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41 results on '"Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID"'

1. In Vivo Fast Nonlinear Microscopy Reveals Impairment of Fast Axonal Transport Induced by Molecular Motor Imbalances in the Brain of Zebrafish Larvae

Author: Baptiste Grimaud, Maxence Frétaud, Feriel Terras, Antoine Bénassy, Karine Duroure, Valérie Bercier, Gaëlle Trippé-Allard, Rabei Mohammedi, Thierry Gacoin, Filippo Del Bene, François Marquier, Christelle Langevin, François Treussart, Treussart, François, APPEL À PROJETS TRANSNATIONAL SUR LA NANOMÉDECINE - - MoDiaNo2018 - ANR-18-ENM3-0002 - ERAnet EURONANOMED - VALID, Enabling Vision Restoration - - FOReSIGHT2018 - ANR-18-IAHU-0001 - IAHU - VALID, Comprendre comment l'homéostasie du transport axonal est médiée par le 'tubulin code' - - CodeAx2020 - ANR-20-CE13-0011 - AAPG2020 - VALID, iReelAx : Analyse interspécifique des fonctions de Reelin dans le câblage des circuits et les troubles neurodéveloppementaux - - iReelAx2019 - ANR-19-CE16-0017 - AAPG2019 - VALID, Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID, Laboratoire Lumière, Matière et Interfaces (LuMIn), CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay), Plateforme d'Infectiologie Expérimentale des Rongeurs et Poissons (IERP (UE 0907)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Virologie et Immunologie Moléculaires (VIM (UR 0892)), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), VIB Center for Brain and Disease Research, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Laboratoire de physique de la matière condensée (LPMC), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), MITI CNRS- Fondation pour la recherche médicale (grant #MND202003011485)- FWO Fellowship (#12Y9120N), ANR-18-ENM3-0002,MoDiaNo(2018), ANR-18-IAHU-0001,FOReSIGHT,Enabling Vision Restoration(2018), ANR-20-CE13-0011,CodeAx,Comprendre comment l'homéostasie du transport axonal est médiée par le 'tubulin code'(2020), ANR-19-CE16-0017,iReelAx,iReelAx : Analyse interspécifique des fonctions de Reelin dans le câblage des circuits et les troubles neurodéveloppementaux(2019), and ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011)
Subjects: [PHYS.PHYS.PHYS-OPTICS] Physics [physics]/Physics [physics]/Optics [physics.optics], [PHYS.PHYS.PHYS-OPTICS]Physics [physics]/Physics [physics]/Optics [physics.optics], second harmonic generation, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, General Engineering, General Physics and Astronomy, nonlinear nanocrystal, disease models, molecular motor, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, zebrafish larva, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], General Materials Science, two-photon microscopy, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], axonal transport, single nanoparticle tracking
Abstract: International audience; Cargo transport by molecular motors along microtubules is essential for the function of eucaryotic cells, in particular neurons in which axonal transport defects constitute the early pathological features of neurodegenerative diseases. Mainly studied in motor and sensory neurons, axonal transport is still difficult to characterize in neurons of the brain in absence of appropriate in vivo tools. Here, we measured fast axonal transport by tracing the second harmonic generation (SHG) signal of potassium titanyl phosphate (KTP) nanocrystals endocytosed by brain neurons of zebrafish (Zf) larvae. Thanks to the optical translucency of Zf larvae and of the perfect photostability of nanoKTP SHG, we achieved a high scanning speed of 20 frames (of ≈ 90 μ m×60 μ m size) per second in Zf brain. We focused our study on endolysosomal vesicle transport in axons of known polarization, separately analyzing kinesin and dynein motor-driven displacements. To validate our assay, we used either loss-of-function mutations of dynein or kinesin 1 or the dynein inhibitor dynapyrazole, and quantified several transport parameters. We successfully demonstrated that dynapyrazole reduces nanoKTP mobile fraction and retrograde run length consistently, while the retrograde run length increased in kinesin 1 mutants. Taking advantage of nanoKTP SHG directional emission, we also quantified fluctuations of vesicle orientation. Thus, by combining endocytosis of nanocrystals having non-linear response, fast two-photon microscopy, and high-throughput analysis, we are able to finely monitor fast axonal transport in vivo in the brain of a vertebrate, and reveal subtle axonal transport alterations. The high spatiotemporal resolution achieved in our model may be relevant to precisely investigate axonal transport impairment associated to disease models.
Published: 2022
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2. Rolling Balance Board Robust Stabilization: A MID-based Design

Author: Amina BENARAB, Molnar, Csenge A., Islam Boussaada, Karim Trabelsi, Tamás Insperger, Silviu-Iulian Niculescu, BENARAB, Amina, Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID, Laboratoire des signaux et systèmes (L2S), CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Polytechnique des Sciences Avancées (IPSA), Dynamical Interconnected Systems in COmplex Environments (DISCO), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire des signaux et systèmes (L2S), CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Budapest University of Technology and Economics [Budapest] (BME), and ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011)
Subjects: [INFO.INFO-SY] Computer Science [cs]/Systems and Control [cs.SY], exponential stability, [MATH.MATH-GM] Mathematics [math]/General Mathematics [math.GM], [MATH] Mathematics [math], [SPI.AUTO]Engineering Sciences [physics]/Automatic, Multiplicity-Induced-Dominancy, [MATH.MATH-GM]Mathematics [math]/General Mathematics [math.GM], Human balance, [SPI.AUTO] Engineering Sciences [physics]/Automatic, Control and Systems Engineering, [INFO.INFO-SY]Computer Science [cs]/Systems and Control [cs.SY], [NLIN] Nonlinear Sciences [physics], [NLIN]Nonlinear Sciences [physics], [MATH]Mathematics [math]
Abstract: International audience; This paper considers the stabilization of a rolling balance board by means of the multiplicity-induceddominancy property. A two degree-of-freedom mechanical model of a human balancing on a rolling balance board is analyzed in the sagittal plane. The human body is modeled by an inverted pendulum which connects to the balance board through the ankle joint. The system is stabilized by the ankle torque managed by the central nervous system (CNS). The action of the CNS is modeled by a delayed full state feedback: a pointwise delay stands for all latencies in the neuromechanical system (reaction time, neuromechanical lag, etc.). The aim of the paper is to achieve a good occurrence in terms of the decay rate, it shows the links with dominancy and with the exponential stability property of the solution.
Published: 2022
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3. CD38‐NADase is a new major contributor to Duchenne muscular dystrophic phenotype

Author: Antoine de Zélicourt, Abdallah Fayssoil, Mbarka Dakouane‐Giudicelli, Isley De Jesus, Ahmed Karoui, Faouzi Zarrouki, Florence Lefebvre, Arnaud Mansart, Jean‐Marie Launay, Jerome Piquereau, Mariana G Tarragó, Marcel Bonay, Anne Forand, Sophie Moog, France Piétri‐Rouxel, Elise Brisebard, Claudia C S Chini, Sonu Kashyap, Matthew J Fogarty, Gary C Sieck, Mathias Mericskay, Eduardo N Chini, Ana Maria Gomez, José‐Manuel Cancela, Sabine de la Porte, Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Signalisation et physiopathologie cardiovasculaire (CARPAT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Infection et inflammation (2I), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Mayo Clinic [Rochester], Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), BABARIT, Candice, Blanc 2013 - Arythmies dépendantes du calcium intracellulaire : mécanismes de la tachycardie ventriculaire catécholergique. - - ARyRthmia2013 - ANR-13-BSV1-0023 - Blanc 2013 - VALID, Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID, Mécanismes proarythmiques dépendant du sodium et du calcium - - NaCaR2019 - ANR-19-CE14-0031 - AAPG2019 - VALID, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Physiopathologie Animale et bioThérapie du muscle et du système nerveux (PAnTher), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Expertise en Anatomie Pathologique (APEX), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Mayo Clinic, This research has been supported by grants from CNRS, INSERM, and Paris-Saclay University. Funding for this work was provided by AFM-telethon grants(JMC, SDP, and AZ). AZ is a recipient of a PhD fellowship from the Paris-SudUniversity. This work was also partly funded by the Fondation de France (JMC),ANRs (NAD-Heart #17-CE17-0015-01to MM, and ANR-19-CE14-0031-01andANR-13-BSV1-0023-01to AMG), and NIH AG58812to ENC. INSERM U1180is amember of the Laboratory of Excellence LERMIT supported by a grant fromANR (ANR-10-LABX-33) under the program'Investissements d’Avenir'ANR-11-IDEX-0003-01. The authors thank the radiology department of the RaymondPoincare Hospital. The authors thank Sanofi for providing isatuximab. Theauthors thank Frances Lund for providing CD38/mice and the platform forimmortalization of human cells'MyoLine'from the Institut of Myology forproviding the DMD and healthy subject cell lines. Graphical abstract has beencreated with BioRender.com.ENC, J-MC, SP, and AZ have patents on the use of CD38inhibitors, ANR-13-BSV1-0023,ARyRthmia,Arythmies dépendantes du calcium intracellulaire : mécanismes de la tachycardie ventriculaire catécholergique.(2013), ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), and ANR-19-CE14-0031,NaCaR,Mécanismes proarythmiques dépendant du sodium et du calcium(2019)
Subjects: calcium, [SDV]Life Sciences [q-bio], NAD, ADP-ribosyl Cyclase 1, [SDV] Life Sciences [q-bio], Muscular Dystrophy, Duchenne, Mice, NAD+ Nucleosidase, Phenotype, NAD+, DMD, Mice, Inbred mdx, Animals, Humans, Molecular Medicine, Myocytes, Cardiac, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Muscle, Skeletal, cardiomyopathy, CD38, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: ENC, J-MC, SP, and AZ have patents on the use of CD38inhibitors ENC, J-MC, SP, and AZ have patents on the use of CD38inhibitors ENC, J-MC, SP, and AZ have patents on the use of CD38inhibitors; International audience; Duchenne muscular dystrophy (DMD) is characterized by progressive muscle degeneration. Two important deleterious features are a Ca2+ dysregulation linked to Ca2+ influxes associated with ryanodine receptor hyperactivation, and a muscular nicotinamide adenine dinucleotide (NAD+ ) deficit. Here, we identified that deletion in mdx mice of CD38, a NAD+ glycohydrolase-producing modulators of Ca2+ signaling, led to a fully restored heart function and structure, with skeletal muscle performance improvements, associated with a reduction in inflammation and senescence markers. Muscle NAD+ levels were also fully restored, while the levels of the two main products of CD38, nicotinamide and ADP-ribose, were reduced, in heart, diaphragm, and limb. In cardiomyocytes from mdx/CD38-/- mice, the pathological spontaneous Ca2+ activity was reduced, as well as in myotubes from DMD patients treated with isatuximab (SARCLISA® ) a monoclonal anti-CD38 antibody. Finally, treatment of mdx and utrophin-dystrophin-deficient (mdx/utr-/- ) mice with CD38 inhibitors resulted in improved skeletal muscle performances. Thus, we demonstrate that CD38 actively contributes to DMD physiopathology. We propose that a selective anti-CD38 therapeutic intervention could be highly relevant to develop for DMD patients.
Published: 2022
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4. Exploring fundamental aspects of the structural organization in weberite-type tantalate oxides

Author: Gussev, Igor, Baldinozzi, Gianguido, O'Quinn, Eric, Neuefeind, Jörg, Lang, Maik, Baldinozzi, Gianguido, Physics: Atoms, Light, Matter - - PALM2010 - ANR-10-LABX-0039 - LABX - VALID, and Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID
Subjects: [CHIM.MATE] Chemical Sciences/Material chemistry, Mesoscale organisation, Total scattering, Neutron scattering, Fluorite structures, Pair distribution function PDF, [CHIM.CRIS] Chemical Sciences/Cristallography, [PHYS.COND.CM-MS] Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci]
Abstract: The design of advanced energy-related materials that are specifically engineered to maintain structural stability in a variety of harsh operating conditions, such as high pressure, temperature, and radiation fields, requires the development of specific experimental techniques and analyses that address the organization of complex materials over length scales that range from the interatomic distances to several hundreds of nanometers. Such structural characterization is important as compositional and structural disorder forms as a consequence of exposure to extremes that impact thermal, mechanical, and chemical properties. Weberite-type tantalate oxides (A3TaO7) are promising candidates for many energy-related applications, but there is only a limited understanding of how their atomic-scale structure changes as a result of exposure to extremes (e.g., high temperature and ion irradiation). We performed state-of-the-art neutron total scattering experiments across a compositional range of weberite-type tantalate oxides and analyzed the real space, short-range pair correlation functions to establish evidence that their local atomic arrangements adopt an organization different from their well-known ‘average’ structure across longer length scales. This finding appears to be a general phenomenon for a range of weberite-type oxides structures, spanning from fully ordered (orthorhombic Pr3TaO7) to fully disordered (cubic Yb3TaO7). Comparing short- and long-range structural behaviors across the compositional series have revealed a complex organization of structural correlations across different length scales: the short-range analysis suggests a strong dependence on the ionic radius of the A-site cation and the distortion of a local structural motif that monotonically increases across the compositional series, while the long-range analysis confirmed the existence of three distinct structure types. This behavior is explained by the incompatibility of tilt systems in the long-range structure due to the increasing local distortions.Acknowledgment: This work was supported in part by the French Grant ANR-10-LABX-0039-PALM and by the Joint Ph.D. Programme of Université Paris-Saclay as part of the « Investissements d’Avenir » program grant number ANR-11-IDEX-0003.
Published: 2022

5. Identification of Small Molecules Inhibiting Cardiomyocyte Necrosis and Apoptosis by Autophagy Induction and Metabolism Reprogramming

Author: Dawei Liu, Félix Peyre, Yahir Alberto Loissell-Baltazar, Delphine Courilleau, Sandra Lacas-Gervais, Valérie Nicolas, Eric Jacquet, Svetlana Dokudovskaya, Frédéric Taran, Jean-Christophe Cintrat, Catherine Brenner, JACQUET, ERIC, Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID, Research Laboratory on Drugs and Therapeutic Innovation - - LERMIT2010 - ANR-10-LABX-0033 - LABX - VALID, Lanzhou University, Aspects métaboliques et systémiques de l'oncogénèse pour de nouvelles approches thérapeutiques (METSY), Institut Gustave Roussy (IGR)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Ingénierie et Plateformes au Service de l'Innovation Thérapeutique (IPSIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), CCMA - Centre Commun de Microscopie Appliquée, Université Côte d'Azur (UCA), Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Service de Chimie Bio-Organique et de Marquage (SCBM), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-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 National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-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 National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), and ANR-10-LABX-0033,LERMIT,Research Laboratory on Drugs and Therapeutic Innovation(2010)
Subjects: QH301-705.5, screening, cardiotoxicity, Apoptosis, General Medicine, Hydrogen Peroxide, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Rats, Necrosis, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, cardioprotection, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Autophagy, mitochondrion, Animals, Humans, apoptosis, autophagy, Myocytes, Cardiac, Biology (General)
Abstract: International audience; Improvement of anticancer treatments is associated with increased survival of cancer patients at risk of cardiac disease. Therefore, there is an urgent need for new therapeutic molecules capable of preventing acute and long-term cardiotoxicity. Here, using commercial and home-made chemolibraries, we performed a robust phenotypic high-throughput screening in rat cardiomyoblast cell line H9c2, searching for small molecules capable of inhibiting cell death. A screen of 1600 compounds identified six molecules effective in preventing necrosis and apoptosis induced by H$_2$O$_2$ and camptothecin in H9c2 cells and in rat neonatal ventricular myocytes. In cells treated with these molecules, we systematically evaluated the expression of BCL-2 family members, autophagy progression, mitochondrial network structure, regulation of mitochondrial fusion/fission, reactive oxygen species, and ATP production. We found that these compounds affect autophagy induction to prevent cardiac cell death and can be promising cardioprotective drugs during chemotherapy.
Published: 2021
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6. Collective Effects in Ionic Liquid [emim][Tf2N] and Ionic Paramagnetic Nitrate Solutions without Long-Range Structuring

Author: Eni Kume, Nicolas Martin, Peter Dunne, Patrick Baroni, Laurence Noirez, Laboratoire Léon Brillouin (LLB - UMR 12), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), LLB - Nouvelles frontières dans les matériaux quantiques (NFMQ), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de Physique et Chimie des Matériaux de Strasbourg (IPCMS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), European Project: 766007,MAMI, NOIREZ, Laurence, Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID, and Magnetics and Microhydrodynamics - from guided transport to delivery - MAMI - 766007 - INCOMING
Subjects: paramagnetic liquids, [PHYS]Physics [physics], ionic liquids, mechanical measurements, shear elasticity, neutron scattering, Organic Chemistry, Pharmaceutical Science, [PHYS.COND.CM-MS] Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], [PHYS] Physics [physics], Analytical Chemistry, Chemistry (miscellaneous), Drug Discovery, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], Molecular Medicine, Physical and Theoretical Chemistry
Abstract: International audience; Mesoscopic shear elasticity has been revealed in ordinary liquids both experimentally by reinforcing the liquid/surface interfacial energy and theoretically by nonextensive models. The elastic effects are here examined in the frame of small molecules with strong electrostatic interactions such as room temperature ionic liquids [emim][Tf2N] and nitrate solutions exhibiting paramagnetic properties. We first show that these charged fluids also exhibit a nonzero lowfrequency shear elasticity at the submillimeter scale, highlighting their resistance to shear stress. A neutron scattering study completes the dynamic mechanical analysis of the paramagnetic nitrate solution, evidencing that the magnetic properties do not induce the formation of a structure in the solution. We conclude that the elastic correlations contained in liquids usually considered as viscous away from any phase transition contribute in an effective way to collective effects under external stress or mechanical and magnetic fields.
Published: 2022
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7. From hidden shear-elasticity to opto-and thermo-elasticity in confined polymer melts and viscous liquids

Author: Noirez, Laurence, Kume, Eni, Baroni, Patrick, LLB - Nouvelles frontières dans les matériaux quantiques (NFMQ), Laboratoire Léon Brillouin (LLB - UMR 12), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay, ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), European Project: 766007,MAMI, NOIREZ, Laurence, Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID, Magnetics and Microhydrodynamics - from guided transport to delivery - MAMI - 766007 - INCOMING, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
Subjects: Condensed Matter::Soft Condensed Matter, Physics::Fluid Dynamics, [PHYS.COND.CM-SCM]Physics [physics]/Condensed Matter [cond-mat]/Soft Condensed Matter [cond-mat.soft], [PHYS.COND.CM-SCM] Physics [physics]/Condensed Matter [cond-mat]/Soft Condensed Matter [cond-mat.soft]
Abstract: From the newly identified low frequency liquid elasticity, it turns out the possibility to reveal novel dynamic properties of liquids at mesoscopic scale. We present two examples illustrating the impact of the mesoscopic liquid elasticity in optics and thermodynamics. We show strain induced optical effects and thermo-induced effects that occur in the liquid state and reveal the need to take into consideration the elastic character of fluids at small scale. The fluids are submitted to a low frequency (~ Hz) mechanical shear strain (external stress). We probe the dynamic response by two methods, either accessing instant optical response of the liquid phase of liquid crystals and or probing the thermal response upon mechanical deformation. It is shown that the isotropic phase of liquid crystals can exhibit a dynamic birefringence in the isotropic phase while ordinary liquids exhibit cold and cold thermal waves upon low frequency excitation.
Published: 2021

8. Azetidinimines as a novel series of non-covalent broad-spectrum inhibitors of β-lactamases with submicromolar activities against carbapenemases KPC-2 (class A), NDM-1 (class B) and OXA-48 (class D)

Author: Mohamed Benchekroun, Saoussen Oueslati, Sandrine Ventre, Kamsana Vijayakumar, Eddy Elisée, Laetitia A. Nguyen, Edithe Selwa, Robert H. Dodd, Linda Tlili, Alain Pruvost, Pascal Retailleau, Thierry Naas, Agustin Zavala, Bogdan I. Iorga, Agathe C. A. D'Hollander, Eugénie Romero, Cynthia Exilie, Kevin Cariou, Corinne Minard, Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-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 National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ecologie et Evolution de la Résistance aux Antibiotiques / Ecology and Evolution of Antibiotics Resistance (EERA), Institut Pasteur [Paris] (IP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), This work was supported by the Laboratory of Excellence in Research on Medication and Innovative Therapeutics (LERMIT, grant ANR-10-LABX-33 under the program Investissements d’Avenir ANR-11-IDEX-0003-01), the FCS Campus Paris-Saclay pre-maturation program (project Inhibase), the SATT Paris-Saclay (project CARBAMAT), the JPIAMR transnational project DesInMBL (grant ANR-14-JAMR-0002) and the Région Ile-de-France (DIM Malinf). The authors also thank CNRS, AP-HP, Université Paris-Saclay, and ICSN, for financial support., ANR-10-LABX-0033,LERMIT,Research Laboratory on Drugs and Therapeutic Innovation(2010), ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), ANR-14-JAMR-0002,DesInMBL,Structure-guided design of pan inhibitors of metallo-ß-lactamases(2014), Institut Pasteur [Paris]-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Cariou, Kevin, Research Laboratory on Drugs and Therapeutic Innovation - - LERMIT2010 - ANR-10-LABX-0033 - LABX - VALID, Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID, and programmation conjointe européenne sur la résistance antimicrobienne - Structure-guided design of pan inhibitors of metallo-ß-lactamases - - DesInMBL2014 - ANR-14-JAMR-0002 - JPI AMR - VALID
Subjects: Imipenem, Non covalent, Antibiotics, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, medicine.disease_cause, 01 natural sciences, Broad spectrum, Catalytic Domain, Drug Discovery, polycyclic compounds, OXA-48, chemistry.chemical_classification, 0303 health sciences, biology, Escherichia coli Proteins, General Medicine, Ynamides, Anti-Bacterial Agents, Molecular Docking Simulation, Microsomes, Liver, beta-Lactamase Inhibitors, medicine.drug, Gram-negative bacteria, Carbapenemase inhibitors, medicine.drug_class, Stereochemistry, Azetidinimines, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, Microbial Sensitivity Tests, NDM-1, beta-Lactamases, Bacterial resistance, KPC-2, Cell Line, Inhibitory Concentration 50, Structure-Activity Relationship, 03 medical and health sciences, Antibiotic resistance, Gram-Negative Bacteria, medicine, Humans, Escherichia coli, Cell Proliferation, 030304 developmental biology, Pharmacology, Binding Sites, 010405 organic chemistry, Organic Chemistry, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, 0104 chemical sciences, Enzyme, chemistry, Azetidines
Abstract: International audience; The occurrence of resistances in Gram negative bacteria is steadily increasing to reach extremely worrying levels and one of the main causes of resistance is the massive spread of very efficient β-lactamases which render most β-lactam antibiotics useless. Herein, we report the development of a series of imino-analogues of β-lactams (namely azetidinimines) as efficient non-covalent inhibitors of β-lactamases. Despite the structural and mechanistic differences between serine-β-lactamases KPC-2 and OXA-48 and metallo-β-lactamase NDM-1, all three enzymes can be inhibited at a submicromolar level by compound 7dfm, which can also repotentiate imipenem against a resistant strain of Escherichia coli expressing NDM-1. We show that 7dfm can efficiently inhibit not only the three main clinically-relevant carbapenemases of Ambler classes A (KPC-2), B (NDM-1) and D (OXA-48) with Ki’s below 0.3 μM, but also the cephalosporinase CMY-2 (class C, 86% inhibition at 10 μM). Our results pave the way for the development of a new structurally original family of non-covalent broad-spectrum inhibitors of β-lactamases.
Published: 2021
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9. From Linear to Harmonic Thermal response of mesoscopic liquids upon mechanical shear strain

Author: Kume, E, Noirez, Laurence, LLB - Nouvelles frontières dans les matériaux quantiques (NFMQ), Laboratoire Léon Brillouin (LLB - UMR 12), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), European Project: 766007,MAMI, NOIREZ, Laurence, Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID, Magnetics and Microhydrodynamics - from guided transport to delivery - MAMI - 766007 - INCOMING, and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay
Subjects: [PHYS]Physics [physics], [PHYS.COND]Physics [physics]/Condensed Matter [cond-mat], [PHYS.COND] Physics [physics]/Condensed Matter [cond-mat], [PHYS] Physics [physics]
Published: 2020

10. Distinctive Cellular and Metabolic Reprogramming in Porcine Lung Mononuclear Phagocytes Infected With Type 1 PRRSV Strains

Author: Crisci, Elisa, Moroldo, Marco, Vu Manh, Thien-Phong, Mohammad, Ammara, Jourdren, Laurent, Urien, Celine, Bouguyon, Edwige, Bordet, Elise, Bevilacqua, Claudia, Bourge, Mickael, Pezant, Jérémy, Pléau, Alexis, Boulesteix, Olivier, Schwartz, Isabelle, Bertho, Nicolas, Giuffra, Elisabetta, Génétique Animale et Biologie Intégrative (GABI), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biologie, Epidémiologie et analyse de risque en Santé Animale (BIOEPAR), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Virologie et Immunologie Moléculaires (VIM (UR 0892)), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), European Project: 609398,EC:FP7:PEOPLE,FP7-PEOPLE-2013-COFUND,AGREENSKILLSPLUS(2014), European Project: 633184,H2020,H2020-SFS-2014-2,SAPHIR(2015), Giuffra, Elisabetta, ERA-NET sur la Santé et Bien être animal ANIHWA - Control of highly virulent pathogenic European porcine reproductive and respiratory syndrome viruses - - KILLeuPRRSV2014 - ANR-14-ANWA-0005 - ANIHWA - VALID, Développment d'une infrastructure française distribuée coordonnée - - France-BioImaging2010 - ANR-10-INBS-0004 - INBS - VALID, Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, AgreenSkills+ - AGREENSKILLSPLUS - - EC:FP7:PEOPLE2014-05-05 - 2019-05-04 - 609398 - VALID, Strengthening Animal Production and Health through the Immune Response - SAPHIR - - H20202015-03-01 - 2019-02-28 - 633184 - VALID, GenomiqueENS (Genomique ENS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris, Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), Cytométrie (CYTO), Département Plateforme (PF I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), ANR-14-ANWA-0005,KILLeuPRRSV,Control of highly virulent pathogenic European porcine reproductive and respiratory syndrome viruses(2014), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), Université Paris-Saclay-AgroParisTech-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Oniris, UMR BioEpAR, PRES Université Nantes Angers Le Mans (UNAM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), and Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS)
Subjects: lcsh:Immunologic diseases. Allergy, pig, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Swine, PRRSV-1 pig lung mononuclear phagocytes gene expression immunogenomics machine learning, [SDV]Life Sciences [q-bio], Immunology, Porcine Reproductive and Respiratory Syndrome, [SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, lung mononuclear phagocytes, immunogenomics, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Monocytes, PRRSV-1, machine learning, gene expression, Animals, Female, Porcine respiratory and reproductive syndrome virus, Transcriptome, lcsh:RC581-607, Lung, Original Research
Abstract: International audience; Porcine reproductive and respiratory syndrome (PRRS) has an extensive impact on pig production. The causative virus (PRRSV) is divided into two species, PRRSV-1 (European origin) and PRRSV-2 (North American origin). Within PRRSV-1, PRRSV-1.3 strains, such as Lena, are more pathogenic than PRRSV-1.1 strains, such as Flanders 13 (FL13). To date, the molecular interactions of PRRSV with primary lung mononuclear phagocyte (MNP) subtypes, including conventional dendritic cells types 1 (cDC1) and 2 (cDC2), monocyte-derived DCs (moDC), and pulmonary intravascular macrophages (PIM), have not been thoroughly investigated. Here, we analyze the transcriptome profiles of in vivo FL13-infected parenchymal MNP subpopulations and of in vitro FL13-and Lena-infected parenchymal MNP. The cell-specific expression profiles of in vivo sorted cells correlated with their murine counterparts (AM, cDC1, cDC2, moDC) with the exception of PIM. Both in vivo and in vitro, FL13 infection altered the expression of a low number of host genes, and in vitro infection with Lena confirmed the higher ability of this strain to modulate host response. Machine learning (ML) and gene set enrichment analysis (GSEA) unraveled additional relevant genes and pathways modulated by FL13 infection that were not identified by conventional analyses. GSEA increased the cellular pathways enriched in the FL13 data set, but ML allowed a more complete comprehension of functional profiles during FL13 in vitro infection. Data indicates that cellular reprogramming differs upon Lena and FL13 infection and that the latter might keep antiviral and inflammatory macrophage/ DC functions silent. Although the slow replication kinetics of FL13 likely contribute to differences in cellular gene expression, the data suggest distinct mechanisms of interaction of the two viruses with the innate immune system during early infection.
Published: 2020
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11. Differential activity and selectivity of N‐terminal modified CXCL12 chemokines at the CXCR4 and ACKR3 receptors

Author: Carmen Gallego, Françoise Bachelerie, Françoise Baleux, Erika Cecon, Agnieszka Jaracz-Ros, Pasquale Cutolo, Angélique Levoye, Irina Kufareva, Guillaume Bernadat, Martin Gustavsson, Tracy M. Handel, Inflammation, microbiome, immunosurveillance (MI2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Biomolécules : Conception, Isolement, Synthèse (BioCIS), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-CY Cergy Paris Université (CY), Skaggs School of Pharmacy and Pharmaceutical Sciences [San Diego], University of California [San Diego] (UC San Diego), University of California-University of California, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chimie des Biomolécules - Chemistry of Biomolecules, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université Sorbonne Paris Nord, This work was supported by grants from Ensemble Contre le SIDA (SIDACTION), the Institut National de la Santé et de la Recherche Médicale (INSERM), GIS-Network for Rare Diseases and the Agence Nationale de Recherches sur le SIDA (ANRS). We thank members of the Dr. F. Arenzana-Seisdedos laboratory (Laboratoire de Pathogénie Virale, Institut Pasteur, Paris, France) and Dr. R. Jockers (Institut Cochin, Paris, France), who provided critical discussion. We also thank E. Trinquet, N. Gregor and F. Maurin (CisBio International, Marcoule, France) for technical support in HTRF assays. AL was supported by Roux postdoctoral fellowship from Pasteur Institute. I.K. and T.M.H. are supported by NIH R01 grants AI118985 and GM117424. C.G. was beneficiary of a fellowship from Marie Skłodowska-Curie Innovative Training Networks (ITN-ETN) 'ONCOgenic Receptor Network of Excellence and Training' (MSCA-ITN-2014-ETN) and from Fondation pour la Recherche Médicale (FDT201805005700). A.J-R., P.C., C.G., and F. Bachelerie are members of the LabEx LERMIT supported by ANR grant (ANR-10-LABX-33) under the program 'Investissements d'Avenir' (ANR-11-IDEX-0003-01)., ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), ANR-10-LABX-0033,LERMIT,Research Laboratory on Drugs and Therapeutic Innovation(2010), European Project: 641833,H2020,H2020-MSCA-ITN-2014,ONCORNET(2015), University of California (UC)-University of California (UC), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Baleux, Françoise, Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID, Research Laboratory on Drugs and Therapeutic Innovation - - LERMIT2010 - ANR-10-LABX-0033 - LABX - VALID, and ONCOgenic Receptor Network of Excellence and Training - ONCORNET - - H20202015-01-01 - 2018-12-31 - 641833 - VALID
Subjects: 0301 basic medicine, Protein Conformation, alpha-Helical, ACKR3, Chemokine, Benzylamines, Protein Conformation, [SDV]Life Sciences [q-bio], Gene Expression, pluridimensional efficacy Receptors, MESH: Amino Acid Sequence, Cyclams, CXCR4, MESH: Recombinant Proteins, Chemokine receptor, 0302 clinical medicine, Heterocyclic Compounds, GPCR signaling, Receptors, Cyclic AMP, 2.1 Biological and endogenous factors, Immunology and Allergy, MESH: Molecular Dynamics Simulation, Aetiology, CXCR, Receptor, beta-Arrestins, MESH: Cyclic AMP, biology, MESH: Receptors, CXCR, CXCL12, Recombinant Proteins, Cell biology, [SDV] Life Sciences [q-bio], pluridimensional efficacy, 030220 oncology & carcinogenesis, MESH: HEK293 Cells, embryonic structures, MESH: Oligopeptides, MESH: Protein Conformation, beta-Strand, biological phenomena, cell phenomena, and immunity, MESH: Chemokine CXCL12, Selectivity, chemokine variants, MESH: Chemokine CXCL11, Oligopeptides, Biotechnology, Protein Binding, Agonist, Receptors, CXCR4, MESH: Mutation, MESH: Gene Expression, MESH: Heterocyclic Compounds, medicine.drug_class, Signal Transduction and Genes, 1.1 Normal biological development and functioning, Immunology, Molecular Dynamics Simulation, Article, MESH: Receptors, CXCR4, GPCR Signaling, Vaccine Related, 03 medical and health sciences, MESH: beta-Arrestins, Underpinning research, Biodefense, medicine, Humans, MESH: Protein Binding, Protein Interaction Domains and Motifs, Amino Acid Sequence, Receptors, CXCR, MESH: Protein Conformation, alpha-Helical, MESH: Protein Interaction Domains and Motifs, Binding Sites, MESH: Humans, Prevention, alpha-Helical, Cell Biology, biological factors, Chemokine CXCL12, Chemokine CXCL11, Emerging Infectious Diseases, 030104 developmental biology, HEK293 Cells, MESH: Binding Sites, Mutation, biology.protein, beta-Strand, Protein Conformation, beta-Strand, Biochemistry and Cell Biology
Abstract: Chemokines play critical roles in numerous physiologic and pathologic processes through their action on seven-transmembrane (TM) receptors. The N-terminal domain of chemokines, which is a key determinant of signaling via its binding within a pocket formed by receptors’ TM helices, can be the target of proteolytic processing. An illustrative case of this regulatory mechanism is the natural processing of CXCL12 that generates chemokine variants lacking the first two N-terminal residues. Whereas such truncated variants behave as antagonists of CXCR4, the canonical G protein-coupled receptor of CXCL12, they are agonists of the atypical chemokine receptor 3 (ACKR3/CXCR7), suggesting the implication of different structural determinants in the complexes formed between CXCL12 and its two receptors. Recent analyses have suggested that the CXCL12 N-terminus first engages the TM helices of ACKR3 followed by the receptor N-terminus wrapping around the chemokine core. Here we investigated the first stage of ACKR3-CXCL12 interactions by comparing the activity of substituted or N-terminally truncated variants of CXCL12 toward CXCR4 and ACKR3. We showed that modification of the first two N-terminal residues of the chemokine (K1R or P2G) does not alter the ability of CXCL12 to activate ACKR3. Our results also identified the K1R variant as a G protein-biased agonist of CXCR4. Comparative molecular dynamics simulations of the complexes formed by ACKR3 either with CXCL12 or with the P2G variant identified interactions between the N-terminal 2–4 residues of CXCL12 and a pocket formed by receptor's TM helices 2, 6, and 7 as critical determinants for ACKR3 activation.
Published: 2020
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12. Multimodal Imaging Mass Spectrometry to Identify Markers of Pulmonary Arterial Hypertension in Human Lung Tissue Using MALDI-ToF, ToF-SIMS, and Hybrid SIMS

Author: Morad K. Nakhleh, Marc Humbert, Nicolas Elie, Alain Brunelle, Quentin P. Vanbellingen, Julia Zakel, Alexander Pirkl, David Touboul, Pierre Chaurand, Maria-Rosa Ghigna, Elie Fadel, Sylvia Cohen-Kaminsky, Marceau Quatredeniers, Jean-Pierre Le Caer, Sébastien J. Dumas, Sebastiaan Van Nuffel, Brunelle, Alain, Un grand défi pour l'imagerie par spectrométrie de masse - - DEFIMAGE2015 - ANR-15-CE29-0007 - AAPG2015 - VALID, Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID, Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), INSERM UMR_S 999 «Pulmonary Hypertension: Pathophysiology and Novel Therapies», Hôpital Marie Lannelongue, 92350 Le Plessis-Robinson, France, IONTOF GmbH, Université de Montréal (UdeM), Laboratoire d'Archéologie Moléculaire et Structurale (LAMS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), ANR-15-CE29-0007,DEFIMAGE,Un grand défi pour l'imagerie par spectrométrie de masse(2015), ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), University of Montreal [Montréal, Canada], and Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: PTEN, Pathology, medicine.medical_specialty, [CHIM.ANAL] Chemical Sciences/Analytical chemistry, IMAGES, Early detection, Spectrometry, Mass, Secondary Ion, 010402 general chemistry, Diagnostic tools, Mass spectrometry, 01 natural sciences, Mass spectrometry imaging, Analytical Chemistry, Human lung, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, NANOPARTICLES, medicine, SUBLIMATION, Humans, CYCLE, MULTIVARIATE-ANALYSIS, Multimodal imaging, Pulmonary Arterial Hypertension, Chemistry, 010401 analytical chemistry, 3. Good health, 0104 chemical sciences, Secondary ion mass spectrometry, medicine.anatomical_structure, RESOLUTION, Potential biomarkers, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Abstract: International audience; Pulmonary arterial hypertension (PAH) is a rare and deadly disease affecting roughly 15–60 people per million in Europe with a poorly understood pathology. There are currently no diagnostic tools for early detection nor does a curative treatment exist. The lipid composition of arteries in lung tissue samples from human PAH and control patients were investigated using matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) combined with time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging. Using random forests as an IMS data analysis technique, it was possible to identify the ion at m/z 885.6 as a marker of PAH in human lung tissue. The m/z 885.6 ion intensity was shown to be significantly higher around diseased arteries and was confirmed to be a diacylglycerophosphoinositol PI(C18:0/C20:4) via MS/MS using a novel hybrid SIMS instrument. The discovery of a potential biomarker opens up new research avenues which may finally lead to a better understanding of the PAH pathology and highlights the vital role IMS can play in modern biomedical research.
Published: 2020
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13. Joint prediction of multiple scores captures better individual traits from brain images

Author: Danilo Bzdok, Gaël Varoquaux, Mehdi Rahim, Bertrand Thirion, Irène Buvat, Modelling brain structure, function and variability based on high-field MRI data (PARIETAL), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-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 Paris-Saclay-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)-Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Imagerie Moléculaire in Vivo (IMIV - U1023 - ERL9218), Service Hospitalier Frédéric Joliot (SHFJ), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), ANR-11-BINF-0004,NiConnect,Outils pour la Recherche Clinique par cartographie de la connectivité cérébrale fonctionnelle(2011), ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Service NEUROSPIN (NEUROSPIN), 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 Paris-Saclay, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), Rahim, Mehdi, Bio-informatique - Outils pour la Recherche Clinique par cartographie de la connectivité cérébrale fonctionnelle - - NiConnect2011 - ANR-11-BINF-0004 - BINF - VALID, and Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID
Subjects: 0301 basic medicine, Disease status, Cognitive Neuroscience, Schizophrenia (object-oriented programming), Population, [INFO.INFO-IM] Computer Science [cs]/Medical Imaging, Individuality, Machine learning, computer.software_genre, Brain mapping, 03 medical and health sciences, 0302 clinical medicine, [STAT.ML]Statistics [stat]/Machine Learning [stat.ML], Alzheimer Disease, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Computer Simulation, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], education, Brain Mapping, Brain organization, education.field_of_study, business.industry, Brain, Magnetic Resonance Imaging, [STAT.ML] Statistics [stat]/Machine Learning [stat.ML], Phenotype, 030104 developmental biology, Neurology, Schizophrenia, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Data mining, Artificial intelligence, business, Joint (audio engineering), Psychology, computer, Algorithms, 030217 neurology & neurosurgery
Abstract: International audience; To probe individual variations in brain organization, population imaging relates features of brain images to rich descriptions of the subjects such as genetic information or behavioral and clinical assessments. Capturing common trends across these measurements is important: they jointly characterize the disease status of patient groups. In particular, mapping imaging features to behavioral scores with predictive models opens the way toward more precise diagnosis. Here we propose to jointly predict all the dimensions (behavioral scores) that make up the individual profiles, using so-called multi-output models. This approach often boosts prediction accuracy by capturing latent shared information across scores. We demonstrate the efficiency of multi-output models on two independent resting-state fMRI datasets targeting different brain disorders (Alzheimer's Disease and schizophrenia). Furthermore, the model with joint prediction generalizes much better to a new cohort: a model learned on one study is more accurately transferred to an independent one. Finally, we show how multi-output models can easily be extended to multi-modal settings, combining heterogeneous data sources for a better overall accuracy.
Published: 2017
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14. Stability and Reachability analysis for a controlled heterogeneous population of cells

Author: Hasnaa Zidani, Cécile Carrère, Laboratoire Jacques-Louis Lions (LJLL), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut de Mathématiques de Marseille (I2M), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Optimisation et commande (OC), Unité de Mathématiques Appliquées (UMA), École Nationale Supérieure de Techniques Avancées (ENSTA Paris)-École Nationale Supérieure de Techniques Avancées (ENSTA Paris), ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), Carrère, Cécile, Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID, and Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU)
Subjects: 0209 industrial biotechnology, Mathematical optimization, Control and Optimization, Computer science, Population, Stability (learning theory), Nonlinear optimal control, [SDV.CAN]Life Sciences [q-bio]/Cancer, 02 engineering and technology, 01 natural sciences, Applications to chemotherapy, 020901 industrial engineering & automation, [SDV.CAN] Life Sciences [q-bio]/Cancer, Reachability, Dynamical programming, Reachability anal- ysis, [MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP], Non-linear optimal control, [MATH.MATH-AP] Mathematics [math]/Analysis of PDEs [math.AP], 0101 mathematics, education, education.field_of_study, Applied Mathematics, Numerical analysis, [MATH.MATH-OC] Mathematics [math]/Optimization and Control [math.OC], [MATH.MATH-NA] Mathematics [math]/Numerical Analysis [math.NA], 010101 applied mathematics, Heterogeneous population, Control and Systems Engineering, [MATH.MATH-OC]Mathematics [math]/Optimization and Control [math.OC], Software, [MATH.MATH-NA]Mathematics [math]/Numerical Analysis [math.NA]
Abstract: International audience; This paper is devoted to the study of a controlled population of cells. The modelling of the problem leads to a mathematical formulation of stability and reachability properties of some controlled systems under uncertainties. We use the Hamilton-Jacobi (HJ) approach to address theses problems and to design a numerical method that we analyse on several numerical simulations.
Published: 2020

15. Foreign Shocks as Granular Fluctuations

Author: Julian di Giovanni, Andrei A. Levchenko, Isabelle Mejean, Mundell, Melissa, Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID, Centres d'excellences - Réguler l'économie au service de la société - - ECODEC2011 - ANR-11-LABX-0047 - LABX - VALID, and Equipements d'excellence - Développement et construction d'un Centre d'Accès Sécurisé Distant aux données confidentielles (CASD) pour la recherche française en sciences sociales et en économie. - - CASD2010 - ANR-10-EQPX-0017 - EQPX - VALID
Subjects: Micro level, shock transmission, International trade, Monetary economics, granularity, aggregate fluctuations, Business cycle, Economics, Macro level, ddc:330, Macro, [SHS.ECO] Humanities and Social Sciences/Economics and Finance, Granularity, E32, Stylized fact, L14, Shock transmission, F15, international trade, Baseline model, Input linkages, Aggregate fluctuations, input linkages, F44, F23, F62
Abstract: This paper uses a data set covering the universe of French firm-level sales, imports, and exports over the period 1993-2007 and a quantitative multi-country model to study the international transmission of business cycle shocks at both the micro and the macro levels. The largest firms are both important enough to generate aggregate fluctuations (Gabaix 2011), and most likely to be internationally connected. This implies that foreign shocks are transmitted to the domestic economy primarily through the largest firms. We first document a novel stylized fact: larger French firms are significantly more sensitive to foreign GDP growth. We then implement a quantitative framework calibrated to the full extent of observed heterogeneity in firm size, exporting, and importing. We simulate the propagation of foreign shocks to the French economy and report one micro and one macro finding. At the micro level, heterogeneity across firms predominates: 40-85 percent of the impact of foreign fluctuations on French GDP is accounted for by the 'foreign granular residual'-the term capturing the fact that larger firms are more affected by the foreign shocks. At the macro level, firm heterogeneity dampens the impact of foreign shocks, with the GDP responses 10-20 percent larger in a representative firm model compared to the baseline model.
Published: 2020
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16. Fluorescein derivatives as fluorescent probes for ph monitoring along recent biological applications

Author: Anne Gaucher, Florent Le Guern, Martin Rottman, Vanessa Mussard, Damien Prim, Institut Lavoisier de Versailles (ILV), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Agence Nationale de la Recherche, ANR, Funding: This work was supported by the French National Research Agency under the program CHARMMMAT ANR-11-LABX-0039-grant., ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), HAL UVSQ, Équipe, and Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID
Subjects: Fluorophore, Application, PH-sensitive, [SDV]Life Sciences [q-bio], Nanotechnology, Review, Biosensing Techniques, 010402 general chemistry, 01 natural sciences, Ph monitoring, Catalysis, Cellular life, Imaging, Inorganic Chemistry, lcsh:Chemistry, chemistry.chemical_compound, Dyad, Organelle, Animals, Humans, Physical and Theoretical Chemistry, Fluorescein, Molecular Biology, lcsh:QH301-705.5, Spectroscopy, Fluorescent Dyes, Molecular Structure, Bacteria, 010405 organic chemistry, Organic Chemistry, General Medicine, Physical interaction, Electrochemical Techniques, Hydrogen-Ion Concentration, Probe, Fluorescence, 0104 chemical sciences, Computer Science Applications, Molecular Imaging, [SDV] Life Sciences [q-bio], chemistry, lcsh:Biology (General), lcsh:QD1-999, Cell
Abstract: International audience; Potential of hydrogen (pH) is one of the most relevant parameters characterizing aqueous solutions. In biology, pH is intrinsically linked to cellular life since all metabolic pathways are implicated into ionic flows. In that way, determination of local pH offers a unique and major opportunity to increase our understanding of biological systems. Whereas the most common technique to obtain these data in analytical chemistry is to directly measure potential between two electrodes, in biological systems, this information has to be recovered in-situ without any physical interaction. Based on their non-invasive optical properties, fluorescent pH-sensitive probe are pertinent tools to develop. One of the most notorious pH-sensitive probes is fluorescein. In addition to excellent photophysical properties, this fluorophore presents a pH-sensitivity around neutral and physiologic domains. This review intends to shed new light on the recent use of fluorescein as pH-sensitive probes for biological applications, including targeted probes for specific imaging, flexible monitoring of bacterial growth, and biomedical applications.
Published: 2020
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17. Pulsed-laser irradiation of multifunctional gold nanoshells to overcome trastuzumab resistance in HER2-overexpressing breast cancer

Author: Marthe Rigal, Toni Nunes, Christophe Leboeuf, Thomas Pons, Khanh Van Do, Xue Hou, Mélanie Di Benedetto, Benoit Caron, Bruno Palpant, Guilhem Bousquet, Anne Janin, Cancer et Transplantation : Physiopathologie et Réponse Thérapeutique (UMR 1165), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Physique et d'Etude des Matériaux (LPEM), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Photonique Quantique et Moléculaire (LPQM), École normale supérieure - Cachan (ENS Cachan)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Groupe d'Etude de la Matière Condensée (GEMAC), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences de la Terre de Paris (iSTeP), Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Gvh et Gvl : Physiopathologie Chez l'Homme et Chez l'Animal, Incidence et Role Therapeutique, ESPCI ParisTech-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec-École normale supérieure - Cachan (ENS Cachan), Ratajczak, Philippe, Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID, Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Laboratoire de Physique et d'Etude des Matériaux (UMR 8213) (LPEM), Service de Pharmacie [Hôpital Avicenne - APHP], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de pathologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Service d'Oncologie Médicale [AP-HP Hôpital Avicenne], Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], This work received financial support from Labex LaSIPS (ANR-10-LABX0040– LaSIPS) managed by the French National Research Agency under the 'Investissements d’avenir' program (n°ANR-11-IDEX-0003–02), from the 'Plan Cancer' managed by the French ITMO Cancer (n°17CP077–00, project HEPPROS) and from the Institut d’Alembert in Ecole Normale Supérieure Paris-Saclay (FR CNRS 3242) (GESPER project)., ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut national des sciences de l'Univers (INSU - CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)
Subjects: 0301 basic medicine, Cancer Research, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Receptor, ErbB-2, Gene Dosage, Mice, Antineoplastic Agents, Immunological, 0302 clinical medicine, Trastuzumab, skin and connective tissue diseases, Trastuzumab resistance, ComputingMilieux_MISCELLANEOUS, Drug Carriers, Neovascularization, Pathologic, Chemistry, HER2-overexpressing breast cancer, Silicon Dioxide, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Magnetic Resonance Imaging, Photothermal therapy, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Oncology, Colloidal gold, 030220 oncology & carcinogenesis, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Female, medicine.drug, Hyperthermia, Cell Survival, Functionalized gold nanoparticles, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, Resistance reversion, 03 medical and health sciences, Breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Cell Line, Tumor, medicine, Animals, Humans, [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, neoplasms, Lasers, Nanoshells, Research, Phototherapy, medicine.disease, Xenograft Model Antitumor Assays, Nanoshell, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, Femtosecond laser, Disease Models, Animal, 030104 developmental biology, Gene Expression Regulation, Drug Resistance, Neoplasm, Apoptosis, Cancer research, Gold
Abstract: Background HER2-overexpressing metastatic breast cancers are challenging practice in oncology when they become resistant to anti-HER2 therapies such as trastuzumab. In these clinical situations, HER2-overexpression persists in metastatic localizations, and can thus be used for active targeting using innovative therapeutic approaches. Functionalized gold nanoparticles with anti-HER2 antibody can be stimulated by near-infrared light to induce hyperthermia. Methods Here, hybrid anti-HER2 gold nanoshells were engineered for photothermal therapy to overcome trastuzumab resistance in HER2-overexpressing breast cancer xenografts. Results When gold nanoshells were administered in HER2-tumor xenografts, no toxicity was observed. A detailed pharmacokinetic study showed a time-dependent accumulation of gold nanoshells within the tumors, significantly greater with functionalized gold nanoshells at 72 h. This enabled us to optimize the treatment protocol and irradiate the mice when the anti-HER2 gold nanoshells had accumulated most in the tumors. After weekly injections of anti-HER2 gold nanoshells, and repeated irradiations with a femtosecond-pulsed laser over four weeks, tumor growth was significantly inhibited. Detailed tissue microscopic analyses showed that the tumor growth inhibition was due to an anti-angiogenic effect, coherent with a preferential distribution of the nanoshells in tumor microvessels. We also showed a direct tumor cell effect with apoptosis and inhibition of proliferation, coherent with an immune-mediated targeting of tumor cells by anti-HER2 nanoshells. Conclusion This preclinical study thus supports the use of anti-HER2 gold nanoshells and photothermal therapy to overcome trastuzumab resistance in HER2-overexpressing breast cancer. Electronic supplementary material The online version of this article (10.1186/s13046-019-1305-x) contains supplementary material, which is available to authorized users.
Published: 2019
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18. Substrate binding mode and catalytic mechanism of human heparan sulfate d-glucuronyl C5 epimerase

Author: Emeline Richard, Véronique Roig-Zamboni, Hugues Lortat-Jacob, Firas Fadel, Jérôme Hénault, Adeline Goulet, Christine Le Narvor, Yves Bourne, David Bonnaffé, Vincent Delauzun, C. Debarnot, Yoan R. Monneau, Bernard Priem, Romain R. Vivès, Architecture et fonction des macromolécules biologiques (AFMB), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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 Chimie Moléculaire et des Matériaux d'Orsay (ICMMO), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Centre de Recherches sur les Macromolécules Végétales (CERMAV), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'ingénierie des systèmes macromoléculaires (LISM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010), ANR-10-LABX-0049,GRAL,Grenoble Alliance for Integrated Structural Cell Biology(2010), ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), LCOM eG2M, Inst Chim Mol & Mat Orsay, LabEx LERMIT,UMR 8182, Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur les Macromolécules Végétales (CERMAV ), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-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)-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), Bourne, Yves, Infrastructure Française pour la Biologie Structurale Intégrée - - FRISBI2010 - ANR-10-INBS-0005 - INBS - VALID, Grenoble Alliance for Integrated Structural Cell Biology - - GRAL2010 - ANR-10-LABX-0049 - LABX - VALID, and Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID
Subjects: MESH: Heparin, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Oligosaccharides, Isomerase, Uronic acid, catalytic mechanism, Crystallography, X-Ray, 01 natural sciences, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Substrate Specificity, chemistry.chemical_compound, MESH: Structure-Activity Relationship, Glucuronic Acid, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Trisaccharide, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], chemistry.chemical_classification, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Multidisciplinary, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Nuclear magnetic resonance spectroscopy, Heparan sulfate, Biological Sciences, MESH: Carbohydrate Epimerases, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [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], MESH: Glucuronic Acid, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, MESH: HEK293 Cells, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, heparan sulfate, substrate distortion, Stereochemistry, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Catalysis, Structure-Activity Relationship, 03 medical and health sciences, Humans, Binding site, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, 030304 developmental biology, X-ray crystallography, Binding Sites, MESH: Humans, Heparin, 010405 organic chemistry, Mandelate racemase, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Active site, MESH: Catalysis, MESH: Crystallography, X-Ray, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 0104 chemical sciences, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, HEK293 Cells, chemistry, MESH: Binding Sites, C5 epimerization, biology.protein, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, MESH: Substrate Specificity, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Carbohydrate Epimerases, MESH: Oligosaccharides
Abstract: Heparan sulfate (HS) is a linear, complex polysaccharide that modulates the biological activities of proteins through binding sites made by a series of Golgi-localized enzymes. Of these, glucuronyl C5-epimerase (Glce) catalyzes C5-epimerization of the HS component, d -glucuronic acid (GlcA), into l -iduronic acid (IdoA), which provides internal flexibility to the polymer and forges protein-binding sites to ensure polymer function. Here we report crystal structures of human Glce in the unbound state and of an inactive mutant, as assessed by real-time NMR spectroscopy, bound with a (GlcA-GlcNS) n substrate or a (IdoA-GlcNS) n product. Deep infiltration of the oligosaccharides into the active site cleft imposes a sharp kink within the central GlcNS-GlcA/IdoA-GlcNS trisaccharide motif. An extensive network of specific interactions illustrates the absolute requirement of N -sulfate groups vicinal to the epimerization site for substrate binding. At the epimerization site, the GlcA/IdoA rings are highly constrained in two closely related boat conformations, highlighting ring-puckering signatures during catalysis. The structure-based mechanism involves the two invariant acid/base residues, Glu499 and Tyr578, poised on each side of the target uronic acid residue, thus allowing reversible abstraction and readdition of a proton at the C5 position through a neutral enol intermediate, reminiscent of mandelate racemase. These structures also shed light on a convergent mechanism of action between HS epimerases and lyases and provide molecular frameworks for the chemoenzymatic synthesis of heparin or HS analogs.
Published: 2019
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19. Partial Transformation of Imogolite by Decylphosphonic Acid Yields an Interface Active Composite Material

Author: Fabienne Testard, Tobias Lange, Frédéric Gobeaux, Sophie Charton, Antoine Thill, Thibault Charpentier, Laboratoire Interdisciplinaire sur l'Organisation Nanométrique et Supramoléculaire (LIONS), 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-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-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-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Laboratoire Structure et Dynamique par Résonance Magnétique (LCF) (LSDRM), Département de recherche sur les procédés pour la mine et le recyclage du combustible (DMRC), CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), C'Nano-IdFAmont-Aval CEA program, ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), 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), Palacin, Serge, and Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID
Subjects: Materials science, Scanning electron microscope, Infrared spectroscopy, Imogolite, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Lamellar phase, Electrochemistry, General Materials Science, Reactivity (chemistry), Composite material, Spectroscopy, [CHIM.MATE] Chemical Sciences/Material chemistry, Surfaces and Interfaces, [CHIM.MATE]Chemical Sciences/Material chemistry, 021001 nanoscience & nanotechnology, Condensed Matter Physics, 0104 chemical sciences, 3. Good health, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, [CHIM.THEO] Chemical Sciences/Theoretical and/or physical chemistry, Transmission electron microscopy, Surface modification, 0210 nano-technology, Dispersion (chemistry)
Abstract: International audience; The phosphonic acid moiety is commonly used as an anchoring group for the surface modification of imogolite. However, the impact of the reaction on its structure has never been clearly analyzed before. We study the reaction of imogolite and decylphosphonic acid by combining infrared spectroscopy, X-ray scattering, scanning electron microscopy, transmission electron microscopy and solid-state nuclear magnetic resonance spectroscopy. Instead of a surface functionalization, we observe the formation of a lamellar phase interconnected with imogolite bundles. Although we find no evidence for grafted imogolite tubes, we observe the expected dispersion characteristics and stabilization of water in toluene emulsions described in literature. Based on the surface chemistry of imogolite we propose an explanation for the observed reactivity and link the structural features of the obtained composite material to its dispersibility in toluene and its observed properties at the toluene-water interface.
Published: 2019
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20. HIV-1 Envelope Overcomes NLRP3-Mediated Inhibition of F-Actin Polymerization for Viral Entry

Author: Haithem Dakhli, David M. Ojcius, Maxime Thoreau, Héla Saïdi, Eric Solary, Awatef Allouch, Jean-Luc Perfettini, Olivier Lambotte, Marina Caillet, Eric Deutsch, Olivier Delelis, Qiuji Wu, Zeinaf Muradova, Mauro Piacentini, Gianfranco Pancino, Roger Le Grand, Syed Qasim Raza, Audrey Paoletti, Asier Sáez-Cirión, Béatrice Poirier-Beaudouin, Nathalie Dereuddre-Bosquet, Frédéric Subra, Laurent Voisin, Guido Kroemer, Marie-Lise Gougeon, Roberta Nardacci, Frédéric Law, Radiothérapie moléculaire (UMR 1030), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Apoptose, cancer et immunité (U848), Immunité Anti-virale, Biothérapie et Vaccins (IABV), Institut Pasteur [Paris] (IP), Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Istituto Nazionale di Malattie Infettive 'Lazzaro Spallanzani' (INMI), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, HIV, Inflammation et persistance - HIV, Inflammation and Persistence, University of the South Pacific (USP), Université Paris Diderot - Paris 7 (UPD7), Hématopoïèse normale et pathologique, Département de radiothérapie [Gustave Roussy], Institut Gustave Roussy (IGR), Università degli Studi di Roma Tor Vergata [Roma], Agence Nationale de la RechercheFrench National Research Agency (ANR) [ANR-10-IBHU-0001, ANR-10-LABX33, ANR-11-IDEX-003-01], Electricite de France, MIUR (FIRB)Ministero dell' Istruzione, dell' Universita e della Ricerca (MIUR), Ministry of Health of Italy 'Ricerca Finalizzata', ANR under the program 'Investissements d'Avenir'French National Research Agency (ANR) [ANR-10-LABX-33, ANR-11-IDEX-0003-01], Fondation Gustave Roussy, AIRCAssociazione Italiana per la Ricerca sul Cancro (AIRC), European Commission 'Transpath' Marie Curie Project, Agence Nationale de Recherche sur le Sida et sur les Hepatites (ANRSH)French National Research Agency (ANR), Higher Education Commission (Pakistan)Higher Education Commission of Pakistan, Laboratory of Excellence LERMIT, Institut National du CancerInstitut National du Cancer (INCA) France [INCA 9414], Canceropole Ile-de-FranceRegion Ile-de-France, Institut National du Cancer (INCa)Institut National du Cancer (INCA) France, NATIXIS, Sidaction, French National Agency for Research on AIDS and Viral Hepatitis (ANRSH)French National Research Agency (ANR), Ligue contre le Cancer (equipe labellisee), Agence National de la Recherche (ANR) -Projets blancsFrench National Research Agency (ANR), Institut Universitaire de France, Ministry of Health of Italy 'Ricerca Corrente', LabEx Immuno-Oncology, RHU Torino Lumiere, SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE), SIRIC Cancer Research and Personalized Medicine (CARPEM), MIUR (PRIN 2012)Ministero dell' Istruzione, dell' Universita e della Ricerca (MIUR), We gratefully acknowledge Y. Lecluse and S. Salome-Desnoulez for technical support., ANR-10-IBHU-0001,MMO (IHU-CANCER),Institut de Médecine Personnalisée du Cancer(2010), ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), European Project: 289964,EC:FP7:PEOPLE,FP7-PEOPLE-2011-ITN,TRANSPATH(2011), Leriche, Marianne, Instituts Hospitalo-Universitaires B - Institut de Médecine Personnalisée du Cancer - - MMO (IHU-CANCER)2010 - ANR-10-IBHU-0001 - IBHU - VALID, Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID, Transglutaminase in disease: a novel therapeutic target? - TRANSPATH - - EC:FP7:PEOPLE2011-11-01 - 2015-10-31 - 289964 - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Institut Pasteur [Paris], and HIV, Inflammation et persistance
Subjects: 0301 basic medicine, CBL, Settore BIO/06, CXCR4, General Biochemistry, Genetics and Molecular Biology, HIV, NLRP3, P2Y2, inflammasome, viral entry, Polymerization, 03 medical and health sciences, 0302 clinical medicine, Viral entry, NLR Family, Pyrin Domain-Containing 3 Protein, medicine, Humans, [INFO.INFO-DL]Computer Science [cs]/Digital Libraries [cs.DL], Receptor, lcsh:QH301-705.5, Actin, biology, integumentary system, Chemistry, Purinergic receptor, Inflammasome, Virus Internalization, Actins, 3. Good health, Cell biology, Ubiquitin ligase, 030104 developmental biology, lcsh:Biology (General), biology.protein, HIV-1, Phosphorylation, [INFO.INFO-DL] Computer Science [cs]/Digital Libraries [cs.DL], 030217 neurology & neurosurgery, medicine.drug, Signal Transduction
Abstract: Summary: Purinergic receptors and nucleotide-binding domain leucine-rich repeat containing (NLR) proteins have been shown to control viral infection. Here, we show that the NLR family member NLRP3 and the purinergic receptor P2Y2 constitutively interact and regulate susceptibility to HIV-1 infection. We found that NLRP3 acts as an inhibitory factor of viral entry that represses F-actin remodeling. The binding of the HIV-1 envelope to its host cell receptors (CD4, CXCR4, and/or CCR5) overcomes this restriction by stimulating P2Y2. Once activated, P2Y2 enhances its interaction with NLRP3 and stimulates the recruitment of the E3 ubiquitin ligase CBL to NLRP3, ultimately leading to NLRP3 degradation. NLRP3 degradation is permissive for PYK2 phosphorylation (PYK2Y402∗) and subsequent F-actin polymerization, which is required for the entry of HIV-1 into host cells. Taken together, our results uncover a mechanism by which HIV-1 overcomes NLRP3 restriction that appears essential for the accomplishment of the early steps of HIV-1 entry. : Paoletti et al. identified a constitutive interaction between NLRP3 and P2Y2 that regulates HIV-1 entry into target cells. They revealed that NLRP3 represses viral entry by impairing F-actin reorganization. HIV-1 overcomes this host cellular resistance by inducing NLRP3 degradation through the activation of P2Y2-dependent signaling pathway. Keywords: NLRP3, P2Y2, CBL, inflammasome, viral entry, HIV
Published: 2019
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21. Performance evaluation of molecular docking and free energy calculations protocols using the D3R Grand Challenge 4 dataset

Author: Bogdan I. Iorga, Ludovic Chaput, Bert L. de Groot, Nawel Mele, Eddy Elisée, Vytautas Gapsys, Edithe Selwa, Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Max Planck Institute for Biophysical Chemistry (MPI-BPC), Max-Planck-Gesellschaft, Maladies rénales fréquentes et rares : des mécanismes moléculaires à la médecine personnalisée (CoRaKID), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Research reported in this publication was supported by grants ANR-10-LABX-33 (LabEx LERMIT) and ANR-14-JAMR-0002 (JPIAMR) from the French National Research Agency (ANR), by the Région Ile-de-France (DIM Malinf), by the Université Paris- Saclay (Globetalkers 2019) and by European Research Council grant ERC-2012-ADG_20120314 (Grant Agreement 322947)., ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), ANR-14-JAMR-0002,DesInMBL,Structure-guided design of pan inhibitors of metallo-ß-lactamases(2014), European Project: 322947,EC:FP7:ERC,ERC-2012-ADG_20120314,OSAI(2013), IORGA, Bogdan, Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID, programmation conjointe européenne sur la résistance antimicrobienne - Structure-guided design of pan inhibitors of metallo-ß-lactamases - - DesInMBL2014 - ANR-14-JAMR-0002 - JPI AMR - VALID, Membranous nephropathy : a model for solving organ-specific auto-immunity (OSAI) - OSAI - - EC:FP7:ERC2013-05-01 - 2018-04-30 - 322947 - VALID, Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), and Common and Rare Kidney Diseases = Maladies Rénales Fréquentes et Rares: des Mécanismes Moléculaires à la Médecine Personnalisée (CORAKID)
Subjects: Protein Conformation, Computer science, Entropy, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Crystallography, X-Ray, Ligands, computer.software_genre, 01 natural sciences, Molecular dynamics, Software, 0103 physical sciences, Drug Discovery, Humans, Physical and Theoretical Chemistry, Binding Sites, 010304 chemical physics, business.industry, 0104 chemical sciences, Computer Science Applications, Molecular Docking Simulation, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, 010404 medicinal & biomolecular chemistry, [CHIM.THEO] Chemical Sciences/Theoretical and/or physical chemistry, Workflow, Docking (molecular), Drug Design, Computer-Aided Design, Thermodynamics, Data mining, business, computer, Protein Binding
Abstract: International audience; Using the D3R Grand Challenge 4 dataset containing Beta-secretase 1 (BACE) and Cathepsin S (CatS) inhibitors, we have evaluated the performance of our in-house docking workflow that involves in the first step the selection of the most suitable docking software for the system of interest based on structural and functional information available in public databases, followed by the docking of the dataset to predict the binding modes and ranking of ligands. The macrocyclic nature of the BACE ligands brought additional challenges, which were dealt with by a careful preparation of the three-dimensional input structures for ligands. This provided top-performing predictions for BACE, in contrast with CatS, where the predictions in the absence of guiding constraints provided poor results. These results highlight the importance of previous structural knowledge that is needed for correct predictions on some challenging targets. After the end of the challenge, we also carried out free energy calculations (i.e. in a non-blinded manner) for CatS using the pmx software and several force fields (AMBER, Charmm). Using knowledge-based starting pose construction allowed reaching remarkable accuracy for the CatS free energy estimates. Interestingly, we show that the use of a consensus result, by averaging the results from different force fields, increases the prediction accuracy.
Published: 2019
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22. The BET Bromodomain Inhibitor I-BET-151 Induces Structural and Functional Alterations of the Heart Mitochondria in Healthy Male Mice and Rats

Author: Christine Péchoux, Natalia Gambaryan, Marc Humbert, Fabrice Antigny, Sharon Mumby, Angèle Boet, Ian M. Adcock, Benoit Ranchoux, Mélanie Gressette, Catherine Rucker-Martin, Mélanie Lambert, Valérie Domergue, David Montani, Anne Garnier, Jérôme Piquereau, Frédéric Perros, Perros, Frédéric, Jeunes Chercheuses et Jeunes Chercheurs - Mécanismes épigénétiques dans l'inflammation et le remodelage vasculaire de l'hypertension pulmonaire - - EMIR2013 - ANR-13-JSV1-0011 - JC - VALID, Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID, Signalisation et physiopathologie cardiovasculaire (UMRS1180), Institut National de la Santé et de la Recherche Médicale (INSERM), Hypertension arterielle pulmonaire physiopathologie et innovation thérapeutique, Centre Chirurgical Marie Lannelongue (CCML)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Saclay, Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), Réanimation des cardiopathies congénitales [Le Plessis-Robinson] (Centre chirurgical Marie Lannelongue), Centre Chirurgical Marie Lannelongue (CCML), Génétique Animale et Biologie Intégrative (GABI), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Institut Paris Saclay d’Innovation Thérapeutique (IPSIT), Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), This work was supported by research grants from INSERM, National Funding Agency for Research (ANR) (Grant ANR-13-JSV1-0011-01), Laboratoire d’Excellence (LabEx) en Recherche sur le Médicament et l’Innovation Thérapeutique (LERMIT), Assistance Publique Hôpitaux de Paris (Département Hospitalo-Universitaire Thorax Innovation), Legs Poix (Chancellerie des Universités de Paris). F.A. was supported by a post-doctoral grant from Aviesan and by Lefoulon Delalande Institute. INSERM UMR_S 999 research unit, ANR-13-JSV1-0011,EMIR,Mécanismes épigénétiques dans l'inflammation et le remodelage vasculaire de l'hypertension pulmonaire(2013), ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), Centre chirurgical Marie Lannelongue-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre chirurgical Marie Lannelongue, and AgroParisTech-Institut National de la Recherche Agronomique (INRA)
Subjects: Male, 0301 basic medicine, Chemistry, Multidisciplinary, Cardiomyopathy, MELANOMA, Mitochondrion, Mitochondria, Heart, lcsh:Chemistry, Electrocardiography, 0302 clinical medicine, Medicine, Citrate synthase, lcsh:QH301-705.5, Spectroscopy, biology, COMBINING BET, General Medicine, 3. Good health, Computer Science Applications, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, mitochondria, Chemistry, medicine.anatomical_structure, Organ Specificity, 030220 oncology & carcinogenesis, Physical Sciences, HDAC INHIBITORS, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, medicine.medical_specialty, PROTEINS, 0699 Other Biological Sciences, bromodomain and extra-terminal domain, cardiotoxicity, heart, Heterocyclic Compounds, 4 or More Rings, Article, Catalysis, Inorganic Chemistry, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, bromodomain and extra-terminal domain inhibitor, medicine.artery, Internal medicine, 0399 Other Chemical Sciences, C-MYC, Animals, STRATEGY, Rats, Wistar, Physical and Theoretical Chemistry, Molecular Biology, 0604 Genetics, Cardiotoxicity, Aorta, Science & Technology, Chemical Physics, business.industry, Organic Chemistry, Skeletal muscle, medicine.disease, Bromodomain, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, lcsh:Biology (General), lcsh:QD1-999, Pulmonary artery, biology.protein, business
Abstract: The bromodomain and extra-terminal domain family inhibitors (BETi) are a promising new class of anticancer agents. Since numerous anticancer drugs have been correlated to cardiomyopathy, and since BETi can affect non-cancerous tissues, we aimed to investigate in healthy animals any ultrastructural BETi-induced alterations of the heart as compared to skeletal muscle. Male Wistar rats were either treated during 3 weeks with I-BET-151 (2 or 10 mg/kg/day) (W3) or treated for 3 weeks then allowed to recover for another 3 weeks (W6) (3-weeks drug washout). Male C57Bl/6J mice were only treated during 5 days (50 mg/kg/day). We demonstrated the occurrence of ultrastructural alterations and progressive destruction of cardiomyocyte mitochondria after I-BET-151 exposure. Those mitochondrial alterations were cardiac muscle-specific, since the skeletal muscles of exposed animals were similar in ultrastructure presentation to the non-exposed animals. I-BET-151 decreased the respiration rate of heart mitochondria in a dose-dependent manner. At the higher dose, it also decreased mitochondrial mass, as evidenced by reduced right ventricular citrate synthase content. I-BET-151 reduced the right and left ventricular fractional shortening. The concomitant decrease in the velocity-time-integral in both the aorta and the pulmonary artery is also suggestive of an impaired heart function. The possible context-dependent cardiac side effects of these drugs have to be appreciated. Future studies should focus on the basic mechanisms of potential cardiovascular toxicities induced by BETi and strategies to minimize these unexpected complications.
Published: 2019
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23. Blinded evaluation of cathepsin S inhibitors from the D3RGC3 dataset using molecular docking and free energy calculations

Author: Eddy Elisée, Ludovic Chaput, Bogdan I. Iorga, Edithe Selwa, Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Région Ile-de-France (Conseil Régional, Île-de-France, DIM Malinf), ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), ANR-14-JAMR-0002,DesInMBL,Structure-guided design of pan inhibitors of metallo-ß-lactamases(2014), IORGA, Bogdan, Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID, programmation conjointe européenne sur la résistance antimicrobienne - Structure-guided design of pan inhibitors of metallo-ß-lactamases - - DesInMBL2014 - ANR-14-JAMR-0002 - JPI AMR - VALID, and Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Computer science, Protein Data Bank (RCSB PDB), Computational biology, Molecular Dynamics Simulation, Crystallography, X-Ray, Ligands, 01 natural sciences, 03 medical and health sciences, Molecular dynamics, Structure-Activity Relationship, 0103 physical sciences, Drug Discovery, Physical and Theoretical Chemistry, Enzyme Inhibitors, Databases, Protein, ComputingMilieux_MISCELLANEOUS, Binding Sites, 010304 chemical physics, Molecular Structure, chEMBL, Cathepsins, Computer Science Applications, Molecular Docking Simulation, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, [CHIM.THEO] Chemical Sciences/Theoretical and/or physical chemistry, 030104 developmental biology, Docking (molecular), Drug Design, Solvents, Computer-Aided Design, Thermodynamics, BindingDB, PubChem, Protein Binding
Abstract: During the last few years, we have developed a docking protocol involving two steps: (i) the choice of the most appropriate docking software and parameters for the system of interest using structural and functional information available in public databases (PDB, ChEMBL, PubChem Assay, BindingDB, etc.); (ii) the docking of ligand dataset to provide a prediction for the binding modes and ranking of ligands. We applied this protocol to the D3R Grand Challenge 3 dataset containing cathepsin S (CatS) inhibitors. Considering the size and conformational flexibility of ligands, the docking calculations afforded reasonable overall pose predictions, which are however dependent on the specific nature of each ligand. As expected, the correct ranking of docking poses is still challenging. Post-processing of docking poses with molecular dynamics simulations in explicit solvent provided a significantly better prediction, whereas free energy calculations on a subset of compounds brought no significant improvement in the ranking prediction compared with the direct ranking obtained from the scoring function.
Published: 2019
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24. Merging datasets for photometric study

Author: Belgacem, Ines, Schmidt, Frederic, Jonniaux, Grégory, Belgacem, Ines, Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID, Géosciences Paris Saclay (GEOPS), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Airbus Defence and Space [Toulouse], Airbus Defence & Space, Toulouse, France and the French National re-search Agency (ANR) as part of the « Investissement d’Avenir » program, through the 'IDI 2016' project funded by the IDEX, and ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011)
Subjects: [PHYS.ASTR.EP] Physics [physics]/Astrophysics [astro-ph]/Earth and Planetary Astrophysics [astro-ph.EP], [SDU.STU.PL]Sciences of the Universe [physics]/Earth Sciences/Planetology, [PHYS.ASTR.EP]Physics [physics]/Astrophysics [astro-ph]/Earth and Planetary Astrophysics [astro-ph.EP], Physics::Space Physics, Astrophysics::Instrumentation and Methods for Astrophysics, Astrophysics::Earth and Planetary Astrophysics, [SDU.STU.PL] Sciences of the Universe [physics]/Earth Sciences/Planetology
Abstract: International audience; We have developed tools to study the photometry of Europa using a Bayesian approach. We merged datasets from New Horizons' LORRI and Voyager's ISS cameras to maximize coverage. We encountered issues of absolute calibration and compatibility of the data and we propose here a way to efficiently merge datasets from different cameras. We also propose a way to estimate correction coefficients for the absolute calibration of each individual image at the same time as the photometric behavior. We use here the Hapke model and realize a Bayesian inversion of the Hapke parameters on 20 areas of interest on Jupiter's moon Europa as well as correction coefficients for a collection of 57 images from LORRI and ISS.
Published: 2019

25. Proposition d’une méthode visant à estimer l’énergie apportée par un arc à une anode en Ag-SnO2

Author: Fouque, Aurélien, Bonhomme, Alexandre, Cailletaud, Georges, Chaudot, François, Esin, Vladimir A., Houzé, Frédéric, Landfried, Romaric, Lisnyak, Marina, Ponthenier, Jean-Luc, Testé, Philippe, Houzé, Frédéric, Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID, Schneider Electric ( SE), Laboratoire Génie électrique et électronique de Paris (GeePs), Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre des Matériaux (MAT), MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), and ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011)
Subjects: [SPI]Engineering Sciences [physics], [SPI] Engineering Sciences [physics], ComputingMilieux_MISCELLANEOUS
Abstract: National audience
Published: 2019

26. Estimation of Hapke's Parameters on Selected Areas of Eurapa Using a Bayesian Approach

Author: Belgacem, Ines, Schmidt, Frédéric, Jonniaux, Grégory, Géosciences Paris Saclay (GEOPS), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Airbus Defence and Space [Toulouse], Airbus Defence & Space, ToulouseFrench National re-search Agency (ANR) as part of the « Investissement d’Avenir » program, through the 'IDI 2016' project funded by the IDEX, ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), Belgacem, Ines, and Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID
Subjects: [PHYS.ASTR.EP] Physics [physics]/Astrophysics [astro-ph]/Earth and Planetary Astrophysics [astro-ph.EP], [SDU.STU.PL]Sciences of the Universe [physics]/Earth Sciences/Planetology, [PHYS.ASTR.EP]Physics [physics]/Astrophysics [astro-ph]/Earth and Planetary Astrophysics [astro-ph.EP], Physics::Space Physics, Astrophysics::Earth and Planetary Astrophysics, [SDU.STU.PL] Sciences of the Universe [physics]/Earth Sciences/Planetology
Abstract: International audience; Exploring the icy satellites of the outer planets is a major step in the search for habitabil-ity in our Solar System. This work focuses on Jupiter’s icy moon Europa and the images captured by the Long-Range Reconnaissance Imager (LORRI) on-board the New Horizons spacecraft. Images of the surface were combined to derive photometric and reflectance models.
Published: 2018

27. Modelling competition for light in wheat mixtures

Author: Blanc, Emmanuelle, Thiaville, Louise, Enjalbert, Jerome, Lecarpentier, Christophe, Génétique Quantitative et Evolution - Le Moulon (Génétique Végétale) (GQE-Le Moulon), AgroParisTech-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génétique Diversité et Ecophysiologie des Céréales (GDEC), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), WHEATAMIX - ANR-13-AGRO-0008, EUCARPIA, ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), Lecarpentier, Christophe, and Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID
Subjects: [SDV.SA.AGRO] Life Sciences [q-bio]/Agricultural sciences/Agronomy, [SDV.SA.AGRO]Life Sciences [q-bio]/Agricultural sciences/Agronomy, [INFO.INFO-MO] Computer Science [cs]/Modeling and Simulation, [SDV.EE.IEO] Life Sciences [q-bio]/Ecology, environment/Symbiosis, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: International audience
Published: 2018

28. Interaction between electric arc and Ag-SnO2 electrodes

Author: Fouque, Aurélien, Cailletaud, Georges, Esin, Vladimir A., Landfried, Romaric, Testé, Philippe, Houzé, Frédéric, Bonhomme, Alexandre, Ponthenier, Jean-Luc, Chaudot, François, Houzé, Frédéric, Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID, Schneider Electric ( SE), Laboratoire Génie électrique et électronique de Paris (GeePs), Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre des Matériaux (MAT), MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), and ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011)
Subjects: [SPI.NRJ]Engineering Sciences [physics]/Electric power, [SPI.MAT] Engineering Sciences [physics]/Materials, ComputingMilieux_MISCELLANEOUS, [SPI.MAT]Engineering Sciences [physics]/Materials, [SPI.NRJ] Engineering Sciences [physics]/Electric power
Abstract: International audience
Published: 2018

29. Photometric study of Europa with Hapke model

Author: Belgacem, Ines, Schmidt, Frederic, Jonniaux, Grégory, Belgacem, Ines, Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID, Géosciences Paris Saclay (GEOPS), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Airbus Defence and Space [Toulouse], Airbus Defence & SpaceFrench National re-search Agency (ANR) as part of the « Investissement d’Avenir » program, through the 'IDI 2016' project funded by the IDEX, and ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011)
Subjects: [PHYS.ASTR.EP] Physics [physics]/Astrophysics [astro-ph]/Earth and Planetary Astrophysics [astro-ph.EP], [SDU.STU.PL]Sciences of the Universe [physics]/Earth Sciences/Planetology, [PHYS.ASTR.EP]Physics [physics]/Astrophysics [astro-ph]/Earth and Planetary Astrophysics [astro-ph.EP], [SDU.STU.PL] Sciences of the Universe [physics]/Earth Sciences/Planetology
Abstract: International audience; In the context of ESA's future mission JUICE, this work is the start of a broad investigation on the reflectance models of Jupiter's icy moons. It focuses on Europa and Hapke photometric model using images from the LORRI instrument on New Horizons. The parameters are estimated using a Bayesian approach that has been developed for similar work on Mars. We show that it is possible to constrain Hapke parameters on restricted areas of Europa and that they can be fairly different depending on the regions of interest. However, this study shows limitations that we hope to overcome by including more data from other missions such as Voyager.
Published: 2018

30. ABMA, a small molecule that inhibits intracellular toxins and pathogens by interfering with late endosomal compartments

Author: Didier Sauvaire, Philippe M. Loiseau, Sabrina Kali, Rahima Yousfi, Pascal Clayette, Daniel Gillet, Céline Bouclier, Noël Tordo, Jérôme Laporte, Amélie Goudet, Goulven Merer, Roman Lopez, Michel R. Popoff, Sandrine Cojean, Valérie Pons, Céline Aubenque, Claire Boulogne, Emmanuel Lemichez, Annette Fischer, Jean-Christophe Cintrat, Laetitia Panigai, Yu Wu, Cynthia Gillet, Roger Le Grand, Thomas Rudel, Robert A. Davey, Julien Barbier, Jo-Ana Herweg, Emilie Gobbo, Service d'Ingénierie Moléculaire pour la Santé (ex SIMOPRO) (SIMoS), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-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 National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-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 National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Chimie Bio-Organique et de Marquage (SCBM), Agence nationale de sécurité du médicament et des produits de santé [Saint-Denis] (ANSM), Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Stratégies antivirales, Institut Pasteur [Paris], Texas Biomedical Research Institute, CEA [Fontenay-aux-Roses] (UGRA / SETA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Molécules bioactives, conception, isolement et synthèse (MBCIS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Bactéries anaérobies et Toxines, Pharmacologie des rétrovirus, Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre méditerranéen de médecine moléculaire (C3M), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work has been funded by the joint ministerial program of R&D against CBRNE risks and CEA, and benefited from the core facilities of Imagerie-Gif (http://www.i2bc.paris-saclay.fr), member of IBiSA (http://www.ibisa.net), supported by 'France-BioImaging' (ANR-10-INBS-04–01) and the Labex 'Saclay Plant Science' (ANR-11-IDEX-0003–02). This work was also supported by U.S. National Institutes of Health and National Institute of Allergy and Infectious Diseases grant R01AI063513, Defense Threat Reduction Agency grant HDTRA1–12–1–0002, and the Douglass and Ewing Halsell Foundations. Work on Simkania and Chlamydia was supported by the Deutsche Forschungsgemeinschaft (DFG) Priority programme 1580 to T.R. SIMOPRO and SCBM are members of the Laboratory of Excellence LERMIT supported by a grant from the Agence Nationale de la Recherche (ANR-10-LABX-33) and RetroLeishma project R3, We greatfully thank Anne Doye (Université de Nice Sophia-Antipolis) for technical assistance and Bruno Beaumelle for providing ricin, ANR-11-IDEX-0002,UNITI,Université Fédérale de Toulouse(2011), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), Julius-Maximilians-Universität Würzburg (JMU), Institut Pasteur [Paris] (IP), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Popoff, Michel, Initiative d'excellence - Université Fédérale de Toulouse - - UNITI2011 - ANR-11-IDEX-0002 - IDEX - VALID, Développment d'une infrastructure française distribuée coordonnée - - France-BioImaging2010 - ANR-10-INBS-0004 - INBS - VALID, and Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID
Subjects: 0301 basic medicine, Benzylamines, Endosome, 030106 microbiology, Cell, Golgi Apparatus, lcsh:Medicine, Adamantane, Endosomes, Ricin, Endoplasmic Reticulum, Article, Mice, 03 medical and health sciences, symbols.namesake, ddc:570, Benzyl Compounds, Organelle, medicine, Animals, Humans, lcsh:Science, Pathogen, Toxins, Biological, Multidisciplinary, Chemistry, Antimicrobials, Endoplasmic reticulum, Intracellular parasite, lcsh:R, High-throughput screening, Golgi apparatus, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Cell Compartmentation, 3. Good health, Cell biology, 030104 developmental biology, medicine.anatomical_structure, symbols, Infectious diseases, lcsh:Q, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Lysosomes, Intracellular, HeLa Cells
Abstract: Intracellular pathogenic microorganisms and toxins exploit host cell mechanisms to enter, exert their deleterious effects as well as hijack host nutrition for their development. A potential approach to treat multiple pathogen infections and that should not induce drug resistance is the use of small molecules that target host components. We identified the compound 1-adamantyl (5-bromo-2-methoxybenzyl) amine (ABMA) from a cell-based high throughput screening for its capacity to protect human cells and mice against ricin toxin without toxicity. This compound efficiently protects cells against various toxins and pathogens including viruses, intracellular bacteria and parasite. ABMA provokes Rab7-positive late endosomal compartment accumulation in mammalian cells without affecting other organelles (early endosomes, lysosomes, the Golgi apparatus, the endoplasmic reticulum or the nucleus). As the mechanism of action of ABMA is restricted to host-endosomal compartments, it reduces cell infection by pathogens that depend on this pathway to invade cells. ABMA may represent a novel class of broad-spectrum compounds with therapeutic potential against diverse severe infectious diseases.
Published: 2017
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31. Depth Profiling of Strain in Textured Tungsten Thin Films

Author: Li, Chenyi, Baldinozzi, Gianguido, Lecoeur, Philippe, Maroutian, Thomas, Pontikis, Vassilis, Laboratoire Structures, Propriétés et Modélisation des solides (SPMS), Institut de Chimie du CNRS (INC)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Service des Recherches Métallurgiques Appliquées (SRMA), Département des Matériaux pour le Nucléaire (DMN), CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut d'électronique fondamentale (IEF), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Solides Irradiés (LSI), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X), ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), Baldinozzi, Gianguido, Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID, and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [CHIM.CRIS]Chemical Sciences/Cristallography, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], [CHIM.CRIS] Chemical Sciences/Cristallography, [PHYS.COND.CM-MS] Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci]
Abstract: International audience; The stability of heterophase interfaces between metal systems, their kinetic, structural, and thermomechanical properties are a matter of concern for high demanding applications involved in the development of technological coatings for the first wall materials in fusion reactors and their prototypes (ITER). We would like to discuss preliminary results of X-ray experiments on model coatings made of tungsten, in particular the problems related to strain inhomogeneity in metal films on heterophase substrates. These analyses of nanostructured thin layers can be performed using laboratory grazing incidence diffraction, allows the accurate extraction of quantitative relevant information about the structure (strain and atomic positions) and the microstructure (crystallite size and microstrain), selectively probing the material on a depth of few nanometers. References Results The local strain in the three films is almost identical at a given depth. This suggests that the deposition method produce reliable microstructural characteristics for the three films. In the three films the maximum amplitude of the strain is close to the surface of the films and it decreases smoothly when the depth increases. It seems likely that the larger strain observed close to the surface could be partly related to the interaction of the films with the gases of the ambient atmosphere: nevertheless, these effects seems to remain small and do not seem to require a reassessment of the absorbance of the films. Grazing incidence X-ray diffraction can be a workhorse technique for deriving crystallite size in nanoscale systems due to its non-destructive character, the fast data collection and the relative simplicity of the experimental setup, This information is relevant for an accurate description of nanocrystalline systems prepared as thin films and it can significantly improve the knowledge of their structure-properties relationships. This work was partly supported by Laboratoire d'Excellence Physique Atomes Lumière Matière (LabEx PALM) through a French national grant of Agence Nationale de la Recherche within the "Programme Investissements d'Avenir" with
Published: 2017

32. Towards photometry of Europa

Author: Belgacem, Ines, Schmidt, F., Jonniaux, G., Géosciences Paris Saclay (GEOPS), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Airbus Defence and Space [Toulouse], Airbus Defence & Space, Toulouse, FranceFrench National re-search Agency (ANR) as part of the « Investissement d’Avenir » program, through the 'IDI 2016' project funded by the IDEX, ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), Belgacem, Ines, and Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID
Subjects: [PHYS.ASTR.EP] Physics [physics]/Astrophysics [astro-ph]/Earth and Planetary Astrophysics [astro-ph.EP], [SDU.STU.PL]Sciences of the Universe [physics]/Earth Sciences/Planetology, [PHYS.ASTR.EP]Physics [physics]/Astrophysics [astro-ph]/Earth and Planetary Astrophysics [astro-ph.EP], Physics::Space Physics, Astrophysics::Earth and Planetary Astrophysics, [SDU.STU.PL] Sciences of the Universe [physics]/Earth Sciences/Planetology
Abstract: International audience; Exploring the icy satellites of outter planets is a major step in the search for habitability in our Solar System. This work focuses on Jupiter's icy moon Europa and the images captured by the Long-Range Reconnaissance Imager on-board the New Horizons spacecraft. It is aimed at combining images of the satellite in order to derive photometric reflectance models (i.e. angular response of a surface). It will later be extended to the other two icy Jovian satellites, Ganymede and Callisto and larger data sets.
Published: 2017

33. Détermination des caractéristiques du flux de puissance apporté à des électrodes en AgSnO2 par un arc non stationnaire dans l’air

Author: Testé, Philippe, Landfried, Romaric, Houzé, Frédéric, Fouque, Aurélien, Cailletaud, Georges, Esin, Vladimir A., Bonhomme, Alexandre, Chaudot, François, Ponthenier, Jean-Luc, Laboratoire Génie électrique et électronique de Paris (GeePs), Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Schneider Electric ( SE), Centre des Matériaux (CDM), Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), Centre des Matériaux (MAT), MINES ParisTech - École nationale supérieure des mines de Paris, Houzé, Frédéric, and Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID
Subjects: [SPI]Engineering Sciences [physics], [SPI] Engineering Sciences [physics], ComputingMilieux_MISCELLANEOUS
Abstract: National audience
Published: 2017

34. Blind Pose Prediction, Scoring, and Affinity Ranking of the CSAR 2014 Dataset

Author: Virginie Y. Martiny, François Martz, Bogdan I. Iorga, Edithe Selwa, Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Service de Département de Néphrologie = Service de Néphrologie et Dialyses [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), RONCO, Pierre, and Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID
Subjects: 0301 basic medicine, Molecular model, Computer science, Protein Conformation, General Chemical Engineering, Library and Information Sciences, Machine learning, computer.software_genre, Molecular Docking Simulation, Preliminary analysis, 03 medical and health sciences, Protein structure, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Syk Kinase, Databases, Protein, tRNA Methyltransferases, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], business.industry, TRNA Methyltransferase, Proteins, General Chemistry, computer.file_format, Protein Data Bank, Computer Science Applications, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, Benchmarking, 030104 developmental biology, Docking (molecular), Factor Xa, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Pose prediction, Artificial intelligence, business, computer
Abstract: International audience; The 2014 CSAR Benchmark Exercise was focused on three protein targets: coagulation factor Xa, spleen tyrosine kinase, and bacterial tRNA methyltransferase. Our protocol involved a preliminary analysis of the structural information available in the Protein Data Bank for the protein targets, which allowed the identification of the most appropriate docking software and scoring functions to be used for the rescoring of several docking conformations datasets, as well as for pose prediction and affinity ranking. The two key points of this study were (i) the prior evaluation of molecular modeling tools that are most adapted for each target and (ii) the increased search efficiency during the docking process to better explore the conformational space of big and flexible ligands.
Published: 2016
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35. Efficient Plasma Cell Differentiation and Trafficking Require Cxcr4 Desensitization

Author: Patrice Hemon, Christelle Freitas, Vincent Biajoux, Antoine Sacquin, Karl Balabanian, Jessica Natt, Nagham Alouche, Nicolas Fazilleau, Marion Espéli, Françoise Gaudin, Cytokines, chimiokines et immunopathologie, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Plateforme d’Histologie (PHIC), Institut Paris-Saclay d’Innovation Thérapeutique (IPSIT), ANR-14-ACHN-0008,AUTO-PLASMO,Analyse integrative de la biologie des plasmocytes normaux et pathologiques(2014), ANR-11-IDEX-0003-02/10-LABX-0033,LERMIT,Research Laboratory on Drugs and Therapeutic Innovation(2011), Centre de Physiopathologie Toulouse Purpan (CPTP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paris Saclay d’Innovation Thérapeutique (IPSIT), Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), The study was supported by ANR grant 2010-JCJC-110401 to K.B., by a Junior Team Leader starting grant from the Laboratory of Excellence in Research on Medication and Innovative Therapeutics (LabEx LERMIT) and an ANR @RAction starting grant (ANR-14-ACHN-0008) to M.E., and by the Conseil Re´ gional Midi-Pyre´ ne´ es, Institut National contre le Cancer (INCa, PLBIO10-195 and INCA-6530) and FP7-MC-IRG-256471 to N.F. V.B., J.N., C.F., N.A., F.G., M.E., and K.B. are members of the LabEx LERMIT supported by ANR grant ANR-10-LABX-33 under the program Investissements d’Avenir ANR-11-IDEX-0003-01. V.B. was supported by fellowships from the French Ministry for education and the Fondation pour la Recherche Me´ dicale (FRM). J.N. was a PhD fellow from the LabEx LERMIT. C.F. was supported by the DIM Biotherapies and the Socie´te´ Franc¸ aise d’He´ matologie (SFH). N.A. was supported by a fellowship from the French Ministry for education. A.S. was supported by la Ligue Nationale Contre le Cancer., ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), European Project: 256471,EC:FP7:PEOPLE,FP7-PEOPLE-2009-RG,TFHCELLS(2010), Fazilleau, Nicolas, Accueil de Chercheurs de Haut Niveau - Analyse integrative de la biologie des plasmocytes normaux et pathologiques - - AUTO-PLASMO2014 - ANR-14-ACHN-0008 - @RAction - VALID, Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID, In vivo characterisation of Follicular Helper T cells - TFHCELLS - - EC:FP7:PEOPLE2010-06-01 - 2014-05-31 - 256471 - VALID, and ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2012)
Subjects: 0301 basic medicine, Receptors, CXCR4, [SDV.IMM] Life Sciences [q-bio]/Immunology, Ovalbumin, Primary Immunodeficiency Diseases, Cellular differentiation, Plasma Cells, B-Lymphocyte Subsets, Gene Expression, Mice, Transgenic, Biology, Plasma cell, Antibodies, General Biochemistry, Genetics and Molecular Biology, Mice, 03 medical and health sciences, Immune system, Bone Marrow, Cell Movement, Plasma cell differentiation, medicine, Animals, Humans, Gene Knock-In Techniques, lcsh:QH301-705.5, B cell, Immunologic Deficiency Syndromes, Germinal center, Cell Differentiation, Germinal Center, medicine.disease, Immunity, Humoral, Cell biology, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, lcsh:Biology (General), Desensitization, Immunologic, Hemocyanins, Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunization, Warts, Signal transduction, Haptens, WHIM syndrome, Signal Transduction
Abstract: International audience; CXCR4 plays a central role in B cell immune response, notably by promoting plasma cell (PC) migration and maintenance in the bone marrow (BM). Gain-of-function mutations in CXCR4 affecting receptor desensitization have been reported in the rare immunodeficiency called WHIM syndrome (WS). Despite lymphopenia, patients mount an immune response but fail to maintain it over time. Using a knockin mouse model phenocopying WS, we showed that, counter-intuitively, a gain of Cxcr4 function inhibited the maintenance of antibody titers after immunization. Although the Cxcr4 mutation intrinsically and locally promoted germinal center response and PC differentiation, antigen-specific PCs were barely detected in the BM, a defect mirrored by early accumulation of immature plasmablasts potentially occupying the survival niches for long-lived PCs. Therefore, fine-tuning of Cxcr4 desensitization is critically required for efficient PC differentiation and maintenance, and absence of such a regulatory process may account for the defective humoral immunity observed in WS patients.
Published: 2016
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36. Relaxation of Loaded ESCRT-III Spiral Springs Drives Membrane Deformation

Author: Nicolas Chiaruttini, Simon Scheuring, Aurélien Roux, Lorena Redondo-Morata, Martin Lenz, Frédéric Humbert, Adai Colom, Biochemistry Department - University of Geneva, University of Geneva [Switzerland], BIO-AFM-LAB Bio Atomic Force Microscopy Laboratory (Bio-AFM-Lab), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Swiss National Centre for Competence in Research Programme Chemical Biology (NCCR-Chemical Biology), Laboratoire de Physique Théorique et Modèles Statistiques (LPTMS), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), AR acknowledges funding support from: Human Frontier Science Program (HFSP), Young Investigator Grant #RGY0076-2008: the European Research Council (ERC), starting (consolidator) grant #311536-MEMFIS: the Swiss National Fund for Research, grants #131003A_130520 and #131003A_149975. NC acknowledges the European Commission for the Marie-Curie post-doctoral fellowship CYTOCUT #300532-2011. SS acknowledges funding support from: Agence Nationale de la Recherche, France (ANR), ANR-Nano (ANR-12-BS10-009-01) and ANR-BBMS (ANR-12-BSV8-0006-01) grants, and a European Research Council (ERC) Starting Grant (#310080). ML's group belongs to the CNRS consortium CellTiss and is supported by grants from Université Paris-Sud and CNRS, Marie Curie Integration Grant PCIG12-GA-2012-334053 and 'Investissements d'Avenir' LabEx PALM (ANR-10-LABX-0039-PALM)., ANR-12-BS10-0009,Opt-Spect-HS-AFM,Intégration de la microscopie optique avec la microscopie à forces atomiques à haute vitesse et développement de la spectroscopie moléculaire de forces à haute vitesse(2012), ANR-12-BSV8-0006,AFM-2-BioMed,Assemblage des proteines dans des membranes de tissus sains et pathologiques par Microscopie à Force Atomique(2012), ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), European Project: 311536,EC:FP7:ERC,ERC-2012-StG_20111109,MEMFIS(2013), European Project: 300532,EC:FP7:PEOPLE,FP7-PEOPLE-2011-IEF,CYTOCUT(2012), European Project: 310080,EC:FP7:ERC,ERC-2012-StG_20111109,MEM-STRUCT-AFM(2013), Université de Genève = University of Geneva (UNIGE), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM) - Aix Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS) - Université Paris-Sud - Paris 11 (UP11), ANR-11-IDEX-0003-02/10-LABX-0039, PALM, Physics: Atoms, Light, Matter(2011), European Project : 300532, EC:FP7:PEOPLE, FP7-PEOPLE-2011-IEF, CYTOCUT(2012), Le Vaou, Claudine, BLANC - Intégration de la microscopie optique avec la microscopie à forces atomiques à haute vitesse et développement de la spectroscopie moléculaire de forces à haute vitesse - - Opt-Spect-HS-AFM2012 - ANR-12-BS10-0009 - BLANC - VALID, BLANC - Assemblage des proteines dans des membranes de tissus sains et pathologiques par Microscopie à Force Atomique - - AFM-2-BioMed2012 - ANR-12-BSV8-0006 - BLANC - VALID, Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID, Mechanical Understanding of Membrane Fission in Endocytosis and Cytokinesis - MEMFIS - - EC:FP7:ERC2013-01-01 - 2017-12-31 - 311536 - VALID, Cytokinesis’ final cut: mechanics of abscission and ESCRT-III mediated membrane fission. - CYTOCUT - - EC:FP7:PEOPLE2012-07-01 - 2014-06-30 - 300532 - VALID, and The Structure and Assembly of Membrane Proteins in Native Membranes studied by AFM - MEM-STRUCT-AFM - - EC:FP7:ERC2013-01-01 - 2017-12-31 - 310080 - VALID
Subjects: Models, Molecular, [PHYS]Physics [physics], Endosomal Sorting Complexes Required for Transport, Biochemistry, Genetics and Molecular Biology(all), Viral budding, Lipid Bilayers, Intracellular Membranes, macromolecular substances, Biology, Curvature, General Biochemistry, Genetics and Molecular Biology, ESCRT, [PHYS] Physics [physics], Membrane, Rigidity (electromagnetism), Biochemistry, Polymerization, Membrane curvature, Yeasts, ddc:540, Biophysics, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Lipid bilayer, Virus Release
Abstract: International audience; 13 ESCRT-III is required for lipid membrane remodeling in many cellular processes, from abscission 14 to viral budding and multi-vesicular body biogenesis. However, how ESCRT-III polymerization 15 generates membrane curvature remains debated. Here we show that Snf7, the main component 16 of ESCRT-III, polymerizes into spirals at the surface of lipid bilayers. When covering the entire 17 membrane surface, these spirals stopped growing when densely packed: they had a polygonal 18 shape, suggesting that lateral compression could deform them. We reasoned that Snf7 spirals 19 could function as spiral springs. By measuring the polymerization energy and the rigidity of Snf7 20 filaments, we showed that they were deformed while growing in a confined area. Furthermore, 21 we observed that the elastic expansion of compressed Snf7 spirals generated an area difference 22 between the two sides of the membrane and thus curvature. This spring-like activity underlies the 23 driving force by which ESCRT-III could mediate membrane deformation and fission. 24 2
Published: 2015
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37. Update on SAMPIC, WTDC digitizer chip for picosecond time measurement

Author: Breton, D., Delagnes, E., Grabas, H., Lemaire, O., Maalmi, J., Rusquart, P., Vallerand, P., Laboratoire de l'Accélérateur Linéaire (LAL), Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Sud - Paris 11 (UP11), Département d'Electronique, des Détecteurs et d'Informatique pour la Physique (ex SEDI) (DEDIP), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), 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, SERDI, ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), Starita, Sabine, Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID, and Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [PHYS.HEXP] Physics [physics]/High Energy Physics - Experiment [hep-ex], [PHYS.HEXP]Physics [physics]/High Energy Physics - Experiment [hep-ex], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2015

38. Certifying the interoperability of RDF database systems

Author: Karima Rafes, Nauroy, J., Germain, C., BorderCloud [Issy-les-Moulineaux], Machine Learning and Optimisation (TAO), Laboratoire de Recherche en Informatique (LRI), Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Université Paris-Sud - Paris 11 (UP11), FUI TIMCO, France Grilles, ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), Rafes, Karima, Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID, Centre National de la Recherche Scientifique (CNRS)-Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université Paris-Sud - Paris 11 (UP11)-Laboratoire de Recherche en Informatique (LRI), and Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec
Subjects: [INFO.INFO-SY] Computer Science [cs]/Systems and Control [cs.SY], [INFO.INFO-DB]Computer Science [cs]/Databases [cs.DB], [INFO.INFO-WB] Computer Science [cs]/Web, InformationSystems_INFORMATIONSTORAGEANDRETRIEVAL, [INFO.INFO-WB]Computer Science [cs]/Web, InformationSystems_DATABASEMANAGEMENT, interoperability, SPARQL, ACM: H.: Information Systems/H.3: INFORMATION STORAGE AND RETRIEVAL/H.3.5: Online Information Services/H.3.5.2: Web-based services, [INFO.INFO-PF]Computer Science [cs]/Performance [cs.PF], [INFO.INFO-PF] Computer Science [cs]/Performance [cs.PF], ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Linked Data Quality, [INFO.INFO-SY]Computer Science [cs]/Systems and Control [cs.SY], [INFO.INFO-DB] Computer Science [cs]/Databases [cs.DB], ACM: H.: Information Systems/H.2: DATABASE MANAGEMENT
Abstract: International audience; In March 2013, the W3C recommended SPARQL 1.1 to retrieve and manipulate decentralized RDF data. Real-world usage requires advanced features of SPARQL 1.1. recommendations As these are not consistently implemented, we propose a test framework named TFT (Tests for Triple stores) to test the interoperability of the SPARQL end-point of RDF database systems. This framework can execute the W3C's SPARQL 1.1 test suite and also its own tests of interoperability. To help the developers and end-users of RDF databases, we perform daily tests on Jena-Fuseki, Marmotta-KiWistore, 4Store and three other commercial databases. With these tests, we have built a scoring system named SPARQLScore and share our results on the website http://sparqlscore.com.
Published: 2015

39. Extracting Brain PET-MRI Joint Structures for Statistical Analysis

Author: Rahim, Mehdi, Service NEUROSPIN (NEUROSPIN), 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 Paris-Saclay, Service Hospitalier Frédéric Joliot (SHFJ), Modelling brain structure, function and variability based on high-field MRI data (PARIETAL), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Service NEUROSPIN (NEUROSPIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Lidex PIM, ANR-11-BINF-0003,MAPPING,Vers une cartographie haute résolution des interactions protéiques à l'échelle du génome.(2011), ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), Université Paris-Saclay-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), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Rahim, Mehdi, Vers une cartographie haute résolution des interactions protéiques à l'échelle du génome. - - MAPPING2011 - ANR-11-BINF-0003 - BINF - VALID, and Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID
Subjects: [INFO.INFO-LG]Computer Science [cs]/Machine Learning [cs.LG], [INFO.INFO-IM] Computer Science [cs]/Medical Imaging, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, [INFO.INFO-LG] Computer Science [cs]/Machine Learning [cs.LG]
Abstract: International audience; Within the context of brain image analysis, classical mono-modality analysis could be significantly improved by combining different image modalities. Indeed, Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) joint analysis bring complementary informations, as PET gives access, for example, to quantitative brain neurotransmission parameters, while MRI good spatial resolution can be used to differentiate between specific brain structures. The major impediments of brain image statistical analysis are often related to the small number of available samples compared to the large size of the multi-modal images, as well as the image low signal to noise ratio (SNR). Our aim is to overcome these limitations, by taking advantage of the additional information provided by the different modalities: for instance, functional MRI can provide relevant data decompositions that improve the sensitivity of statistical analyses. In this presentation, I will present a statistical and classification framework that relied on both modalities, and also preliminary experiments on clinical studies such as the early detection of the Alzheimer's Disease, by using [18F]-FDG PET and resting-state fMRI data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The approach takes into account the structure of the multimodal images, and also the patterns that better match the underlying physiopathology.
Published: 2014

40. Formulation and pharmacokinetics of thermosensitive stealth® liposomes encapsulating 5-Fluorouracil

Author: Jean-Michel Escoffre, Elias Fattal, Stéphanie Denis, Nicolas Tsapis, Claire Gueutin, Juliette Vergnaud, Anthony Novell, Hélène Chacun, Chantal Al Sabbagh, Patricia Calleja-Gonzalez, Ayache Bouakaz, Laboratory of Excellence in Research on Medication and Innovative Therapeutics (LERMIT), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Galien Paris-Sud (IGPS), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), This research work was funded by Agence Nationale de la Recherche (ANR-2010-TecSan-007). Institut Galien Paris Sud is a member of the Laboratory of Excellence LERMIT supported by a grant from ANR (ANR-10-LABX-33). Authors would like to thank A. Maksimenko for help with the tumor model and H. Bénech for help with PK analysis., ANR-07-TECS-0007,ID2U,Instrument Dextre robotisé à retour d'effort et Usage Unique, pour la chirurgie mini-invasive(2007), ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Escoffre, Jean-Michel, Technologies pour la santé - Instrument Dextre robotisé à retour d'effort et Usage Unique, pour la chirurgie mini-invasive - - ID2U2007 - ANR-07-TECS-0007 - TECSAN - VALID, and Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID
Subjects: Hyperthermia, Male, copper-polyethylenimine complex, Antimetabolites, Antineoplastic, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, 1,2-Dipalmitoylphosphatidylcholine, Stereochemistry, 5-Fluorouracil, Pharmacology toxicology, Pharmaceutical Science, [SDV.CAN]Life Sciences [q-bio]/Cancer, Focused ultrasound, Polyethylene Glycols, Mice, [SDV.CAN] Life Sciences [q-bio]/Cancer, Pharmacokinetics, Medicine, Animals, Humans, Polyethyleneimine, Pharmacology (medical), Tissue Distribution, thermosensitive stealth® liposomes, Stealth liposomes, Pharmacology, Liposome, Mice, Inbred BALB C, business.industry, Phosphatidylethanolamines, Organic Chemistry, Hyperthermia, Induced, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Drug Liberation, Cholesterol, Fluorouracil, Liposomes, Drug release, focused ultrasound, Molecular Medicine, business, pharmacokinetics, HT29 Cells, Biotechnology, Biomedical engineering, medicine.drug
Abstract: International audience; PURPOSE:We optimize the encapsulation and investigate the pharmacokinetics of 5-Fluorouracil (5-FU) delivered by thermosensitive stealth(®) liposomes (TSLs) designed to trigger drug release upon hyperthermia using focused ultrasound (FUS).METHODS:5-FU was encapsulated into liposomes made of 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine/cholesterol/1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-PEG2000 either as a free molecule or complexed with copper-polyethylenimine. Heat-triggered drug release was evaluated using either a water bath or FUS. Formulation cytotoxicity was assessed on HT-29 cell line by MTS assay. Pharmacokinetics and biodistribution of 5-FU were evaluated in HT-29-tumor bearing mice.RESULTS:5-FU was easily encapsulated using the lipid hydration method (encapsulation efficacy of 13%) but poorly retained upon dilution. 5-FU complexation with copper-polyethylenimine improved 5-FU retention into liposomes and allowed to obtain an encapsulation efficacy of 37%. At 42°C, heat-triggered 5-FU release from TSLs was 63% using a water bath and 68% using FUS, within 10 min, whereas it remained below 20% for the non-thermosensitive formulation. The MTS assay revealed that formulation toxicity arose from 5-FU and not from the excipients. In addition, 5-FU complex encapsulation into TSLs induces a reduction of the IC50 from 115 down to 49 μM. Pharmacokinetics reveals a longer circulation of encapsulated 5-FU and a more important body exposure, although tumor passive targeting is not significantly higher than free 5-FU.CONCLUSIONS:Complexation of 5-FU with copper-polyethylenimine appears an interesting strategy to improve 5-FU retention into TSLs in vitro and in vivo. TSLs allow heat-triggered release of the drug within 10 min at 42°C, a reasonable time for future in vivo experiments.
Published: 2014
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41. Over one Century of Spectrum Analysis in Delay Systems: An Overview and New Trends in Pole Placement Methods

Author: Amina BENARAB, Islam Boussaada, Silviu-Iulian Niculescu, Karim Trabelsi, Laboratoire des signaux et systèmes (L2S), CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Polytechnique des Sciences Avancées (IPSA), Dynamical Interconnected Systems in COmplex Environments (DISCO), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire des signaux et systèmes (L2S), CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), BENARAB, Amina, and Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID
Subjects: [INFO.INFO-SY] Computer Science [cs]/Systems and Control [cs.SY], Delay, Pole assignment, [MATH.MATH-GM] Mathematics [math]/General Mathematics [math.GM], [MATH] Mathematics [math], Pole placement, [SPI.AUTO]Engineering Sciences [physics]/Automatic, [SPI.AUTO] Engineering Sciences [physics]/Automatic, [MATH.MATH-GM]Mathematics [math]/General Mathematics [math.GM], Control and Systems Engineering, [INFO.INFO-SY]Computer Science [cs]/Systems and Control [cs.SY], [NLIN] Nonlinear Sciences [physics], [NLIN]Nonlinear Sciences [physics], [MATH]Mathematics [math], Stability
Abstract: International audience; Pole placement represents a classical method for controlling finite-dimensional linear timeinvariant systems, largely covered in the open literature. Basically, it consists of placing the poles of the closed-loop system in some predetermined loci in the complex plane. This paper discusses some of the extensions of this method to linear systems described by delay-differential equations. Among others, the finite spectrum assignment (FSA), the continuous pole placement (CPP) and the partial pole placement (PPP) approaches are presented and illustrated through some simple low-order dynamical systems.

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