the Mouse 5-HT3 Receptor

Author

Aline Desmyter, Horst Vogel, Lamia Mebarki, Takashi Tomizaki, Ruud Hovius, Romain Wyss, Sonja Minniberger, Xiao-Dan Li, Christophe Moreau, Lucie Peclinovska, Ghérici Hassaine, Cédric Deluz, Hugues Nury, Luigino Grasso, Henning Stahlberg, Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Fédérale de Lausanne (EPFL), Biozentrum, University of Basel (Unibas), Architecture et fonction des macromolécules biologiques (AFMB), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie structurale (IBS - UMR 5075), 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)-Centre National de la Recherche Scientifique (CNRS), Laboratory of Biomolecular Research, Paul Scherrer Institute (PSI), Biozentrum [Basel, Suisse], Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Institut de biologie structurale (IBS - UMR 5075 ), 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), 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 Lacapere, Jean-Jacques

Subjects
0301 basic medicine, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Gene Expression, Crystallography, X-Ray, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, law.invention, MESH: Recombinant Proteins, Mice, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Animals, Integral membrane protein, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Protein Stability, Peripheral membrane protein, MESH: Camelus, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Recombinant Proteins, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Biochemistry, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Recombinant DNA, MESH: Membrane Proteins, MESH: Cryoelectron Microscopy, Antibody, Camelus, MESH: Gene Expression, MESH: Receptors, Serotonin, 5-HT3, Cys-loop receptor, VHH, 5-HT3 receptor, Antibodies, Cell Line, 03 medical and health sciences, MESH: Protein Stability, Animals, Humans, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], MESH: Mice, 5-HT receptor, MESH: Humans, MESH: Antibodies, Cryoelectron Microscopy, Membrane Proteins, MESH: Crystallography, X-Ray, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Lama antibody, MESH: Cell Line, 030104 developmental biology, Membrane protein, Cell culture, biology.protein, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Receptors, Serotonin, 5-HT3, Stable cell line
Abstract

International audience; There is growing interest in the use of mammalian protein expression systems, and in the use of antibody-derived chaperones, for structural studies. Here, we describe protocols ranging from the production of recombinant membrane proteins in stable inducible cell lines to biophysical characterization of purified membrane proteins in complex with llama antibody domains. These protocols were used to solve the structure of the mouse 5-HT3 serotonin receptor but are of broad applicability for crystallization or cryo-electron microscopy projects.

Published
2018
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21. PARASOL : AGROFORESTERIE EN SYSTÈME D’ÉLEVAGE OVIN - Étude de son potentiel dans le cadre de l'adaptation au changement climatique

Author

Camille Béral, Donato Andueza, Cécile Ginane, Mickaël Bernard, Fabien Liagre, Nicolas Girardin, Jean Claude Emile, Sandra NOVAK, David Grandgirard, Véronique Deiss, Dorothée Bizeray-Filoche, Jean Christophe Moreau, Eric Pottier, Agroof SCOP, Unité Mixte de Recherche sur les Herbivores - UMR 1213 (UMRH), Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Herbipôle, Institut National de la Recherche Agronomique (INRA), Fourrages Environnement Ruminants Lusignan (FERLUS), UniLaSalle, Institut de l'élevage (IDELE), Agroof, Inra, and Idele

Subjects
[SDV.SA.SF]Life Sciences [q-bio]/Agricultural sciences/Silviculture, forestry, [SDV.SA.SPA]Life Sciences [q-bio]/Agricultural sciences/Animal production studies
Published
2018

22. Les systèmes d’élevage d’herbivores face au changement climatique en France : quelques conclusions d’une série d’études menées de 2006 à 2009 (projet Acta/Mires)

Author

Jean-Christophe Moreau

Subjects
Herbivore, Biomass (ecology), General Veterinary, business.industry, media_common.quotation_subject, Climate change, Climatic changes, livestock farming systems, fodder resources, Forestry, changement climatique, systèmes d’élevage, ressources fourragères, Adaptability, Livestock farming, Geography, Fodder, Agriculture, Livestock, business, media_common
Abstract

Herbovore livestock farming systems and climatic changes in france : conclusions from a series of studies from 2006 to 2009 (the acta/ mires project). Four partners are involved in the ACTA project called “Study of the sensitiveness to climatic changes of the large scale farms and herbivore livestock farming systems” ; these are Arvalis, Inra (national institute for agronomic research), the French Livestock Institute and Meteo France. As part of this programme, simulations based on the STICS farming model were achieved in order to estimate consequences of climatic changes on biomass production of lucerne, corn and grasses. Mid-term (2020-2049) and long-term (2070-2099) basic climatic data to implement such simulations were transmitted by Meteo France according to two socio-demographic scenari (A2 and B1) provided by the 4th report of the GIEC 4 group (government experts). Those simulations include the C0² enrichment effect of atmosphere on photosynthesis and transpiration. Moreover, through the calculation of numerous agro-climatic indicators, we looked into the availability and accessibility to those fodder resources and into the frequency of some climatic risks. Leaning on livestock systems having features of rather different areas regarding the extent and the impact of climatic change, we took into consideration direct consequences of climatic change on fodder farming achieved in those systems, in order to explore the evolution of those particular systems’ balances and to evaluate adapting ways enabling to come back to satisfying and secure balances. These works underline adaptability of those systems to have production levels steady in a near future but put forward less favorable breaking downs in a distant future., Dans le cadre du projet ACTA «Étude de la sensibilité des systèmes de grandes cultures et d’élevages herbivores aux changements climatiques», associant quatre partenaires : ARVALIS, l’INRA, l’Institut de l’Élevage et Météo France, et à partir des données climatiques simulées par Météo-France à moyen (2020-2049) et long terme (2070-2099) selon deux scénarios socio-démographiques (A2 et B1) issus du 4ème rapport du Groupe d’experts intergouvernemental (GIEC 4), des simulations utilisant le modèle de culture STICS (Simulateur multidisciplinaire pour les cultures standard) ont été réalisées pour évaluer les conséquences du changement climatique sur la production de biomasse de la luzerne, du maïs et de prairies à base de graminées. Ces simulations intègrent l’effet de l’enrichissement de l’atmosphère en CO2 sur la photosynthèse et la transpiration. Par ailleurs, au travers du calcul de nombreux indicateurs agro-climatiques, l’étude s’est penchée sur la disponibilité et l’accessibilité à ces ressources fourragères, et sur la fréquence de certains aléas climatiques. En prenant appui sur des systèmes d’élevage caractéristiques de zones bien différentes quant à l’ampleur et l’impact du changement climatique, les conséquences directes du changement climatique sur les cultures fourragères pratiquées dans ces systèmes ont été intégrées afin d’explorer l’évolution des équilibres propres à ces systèmes et évaluer les voies d’adaptation permettant de revenir à des équilibres satisfaisants et sécurisés. Ces travaux soulignent les capacités adaptatives de ces systèmes à maintenir leurs niveaux de production dans le futur proche mais ils mettent en avant des ruptures moins favorables à plus long terme., Moreau Jean-Christophe. Les systèmes d’élevage d’herbivores face au changement climatique en France : quelques conclusions d’une série d’études menées de 2006 à 2009 (projet Acta/Mires). In: Bulletin de l'Académie Vétérinaire de France tome 168 n°2, 2015. pp. 133-138.

Published
2015
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23. Functional mapping of the N-terminal arginine cluster and C-terminal acidic residues of Kir6.2 channel fused to a G protein-coupled receptor

Author

Maria Antonietta Principalli, Jean Revilloud, Leonardo Darré, Karla Langer, Carmen Domene, Anaëlle Rongier, Anne-Claire Godet, Christophe Moreau, Laura Lemel, Michel Vivaudou, 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), Department of Chemistry, King‘s College London, Department of Biochemistry [Oxford], University of Oxford, 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 University of Oxford [Oxford]

Subjects
0301 basic medicine, Stereochemistry, Xenopus, Allosteric regulation, Biophysics, Molecular Dynamics Simulation, Arginine, Biochemistry, Article, Receptors, G-Protein-Coupled, 03 medical and health sciences, ion channel-coupled receptor (ICCR), Animals, Amino Acid Sequence, Potassium Channels, Inwardly Rectifying, Ion channel, ComputingMilieux_MISCELLANEOUS, G protein-coupled receptor, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Chemistry, protein engineering, Cell Biology, Kir6.2, Protein engineering, electrophysiology, Fusion protein, Potassium channel, 030104 developmental biology, Mutagenesis, Site-Directed, Oocytes, muscarinic receptor, molecular dynamics simulations, Linker, Ion Channel Gating
Abstract

Ion channel-coupled receptors (ICCRs) are original man-made ligand-gated ion channels created by fusion of G protein-coupled receptors (GPCRs) to the inward-rectifier potassium channel Kir6.2. GPCR conformational changes induced by ligand binding are transduced into electrical current by the ion channel. This functional coupling is closely related to the length of the linker region formed by the GPCR C-terminus (C-ter) and Kir6.2 N-terminus (N-ter). Manipulating the GPCR C-ter length allows to finely tune the channel regulation, both in amplitude and sign (opening or closing Kir6.2). In this work, we demonstrate that the primary sequence of the channel N-terminal domain is an additional parameter for the functional coupling with GPCRs. As for all Kir channels, a cluster of basic residues is present in the N-terminal domain of Kir6.2 and is composed of 5 arginines which are proximal to the GPCR C-ter in the fusion proteins. Using a functional mapping approach, we demonstrate the role of specific arginines (R27 and R32) for the function of ICCRs, indicating that the position and not the cluster of positively-charged arginines is critical for the channel regulation by the GPCR. Following observations provided by molecular dynamics simulation, we explore the hypothesis of interaction of these arginines with acidic residues, and using site-directed mutagenesis, we identified aspartate D307 and glutamate E308 residues as critical for the function of ICCRs. These results demonstrate the critical role of the N-terminal and C-terminal charged residues of Kir6.2 for its allosteric regulation by the fused GPCR.

Published
2017
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24. Ion Channels as Reporters of Membrane Receptor Function: Automated Analysis in Xenopus Oocytes

Author

Michel, Vivaudou, Zlatomir, Todorov, Gina Catalina, Reyes-Mejia, and Christophe, Moreau

Subjects
Automation, Laboratory, Xenopus laevis, G Protein-Coupled Inwardly-Rectifying Potassium Channels, Cell Membrane, Oocytes, Animals, Female, Xenopus Proteins, Electrophysiological Phenomena, Receptors, G-Protein-Coupled, Signal Transduction
Abstract

G-protein-coupled receptors (GPCR) are the most widely used system of communication used by cells. They sense external signals and translate them into intracellular signals. The information is carried mechanically across the cell membrane, without perturbing its integrity. Agonist binding on the extracellular side causes a change in receptor conformation which propagates to the intracellular side and causes release of activated G-proteins, the first messengers of a variety of signaling cascades.Permitting access to powerful electrophysiological techniques, ion channels can be employed to monitor precisely the most proximal steps of GPCR signaling, receptor conformational changes, and G-protein release. The former is achieved by physical attachment of a potassium channel to the GPCR to create an Ion-Channel Coupled Receptor (ICCR). The latter is based on the use of G-protein-regulated potassium channels (GIRK). We describe here how these two systems may be used in the Xenopus oocyte heterologous system with a robotic system for increased throughput.

Published
2017

25. Ion Channels as Reporters of Membrane Receptor Function: Automated Analysis in Xenopus Oocytes

Author

Zlatomir Todorov, Michel Vivaudou, Gina Catalina Reyes-Mejia, Christophe Moreau, 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), ANR-11-RPIB-0022,VenomPicoScreen,Découverte de principes actifs à partir de venins en utilisant des bicouches artificielles miniaturisées(2011), ANR-11-LABX-0015,ICST,Canaux ioniques d'intérêt thérapeutique(2011), European Project: NIH, Centre National de la Recherche Scientifique (CNRS)-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)

Subjects
0301 basic medicine, MESH: Signal Transduction, G-protein-coupled receptor, Robot, Ion-channel-coupled receptor, Xenopus, MESH: Automation, Laboratory, MESH: Receptors, G-Protein-Coupled, MESH: Oocytes, 03 medical and health sciences, 0302 clinical medicine, MESH: Xenopus laevis, Two-electrode voltage clamp, MESH: Animals, G protein-coupled inwardly-rectifying potassium channel, Potassium channel, MESH: Electrophysiological Phenomena, MESH: Xenopus Proteins, Ion channel, G protein-coupled receptor, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Chemistry, biology.organism_classification, Molecular biology, 030104 developmental biology, Second messenger system, Biophysics, Signal transduction, Xenopus oocyte, MESH: Female, 030217 neurology & neurosurgery, Intracellular, MESH: G Protein-Coupled Inwardly-Rectifying Potassium Channels, MESH: Cell Membrane
Abstract

International audience; G-protein-coupled receptors (GPCR) are the most widely used system of communication used by cells. They sense external signals and translate them into intracellular signals. The information is carried mechanically across the cell membrane, without perturbing its integrity. Agonist binding on the extracellular side causes a change in receptor conformation which propagates to the intracellular side and causes release of activated G-proteins, the first messengers of a variety of signaling cascades.Permitting access to powerful electrophysiological techniques, ion channels can be employed to monitor precisely the most proximal steps of GPCR signaling, receptor conformational changes, and G-protein release. The former is achieved by physical attachment of a potassium channel to the GPCR to create an Ion-Channel Coupled Receptor (ICCR). The latter is based on the use of G-protein-regulated potassium channels (GIRK). We describe here how these two systems may be used in the Xenopus oocyte heterologous system with a robotic system for increased throughput.

Published
2017
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26. Deciphering key residues involved in the virulence-promoting interactions between Streptococcus pneumoniae and human plasminogen

Author

Anne Marie Di Guilmi, Christine Gaboriaud, Christophe Moreau, Nicole M. Thielens, Thierry Vernet, Rémi Terrasse, 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), Centre National de la Recherche Scientifique (CNRS)-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)

Subjects
0301 basic medicine, crystal structure, bacterial pathogenesis, Protein Conformation, Host–pathogen interaction, 030106 microbiology, Virulence, cell surface receptor, host-pathogen interaction, medicine.disease_cause, Biochemistry, Protein–protein interaction, protein-protein interaction, 03 medical and health sciences, Immune system, Cell surface receptor, Streptococcus pneumoniae, medicine, Humans, Amino Acid Sequence, Receptor, Molecular Biology, Glyceraldehyde 3-phosphate dehydrogenase, peptide array, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Glyceraldehyde-3-Phosphate Dehydrogenases, Streptococcus, Cell Biology, Surface Plasmon Resonance, Kinetics, 030104 developmental biology, gram-positive bacteria, Protein Structure and Folding, biology.protein, plasminogen, Thermodynamics, Protein Binding
Abstract

International audience; Bacterial pathogens recruit circulating proteins to their own surfaces, coopting the host protein functions as a mechanism of virulence. Particular attention has focused on the binding of plasminogen (Plg) to bacterial surfaces, as it has been shown that this interaction contributes to bacterial adhesion to host cells, invasion of host tissues and evasion of the immune system. Several bacterial proteins are known to serve as receptors for Plg including glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a cytoplasmic enzyme that appears on the cell surface in this moonlighting role. Although Plg typically binds to these receptors via several lysine-binding domains, the specific interactions that occur have not been documented in all cases. However, identification of the relevant residues could help define strategies for mitigating the virulence of important human pathogens, like Streptococcus pneumoniae (Sp). To shed light on this question, we have described a combination of peptide-spot array screening, competition and SPR assays, high-resolution crystallography and mutational analyses to characterize the interaction between SpGAPDH and Plg. We identified three SpGAPDH lysire residues that were instrumental in defining the kinetic and thermodynamic parameters of the interaction. Altogether, the integration of the data presented in this work allows us to propose a structural model for the molecular interaction of the SpGAPDH-Plg complex.

Published
2017
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27. Tuning the allosteric regulation of artificial muscarinic and dopaminergic ligand-gated potassium channels by protein engineering of G protein-coupled receptors

Author

Argel Estrada-Mondragon, Julien P. Dupuis, Serge Crouzy, Michel Vivaudou, Katarzyna Nieścierowicz, Christophe Moreau, Nicolas Sapay, Jean Revilloud, Amandine Trouchet, Lydia N. Caro, 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), 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), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), ANR-09-PIRI-0010,ICCR(2009), ANR-11-RPIB-0022,VenomPicoScreen,Découverte de principes actifs à partir de venins en utilisant des bicouches artificielles miniaturisées(2011), ANR-11-LABX-0015,ICST,Canaux ioniques d'intérêt thérapeutique(2011), 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 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)

Subjects
0301 basic medicine, Dopamine, Recombinant Fusion Proteins, Xenopus, Gating, Protein Engineering, Article, Receptors, G-Protein-Coupled, SK channel, 03 medical and health sciences, 0302 clinical medicine, Allosteric Regulation, Animals, Potassium Channels, Inwardly Rectifying, Ion channel, Receptor, Muscarinic M2, Multidisciplinary, Voltage-gated ion channel, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Receptors, Dopamine D2, Inward-rectifier potassium ion channel, Chemistry, Ligand-Gated Ion Channels, Light-gated ion channel, Acetylcholine, 3. Good health, 030104 developmental biology, Biochemistry, Biophysics, Ligand-gated ion channel, 030217 neurology & neurosurgery, Ion channel linked receptors
Abstract

Ligand-gated ion channels enable intercellular transmission of action potential through synapses by transducing biochemical messengers into electrical signal. We designed artificial ligand-gated ion channels by coupling G protein-coupled receptors to the Kir6.2 potassium channel. These artificial channels called ion channel-coupled receptors offer complementary properties to natural channels by extending the repertoire of ligands to those recognized by the fused receptors, by generating more sustained signals and by conferring potassium selectivity. The first artificial channels based on the muscarinic M2 and the dopaminergic D2L receptors were opened and closed by acetylcholine and dopamine, respectively. We find here that this opposite regulation of the gating is linked to the length of the receptor C-termini, and that C-terminus engineering can precisely control the extent and direction of ligand gating. These findings establish the design rules to produce customized ligand-gated channels for synthetic biology applications.

Published
2017
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28. Mock-up Study of the Effect of Wall distance on the Thermal Rating of Power Cables in Ventilated Tunnels

Author

Julien Pellé, Souad Harmand, Fahd Boukrouche, O. Moreau, François Beaubert, Christophe Moreau, Laboratoire d'Automatique, de Mécanique et d'Informatique industrielles et Humaines - UMR 8201 (LAMIH), and INSA Institut National des Sciences Appliquées Hauts-de-France (INSA Hauts-De-France)-Centre National de la Recherche Scientifique (CNRS)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)

Subjects
Convection, Engineering, 020209 energy, Energy Engineering and Power Technology, 02 engineering and technology, Physics::Fluid Dynamics, Heating, symbols.namesake, Mathematical model, Thermal, 0202 electrical engineering, electronic engineering, information engineering, Electrical and Electronic Engineering, Simulation, Power cables, Power transmission, Temperature measurement, Turbulence, business.industry, Reynolds number, Mechanics, [SPI.MECA]Engineering Sciences [physics]/Mechanics [physics.med-ph], Nusselt number, Mockup, Heat transfer, symbols, business, Cooling
Abstract

International audience; Power transmission through power cables installed in ventilated tunnels is increasingly used worldwide and offers a complex thermal environment. Established correlations currently in use have been deduced from a nonfully developed turbulent flow and the effect of the proximity to a tunnel wall is not accounted for. This paper details the experimental and numerical investigations conducted on a mock-up of the heat transfer from a single cable in a fully developed turbulent airflow, with emphasis on the effect of the cable spacing from the tunnel wall. Nusselt numbers have been compared for different spacing and Reynolds numbers. The overall heat transfer is found to be meaningfully lower than in previous studies as only a third of the heat transfer is found, possible explanation of these differences are given in this paper. A threshold value is observed for the heat transfer while the cable rating depreciation is more gradual. The radiative heat exchange is found to be up to 30% of the total heat loss. An improved cooling law for the case of a single cable in tunnel taking into account the proximity of the wall has been developed from this study and confronted to the experimental and simulated data.

Published
2017
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29. Mortar Dating Methodology: Assessing Recurrent Issues and Needs for Further Research

Author

Mark Van Strydonck, Laura Panzeri, Petra Urbanová, Christophe Moreau, Anna Galli, Marta Caroselli, Sophie Hueglin, Tomasz Goslar, Justyna Czernik, F. Maspero, Pierre Guibert, Danuta Michalska, Isabella Passariello, Laurent Fontaine, Manuela Capano, Åsa Ringbom, Fabio Marzaioli, Alf Lindroos, Mathieu Boudin, Anna Addis, Roald Hayen, Irka Hajdas, Elisabetta Boaretto, Gilberto Artioli, Jan Heinemeier, Michele Secco, Filippo Terrasi, Hayen, Roald, Van Strydonck, Mark, Fontaine, Laurent, Boudin, Mathieu, Lindroos, Alf, Heinemeier, Jan, Ringbom, Ã sa, Michalska, Danuta, Hajdas, Irka, Hueglin, Sophie, Marzaioli, Fabio, Terrasi, Filippo, Passariello, Isabella, Capano, Manuela, Maspero, Francesco, Panzeri, Laura, Galli, Anna, Artioli, Gilberto, Addis, Anna, Secco, Michele, Boaretto, Elisabetta, Moreau, Christophe, Guibert, Pierre, Urbanova, Petra, Czernik, Justyna, Goslar, Tomasz, Caroselli, Marta, Unité de chimie organique moléculaire et macromoléculaire (UCO2M), Le Mans Université (UM)-Centre National de la Recherche Scientifique (CNRS), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Centre européen de recherche et d'enseignement des géosciences de l'environnement (CEREGE), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Collège de France (CdF)-Institut national des sciences de l'Univers (INSU - CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), CNR Institute for Photonics and Nanotechnologies (IFN), Consiglio Nazionale delle Ricerche [Roma] (CNR), Max Planck Weizmann Center for Integrative Archaeology and Anthropology (WPWC), Max Planck Institute for Evolutionary Anthropology, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft-Weizmann Institute of Science, Laboratoire de Recherche en Sciences Humaines (Lares-Las), Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), IRAMAT-Centre de recherche en physique appliquée à l’archéologie (IRAMAT-CRP2A), Institut de Recherches sur les Archéomatériaux (IRAMAT), Université de Technologie de Belfort-Montbeliard (UTBM)-Université d'Orléans (UO)-Université Bordeaux Montaigne-Centre National de la Recherche Scientifique (CNRS)-Université de Technologie de Belfort-Montbeliard (UTBM)-Université d'Orléans (UO)-Université Bordeaux Montaigne-Centre National de la Recherche Scientifique (CNRS), Faculty of Physics, Adam Mickiewicz University in Poznań (UAM), Le Mans Université (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Collège de France (CdF (institution))-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Weizmann Institute of Science [Rehovot, Israël]-Max Planck Institute for Evolutionary Anthropology [Leipzig], Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Montaigne-Université de Technologie de Belfort-Montbeliard (UTBM)-Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Montaigne-Université de Technologie de Belfort-Montbeliard (UTBM), Institut Royal du Patrimoine Artistique | Royal Institute for Cultural Heritage (KIK-IRPA), Åbo Akademi University [Turku], Aarhus University [Aarhus], Newcastle University [Newcastle], Seconda Università degli studi di Napoli, Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Universita degli Studi di Padova, Max Planck Institute for Evolutionary Anthropology [Leipzig], Max-Planck-Gesellschaft-Max-Planck-Gesellschaft-Weizmann Institute of Science [Rehovot, Israël], CEA- Saclay (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Poznań Radiocarbon Laboratory | Poznańskie Laboratorium Radiowęglowe, Scuola universitaria professionale della Svizzera italiana = University of Applied Sciences and Arts of Southern Switzerland [Manno] (SUPSI), Seconda Università degli Studi di Napoli = Second University of Naples, Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Università degli Studi di Padova = University of Padua (Unipd), Université de Technologie de Belfort-Montbeliard (UTBM)-Université d'Orléans (UO)-Université Bordeaux Montaigne (UBM)-Centre National de la Recherche Scientifique (CNRS)-Université de Technologie de Belfort-Montbeliard (UTBM)-Université d'Orléans (UO)-Université Bordeaux Montaigne (UBM)-Centre National de la Recherche Scientifique (CNRS), Hayen, R, Van Strydonck, M, Fontaine, L, Boudin, M, Lindroos, A, Heinemeier, J, Ringbom, Å, Michalska, D, Hajdas, I, Hueglin, S, Marzaioli, F, Terrasi, F, Passariello, I, Capano, M, Maspero, F, Panzeri, L, Galli, A, Artioli, G, Addis, A, Secco, M, Boaretto, E, Moreau, C, Guibert, P, Urbanova, P, Czernik, J, Goslar, T, and Caroselli, M

Subjects
010506 paleontology, Archeology, Optically stimulated luminescence, 01 natural sciences, Civil engineering, law.invention, law, Absolute dating, [CHIM]Chemical Sciences, 0601 history and archaeology, CARBONATE, Radiocarbon dating, lime, OSL, 0105 earth and related environmental sciences, 060102 archaeology, Archeology (arts and humanities), Dating methodologies in archaeology, 06 humanities and the arts, AMS C-14, LIME MORTARS, radiocarbon AMS dating, mortar dating, General Earth and Planetary Sciences, Environmental science, Mortar, Earth and Planetary Sciences (all)
Abstract

Absolute dating of mortars is crucial when trying to pin down construction phases of archaeological sites and historic stone buildings to a certain point in time or to confirm, but possibly also challenge, existing chronologies. To evaluate various sample preparation methods for radiocarbon (14C) dating of mortars as well as to compare different dating methods, i.e.14C and optically stimulated luminescence (OSL), a mortar dating intercomparison study (MODIS) was set up, exploring existing limits and needs for further research. Four mortar samples were selected and distributed among the participating laboratories: one of which was expected not to present any problem related to the sample preparation methodologies for anthropogenic lime extraction, whereas all others addressed specific known sample preparation issues. Data obtained from the various mortar dating approaches are evaluated relative to the historical framework of the mortar samples and any deviation observed is contextualized to the composition and specific mineralogy of the sampled material.

Published
2017
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32. Structures of parasite calreticulins provide insights into their flexibility and dual carbohydrate/peptide-binding properties

Author

Emmanuelle Laffly, Anne Chouquet, Nicole M. Thielens, Christophe Moreau, Christine Gaboriaud, Gianluca Cioci, Arturo Ferreira, Marina Iannello, 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), Institute of Biomedical Sciences, Universidad de Chile = University of Chile [Santiago] (UCHILE), Centre National de la Recherche Scientifique (CNRS)-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)

Subjects
0301 basic medicine, Peptide binding, Computational biology, parasites, Biochemistry, calreticulin, 03 medical and health sciences, 0302 clinical medicine, Molecular recognition, Protein structure, Calcium-binding protein, parasitic diseases, Taenia solium, medicine, General Materials Science, protein structure, X-ray crystallography, Crystallography, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Endoplasmic reticulum, General Chemistry, Condensed Matter Physics, solution scattering, Research Papers, 3. Good health, medicine.drug_formulation_ingredient, 030104 developmental biology, QD901-999, 030220 oncology & carcinogenesis, Chaperone (protein), biology.protein, molecular recognition, Calreticulin
Abstract

New insights into calreticulins are obtained by studying parasite species and combining a dissection strategy, X-ray crystallography and SAXS., Calreticulin (CRT) is a multifaceted protein, initially discovered as an endoplasmic reticulum (ER) chaperone protein, that is essential in calcium metabolism. Various implications in cancer, early development and immunology have been discovered more recently for CRT, as well as its role as a dominant ‘eat-me’ prophagocytic signal. Intriguingly, cell-surface exposure/secretion of CRT is among the infective strategies used by parasites such as Trypanosoma cruzi, Entamoeba histolytica, Taenia solium, Leishmania donovani and Schistosoma mansoni. Because of the inherent flexibility of CRTs, their analysis by X-ray crystallography requires the design of recombinant constructs suitable for crystallization, and thus only the structures of two very similar mammalian CRT lectin domains are known. With the X-ray structures of two distant parasite CRTs, insights into species structural determinants that might be harnessed to fight against the parasites without affecting the functions of the host CRT are now provided. Moreover, although the hypothesis that CRT can exhibit both open and closed conformations has been proposed in relation to its chaperone function, only the open conformation has so far been observed in crystal structures. The first evidence is now provided of a complex conformational transition with the junction reoriented towards P-domain closure. SAXS experiments also provided additional information about the flexibility of T. cruzi CRT in solution, thus complementing crystallographic data on the open conformation. Finally, regarding the conserved lectin-domain structure and chaperone function, evidence is provided of its dual carbohydrate/protein specificity and a new scheme is proposed to interpret such unusual substrate-binding properties. These fascinating features are fully consistent with previous experimental observations, as discussed considering the broad spectrum of CRT sequence conservations and differences.

Published
2016
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33. Mortar Dating Methodology: Intercomparison of Available Methods

Author

Roald Hayen, Mark van Strydonck, Mathieu Boudin, Alf Lindroos, Jan Heinemeier, Åsa Ringbom, Danuta Michalska, Irka Hajdas, Sophie Hueglin, Fabio Marzaioli, Filippo Terrasi, Isabella Passariello, Manuela Capano, Francesco Maspero, Laura Panzeri, Anna Galli, Pierre Guibert, Petra Urbanova, Anna Addis, Michele Secco, Elisabetta Boaretto, Christophe Moreau, Laurent Fontaine, Institut Royal du Patrimoine Artistique, Åbo Akademi University [Turku], Aarhus University [Aarhus], Adam Mickiewicz University in Poznań (UAM), Université de Genève (UNIGE), Newcastle University [Newcastle], Università degli studi della Campania 'Luigi Vanvitelli', Centre européen de recherche et d'enseignement des géosciences de l'environnement (CEREGE), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Collège de France (CdF)-Institut national des sciences de l'Univers (INSU - CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Dipartimento di Fisica [Milano], Politecnico di Milano [Milan] (POLIMI), IRAMAT-Centre de recherche en physique appliquée à l’archéologie (IRAMAT-CRP2A), Institut de Recherches sur les Archéomatériaux (IRAMAT), Université de Technologie de Belfort-Montbeliard (UTBM)-Université d'Orléans (UO)-Université Bordeaux Montaigne-Centre National de la Recherche Scientifique (CNRS)-Université de Technologie de Belfort-Montbeliard (UTBM)-Université d'Orléans (UO)-Université Bordeaux Montaigne-Centre National de la Recherche Scientifique (CNRS), Universita degli Studi di Padova, Weizmann Institute of Science, Université de Nantes (UN), Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Collège de France (CdF (institution))-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Dipartimento di Fisica [Politecnico Milano], Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Montaigne-Université de Technologie de Belfort-Montbeliard (UTBM)-Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Montaigne-Université de Technologie de Belfort-Montbeliard (UTBM), Weizmann Institute of Science [Rehovot, Israël], Institut Royal du Patrimoine Artistique | Royal Institute for Cultural Heritage (KIK-IRPA), Université de Genève = University of Geneva (UNIGE), Università degli studi della Campania 'Luigi Vanvitelli' = University of the Study of Campania Luigi Vanvitelli, Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Dipartimento di Fisica [Politecnico Milano] (POLIMI), Université de Technologie de Belfort-Montbeliard (UTBM)-Université d'Orléans (UO)-Université Bordeaux Montaigne (UBM)-Centre National de la Recherche Scientifique (CNRS)-Université de Technologie de Belfort-Montbeliard (UTBM)-Université d'Orléans (UO)-Université Bordeaux Montaigne (UBM)-Centre National de la Recherche Scientifique (CNRS), and Università degli Studi di Padova = University of Padua (Unipd)

Subjects
[SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2016
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34. A thermal study of power cables cooling in tunnels

Author

Souad Harmand, Julien Pellé, Christophe Moreau, F. Boukrouche, O. Moreau, François Beaubert, Laboratoire d'Automatique, de Mécanique et d'Informatique industrielles et Humaines - UMR 8201 (LAMIH), Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Centre National de la Recherche Scientifique (CNRS)-INSA Institut National des Sciences Appliquées Hauts-de-France (INSA Hauts-De-France), EDF R&D (EDF R&D), EDF (EDF), and INSA Institut National des Sciences Appliquées Hauts-de-France (INSA Hauts-De-France)-Centre National de la Recherche Scientifique (CNRS)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)

Subjects
History, Engineering, 020209 energy, Airflow, Mechanical engineering, 02 engineering and technology, Power delivery, Education, Physics::Fluid Dynamics, 0203 mechanical engineering, Thermal, 0202 electrical engineering, electronic engineering, information engineering, Power transmission, Radiation, business.industry, Turbulence, Mechanics, [SPI.MECA]Engineering Sciences [physics]/Mechanics [physics.med-ph], Nusselt number, Computer Science Applications, Power (physics), 020303 mechanical engineering & transports, Thermal radiation, Heat transfer, Forced convection, Fully turbulent flow, business
Abstract

International audience; Power transmission through power cables installed in ventilated tunnels has been increasingly used worldwide and offers a complex thermal environment. Established correlations currently in use have been deduced from a non-fully developed turbulent flow. This paper details the experimental investigation of the heat transfer from a single cable in a fully developed turbulent air flow, with emphasis on the effect of the cable spacing from the tunnel wall. Nusselt numbers have been compared for different spacing and velocities. The overall heat transfer is found to be meaningfully lower than in previous studies and no threshold spacing value for the average heat transfer to decrease is clearly found. Thermal radiation is found to greatly impact the cable cooling profile.

Published
2016
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35. Structural and Functional Characterization of a Single-Chain Form of the Recognition Domain of Complement Protein C1q

Author

Barbara Bottazzi, Christophe Moreau, Nicole M. Thielens, Anne Chouquet, Christine Gaboriaud, Berhane Ghebrehiwet, Isabelle Bally, 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), Immunopharmacology Laboratory, Humanitas Research Hospital, Department of Medicine, Stony Brook University [SUNY] (SBU), State University of New York (SUNY)-State University of New York (SUNY), ISBG: SPR, mass spectrometry, analytical ultracentrifugation, N-terminal sequencing, ANR-09-PIRI-0021,STR-ASS-DEF-COL(2009), Centre National de la Recherche Scientifique (CNRS)-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)

Subjects
lcsh:Immunologic diseases. Allergy, 0301 basic medicine, innate immune recognition, Immunology, chemical and pharmacologic phenomena, Biology, law.invention, 03 medical and health sciences, Classical complement pathway, fluids and secretions, law, immune system diseases, Heterotrimeric G protein, Immunology and Allergy, complement, Globular Region, skin and connective tissue diseases, Complement C1q, C1q, Original Research, X-ray crystallography, Pentraxins, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], protein engineering, Protein engineering, Complement system, 030104 developmental biology, Biochemistry, Recombinant DNA, Biophysics, biology.protein, lcsh:RC581-607, surface plasmon resonance
Abstract

International audience; Complement C1q is a soluble pattern recognition molecule comprising six heterotrimeric subunits assembled from three polypeptide chains (A-C). Each heterotrimer forms a collagen-like stem prolonged by a globular recognition domain. These recognition domains sense a wide variety of ligands, including pathogens and altered-self components. Ligand recognition is either direct or mediated by immunoglobulins or pentraxins. Multivalent binding of C1q to its targets triggers immune effector mechanisms mediated via its collagen-like stems. The induced immune response includes activation of the classical complement pathway and enhancement of the phagocytosis of the recognized target. We report here, the first production of a single-chain recombinant form of human C1q globular region (C1q-scGR). The three monomers have been linked in tandem to generate a single continuous polypeptide, based on a strategy previously used for adiponectin, a protein structurally related to C1q. The resulting C1q-scGR protein was produced at high yield in stably transfected 293-F mammalian cells. Recombinant C1q-scGR was correctly folded, as demonstrated by its X-ray crystal structure solved at a resolution of 1.35 Å. Its interaction properties were assessed by surface plasmon resonance analysis using the following physiological C1q ligands: the receptor for C1q globular heads, the long pentraxin PTX3, calreticulin, and heparin. The 3D structure and the binding properties of C1q-scGR were similar to those of the three-chain fragment generated by collagenase digestion of serum-derived C1q. Comparison of the interaction properties of the fragments with those of native C1q provided insights into the avidity component associated with the hexameric assembly of C1q. The interest of this functional recombinant form of the recognition domains of C1q in basic research and its potential biomedical applications are discussed.

Published
2016
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36. Radiocarbon Dating of the Decorated Cosquer Cave (France)

Author

Hélène Valladas, Christophe Moreau, Evelyne Kaltnecker, Luc Vanrell, Xavier Delestre, Anita Quiles, Emmanuelle Delqué-Količ, Edwige Pons-Branchu, Michel Olive, Géochrononologie Traceurs Archéométrie (GEOTRAC), Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut français d'archéologie orientale du Caire (IFAO), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Laboratoire de mesure du carbone 14 (LMC14 - UMS 2572), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)

Subjects
010506 paleontology, Archeology, geography, geography.geographical_feature_category, 060102 archaeology, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, 06 humanities and the arts, Soil surface, 14C dating, 01 natural sciences, Archaeology, law.invention, Paleontology, decorated Cosquer cave, Cave, Paleolithic, law, visual_art, visual_art.visual_art_medium, General Earth and Planetary Sciences, 0601 history and archaeology, Radiocarbon dating, Charcoal, Geology, 0105 earth and related environmental sciences
Abstract

The Grotte Cosquer (southeastern France) is a Paleolithic painted cave only accessible by a deep-water dive. The cave has yielded numerous Paleolithic engravings and drawings, which were produced from wood charcoal. This article presents new radiocarbon dates obtained on samples collected in 2012 directly on 17 parietal representations and at the soil surface, and discusses the 14C results obtained since the discovery of the cave in 1992. A total of 41 samples were dated with ages ranging from 33,000 to 20,000 cal BP. They show that the cave was intermittently decorated over about 10,000 yr.

Published
2016
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37. Kir6.2 activation by sulfonylurea receptors: a different mechanism of action for SUR1 and SUR2A subunits via the same residues

Author

Maria Antonietta Principalli, Michel Vivaudou, Julien P. Dupuis, Jean Revilloud, Christophe Moreau, 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), Institut Interdisciplinaire de Neurosciences (IINS), Centre National de la Recherche Scientifique (CNRS), ANR-11-LABX-0015,ICST,Canaux ioniques d'intérêt thérapeutique(2011), European Project: NIH, Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Institut Interdisciplinaire des Neurosciences de Bordeaux, 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
0303 health sciences, Transmembrane channels, endocrine system, Physiology, Inward-rectifier potassium ion channel, [SDV]Life Sciences [q-bio], Diazoxide, ATP-sensitive K+ channels, Voltage-gated potassium channel, Kir6.2, functional coupling, Biology, Potassium channel, SK channel, 03 medical and health sciences, 0302 clinical medicine, Biochemistry, Physiology (medical), Biophysics, Sulfonylurea receptor, ATP‐sensitive K+ channels, Patch clamp, 030217 neurology & neurosurgery, 030304 developmental biology, Original Research
Abstract

International audience; ATP-sensitive potassium channels (K-ATP channels) play a key role in adjusting the membrane potential to the metabolic state of cells. They result from the unique combination of two proteins: the sulfonylurea receptor (SUR), an ATP-binding cassette (ABC) protein, and the inward rectifier K(+) channel Kir6.2. Both subunits associate to form a heterooctamer (4 SUR/4 Kir6.2). SUR modulates channel gating in response to the binding of nucleotides or drugs and Kir6.2 conducts potassium ions. The activity of K-ATP channels varies with their localization. In pancreatic β-cells, SUR1/Kir6.2 channels are partly active at rest while in cardiomyocytes SUR2A/Kir6.2 channels are mostly closed. This divergence of function could be related to differences in the interaction of SUR1 and SUR2A with Kir6.2. Three residues (E1305, I1310, L1313) located in the linker region between transmembrane domain 2 and nucleotide-binding domain 2 of SUR2A were previously found to be involved in the activation pathway linking binding of openers onto SUR2A and channel opening. To determine the role of the equivalent residues in the SUR1 isoform, we designed chimeras between SUR1 and the ABC transporter multidrug resistance-associated protein 1 (MRP1), and used patch clamp recordings on Xenopus oocytes to assess the functionality of SUR1/MRP1 chimeric K-ATP channels. Our results reveal that the same residues in SUR1 and SUR2A are involved in the functional association with Kir6.2, but they display unexpected side-chain specificities which could account for the contrasted properties of pancreatic and cardiac K-ATP channels.

Published
2015
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39. How to Boost Product Line Engineering with MBSE - A Case Study of a Rolling Stock Product Line

Author

Christophe Moreau, Marco Ferrogalini, and Hugo Guillermo Chalé Góngora

Subjects
Engineering, business.industry, Systems Modeling Language, Product line, Product family, Domain engineering, business, Software product line, Stock (geology), Manufacturing engineering
Abstract

This paper presents the first results of current product line engineering efforts at Alstom Transport. It describes the background that has led us to these efforts as well as the approach that we have adopted on Model-Based Systems Engineering (MBSE) and Product Line Engineering (PLE). We present a real-life application of MBSE and PLE that “goes beyond” SysML along with a quick overview of the first results stemming from this application to Rolling Stock systems.

Published
2015
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40. Consolidation or initial design? Radiocarbon dating of ancient iron alloys sheds light on the reinforcements of French Gothic Cathedrals

Author

Christophe Moreau, Emmanuelle Delqué-Količ, Stéphanie Leroy, Jean-Pascal Dumoulin, Philippe Dillmann, Maxime l'Héritier, Laboratoire Archéomatériaux et Prévision de l'Altération (LAPA - UMR 3685), Nanosciences et Innovation pour les Matériaux, la Biomédecine et l'Energie (ex SIS2M) (NIMBE UMR 3685), Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), IRAMAT - Laboratoire Métallurgies et Cultures (IRAMAT - LMC), Institut de Recherches sur les Archéomatériaux (IRAMAT), Université de Technologie de Belfort-Montbeliard (UTBM)-Université d'Orléans (UO)-Université Bordeaux Montaigne-Centre National de la Recherche Scientifique (CNRS)-Université de Technologie de Belfort-Montbeliard (UTBM)-Université d'Orléans (UO)-Université Bordeaux Montaigne-Centre National de la Recherche Scientifique (CNRS), Centre de recherches historiques : histoire des pouvoirs, savoirs et sociétés, Université Paris 8 Vincennes-Saint-Denis (UP8), Laboratoire de mesure du carbone 14 (LMC14 - UMS 2572), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), and Université de Technologie de Belfort-Montbeliard (UTBM)-Université d'Orléans (UO)-Université Bordeaux Montaigne (UBM)-Centre National de la Recherche Scientifique (CNRS)-Université de Technologie de Belfort-Montbeliard (UTBM)-Université d'Orléans (UO)-Université Bordeaux Montaigne (UBM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Data source, 010506 paleontology, Archeology, 060102 archaeology, Iron alloys, 06 humanities and the arts, 01 natural sciences, Archaeology, Medieval architecture, law.invention, law, [CHIM]Chemical Sciences, 0601 history and archaeology, Radiocarbon dating, Architecture, Geology, Radiocarbon dating Iron reinforcements Gothic Cathedrals, 0105 earth and related environmental sciences
Abstract

International audience; Large quantities of iron reinforcements, found in most Gothic monuments, are a data source for the interpretation of medieval architecture however their role both in contemporary engineering theory and the technical reality of construction yards has not yet been specified due to the difficulty of directly dating them. We present here an original radiocarbon dating methodology to date metal itself. Radiocarbon dates were measured for iron reinforcements used in specific parts of Bourges and Beauvais cathedrals, two iconic buildings in the development of French gothic architecture. Coupled with archaeometric and archaeological data, the new chronological results illuminate the major and active roles played by iron in the strategy of the building yards. At Bourges, iron was assimilated into the cathedral's construction strategy, whereas at Beauvais iron was integrated from the initial design, added to the monument following the vicissitudes of the building yard, and still used during the modern period. Thus, through decisive advances in radiocarbon dating of iron artefacts, the evolution of medieval architectural and engineering thought and action has been more reliably reconstructed.

Published
2015
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41. Ion Channel Reporter for Monitoring the Activity of Engineered GPCRs

Author

Lydia N. Caro, Michel Vivaudou, Katarzyna Niescierowicz, Christophe Moreau, and Jean Revilloud

Subjects
biology, Biochemistry, G protein, Protein purification, Biophysics, Xenopus, Binding site, biology.organism_classification, Receptor, Intracellular, Ion channel, G protein-coupled receptor
Abstract

Ion channel-coupled receptor (ICCR) is a recent technology based on the fusion of G protein-coupled receptors (GPCRs) to an ion channel. Binding of ligands on the GPCR triggers conformational changes of the receptor that are mechanically transmitted to the ion channel gates, generating an electrical signal easily detectable with conventional electrophysiological techniques. ICCRs are heterologously expressed in Xenopus oocytes and offers several advantages such as: (i) real-time recordings on single cells, (ii) standard laboratory environment and inexpensive media for Xenopus oocytes maintenance, (iii) absence of protein purification steps, (iv) sensitivity to agonists and antagonists in concentration-dependent manner, (v) compatibility with a Gi/o protein activation assay based on Kir3.x channels, and (vi) ability to detect receptor activation independently of intracellular effectors. This last characteristic of ICCRs led to the development of a functional assay for G protein-"uncoupled" receptors such as GPCRs optimized for crystallization by alteration of their third intracellular (i3) loop. One of the most widely used approaches consists in replacing the i3 loop with the T4 phage lysozyme (T4L) domain that obstructs the access of G proteins to their binding site. We recently demonstrated that the ICCR technology can functionally characterize GPCRs(T4L). Two-electrode voltage-clamp (TEVC) recordings revealed that apparent affinities and sensitivities to ligands are not affected by T4L insertion, while ICCRs(T4L) displayed a partial agonist phenotype upon binding of full agonists, suggesting that ICCRs could detect intermediate-active states. This chapter aims to provide exhaustive details from molecular biology steps to electrophysiological recordings for the design and the characterization of ICCRs and ICCRs(T4L).

Published
2015
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42. Socialisations familiales et consommations en milieu étudiant

Author

Ludovic Gaussot, Nicolas Palierne, Loïc Le Minor, Groupe de Recherche et d’Etudes Sociologiques sur les sociétés COntemporaines (GRESCO), Université de Poitiers-Institut Sciences de l'Homme et de la Société (IR SHS UNILIM), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Axe 3 (2017-2021) : 'Les frontières du corps ' (MSHS Poitiers), Maison des sciences de l'homme et de la société de Poitiers (MSHS), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Marie Choquet, and Christophe Moreau

Subjects
alcool, [SHS.SOCIO]Humanities and Social Sciences/Sociology, environnement social, fête, ComputingMilieux_MISCELLANEOUS, étudiant, [SHS]Humanities and Social Sciences
Abstract

International audience

Published
2019

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