Author: "Centre de biophysique moléculaire (CBM)" - Searchworks@Jio Institute Digital Library Search Results

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2,625 results on '"Centre de biophysique moléculaire (CBM)"'

1. Modelling Tetraselmis sp. growth-kinetics and optimizing bioactive-compound production through environmental conditions

Author: Bilel Hadrich, Imen Fendri, Chantal Pichon, Faiez Hentati, Mohamed Barkallah, Philippe Michaud, Mouna Dammak, Michel Denis, Slim Abdelkafi, Hajer Ben Hlima, Frapart, Isabelle, Unité de Biotechnologie des Algues, Biological Engineering Department, National School of Engineers of Sfax, Université de Sfax - University of Sfax, École Nationale d'Ingénieurs de Sfax | National School of Engineers of Sfax (ENIS), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Service de Maladies infectieuses et tropicales [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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Service des maladies infectieuses et tropicales [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Toxicology-Microbiology and Environmental Health Unit (UR11ES70), Faculty of Sciences, Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut méditerranéen d'océanologie (MIO), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Institut Pascal - Clermont Auvergne ( IP ), Sigma CLERMONT ( Sigma CLERMONT ) -Université Clermont Auvergne ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Sfax, Centre de biophysique moléculaire ( CBM ), Université d'Orléans ( UO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut méditerranéen d'océanologie ( MIO ), Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -Université de Toulon ( UTLN ) -Centre National de la Recherche Scientifique ( CNRS ), National School of Engineers of Sfax, Service des Maladies Infectieuses et Tropicales [CHU Tenon], CHU Tenon [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université
Subjects: Chlorophyll, 0106 biological sciences, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Light, Starch, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, [SDV]Life Sciences [q-bio], [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], 010501 environmental sciences, 01 natural sciences, chemistry.chemical_compound, [ SDV.BBM.BC ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], [CHIM.GENI]Chemical Sciences/Chemical engineering, Optimal culture conditions, Chlorophyta, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.IDA]Life Sciences [q-bio]/Food engineering, Microalgae, [ CHIM.GENI ] Chemical Sciences/Chemical engineering, Waste Management and Disposal, Carotenoid, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, biology, [CHIM.ORGA]Chemical Sciences/Organic chemistry, [ SDV.IDA ] Life Sciences [q-bio]/Food engineering, [CHIM.MATE]Chemical Sciences/Material chemistry, General Medicine, Chlorophylls, Bioactive compound, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, [SDV] Life Sciences [q-bio], [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], [ SDV.BBM.BP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Environmental Engineering, Bioengineering, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [ CHIM.ORGA ] Chemical Sciences/Organic chemistry, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, 010608 biotechnology, Tetraselmis, 0105 earth and related environmental sciences, Chromatography, Renewable Energy, Sustainability and the Environment, [ SDV.BC.BC ] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [ SDV.BIO ] Life Sciences [q-bio]/Biotechnology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, biology.organism_classification, Carotenoids, [ CHIM.POLY ] Chemical Sciences/Polymers, Salinity, Kinetics, Light intensity, [CHIM.POLY]Chemical Sciences/Polymers, chemistry, [ CHIM.MATE ] Chemical Sciences/Material chemistry, Gravimetric analysis, [ CHIM.ANAL ] Chemical Sciences/Analytical chemistry, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [ SDV.BBM.BS ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
Abstract: International audience; The aim of this study is to predict Tetraselmis cells growth-kinetic and to induce the synthesis of bioactive compounds (chlorophylls, carotenoids and starch) with high potential for biotechnological applications. Using the statistical criteria, the Baranyi-Roberts model has been selected to estimate the microalgae growth-kinetic values. The simultaneous effects of salinity, light intensity and pH of culture medium were investigated to maximize the production of total chlorophylls, carotenoids and starch. The optimal culture conditions for the production of these compounds were found using Box-Behnken Design. Results have shown that total chlorophyll and carotenoids were attained 21.6mg·g-1DW and 0.042mg·g-1DW, respectively. In addition, the highest starch content of 0.624g·g-1DW has been obtained at neutral pH with high irradiance (182μmolphotonsm-2 s-1) and low salinity (20). A highly correlation (R2 = 0.884) has been found between the gravimetric and flow cytometric measurements of chlorophyll content.
Published: 2018

2. Targeting HER2-breast tumors with scFv-decorated bimodal nanoprobes

Author: Alric, Christophe, Hervé-Aubert, Katel, Aubrey, Nicolas, Melouk, Souad, Lajoie, Laurie, Même, William, Même, Sandra, Courbebaisse, Yann, Ignatova, Anastasia A., Feofanov, Alexey V., Chourpa, Igor, Allard-Vannier, Emilie, Nanomédicaments et Nanosondes, EA 6295 (NMNS), Université de Tours, Infectiologie Santé Publique (ISP-311), Institut National de la Recherche Agronomique (INRA)-Université de Tours, Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), IDPS-Bertin Pharma, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry (IBCh RAS), Russian Academy of Sciences [Moscow] (RAS), Lomonosov Moscow State University (MSU), Université de Tours-Institut National de la Recherche Agronomique (INRA), Université de Tours (UT), Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), French Higher Education and Research ministry under the program 'Investissements d’avenir' Grant Agreement: LabEx MAbImprove ANR-10-LABX-53–01, Russian Foundation for Basic Research (grant 16-54-76013) French Ministry of National Education, Higher Education and Research (MENESR, Project No. 321 MINERVA), Frames of European program ERA-NET RUS PLUS., Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Soucé, Martin, Nanomédicaments et Nanosondes, EA 6295 ( NMNS ), Infectiologie Santé Publique ( ISP-311 ), Institut National de la Recherche Agronomique ( INRA ) -Université de Tours, Génétique, Immunothérapie, Chimie et Cancer ( GICC ), Université de Tours-Centre National de la Recherche Scientifique ( CNRS ), Centre de biophysique moléculaire ( CBM ), Université d'Orléans ( UO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry ( IBCh RAS ), Russian Academy of Sciences [Moscow] ( RAS ), and Lomonosov Moscow State University ( MSU )
Subjects: [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, lcsh:Medical technology, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Receptor, ErbB-2, lcsh:Biotechnology, Magnetic Resonance Imaging (MRI), Contrast Media, Mice, Nude, Breast tumor, Cyanine 5.5, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, chemical and pharmacologic phenomena, Ferric Compounds, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Polyethylene Glycols, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Cell Line, Tumor, lcsh:TP248.13-248.65, Animals, Humans, Human Epithelial growth Receptor 2 (HER2), [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, [ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging, Fluorescent Dyes, [ SDV.SP.MED ] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Research, respiratory system, [ SDV.IB.BIO ] Life Sciences [q-bio]/Bioengineering/Biomaterials, Magnetic Resonance Imaging, [SDV.IB.BIO] Life Sciences [q-bio]/Bioengineering/Biomaterials, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, lcsh:R855-855.5, Iron oxide nanoparticle, Nanoparticles, Female, Single-Chain Antibodies, Single chain variable fragment (scFv)
Abstract: Background Recent advances in nanomedicine have shown the great interest of active targeting associated to nanoparticles. Single chain variable fragments (scFv) of disease-specific antibodies are very promising targeting entities because they are small, not immunogenic and able to bind their specific antigens. The present paper is devoted to biological properties in vitro and in vivo of fluorescent and pegylated iron oxide nanoparticles (SPIONs-Cy-PEG-scFv) functionalized with scFv targeting Human Epithelial growth Receptor 2 (HER2). Results Thanks to a site-selective scFv conjugation, the resultant nanoprobes demonstrated high affinity and specific binding to HER2 breast cancer cells. The cellular uptake of SPIONs-Cy-PEG-scFv was threefold higher than that for untargeted PEGylated iron oxide nanoparticles (SPIONs-Cy-PEG) and is correlated to the expression of HER2 on cells. In vivo, the decrease of MR signals in HER2+ xenograft tumor is about 30% at 24 h after the injection. Conclusions These results all indicate that SPIONs-Cy-PEG-scFv are relevant tumor-targeting magnetic resonance imaging agents, suitable for diagnosis of HER2 overexpressing breast tumor. Electronic supplementary material The online version of this article (10.1186/s12951-018-0341-6) contains supplementary material, which is available to authorized users.
Published: 2018

3. A phosphorylated zinc finger peptide bearing a gadolinium complex for zinc detection by MRI

Author: Kyangwi P. Malikidogo, Agnès Pallier, Frédéric Szeremeta, Célia S. Bonnet, Olivier Sénèque, Physiochimie des Métaux (PMB), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Centre de biophysique moléculaire (CBM), and Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Inorganic Chemistry, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, [CHIM.COOR]Chemical Sciences/Coordination chemistry
Abstract: International audience; Two zinc finger peptides, namely ZFQD(Ln) and ZFQE(Ln) (Ln = Tb or Gd), with an appended Ln(3+) chelate and a phosphoserine able to coordinate the Ln(3+) ion are presented. The two peptides differ by the amino acid anchorage of the chelate, either aspartate (D) or glutamate (E). Both peptides are able to bind Zn2+ and adopt the beta beta alpha fold. Interestingly, ZFQE(Tb) shows a decrease in sensitized Tb3+ luminescence upon Zn2+ binding whereas ZFQD(Tb) does not. The luminescence change upon Zn2+ binding is attributed to a change in hydration number (q) of the Tb3+ ion due to the decoordination of the phosphoserine from the Ln(3+) ion upon Zn2+ binding and peptide folding. This process is highly sensitive to the length of the linker between the Ln chelate and the peptidic backbone. The magnetic properties of the gadolinium analogue ZFQE(Gd) were studied. An impressive relaxivity increase of 140% is observed at 60 MHz and 25 degrees C upon Zn2+ binding. These changes can be attributed to a combined increase effect of the hydration number of Gd3+ and of the rigidity of the system upon Zn2+ binding. Phantom MR images at 9.4 T show a clear signal enhancement in the presence of Zn2+. These zinc finger peptides offer a unique platform to design such Zn-responsive probes.
Published: 2023

4. Mechanostereoselective One-Pot Synthesis of Functionalized Head-to-Head Cyclodextrin [3]Rotaxanes and Their Application as Magnetic Resonance Imaging Contrast Agents

Author: Célia S. Bonnet, Éva Tóth, Matthieu Sollogoub, Mickaël Ménand, Guillaume Vives, Jérémy Scelle, Jean Wilfried Fredy, Grégory Ramniceanu, Bernold Hasenknopf, Bich-Thuy Doan, Institut Parisien de Chimie Moléculaire (IPCM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-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 de Chimie du CNRS (INC), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Parisien de Chimie Moléculaire ( IPCM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Unité de Technologies Chimiques et Biologiques pour la Santé ( UTCBS - UM 4 (UMR 8258 / U1022) ), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de biophysique moléculaire ( CBM ), Université d'Orléans ( UO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-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 d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and ANR-16-CE09-0018,RotaxImage,Imagerie et diagnostic avec des polyrotaxanes(2016)
Subjects: chemistry.chemical_classification, medicine.diagnostic_test, Cyclodextrin, 010405 organic chemistry, Stereochemistry, Chemistry, Head to head, MRI contrast agent, Gadolinium, Organic Chemistry, One-pot synthesis, chemistry.chemical_element, Magnetic resonance imaging, 010402 general chemistry, [ CHIM ] Chemical Sciences, 01 natural sciences, Biochemistry, Combinatorial chemistry, Cycloaddition, 0104 chemical sciences, In vivo, medicine, [CHIM]Chemical Sciences, Physical and Theoretical Chemistry
Abstract: International audience; A versatile, five-component, one-pot synthesis of cyclodextrin (CD) [3]rotaxanes using copper-catalyzed azide–alkyne cycloaddition has been developed. Head-to-head [3]rotaxanes of α-CD selectively functionalized by one or two gadolinium 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid monoamide complexes were obtained mechanostereoselectively. The magnetic resonance imaging efficiency, expressed by the longitudinal proton relaxivity of the rotaxanes, was significantly improved as compared to the functionalized CD. In vitro and in vivo preclinical studies showed a higher contrast and retention in the kidney than gadolinium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid complex, demonstrating the potential of these rotaxanes as MRI contrast agent.
Published: 2017

5. Sustainable computational science: the ReScience initiative

Author: Rougier, Nicolas P, Hinsen, Konrad, Alexandre, Frederic, Arildsen, Thomas, Barba, Lorena A, Benureau, Fabien C.Y, Brown, C. Titus, deBuy, Pierre, Caglayan, Ozan, Davison, Andrew P., Delsuc, Marc-Andre, Detorakis, Georgios, Diem, Alexandra, Drix, Damien, Enel, Pierre, Girard, Benoit, Guest, Olivia, Hall, Matt G, Henriques, Rafael N, Hinaut, Xavier, Jaron, Kamil S, Khamassi, Mehdi, Klein, Almar, Manninen, Tiina, Marchesi, Pietro, McGlinn, Daniel, Metzner, Christoph, Petchey, Owen, Plesser, Hans Ekkehard, Poisot, Timothee, Ram, Karthik, Ram, Yoav, Roesch, Etienne, Rossant, Cyrille, Rostami, Vahid, Shifman, Aaron, Stachelek, Joseph, Stimberg, Marcel, Stollmeier, Frank, Vaggi, Federico, Viejo, Guillaume, Vitay, Julien, Vostinar, Anya E, Yurchak, Roman, Zito, Tiziano, Mnemonic Synergy ( Mnemosyne ), Laboratoire Bordelais de Recherche en Informatique ( LaBRI ), Centre National de la Recherche Scientifique ( CNRS ) -École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Université Sciences et Technologies - Bordeaux 1-Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique ( CNRS ) -École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Université Sciences et Technologies - Bordeaux 1-Université Bordeaux Segalen - Bordeaux 2-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut des Maladies Neurodégénératives [Bordeaux] ( IMN ), Université de Bordeaux ( UB ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Bordeaux ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de biophysique moléculaire ( CBM ), Université d'Orléans ( UO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Electronic Systems - Aalborg University, Aalborg University [Denmark] ( AAU ), Washington State University ( WSU ), CIM - Communication, Information, Médias - EA 1484 ( CIM ), Université Sorbonne Nouvelle - Paris 3, Université Libre de Bruxelles [Bruxelles] ( ULB ), Laboratoire d'Informatique de l'Université du Mans ( LIUM ), Le Mans Université ( UM ), Ecole des Neurosciences de Paris Île de France ( ENP ), Ecole des Neurosciences de Paris, Centre de Biochimie Structurale [Montpellier] ( CBS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire des signaux et systèmes ( L2S ), Université Paris-Sud - Paris 11 ( UP11 ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), University of Southampton [Southampton], Humboldt Universität zu Berlin, Institut cellule souche et cerveau / Stem Cell and Brain Research Institute ( SBRI ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de Physiologie de la Perception et de l'Action ( LPPA ), Collège de France ( CdF ) -Centre National de la Recherche Scientifique ( CNRS ), Institut des Systèmes Intelligents et de Robotique ( ISIR ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), University of Oxford [Oxford], University College of London [London] ( UCL ), Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Knowledge Technology group [Hamburg] ( KT ), Department of Informatics [Hamburg], Universität Hamburg ( UHH ) -Universität Hamburg ( UHH ), Université de Lausanne ( UNIL ), National Coalition of Independent Scholar ( NCIS ), Finnish Meteorological Institute ( FMI ), Vrije Universiteit Amsterdam [Amsterdam] ( VU ), Department of Biology [Charleston], College of Charleston, Universität Zürich [Zürich] ( UZH ), University of Zürich [Zürich] ( UZH ), Institute of Neuroscience and Medicine [Jülich] ( INM-1 ), Université de Montréal, University of California [Berkeley], Department of Biological Sciences [Stanford], Stanford University [Stanford], Department of Psychology, University of Geneva [Switzerland], Swiss Center for Affective Sciences, University of Ottawa [Ottawa], Michigan State University [East Lansing], Institut de la Vision, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut d'études de la cognition ( IEC ), Département d'Etudes Cognitives - ENS Paris ( DEC ), École normale supérieure - Paris ( ENS Paris ) -École normale supérieure - Paris ( ENS Paris ), Max Planck Institute of Experimental Medicine [Göttingen] ( MPI ), Statistical Machine Learning and Parsimony ( SIERRA ), Département d'informatique de l'École normale supérieure ( DI-ENS ), École normale supérieure - Paris ( ENS Paris ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ) -École normale supérieure - Paris ( ENS Paris ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -Inria de Paris, Institut National de Recherche en Informatique et en Automatique ( Inria ), Chemnitz University of Technology, Grinnell College, Laboratoire pour l'utilisation des lasers intenses ( LULI ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -École polytechnique ( X ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), Eberhard Karls Universität Tübingen, Mnemonic Synergy (Mnemosyne), Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Aalborg University [Denmark] (AAU), Washington State University (WSU), University of California [Davis] (UC Davis), University of California (UC), Université libre de Bruxelles (ULB), Laboratoire d'Informatique de l'Université du Mans (LIUM), Le Mans Université (UM), Ecole des Neurosciences de Paris Île de France (ENP), Centre de Biochimie Structurale [Montpellier] (CBS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des signaux et systèmes (L2S), Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), University of Southampton, Humboldt University Of Berlin, Institut cellule souche et cerveau (SBRI), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Physiologie de la Perception et de l'Action (LPPA), Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), Institut des Systèmes Intelligents et de Robotique (ISIR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), AMAC, Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), University of Oxford, University College of London [London] (UCL), Instituto de Medicina Molecular (iMM), Faculdade de Medicina [Lisboa], Universidade de Lisboa = University of Lisbon (ULISBOA)-Universidade de Lisboa = University of Lisbon (ULISBOA), Knowledge Technology group [Hamburg] (KT), University of Hamburg-University of Hamburg, Université de Lausanne = University of Lausanne (UNIL), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), National Coalition of Independent Scholar (NCIS), Finnish Meteorological Institute (FMI), Vrije Universiteit Amsterdam [Amsterdam] (VU), Universität Zürich [Zürich] = University of Zurich (UZH), Institute of Neuroscience and Medicine [Jülich] (INM-1), Université de Montréal (UdeM), Lawrence Berkeley National Laboratory [Berkeley] (LBNL), Department of Biology [Stanford], Stanford University, Université de Genève = University of Geneva (UNIGE), Swiss Center for Affective Sciences (CISA), Michigan State University System, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Labex Institut d'étude de la cognition (IEC), Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Max Planck Institute of Experimental Medicine [Göttingen] (MPI), Max-Planck-Gesellschaft, Statistical Machine Learning and Parsimony (SIERRA), Département d'informatique - ENS Paris (DI-ENS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de Recherche en Informatique et en Automatique (Inria)-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 Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria), Chemnitz University of Technology / Technische Universität Chemnitz, Laboratoire pour l'utilisation des lasers intenses (LULI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Inria Bordeaux - Sud-Ouest, Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), University of California, Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Humboldt-Universität zu Berlin, Institut cellule souche et cerveau (U846 Inserm - UCBL1), Universidade de Lisboa (ULISBOA)-Universidade de Lisboa (ULISBOA), Université de Lausanne (UNIL), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Inria de Paris, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Département d'informatique de l'École normale supérieure (DI-ENS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), and Rougier, Nicolas P.
Subjects: FOS: Computer and information sciences, Technology, Journal, lcsh:QA75.5-76.95, Computational Science, GitHub, Scientific Computing and Simulation, Social Computing, Open Science, Replicability, REPRODUCIBLE RESEARCH, [INFO.INFO-DL]Computer Science [cs]/Digital Libraries [cs.DL], Open peer-review, Digital Libraries (cs.DL), Computational science, Open science, Publication, Reproducible, Replicable, Sustainable, GitHub, Open peer-review, [ INFO.INFO-DL ] Computer Science [cs]/Digital Libraries [cs.DL], Science & Technology, Computer Science, Information Systems, Data Science, Computational science, bepress|Physical Sciences and Mathematics|Computer Sciences, Computer Science - Digital Libraries, Sustainable, Reproducibility, Networking and Information Technology R&D (NITRD), Digital Libraries, Computer Science, Reproducible, Publication, Open science, lcsh:Electronic computers. Computer science, [INFO.INFO-DL] Computer Science [cs]/Digital Libraries [cs.DL], Replicable
Abstract: Computer science offers a large set of tools for prototyping, writing, running, testing, validating, sharing and reproducing results, however computational science lags behind. In the best case, authors may provide their source code as a compressed archive and they may feel confident their research is reproducible. But this is not exactly true. James Buckheit and David Donoho proposed more than two decades ago that an article about computational results is advertising, not scholarship. The actual scholarship is the full software environment, code, and data that produced the result. This implies new workflows, in particular in peer-reviews. Existing journals have been slow to adapt: source codes are rarely requested, hardly ever actually executed to check that they produce the results advertised in the article. ReScience is a peer-reviewed journal that targets computational research and encourages the explicit replication of already published research, promoting new and open-source implementations in order to ensure that the original research can be replicated from its description. To achieve this goal, the whole publishing chain is radically different from other traditional scientific journals. ReScience resides on GitHub where each new implementation of a computational study is made available together with comments, explanations, and software tests., 8 pages, 1 figure
Published: 2017

6. DNA minicircles as novel STAT3 decoy oligodeoxynucleotides endowed with anticancer activity in triple-negative breast cancer

Author: Geoffrey Casas, Federico Perche, Patrick Midoux, Chantal Pichon, Jean-Marc Malinge, perche, federico, Centre de biophysique moléculaire (CBM), and Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: STAT3, DNA minicircle, breast cancer, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, Drug Discovery, Molecular Medicine, MT: Oligonucleotides: Therapies and Applications, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, decoy, therapeutic oligonucleotide, transcription factor
Abstract: International audience; Decoy technology is a versatile and specific DNA oligonucleotide-based targeting strategy of pathogenic transcription factors (TFs). Chemical modifications of linear decoy oligonucleotides have been made to decrease nuclease sensitivity because of the presence of free ends but at the cost of new limitations that affect their use as therapeutic drugs. Although a short DNA minicircle is a phosphodiester nucleic acid without free ends, its potential therapeutic activity as a TF decoy oligonucleotide has not yet been investigated. Here we describe the in vitro and in vivo activity of formulated 95-bp minicircles bearing one or several STAT3 binding sequences in triple-negative breast cancer (TNBC). Minicircles bearing one STAT3 binding site interacted specifically with the active form of STAT3 and inhibited proliferation, induced apoptosis, slowed down cell cycle progression, and decreased STAT3 target gene expression in human and murine TNBC cells. Intratumoral injection of STAT3 minicircles inhibited tumor growth and metastasis in a murine model of TNBC. Increasing the number of STAT3 binding sites resulted in improved anticancer activity, opening the way for a TF multitargeting strategy. Our data provide the first demonstration of minicircles acting as STAT3 decoys and show that they could be an effective therapeutic drug for TNBC treatment.
Published: 2022

7. 55/52Mn2+ Complexes with a Bispidine-Phosphonate Ligand: High Kinetic Inertness for Imaging Applications

Author: Maryame Sy, Daouda Ndiaye, Isidro da Silva, Sara Lacerda, Loïc J. Charbonnière, Éva Tóth, Aline M. Nonat, Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Conditions Extrêmes et Matériaux : Haute Température et Irradiation (CEMHTI), Université d'Orléans (UO)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), and HEP, INSPIRE
Subjects: [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, Inorganic Chemistry, [CHIM.THEO] Chemical Sciences/Theoretical and/or physical chemistry, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [CHIM.COOR]Chemical Sciences/Coordination chemistry, [CHIM.COOR] Chemical Sciences/Coordination chemistry, Physical and Theoretical Chemistry
Abstract: International audience; Bispidine (3,7-diazabicyclo[3.3.1]nonane) provides a rigid and preorganized scaffold that is particularly interesting for the stable and inert complexation of metal ions, especially for their application in medical imaging. In this study, we present the synthesis of two bispidine ligands with N-methanephosphonate (H4L1) and N-methanecarboxylate (H3L2) substituents as well as the physico-chemical properties of the corresponding Mn2+ and Zn2+ complexes. The two complexes [Mn(L-1)](2- )and [Mn(L-2)](-) have relatively moderate thermodynamic stability constants according to potentiometric titration data. However, they both display an exceptional kinetic inertness, as assessed by transmetallation experiments in the presence of 50 equiv excess of Zn2+, showing only similar to 40 and 20% of dissociation for [Mn(L-1)](2- ) and [Mn(L-2)](-), respectively, after 150 days at pH 6 and 37°C. Proton relaxivities amount to r(1 )= 4.31 mM(-1 )s(-1 )([Mn(L-1)](2-)) and 3.64 mM(-1) s(-1 )([Mn(L-2)](-)) at 20 MHz, 25°C, and are remarkable for Mn2+ complexes with one inner-sphere water molecule (q = 1); they are comparable to that of the commercial contrast agent [Gd(DOTA)(H2O)](-). The presence of one inner-sphere water molecule and an associative water exchange mechanism was confirmed by temperature-dependent transverse O-17 relaxation rate measurements, which yielded k(ex)(298) = 0.12 x 10(7) and 5.5 x 10(7) s(-1 )for the water exchange rate of the phosphonate and the carboxylate complex, respectively. In addition, radiolabeling experiments with Mn-52 were also performed with H-2(L-1)(2-) showing excellent radiolabeling properties and quantitative complexation at pH 7 in 15 min at room temperature as well as excellent stability of the complex in various biological media over 24 h.
Published: 2022

8. Reproductives signature revealed by protein profiling and behavioral bioassays in termite

Author: Ruhland, Fanny, Gabant, Guillaume, Toussaint, Timothée, Nemcic, Matej, Cadène, Martine, Lucas, Christophe, Université de Tours (UT), Institut de recherche sur la biologie de l'insecte UMR7261 (IRBI), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université d'Orléans (UO), Région Centre-Val de Loire (APR-IR 2017-00117111 BioControleTermite, APRIA MALDITOF 2018, APR-IA 2012, APR-IA SYMBIOMS 2010), European Project: 773324,ForestValue, and European Project: 508 2699-33931
Subjects: Multidisciplinary, [SDV]Life Sciences [q-bio], [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: Proteins are known to be social interaction signals in many species in the animal kingdom. Common mediators in mammals and aquatic species, they have seldom been identified as such in insects' behaviors. Yet, they could represent an important component to support social signals in social insects, as the numerous physical contacts between individuals would tend to favor the use of contact compounds in their interactions. However, their role in social interactions is largely unexplored: are they rare or simply underestimated? In this preliminary study, we show that, in the termite Reticulitermes flavipes, polar extracts from reproductives trigger body-shaking of workers (a vibratory behavior involved in reproductives recognition) while extracts from workers do not. Molecular profiling of these cuticular extracts using MALDI-TOF mass spectrometry reveals higher protein diversity in reproductives than in workers and a sex-specific composition exclusive to reproductives. While the effects observed with extracts are not as strong as with live termites, these results open up the intriguing possibility that social signaling may not be limited to cuticular hydrocarbons or other non-polar, volatile chemicals as classically accepted. Our results suggest that polar compounds, in particular some of the Cuticular Protein Compounds (CPCs) shown here by MALDI to be specific to reproductives, could play a significant role in insect societies. While this study is preliminary and further comprehensive molecular characterization is needed to correlate the body-shaking triggering effects with a given set of polar compounds, this exploratory study opens new perspectives for understanding the role of polar compounds such as proteins in caste discrimination, fertility signaling, or interspecific insect communication.
Published: 2023

9. Identification of key residues of the DNA glycosylase OGG1 controlling efficient DNA sampling and recruitment to oxidized bases in living cells

Author: Ostiane D’Augustin, Virginie Gaudon, Capucine Siberchicot, Rebecca Smith, Catherine Chapuis, Jordane Depagne, Xavier Veaute, Didier Busso, Anne-Marie Di Guilmi, Bertrand Castaing, J Pablo Radicella, Anna Campalans, Sébastien Huet, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Stabilité génétique, cellules souches et radiations (SGCSR (U_1274 / UMR_E_008)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Ligue contre le Cancer du Grand-Ouest [committee 22], Ligue contre le Cancer du Grand-Ouest [committee 29], Ligue contre le Cancer du Grand-Ouest [committee 35], Ligue contre le Cancer du Grand-Ouest [committee 37], Ligue contre le Cancer du Grand-Ouest [committee 45], Institut Universitaire de France, Region Centre-Val de Loire [2013-00082978, 2017-00117252], Canceropole Grand-Ouest [project CONCERTO] [2018-001240994], Fondation ARC pour la recherche sur le cancer [PDF20181208405, PJA20181207762], Commissariat a l'Energie Atomique (CEA) Radiobiology program, Agence Nationale de la Recherche [PRCI-2018 TG-TOX], Region Bretagne, CEA, Ligue Nationale Contre le Cancer, and Commissariat al'Energie Atomique
Subjects: [SDV.GEN]Life Sciences [q-bio]/Genetics, Genetics
Abstract: The DNA-glycosylase OGG1 oversees the detection and clearance of the 7,8-dihydro-8-oxoguanine (8-oxoG), which is the most frequent form of oxidized base in the genome. This lesion is deeply buried within the double-helix and its detection requires careful inspection of the bases by OGG1 via a mechanism that remains only partially understood. By analyzing OGG1 dynamics in the nucleus of living human cells, we demonstrate that the glycosylase constantly samples the DNA by rapidly alternating between diffusion within the nucleoplasm and short transits on the DNA. This sampling process, that we find to be tightly regulated by the conserved residue G245, is crucial for the rapid recruitment of OGG1 at oxidative lesions induced by laser micro-irradiation. Furthermore, we show that residues Y203, N149 and N150, while being all involved in early stages of 8-oxoG probing by OGG1 based on previous structural data, differentially regulate the sampling of the DNA and recruitment to oxidative lesions.
Published: 2023

10. Gallium-68 Complexes Conjugated to Pittsburgh Compound B: Radiolabeling and Biological Evaluation

Author: Fabien Fillesoye, Fabienne Gourand, Damien Cressier, Auriane Maïza, André F. Martins, Martine Dhilly, Jean-François Morfin, Thang T. Cao Pham, Louisa Barré, Éva Tóth, Carlos F. G. C. Geraldes, Laboratoire de Développements Méthodologiques en Tomographie par Emission de Positions ( LDM-TEP ), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales ( ISTCT ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de biophysique moléculaire ( CBM ), Université d'Orléans ( UO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), University of Coimbra [Portugal] ( UC ), Laboratoire de Développements Méthodologiques en Tomographie par Emission de Positons (LDM-TEP), Service Hospitalier Frédéric Joliot (SHFJ), 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)-Université Paris-Saclay-Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), University of Coimbra [Portugal] (UC), 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)-Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), and Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cancer Research, Amyloid, [SDV]Life Sciences [q-bio], Cerebral amyloidopathies, Gallium Radioisotopes, Mice, Transgenic, Conjugated system, 010402 general chemistry, 01 natural sciences, High-performance liquid chromatography, [ CHIM ] Chemical Sciences, chemistry.chemical_compound, Radiometabolism, In vivo, medicine, Animals, Humans, [CHIM]Chemical Sciences, Radiology, Nuclear Medicine and imaging, Tissue Distribution, Chromatography, High Pressure Liquid, Aniline Compounds, [ SDV ] Life Sciences [q-bio], 010405 organic chemistry, Chemistry, PIB, Amyloidosis, Radiochemistry, Radiosynthesis, Gallium-68, medicine.disease, In vitro, 0104 chemical sciences, 3. Good health, Mice, Inbred C57BL, Thiazoles, PET, Oncology, Positron-Emission Tomography, Automated radiosynthesis, Autoradiography, Female, Radiopharmaceuticals, Pittsburgh compound B, Alzheimer’s disease
Abstract: International audience; PURPOSE:The aim of this work is to develop an efficient and fully automated radiosynthesis of three derivatives of the Pittsburgh compound B labeled with gallium-68 for the detection of amyloid plaques.PROCEDURES:The radiolabeling of the precursors and purification of the radiolabeled agents by high pressure liquid chromatography has been studied prior to their in vitro and in vivo evaluations.RESULTS:The complete process led, in 50 min, to pure Ga-68 products in a 12-38 % yield and with appreciable specific radioactivity (SRA, 85-168 GBq/μmol) which enabled us to demonstrate a considerable in vivo stability of the products. Unfortunately, this result was associated with a poor blood-brain barrier (BBB) permeability and a limited uptake of our compounds by amyloid deposits was observed by in vitro autoradiography.CONCLUSION:Although we have not yet identified a compound able to significantly mark cerebral amyloidosis, this present investigation will likely contribute to the development of more successful Ga-68 radiotracers.
Published: 2016

11. Positive Bioluminescence Imaging of MicroRNA Expression in Small Animal Models Using an Engineered Genetic-Switch Expression System, RILES

Author: Chantal Pichon, Patrick Baril, Frapart, Isabelle, Centre de biophysique moléculaire ( CBM ), Université d'Orléans ( UO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de biophysique moléculaire (CBM), and Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
Subjects: 0301 basic medicine, Genetics, [ SDV ] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], HEK 293 cells, Gene regulatory network, Morphogenesis, Computational biology, Biology, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 030104 developmental biology, RNA interference, microRNA, Gene expression, Bioluminescence imaging, Gene silencing
Abstract: International audience; MicroRNAs (miRNAs) are a class of small, noncoding RNAs which regulate gene expression by directing their target mRNA for degradation or translational repression. Since their discovery in the early 1990s, miRNAs have emerged as key components in the posttranscriptional regulation of gene networks, shaping many biological processes from development, morphogenesis, differentiation, proliferation and apoptosis. Although understanding of the molecular basis of miRNA biology is improving, methods to monitor the dynamic and the spatiotemporal aspects of miRNA expression under physiopathological conditions are required. However, monitoring of miRNAs is difficult due to their small size, low abundance, high degree of sequence similarity, and their dynamic expression pattern which is subjected to tight transcriptional and post-transcriptional controls. Recently, we developed a miRNA monitoring system called RILES, standing for RNAi-inducible expression system, which relies on an engineered regulatable expression system, to switch on the expression of the luciferase gene when the targeted miRNA is expressed in cells. We demonstrated that RILES is a specific, sensitive, and robust method to determine the fine-tuning of miRNA expression during the development of an experimental pathological process in mice. Because RILES offers the possibility for longitudinal studies on individual subjects, sharper insights into miRNA regulation can be generated, with applications in physiology, pathophysiology and development of RNAi-based therapies. This chapter describes methods and protocols to monitor the expression of myomiR-206, -1, and -133 in the tibialis anterior muscle of mice. These protocols can be used and adapted to monitor the expression of other miRNAs in other biological processes.
Published: 2016

12. Protonation of Lipids Impacts the Supramolecular and Biological Properties of Their Self-Assembly

Author: Marie Breton, Nathalie Mignet, Martin Hof, Daniel Scherman, Jean-François Berret, Michel Bessodes, Chantal Pichon, Teresa Kral, Claudie Bourgaux, Unité de pharmacologie chimique et génétique et d'imagerie ( UPCGI - UMR 8151 / UMR_S 1022 ), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Matière et Systèmes Complexes ( MSC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de biophysique moléculaire ( CBM ), Université d'Orléans ( UO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Unité de pharmacologie chimique et génétique et d'imagerie (UPCGI - UMR 8151 / UMR_S 1022 ), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Matière et Systèmes Complexes (MSC (UMR_7057)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), and Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
Subjects: MESH : DNA, 01 natural sciences, chemistry.chemical_compound, Computational chemistry, MESH : Particle Size, Electrochemistry, Organic chemistry, MESH: Animals, General Materials Science, Spectroscopy, Liposome, Molecular Structure, Chemistry, Thiourea, MESH: DNA, Surfaces and Interfaces, Condensed Matter Physics, Lipids, MESH : Microscopy, Electron, Transmission, MESH: Microscopy, Electron, Transmission, lipids (amino acids, peptides, and proteins), Protons, MESH: Cell Line, Tumor, Chemical structure, MESH: Molecular Structure, Supramolecular chemistry, Protonation, 010402 general chemistry, MESH: Hydrodynamics, MESH: Thiourea, Microscopy, Electron, Transmission, Cell Line, Tumor, MESH : Hydrodynamics, Amphiphile, Animals, Humans, MESH : Protons, Molecule, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Thiourea, MESH: Particle Size, Particle Size, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Humans, MESH : Cell Line, Tumor, 010405 organic chemistry, MESH : Humans, MESH : Lipids, DNA, MESH: Lipids, 0104 chemical sciences, Hydrodynamics, MESH: Protons, MESH : Animals, Self-assembly, MESH : Molecular Structure
Abstract: International audience; We assessed in this work how a chemical structure difference could influence a supramolecular organization and then its biological properties. In our case study, we considered two amphiphilic lipidic gene vectors. The chemical difference was situated on their hydrophilic part which was either a pure neutral thiourea head or a mixture of three thiourea function derivatives, thiourea, iminothiol, and charged iminothiol. This small difference was obtained thanks to the last chemical deprotection conditions of the polar head hydroxyl groups. Light, neutron, and X-ray scattering techniques have been used to investigate the spatial structure of the liposomes and lipoplexes formed by the lipids. The chemical structure difference impacts the supramolecular assemblies of the lipids and with DNA as shown by fluorescence correlation spectroscopy (FCS), X-ray, and neutron scattering. Hence the structures formed were found to be highly different in terms of liposomes to DNA ratio and size and polydispersity of the aggregates. Finally, the transfection and internalization results proved that the differences in the structure of the lipid aggregates fully affect the biological properties of the lipopolythiourea compounds. The lipid containing three functions is a better gene transfection agent than the lipid which only contains one thiourea moiety. As a conclusion, we showed that the conditions of the last chemical step can influence the lipidic supramolecular structure which in turn strongly impacts their biological properties.
Published: 2011

13. Intégration de l’exposome dans les activités de l’Anses

Author: Barouki, Robert, Cravedi, Jean-Pierre, Quénel, Philippe, Garric, Jeanne, Kaufmann, Alain, Duché, P, Bonmatin, Jean-Marc, Momas, Isabelle, Ducrot, Christian, Crépet, Amélie, Schuler, Matthieu, Institut National de la Santé et de la Recherche Médicale (INSERM), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), RiverLy - Fonctionnement des hydrosystèmes (RiverLy), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Lausanne = University of Lausanne (UNIL), Impact de l'Activité Physique sur la Santé (IAPS), Université de Toulon (UTLN), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Animal, Santé, Territoires, Risques et Ecosystèmes (UMR ASTRE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Direction de l'Evaluation des Risques (DER), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), and Anses
Subjects: lifetime, santé globale, vie entière, approche holistique, [SDV]Life Sciences [q-bio], Evaluation des risques, multi-expositions, multiple-exposure, global health, holistic approach, Risk assessment, systemic medicine, médecine systémique
Abstract: Anses. (2022). Intégration de l’exposome dans les activités de l’Anses. (Saisine 2022-METH-0197). Maisons-Alfort : Anses, 197 p.; Depuis son émergence en 2005, le concept d’exposome a suscité de nombreux travaux de recherche s’inscrivant dans un continuum de questions à la science quant au rôle des facteurs environnementaux dans le développement des pathologies chroniques qui au cours des dernières décennies se sont hissées au premier rang des causes de mortalité dans les pays développés. L’intérêt qui lui est porté a convaincu, au-delà des équipes de recherche, les décideurs publics avec son introduction dans la loi de modernisation du système de santé du 28 janvier 2016. Ainsi, dans le cadre des dispositions portant sur l’administration générale de la santé, il est écrit que la politique de santé comprend (Article L.1411-1, 1er alinéa) : « La surveillance et l'observation de l'état de santé de la population et l'identification de ses principauxdéterminants, notamment ceux liés à l'éducation et aux conditions de vie et de travail. L'identification de ces déterminants s'appuie sur le concept d'exposome, entendu comme l'intégration sur la vie entière de l'ensemble des expositions qui peuvent influencer la santé humaine. » Dans le cadre des dispositions portant sur la protection et promotion de la santé maternelle et infantile, et plus spécifiquement sur l’organisation générale et les missions l’Article L 2111-1 mentionne que : « L'Etat, les collectivités territoriales et les organismes de sécurité sociale participent, dans les conditions prévues par le présent livre, à la protection et à la promotion de la santé maternelle et infantile qui comprend notamment […] 5° Des actions de prévention et d'information sur les risques pour la santé liés à des facteurs environnementaux, sur la base du concept d'exposome. » L’Anses assure des missions de veille, d’expertise, de recherche et de référence sur un large champ couvrant la santé humaine, la santé et le bien-être animal, ainsi que la santé végétale. Elle offre une lecture transversale des questions sanitaires en évaluant les risques et les bénéfices sanitaires, notamment via le prisme des sciences humaines et sociales. Ses missions de veille, de vigilance et de surveillance permettent de nourrir l'évaluation des risques. L'Agence évalue ainsi un large panel de risques (chimiques, biologiques, physiques...) auxquels un individu peut être exposé, volontairement ou non, à tous les âges et moments desa vie, qu’il s’agisse d’expositions au travail, pendant ses transports, ses loisirs, ou via son alimentation1. Ces risques sont le plus souvent évalués à partir d’une seule source (air, eau, alimentation, poussière, médicaments vétérinaires etc.) et d’une seule voie d’exposition (ingestion, inhalation, contact cutané) en formulant des hypothèses simplifiées d’exposition dans le temps (exposition constante, aiguë et ponctuelle, etc.). Ainsi, l’exposome dont l’objectif est d’étudier le rôle de l’ensemble des facteurs environnementaux rencontrés au cours d’une vie dans le développement des pathologies, reste largement à être décliné par l’Anses tant sur le plan scientifique que méthodologique. Il importe donc pour l’Agence d’évaluer les conséquences concrètes qu’ouvre l’inscription du concept d’exposome au niveau législatif et de l’intégration de ce concept dans le déploiement de ses métiers. Il s’agit d’identifier tant les opportunités, pistes et moyens de sa mise en œuvre que les besoins d’évolution et de compétences nouvelles pour y faire face. (extrait).
Published: 2023

14. Dynamic cardiac SPECT with flow measurement using 3D-ring CZT: when SPECT is inspired by PET

Author: Matthieu Bailly, Aurélien Callaud, Gilles Metrard, Centre Hospitalier Régional d'Orléans (CHRO), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Frapart, Isabelle
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], Radiology, Nuclear Medicine and imaging, General Medicine
Abstract: International audience; No abstract available
Published: 2023

15. OGG1 competitive inhibitors show important off-target effects by directly inhibiting efflux pumps and disturbing mitotic progression

Author: Xhaferr Tanushi, Guillaume Pinna, Marie Vandamme, Capucine Siberchicot, Ostiane D’Augustin, Anne-Marie Di Guilmi, J. Pablo Radicella, Bertrand Castaing, Rebecca Smith, Sebastien Huet, François Leteurtre, Anna Campalans, Stabilité génétique, cellules souches et radiations (SGCSR (U_1274 / UMR_E_008)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Campalans lab received funding from the Commissariat à l'Energie Atomique (CEA) Radiobiology program, Electricité de France and from the Agence Nationale de la Recherche (ANR PRCI-2018 TG-TOX). Castaing lab received funding from Région Centre Val de Loire (MoOGly-2017-00117252)., and Jonchère, Laurent
Subjects: SU0268, OGG1 inhibitor, TH5487, Cell Biology, 8-oxoG, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Base Excision Repair (BER), OGG1, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Developmental Biology
Abstract: One of the most abundant DNA lesions induced by Reactive oxygen species (ROS) is 8-oxoG, a highly mutagenic lesion that compromises genetic instability when not efficiently repaired. 8-oxoG is specifically recognized by the DNA-glycosylase OGG1 that excises the base and initiates the Base Excision Repair pathway (BER). Furthermore, OGG1 has not only a major role in DNA repair but it is also involved in transcriptional regulation. Cancer cells are particularly exposed to ROS, thus challenging their capacity to process oxidative DNA damage has been proposed as a promising therapeutic strategy for cancer treatment. Two competitive inhibitors of OGG1 (OGG1i) have been identified, TH5487 and SU0268, which bind to the OGG1 catalytic pocket preventing its fixation to the DNA. Early studies with these inhibitors show an enhanced cellular sensitivity to cytotoxic drugs and a reduction in the inflammatory response. Our study uncovers two unreported off-targets effects of these OGG1i that are independent of OGG1. In vitro and in cellulo approaches have unveiled that OGG1i TH5487 and SU0268, despite an unrelated molecular structure, are able to inhibit some members of the ABC family transporters, in particular ABC B1 (MDR1) and ABC G2 (BCRP). The inhibition of these efflux pumps by OGG1 inhibitors results in a higher intra-cellular accumulation of various fluorescent probes and drugs, and largely contributes to the enhanced cytotoxicity observed when the inhibitors are combined with cytotoxic agents. Furthermore, we found that SU0268 has an OGG1-independent anti-mitotic activity—by interfering with metaphase completion—resulting in a high cellular toxicity. These two off-target activities are observed at concentrations of OGG1i that are normally used for in vivo studies. It is thus critical to consider these previously unreported non-specific effects when interpreting studies using TH5487 and SU0268 in the context of OGG1 inhibition. Additionally, our work highlights the persistent need for new specific inhibitors of the enzymatic activity of OGG1.
Published: 2023

16. The diversification of the antimicrobial peptides from marine worms is driven by environmental conditions

Author: Renato Bruno, Céline Boidin-Wichlacz, Oleg Melnyk, Daniela Zeppilli, Céline Landon, Frédéric Thomas, Marie-Anne Cambon, Mickael Lafond, Kamel Mabrouk, François Massol, Stéphane Hourdez, Marc Maresca, Didier Jollivet, Aurélie Tasiemski, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Biologie et Ecologie des Ecosystèmes Marins Profonds (BEEP), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie Radicalaire (ICR), Aix Marseille Université (AMU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Ecogéochimie des environnements benthiques (LECOB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Observatoire océanologique de Banyuls (OOB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Adaptation et diversité en milieu marin (ADMM), Institut national des sciences de l'Univers (INSU - CNRS)-Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de microbiologie des environnements extrêmophiles (LM2E), and Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.BA.ZI]Life Sciences [q-bio]/Animal biology/Invertebrate Zoology, Environmental Engineering, External immunity, [SDV]Life Sciences [q-bio], Environmental Chemistry, Environment, Annelids, Polar, Pollution, Waste Management and Disposal, Hydrothermal, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity
Abstract: International audience; Antimicrobial peptides (AMPs) play a key role in the external immunity of animals, offering an interesting model for studying the influence of the environment on the diversification and evolution of immune effectors., alvinellacin (ALV), arenicin (ARE) and polaricin (POL, a novel AMP identified here), characterized from three marine worms inhabiting contrasted habitats (‘hot’ vents, temperate and polar respectively), possess a well conserved BRICHOS domain in their precursor molecule despite a profound amino acid and structural diversification of the C-terminal part containing the core peptide. Data not only showed that ARE, ALV and POL display an optimal bactericidal activity against the bacteria typical of the habitat where each worm species lives but also that this killing efficacy is optimal under the thermochemical conditions encountered by their producers in their environment. Moreover, the correlation between species habitat and the cysteine contents of POL, ARE and ALV led us to investigate the importance of disulfide bridges in their biological efficacy as a function of abiotic pressures (pH and temperature). The construction of variants using non-proteinogenic residues instead of cysteines (α-aminobutyric acid variants) leading to AMPs devoid of disulfide bridges, provided evidence that the disulfide pattern of the three AMPs allows for a better bactericidal activity and suggests an adaptive way to sustain the fluctuations of the worm's environment. This work shows that the external immune effectors exemplified here by BRICHOS AMPs are evolving under strong diversifying environmental pressures to be structurally shaped and more efficient/specific under the ecological niche of their producer.
Published: 2023

17. Hypoxia, but Not Normoxia, Reduces Effects of Resveratrol on Cisplatin Treatment in A2780 Ovarian Cancer Cells: A Challenge for Resveratrol Use in Anticancer Adjuvant Cisplatin Therapy

Author: Agnieszka Synowiec, Klaudia Brodaczewska, Gabriel Wcisło, Aleksandra Majewska, Agata Borkowska, Aleksandra Filipiak-Duliban, Aleksandra Gawrylak, Kinga Wilkus, Katarzyna Piwocka, Agata Kominek, Halina Waś, Sławomir Lewicki, Jacek Siewiera, Cezary Szczylik, Jolanta Szenajch, Jacek Z. Kubiak, Claudine Kieda, Military Institute of Medicine, Warsaw, Centre of Postgraduate Medical Education [Warsaw, Poland] (CPME), Medical University of Warsaw - Poland, University of Warsaw (UW), Nencki Institute of Experimental Biology, Polska Akademia Nauk = Polish Academy of Sciences (PAN), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Ministry of Education and Sciences [425/2016], National Science Center grant [2016/23/B/NZ1/03211], European Social Fund, and Polish Ministry of National Defense [571/2016/DA, 508/2017/DA]
Subjects: ovarian cancer, cisplatin, resveratrol, normoxia, hypoxia, epithelial–mesenchymal transition markers, HIF-1α, VEGF, HIF-1 alpha, Organic Chemistry, [SDV.CAN]Life Sciences [q-bio]/Cancer, General Medicine, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Catalysis, Computer Science Applications, Inorganic Chemistry, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, epithelial-mesenchymal transition markers
Abstract: International audience; Natural compounds, such as resveratrol (Res), are currently used as adjuvants for anticancer therapies. To evaluate the effectiveness of Res for the treatment of ovarian cancer (OC), we screened the response of various OC cell lines to the combined treatment with cisplatin (CisPt) and Res. We identified A2780 cells as the most synergistically responding, thus optimal for further analysis. Because hypoxia is the hallmark of the solid tumor microenvironment, we compared the effects of Res alone and in combination with CisPt in hypoxia (pO(2) = 1%) vs. normoxia (pO(2) = 19%). Hypoxia caused an increase (43.2 vs. 5.0%) in apoptosis and necrosis (14.2 vs. 2.5%), reactive oxygen species production, pro-angiogenic HIF-1a (hypoxia-inducible factor-1a) and VEGF (vascular endothelial growth factor), cell migration, and downregulated the expression of ZO1 (zonula occludens-1) protein in comparison to normoxia. Res was not cytotoxic under hypoxia in contrast to normoxia. In normoxia, Res alone or CisPt+Res caused apoptosis via caspase-3 cleavage and BAX, while in hypoxia, it reduced the accumulation of A2780 cells in the G2/M phase. CisPt+Res increased levels of vimentin under normoxia and upregulated SNAI1 expression under hypoxia. Thus, various effects of Res or CisPt+Res on A2780 cells observed in normoxia are eliminated or diminished in hypoxia. These findings indicate the limitations in using Res as an adjuvant with CisPt therapy in OC.
Published: 2023

18. Characterization of Positively Charged Lipid Shell Microbubbles with Tunable Resistive Pulse Sensing (TRPS) Method: A Technical Note

Author: Michel Bessodes, Anthony Delalande, Michel Bureau, Simona Manta, Nathalie Mignet, Chantal Pichon, Daniel Scherman, Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Unité de pharmacologie chimique et génétique et d'imagerie (UPCGI - UMR 8151 / UMR_S 1022 ), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC), Laboratoire interdisciplinaire pour la sociologie économique (LISE), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre National de la Recherche Scientifique (CNRS), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-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 de Chimie du CNRS (INC), Centre de Recherches sur la Cognition Animale ( CRCA ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique ( CNRS ), Centre de biophysique moléculaire ( CBM ), Université d'Orléans ( UO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Unité de pharmacologie chimique et génétique et d'imagerie ( UPCGI - UMR 8151 / UMR_S 1022 ), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire interdisciplinaire pour la sociologie économique ( LISE ), Centre National de la Recherche Scientifique ( CNRS ) -Conservatoire National des Arts et Métiers [CNAM] ( CNAM ), Unité de Technologies Chimiques et Biologiques pour la Santé ( UTCBS - UM 4 (UMR 8258 / U1022) ), Institut des sciences du cerveau de Toulouse. (ISCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Electromagnetic field, Materials science, Acoustics and Ultrasonics, [SDV]Life Sciences [q-bio], Static Electricity, Biophysics, Ultrafiltration, Nanotechnology, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Light scattering, law.invention, Nanopores, Electromagnetic Fields, Optical microscope, law, Coulter counter, Electrochemistry, Radiology, Nuclear Medicine and imaging, Resistive touchscreen, Microbubbles, [ SDV ] Life Sciences [q-bio], Radiological and Ultrasound Technology, business.industry, Membranes, Artificial, 021001 nanoscience & nanotechnology, Lipids, 0104 chemical sciences, Volumetric flow rate, Nanopore, Optoelectronics, 0210 nano-technology, business
Abstract: International audience; Microbubbles are polydisperse microparticles. Their size distribution cannot be accurately measured from the current methods used, such as optical microscopy, electrical sensing or light scattering. Indeed, these techniques present some limitations when applied to microbubbles, which prompted us to investigate the use of an alternative technique: tunable resistive pulse sensing (TRPS). This technique is based on the principle of the Coulter counter with the advantage of being more flexible compared to other methods using this principle, since the flow rate, the potential difference and the pore size can be modulated. The main limitation of TRPS is that more than one size of nanopore membrane is required to obtain the full size distribution of polydisperse microparticles. To evaluate this technique, the concentration and the size distribution of positively charged microbubbles were studied using TRPS and compared to data obtained using optical microscopy. We describe herein the parameters required for the accurate measurement of microbubble concentration and size distribution by TRPS and present a statistical comparison of the data obtained by TRPS and optical microscopy.
Published: 2015

19. Targeting the cis-dimerization of LINGO-1 with low MW compounds affects its downstream signalling

Author: Cobret, L, De Tauzia, M L, Ferent, J, Traiffort, E, Hénaoui, I, Godin, F, Kellenberger, E, Rognan, D, Pantel, J, Bénédetti, H, Morisset-Lopez, S, Centre de biophysique moléculaire ( CBM ), Université d'Orléans ( UO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Recherches Cliniques de Montréal ( IRCM ), Université de Montréal ( UdeM ), Stéroides et système nerveux : physiopathologie moléculaire et clinique, Université Paris-Sud - Paris 11 ( UP11 ) -IFR93-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de pharmacologie moléculaire et cellulaire ( IPMC ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'Innovation Thérapeutique ( LIT ), Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ), MEDALIS Drug Discovery Center, Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherches Cliniques de Montréal (IRCM), Université de Montréal (UdeM), Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de pharmacologie moléculaire et cellulaire (IPMC), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Laboratoire d'Innovation Thérapeutique (LIT), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de Psychiatrie et Neurosciences (U894), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Frapart, Isabelle, Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), and Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)
Subjects: [SDV] Life Sciences [q-bio], [ SDV ] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract: International audience; Background and PurposeThe transmembrane protein LINGO-1 is a negative regulator in the nervous system mainly affecting axonal regeneration, neuronal survival, oligodendrocyte differentiation and myelination. However, the molecular mechanisms regulating its functions are poorly understood. In the present study, we investigated the formation and the role of LINGO-1 cis-dimers in the regulation of its biological activity.Experimental ApproachLINGO-1 homodimers were identified in both HEK293 and SH-SY5Y cells using co-immunoprecipitation experiments and BRET saturation analysis. We performed a hypothesis-driven screen for identification of small-molecule protein–protein interaction modulators of LINGO-1 using a BRET-based assay, adapted for screening. The compound identified was further assessed for effects on LINGO-1 downstream signalling pathways using Western blotting analysis and AlphaScreen technology.Key ResultsLINGO-1 was present as homodimers in primary neuronal cultures. LINGO-1 interacted homotypically in cis-orientation and LINGO-1 cis-dimers were formed early during LINGO-1 biosynthesis. A BRET-based assay allowed us to identify phenoxybenzamine as the first conformational modulator of LINGO-1 dimers. In HEK-293 cells, phenoxybenzamine was a positive modulator of LINGO-1 function, increasing the LINGO-1-mediated inhibition of EGF receptor signalling and Erk phosphorylationConclusions and ImplicationsOur data suggest that LINGO-1 forms constitutive cis-dimers at the plasma membrane and that low MW compounds affecting the conformational state of these dimers can regulate LINGO-1 downstream signalling pathways. We propose that targeting the LINGO-1 dimerization interface opens a new pharmacological approach to the modulation of its function and provides a new strategy for drug discovery.
Published: 2015

20. Positively charged microbubbles to target nucleic acid delivery with ultrasound

Author: Manta, Simona, Delalande, Anthony, Renault, Gilles, Bureau, Michel Francis, Lebertre, Matthias, Marie, C, Scherman, Daniel, Midoux, Patrick, Mignet, Nathalie, Pichon, Chantal, Frouin, Frédérique, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Transderma Systems, Unité de Technologies Chimiques et Biologiques pour la Santé ( UTCBS - UM 4 (UMR 8258 / U1022) ), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de biophysique moléculaire ( CBM ), Université d'Orléans ( UO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-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 de Chimie du CNRS (INC), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [SDV.IB] Life Sciences [q-bio]/Bioengineering, animal structures, Nanomedicine, Therapy monitoring, Ultrasound, Targeted DNA delivery, [SDV.IB]Life Sciences [q-bio]/Bioengineering, [ SDV.IB ] Life Sciences [q-bio]/Bioengineering
Abstract: Congrès sous l’égide de la Société Française de Génie Biologique et Médical (SFGBM).; National audience; Nucleic acid delivery in vivo via physical means or non-viral vectors still need improvements in particular to reach deep tissues. Sonoporation is highly advantageous for this purpose as ultrasound can be focalised to a particular tissue leading to targeted gene delivery, without alteration of the environing tissues. Few examples of transfection using cationic microbubbles (MBs) and DNA have been reported. We ought to improve the existing systems by developing positively charged MBs able to oscillate in order to follow their fate in vivo and gain in understanding of the pharmacokinetic of the MBs, then target DNA delivery with ultrasound. After optimisation, we obtained MBs in the 1-3 !m range (98% below 10 !m) able to adsorb nucleic acid on their surface. In vitro parameters have been optimised to obtain in vitro transfection both with DNA and siRNA. The systemic injection in mice led to the observation of these MBs in the liver in less than 10 seconds. This investigation allows to address the key parameters to tentatively obtain reproducible gene transfection in vivo.
Published: 2015

21. Synthesis of Heterospirocycles through Gold‐(I) Catalysis: Useful Building Blocks for Medicinal Chemistry

Author: Kossi Efouako Soklou, Hamid Marzag, Karen Plé, Sylvain Routier, Béatrice Vallée, Institut de Chimie Organique et Analytique (ICOA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), PLE, Karen, Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
Subjects: [CHIM.ORGA]Chemical Sciences/Organic chemistry, 010405 organic chemistry, Chemistry, Nitrogen heterocycles, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, Molecular Diversity, Gold catalysis, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, General Chemistry, [CHIM.ORGA] Chemical Sciences/Organic chemistry, 010402 general chemistry, 01 natural sciences, 0104 chemical sciences, Catalysis, Synthetic methods, Organic chemistry, Spiro Compounds
Abstract: International audience; Gold-(I) catalysis was used for the intramolecular cyclization of tertiary alcohols with terminal alkynes to form diverse aza-spirocycles. The reaction was carried out with low catalyst loading under microwave irradiation to give both sulfonylated and acylated spirocyclic nitrogen derivatives. Gram scale spirocyclization was carried out and demonstrates the robustness of the reaction. An intramolecular Mizoroki-Heck reaction was performed to give several tetracyclic spirocycles. Double bond reduction and selective protecting group manipulation gave spiropiperazine and spiromorpholine derivatives. These compounds were incorporated into biologically relevant scaffolds to give the first selective spirocyclic inhibitors of LIMK.
Published: 2021

22. On biosignatures for Mars

Author: Frédéric Foucher, Barbara Cavalazzi, Jorge L. Vago, Laura Clodoré, Keyron Hickman-Lewis, Frances Westall, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of Bologna/Università di Bologna, Agence Spatiale Européenne = European Space Agency (ESA), Frapart, Isabelle, and Westall F., Hickman-Lewis K., Cavalazzi B., Foucher F., Clodoré L., Vago J.L.
Subjects: ALH84001, Physics and Astronomy (miscellaneous), clay, Mars Exploration Program, biosignature, Astrobiology, [SDU] Sciences of the Universe [physics], Mar, carbonate, silica, [SDU]Sciences of the Universe [physics], Space and Planetary Science, Earth and Planetary Sciences (miscellaneous), salt, Ecology, Evolution, Behavior and Systematics
Abstract: In this work, we address the difficulty of reliably identifying traces of life on Mars. Several independent lines of evidence are required to build a compelling body of proof. In particular, we underline the importance of correctly interpreting the geological and mineralogical context of the sites to be explored for the presence of biosignatures. We use as examples to illustrate this, ALH84001 (where knowledge of the geological context was very limited) and other terrestrial deposits, for which this could be properly established. We also discuss promising locations and formations to be explored by ongoing and future rover missions, including Oxia Planum, which, dated at 4.0 Ga, is the most ancient Mars location targeted for investigation yet.
Published: 2021

23. Flow cytometry assay to evaluate lipid production by the marine microalga Tetraselmis sp. using a two stage process

Author: Hajer Ben Hlima, Imen Fendri, Slim Abdelkafi, Fatma Elleuch, Mouna Dammak, Chantal Pichon, Philippe Michaud, Unité de Biotechnologie des Algues, Biological Engineering Department, National School of Engineers of Sfax, Université de Sfax - University of Sfax, Laboratoire de Génie Enzymatique et Microbiologie, Equipe de Biotechnologie des Algues, National Engineering School of Sfax, University of Sfax, 3029 Sfax, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), IRCER - Axe 1 : procédés céramiques (IRCER-AXE1), Institut de Recherche sur les CERamiques (IRCER), Institut des Procédés Appliqués aux Matériaux (IPAM), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut des Procédés Appliqués aux Matériaux (IPAM), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Laboratoire de Biotechnologies des Plantes Appliquées à l’Amélioration des Plantes, Faculté des Sciences, Université de Sfax, Sfax 3038
Subjects: chemistry.chemical_classification, 060102 archaeology, biology, Strain (chemistry), medicine.diagnostic_test, Renewable Energy, Sustainability and the Environment, Chemistry, [SDV]Life Sciences [q-bio], 020209 energy, Biomass, Lipid metabolism, 06 humanities and the arts, 02 engineering and technology, biology.organism_classification, Flow cytometry, Biodiesel production, 0202 electrical engineering, electronic engineering, information engineering, medicine, 0601 history and archaeology, Food science, Autotroph, Tetraselmis, Carotenoid
Abstract: International audience; Tetraselmis sp. strain MD-01, a microalga isolated from the Tunisian marine coast, has been studied for autotrophic lipids production with two stage process. This strategy was conducted for maximum cells production under moderated conditions (2.12 g L−1), followed by cultivation under stressed conditions to induce lipid synthesis. High irradiance (300 μmol m−2 s−1) and nitrogen depletion (S mode) showed better carotenoids accumulation and lower chlorophylls content in microalgae compared to those obtained in biomass cultivated under high irradiance (Sg mode). This two-stage strategy allowed to increase of lipid content in cells cultivated in Sg and S modes from 18% DW (stage I) to 50 and 61.5% DW (stage II), respectively, with an increase of saturated and long chain fatty acids levels. Based on fluorometry analyses, an increase of lipids in Nile-Red stained cells and a decrease of chlorophylls auto-fluorescence under stressed conditions were shown. From spectral data, the lipids: amide I ratio obtained from S mode was 2.17 and 4.45 times higher than that from Sg mode and control conditions, respectively. These results revealed the potential of Tetraselmis strain MD-01 for biodiesel production.
Published: 2021

24. Novel markers to early detect degradation on cellulose nitrate-based heritage at the submicrometer level using synchrotron UV–VIS multispectral luminescence

Author: Maria Elvira Callapez, Maria João Melo, Artur Neves, Ana M. Ramos, Mathieu Thoury, Robert Friedel, Matthieu Réfrégiers, LAQV@REQUIMTE, DCR - Departamento de Conservação e Restauro, DQ - Departamento de Química, Refregiers, Matthieu, Laboratorio Associado para a Quimica Verde (LAQV), Requimte, Universidade do Porto = University of Porto-Departamento de Química (DQ), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto = University of Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Centro Interuniversitário de História das Ciências e da Tecnologia [Caparica] (CIUHCT), University of Maryland [Baltimore], Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), Institut photonique d'analyse non-destructive européen des matériaux anciens (IPANEMA), Muséum national d'Histoire naturelle (MNHN)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), This work was supported by the European Union’s Horizon 2020 Research and Innovation Programme (H2020-NMBP‐35‐2017), Grant agreement no 76081, Project NEMOSINE, 'Innovative packaging solutions for storage and conservation of 20th century cultural heritage of artefacts based on cellulose derivatives, and Fundação para a Ciência e a Tecnologia, Ministério da Ciência Tecnologia e Ensino Superior (FCT/MCTES), Portugal, through doctoral programme CORES-PD/00253/2012, PhD Grant PD/BD/136678/2018 (Artur Neves) and Associate Laboratory for Green Chemistry- LAQV financed by national funds (UIDB/ 50006/2020 and UIDP/50006/2020)., Universidade do Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto-Departamento de Química (DQ), and Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
Subjects: Materials science, [CHIM.ANAL] Chemical Sciences/Analytical chemistry, Photochemistry, Science, Multispectral image, Nanotechnology, 02 engineering and technology, 01 natural sciences, Article, law.invention, Celluloid, chemistry.chemical_compound, Ultraviolet visible spectroscopy, Nitrate, SDG 3 - Good Health and Well-being, law, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, History of chemistry, Cellulose, General, Multidisciplinary, 010401 analytical chemistry, [SHS.ART]Humanities and Social Sciences/Art and art history, 021001 nanoscience & nanotechnology, Synchrotron, 0104 chemical sciences, Optics and photonics, Physical chemistry, chemistry, visual_art, visual_art.visual_art_medium, Degradation (geology), Medicine, [SHS.ART] Humanities and Social Sciences/Art and art history, 0210 nano-technology, Luminescence
Abstract: 20200316 H2020-NMBP‐35‐2017 CORES-PD/00253/2012 PD/BD/136678/2018 UIDB/ 50006/2020 UIDP/50006/2020 Cellulose nitrate (CN) is an intrinsically unstable material that puts at risk the preservation of a great variety of objects in heritage collections, also posing threats to human health. For this reason, a detailed investigation of its degradation mechanisms is necessary to develop sustainable conservation strategies. To investigate novel probes of degradation, we implemented deep UV photoluminescence micro spectral-imaging, for the first time, to characterize a corpus of historical systems composed of cellulose nitrate. The analysis of cinematographic films and everyday objects dated from the nineteenth c./early twentieth c. (Perlov's collection), as well as of photo-aged CN and celluloid references allowed the identification of novel markers that correlate with different stages of CN degradation in artworks, providing insight into the role played by plasticizers, fillers, and other additives in stability. By comparison with photoaged references of CN and celluloid (70% CN and 30% camphor), it was possible to correlate camphor concentration with a higher rate of degradation of the cinematographic films. Furthermore, the present study investigates, at the sub-microscale, materials heterogeneity that correlates to the artworks' history, associating the different emission profiles of zinc oxide to specific color formulations used in the late nineteenth and early twentieth centuries. publishersversion published
Published: 2021

25. Synthesis of Novel 3’,3’‐cyclic Dinucleotide Analogues Targeting STING Protein

Author: Jérémy Magand, Vincent Roy, Hervé Meudal, Stéphanie Rose, Valérie Quesniaux, Dominika Chalupska, Luigi A. Agrofoglio, Institut de Chimie Organique et Analytique (ICOA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Czech Academy of Sciences [Prague] (CAS), Region Centre-Val de Loire (EURO-FéRI EX010381and EURO-FéRI EX010351), FEDER TARGET-Ex EX016008)as well as by GAVO projet (MERSI-CNRS), ICOA comes from CHemBio (FEDER-FSE 2014-2020-EX003677), Techsab (FEDER-FSE 2014-2020-EX011313), RTR Motivhealth (2019-00131403), ANR-11-LABX-0029,SYNORG,Synthèse Organique : des molécules au vivant(2011), and ANR-11-LABX-0018,IRON,Radiopharmaceutiques Innovants en Oncologie et Neurologie(2011)
Subjects: [SDV]Life Sciences [q-bio], Organic Chemistry, [CHIM]Chemical Sciences
Abstract: International audience; The Stimulator of Interferon Genes (STING) plays an important role in innate immunity by inducing type I interferons in response to sensing viral or bacterial cytosolic DNA. Cyclic dinucleotides (CDNs) are known to activate STING. Here, we describe the synthesis and biological evaluation of two new 3’,3’-CDN, in which the internucleotide linkages were replaced, respectively, by a 1,2,3-triazole moiety (as more stable isosteres of phosphate linkers) and an unsaturated carbon chain (as flexibility can led to crucial binding affinity and specificity). Thus, CuAAC and macrocyclization by RCM are the two key steps
Published: 2022

26. Structural and functional determinants of the archaeal 8-oxoguanine-DNA glycosylase AGOG for DNA damage recognition and processing

Author: Franck, Coste, Goffinont, Stéphane, Cros, Julien, Gaudon, Virginie, Martine, Guérin, Garnier, Norbert, Fabrice, Confalonieri, Flament, Didier, Suskiewicz, Marcin Jozef, Bertrand, Castaing, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), 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), Biologie et Ecologie des Ecosystèmes Marins Profonds (BEEP), and Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM]
Abstract: International audience; Abstract 8-Oxoguanine (GO) is a major purine oxidation product in DNA. Because of its highly mutagenic properties, GO absolutely must be eliminated from DNA. To do this, aerobic and anaerobic organisms from the three kingdoms of life have evolved repair mechanisms to prevent its deleterious effect on genetic integrity. The major way to remove GO is the base excision repair pathway, usually initiated by a GO-DNA glycosylase. First identified in bacteria (Fpg) and eukaryotes (OGG1), GO-DNA glycosylases were more recently identified in archaea (OGG2 and AGOG). AGOG is the less documented enzyme and its mode of damage recognition and removing remains to be clarified at the molecular and atomic levels. This study presents a complete structural characterisation of apo AGOGs from Pyrococcus abyssi (Pab) and Thermococcus gammatolerans (Tga) and the first structure of Pab-AGOG bound to lesion-containing single- or double-stranded DNA. By combining X-ray structure analysis, site directed mutagenesis and biochemistry experiments, we identified key amino acid residues of AGOGs responsible for the specific recognition of the lesion and the base opposite the lesion and for catalysis. Moreover, a unique binding mode of GO, involving double base flipping, never observed for any other DNA glycosylases, is revealed. In addition to unravelling the properties of AGOGs, our study, through comparative biochemical and structural analysis, offers new insights into the evolutionary plasticity of DNA glycosylases across all three kingdoms of life.
Published: 2022

27. Aphid BCR4 Structure and Activity Uncover a New Defensin Peptide Superfamily

Author: Karine Loth, Nicolas Parisot, Françoise Paquet, Hugo Terrasson, Catherine Sivignon, Isabelle Rahioui, Mélanie Ribeiro Lopes, Karen Gaget, Gabrielle Duport, Agnès F. Delmas, Vincent Aucagne, Abdelaziz Heddi, Federica Calevro, Pedro da Silva, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Biologie Fonctionnelle, Insectes et Interactions (BF2I), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and AUCAGNE, Vincent
Subjects: Insecticides, defensin peptide, 3D structure, Catalysis, Defensins, Inorganic Chemistry, [CHIM] Chemical Sciences, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, [CHIM]Chemical Sciences, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Cysteine, Disulfides, Physical and Theoretical Chemistry, Molecular Biology, Phylogeny, Spectroscopy, aphid BCR, bioinsecticidal peptide, symbiosis, Organic Chemistry, General Medicine, Computer Science Applications, Biological Control Agents, Aphids, Peptides
Abstract: International audience; Aphids (Hemiptera: Aphidoidea) are among the most detrimental insects for agricultural plants, and their management is a great challenge in agronomical research. A new class of proteins, called Bacteriocyte-specific Cysteine-Rich (BCR) peptides, provides an alternative to chemical insecticides for pest control. BCRs were initially identified in the pea aphid Acyrthosiphon pisum. They are small disulfide bond-rich proteins expressed exclusively in aphid bacteriocytes, the insect cells that host intracellular symbiotic bacteria. Here, we show that one of the A. pisum BCRs, BCR4, displays prominent insecticidal activity against the pea aphid, impairing insect survival and nymphal growth, providing evidence for its potential use as a new biopesticide. Our comparative genomics and phylogenetic analyses indicate that BCRs are restricted to the aphid lineage. The 3D structure of BCR4 reveals that this peptide belongs to an as-yet-unknown structural class of peptides and defines a new superfamily of defensins.
Published: 2022

28. A framework for dissecting affinities of multidrug efflux transporter AcrB to fluoroquinolones

Author: Vergalli, Julia, Chauvet, Hugo, Oliva, Francesco, Pajović, Jelena, Malloci, Giuliano, Vargiu, Attilio, Réfrégiers, Matthieu, Ruggerone, Paolo, Pagès, Jean-Marie, Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), Membranes et cibles thérapeutiques (MCT), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Biomédicale des Armées (IRBA), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), University of Calgary, University of Belgrade [Belgrade], University of Cagliari, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Refregiers, Matthieu, and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA)
Subjects: [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Antibiotics, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Drug development, Permeation and transport, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Bioluminescence imaging
Abstract: International audience; Sufficient concentration of antibiotics close to their target is key for antimicrobial action. Among the tools exploited by bacteria to reduce the internal concentration of antibiotics, multidrug efflux pumps stand out for their ability to capture and expel many unrelated compounds out of the cell. Determining the specificities and efflux efficiency of these pumps towards their substrates would provide quantitative insights into the development of antibacterial strategies. In this light, we developed a competition efflux assay on whole cells, that allows measuring the efficacy of extrusion of clinically used quinolones in populations and individual bacteria. Experiments reveal the efficient competitive action of some quinolones that restore an active concentration of other fluoroquinolones. Computational methods show how quinolones interact with the multidrug efflux transporter AcrB. Combining experiments and computations unveils a key molecular mechanism acting in vivo to detoxify bacterial cells. The developed assay can be generalized to the study of other efflux pumps.
Published: 2022

29. Effect of the alcohol consumption on osteocyte cell processes: a molecular imaging study

Author: Eric Lespessailles, Chantal Pichon, Delphine B. Maurel, S. Pallu, Hechmi Toumi, Hugues Portier, Delphine Benaitreau, Claude Laurent Benhamou, Rustem Uzbekov, Christelle Jaffré, Imagerie Multimodale Multiéchelle et Modélisation du Tissu Osseux et articulaire (I3MTO), Université d'Orléans (UO), Faculté des Sciences du Sport, UFR STAPS, Faculté des Sciences du SportFaculté des Sciences du Sport, UFR STAPS, Laboratoire Mouvement Sport Santé (M2S), École normale supérieure - Cachan (ENS Cachan)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Brest (UBO)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Département des Microscopies, plate-forme R.I.O. de microscopie électronique, Université Francois Rabelais [Tours], Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), École normale supérieure - Cachan (ENS Cachan)-Université de Rennes (UR)-Université de Brest (UBO)-Université de Rennes 2 (UR2)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Caractérisation du tissu osseux par imagerie : techniques et applications, Université d'Orléans ( UO ) -Centre Hospitalier Régional d'Orléans ( CHR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Imagerie Multimodale Multiéchelle et Modélisation du Tissu Osseux et articulaire ( I3MTO ), Université d'Orléans ( UO ), Recombinaions Génétique, Centre National de la Recherche Scientifique ( CNRS ), Centre de biophysique moléculaire ( CBM ), Université d'Orléans ( UO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), UMR S658, and Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Porte Madeleine
Subjects: Genetic Markers, Male, medicine.medical_specialty, Pathology, lacunae, Bone density, [SDV]Life Sciences [q-bio], osteocyte, Real-Time Polymerase Chain Reaction, Osteocytes, Immunoenzyme Techniques, chemistry.chemical_compound, Microscopy, Electron, Transmission, Bone Density, Bone Marrow, lipid, Internal medicine, Lipid droplet, medicine, Animals, RNA, Messenger, Rats, Wistar, Cells, Cultured, Bone mineral, Microscopy, Confocal, [ SDV ] Life Sciences [q-bio], Ethanol, Reverse Transcriptase Polymerase Chain Reaction, apoptosis, dose, Cell Biology, Original Articles, 3. Good health, Molecular Imaging, Rats, Endocrinology, medicine.anatomical_structure, chemistry, Microscopy, Fluorescence, Apoptosis, Osteocyte, Bone Morphogenetic Proteins, Molecular Medicine, Sclerostin, Bone marrow, Paxillin, Alcohol, Immunostaining
Abstract: International audience; We have previously shown microarchitectural tissue changes with cellular modifications in osteocytes following high chronic alcohol dose. The aim of this study was to assess the dose effect of alcohol consumption on the cytoskeleton activity, the cellular lipid content and modulation of differentiation and apoptosis in osteocyte. Male Wistar rats were divided into three groups: Control (C), Alcohol 25% v/v (A25) or Alcohol 35% v/v (A35) for 17 weeks. Bone mineral density (BMD) was assessed by DXA, osteocyte empty lacunae, lacunae surface, bone marrow fat with bright field microscopy. Osteocyte lipid content was analysed with transmission electron microscopy (TEM) and epifluorescence microscopy. Osteocyte apoptosis was analysed with immunolabelling and TEM. Osteocyte differentiation and cytoskeleton activity were analysed with immunolabelling and real time quantitative PCR. At the end of the protocol, BMD was lower in A25 and A35 compared with C, while the bone marrow lipid content was increased in these groups. More empty osteocyte lacunae and osteocyte containing lipid droplets in A35 were found compared with C and A25. Cleaved caspase-3 staining and chromatin condensation were increased in A25 and A35 versus C. Cleaved caspase-3 was increased in A35 versus A25. CD44 and phosphopaxillin stainings were higher in A35 compared with C and A25. Paxillin mRNA expression was higher in A35 versus A25 and C and sclerostin mRNA expression was higher in A35 versus C. We only observed a dose effect of alcohol consumption on cleaved caspase-3 osteocyte immunostaining levels and on the number of lipid droplets in the bone marrow.
Published: 2014

30. NF-kappa B related transgene expression in mouse tibial cranial muscle after pDNA injection followed or not by electrotransfer

Author: Nelly El Shafey, Ch Pichon, M F Bureau, H Ait Bouda, Nathalie Mignet, Antoine Kichler, Patrick Midoux, Daniel Scherman, S Mahindhoratep, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-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 de Chimie du CNRS (INC), Conception et application de molécules bioactives (CAMB), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Technologies Chimiques et Biologiques pour la Santé ( UTCBS - UM 4 (UMR 8258 / U1022) ), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Conception et application de molécules bioactives ( CAMB ), Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de biophysique moléculaire ( CBM ), Université d'Orléans ( UO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), and Frapart, Isabelle
Subjects: PLURONIC BLOCK-COPOLYMERS, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Transgene, [SDV]Life Sciences [q-bio], Biophysics, IκBα, Gene electrotransfer, Biology, Biochemistry, NF-κB, GENE ELECTROTRANSFER, TRANSFECTION, 03 medical and health sciences, DELIVERY, 0302 clinical medicine, Gene expression, medicine, Luciferase, Transgene expression, Molecular Biology, IN-VIVO, 030304 developmental biology, 0303 health sciences, [ SDV ] Life Sciences [q-bio], Electroporation, Skeletal muscle, Transfection, PERMEABILIZATION, Molecular biology, PLASMID DNA ELECTROTRANSFER, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, 030220 oncology & carcinogenesis, Muscle, SKELETAL-MUSCLE, Transcription
Abstract: International audience; Background: When activated, NF-kappa B can promote the nuclear import and transcription of DNA possessing NF-kappa B consensus sequences. Here, we investigated whether NE-kappa B is involved in the plasmid electrotransfer process. Methods: Mouse tibial cranial muscles were transfected with plasmids encoding luciferase bearing or not NF-kappa B consensus sequences. Luciferase transgene expression was evaluated noninvasively by luminescence imaging and the number of pDNA copies in the same muscles by qPCR. RT-PCR of heat shock protein HsP70 mRNA evidenced cell stress. Western blots of phosphorylated I kappa B alpha were studied as a marker of NF-kappa B activation. Results: Intra-muscular injection of a plasmid bearing a weak TATA-like promoter results in a very low muscle transfection level. Electrotransfer significantly increased both the number of pDNA copy and the transgene expression of this plasmid per DNA copy. Insertion of NF-kappa B consensus sequences into pDNA significantly increased the level of gene expression both with and without electrotransfer. Electrotransfer-induced cellular stress was evidenced by increased HsP70 mRNA. Phosphorylated I kappa B alpha was slightly increased by simple pDNA injection and a little more by electrotransfer. We also observed a basal level of phosphorylated I kappa B alpha and thus of free NF-kappa B in the absence of any stimulation. General significance: pDNA electrotransfer can increase transgene expression independently of NF-kappa B. The insertion of NF-kappa B consensus sequences into pDNA bearing a weak TATA-like promoter leads to enhanced transgene expression in muscle with or without gene electrotransfer. Finally, our results suggest that the basal amount of free NF-kappa B in muscle might be sufficient to enhance the activity of pDNA bearing NF-kappa B consensus sequences. (C) 2014 Elsevier B.V. All rights reserved.
Published: 2014

31. LentiRILES, a miRNA-ON sensor system for monitoring the functionality of miRNA in cancer biology and therapy

Author: David Gosset, Loris Roncali, Yoan Laurent, Chantal Pichon, Flora Reverchon, Emmanuel Garcion, Patrick Baril, Audrey Rousseau, Francisco Martin, Patrick Midoux, Claire Loussouarn, Viorel Simion, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Design and Application of Innovative Local Treatments in Glioblastoma (CRCINA-ÉQUIPE 17), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre for Genomics and Oncological Research Pfizer [Granada, Spain] (GENYO), University of Granada [Granada]-Andalusian Regional Government [Granada, Spain], Inca : PL-BIO 2014–2020 (consortium Marengo)Ligue Contre le Cancer [Région du Loiret : 2017-2019]ARD 2020 Biopharmaceuticals [RNA cell factory 2017-2020], ANR-11-LABX-0018,IRON,Radiopharmaceutiques Innovants en Oncologie et Neurologie(2011), ANR-19-ENM3-0003,GLIOSILK,Silk-fibroin interventional nano-trap for the treatment of glioblastoma.(2019), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Universidad de Granada = University of Granada (UGR)-Andalusian Regional Government [Granada, Spain], Bernardo, Elizabeth, Radiopharmaceutiques Innovants en Oncologie et Neurologie - - IRON2011 - ANR-11-LABX-0018 - LABX - VALID, and Silk-fibroin interventional nano-trap for the treatment of glioblastoma. - - GLIOSILK2019 - ANR-19-ENM3-0003 - Euronanomed III - VALID
Subjects: Male, Cell, Apoptosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biosensing Techniques, Mice, SCID, Computational biology, Biology, Cell therapy, Mice, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Movement, Genes, Reporter, microRNA, Biomarkers, Tumor, Tumor Cells, Cultured, medicine, Animals, Humans, Luciferase, Molecular Biology, Gene, Cell Proliferation, miRNA, 030304 developmental biology, 0303 health sciences, Technical Paper, Cell Cycle, Lentivirus, glioblastoma, RNA therapeutics, Cell Biology, Middle Aged, molecular imaging, RILES, 3. Good health, Gene Expression Regulation, Neoplastic, MicroRNAs, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Luminescent Measurements, Female, Molecular imaging, Function (biology), Intracellular
Abstract: International audience; A major unresolved challenge in miRNA biology is the capacity to monitor the spatiotemporal activity of miRNAs expressed in animal disease models. We recently reported that the miRNA-ON monitoring system called RILES (RNAi-inducible expression Luciferase system) implanted in lentivirus expression system (LentiRILES) offers opportunity to decipher the kinetics of miRNA activity in vitro, in relation with their intracellular trafficking in glioblastoma cells. In this study we describe in detail the method for production of LentiRILES stable cell lines and employed it in several applications in the field of miRNA biology and therapy. We show that LentiRILES is a robust, highly specific and sensitive miRNA sensor system that can be used in vitro as a single-cell miRNA monitoring method, cell-based screening platform for miRNA therapeutics and as a tool to analyze the structurefunction relationship of the miRNA duplex. Furthermore, we report the kinetic of miRNA activity upon the intracranial delivery of miRNA mimics in an orthotopic animal model of glioblastoma. This information is exploited to evaluate the tumor suppressive function of miRNA-200c as locoregional therapeutic modality to treat glioblastoma. Our data provide evidence that LentiRILES is a robust system, well-suited to resolve the activity of endogenous and exogenously expressed miRNAs for basic research to gene and cell therapy.
Published: 2021

32. Doxorubicin‐Sensitized Luminescence of NIR‐Emitting Ytterbium Liposomes: Towards Direct Monitoring of Drug Release

Author: Sara Lacerda, Éva Tóth, Frédéric Szeremeta, Sandra Même, Anthony Delalande, Célia S. Bonnet, Stéphane Petoud, Agnès Pallier, Chantal Pichon, Svetlana V. Eliseeva, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Frapart, Isabelle
Subjects: Ytterbium, Luminescence, Materials science, Infrared Rays, [SDV]Life Sciences [q-bio], chemistry.chemical_element, Breast Neoplasms, 02 engineering and technology, 010402 general chemistry, Photochemistry, 01 natural sciences, Catalysis, Polyethylene Glycols, Mice, Cell Line, Tumor, medicine, Animals, Chelation, Doxorubicin, Liposome, Antibiotics, Antineoplastic, Molecular Structure, General Medicine, General Chemistry, 021001 nanoscience & nanotechnology, Magnetic Resonance Imaging, 3. Good health, 0104 chemical sciences, [SDV] Life Sciences [q-bio], Drug Liberation, chemistry, Liposomes, Drug delivery, Nanomedicine, Female, 0210 nano-technology, Preclinical imaging, medicine.drug
Abstract: International audience; Drug-loaded liposomes are typical examples of nanomedicine. We show here that doxorubicin, the anti-cancer agent in the liposomal drug Doxil ® , can sensitize Ytterbium (Yb 3+ ) and generate its near infrared (NIR) emission. When doxorubicin and amphiphilic Yb 3+ chelates are incorporated into liposomes, the sensitized emission of Yb 3+ is dependent on the integrity of the particles which can be used to monitor drug release. We also established the first demonstration that the NIR Yb 3+ emission signal is observable in living mice following intratumoral injection of the Yb 3+ -doxorubicin-liposomes, using a commercial macroscopic setup equipped with a near-infrared camera.
Published: 2021

33. Right ventricular myocardial oxygen tension is reduced in monocrotaline-induced pulmonary hypertension in the rat and restored by myo-inositol trispyrophosphate

Author: Michał Mączewski, Klaudia Brodaczewska, Zuzanna Zambrowska, Marta Oknińska, Urszula Mackiewicz, Karolina Zajda, Cezary Szczylik, Adam Torbicki, Aleksandra Paterek, Claudine Kieda, Centre of Postgraduate Medical Education, Military Institute of Medicine, Warsaw, Centre de biophysique moléculaire (CBM), and Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
Subjects: Male, Ventricular Dysfunction, Right, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Muscle hypertrophy, Hemoglobins, 0302 clinical medicine, Hypoxia, 0303 health sciences, Multidisciplinary, Monocrotaline, Oxygen tension, Treatment Outcome, Cardiology, cardiovascular system, Medicine, medicine.symptom, circulatory and respiratory physiology, medicine.medical_specialty, Cardiotonic Agents, Hypertension, Pulmonary, Inositol Phosphates, Science, Diastole, Article, Contractility, 03 medical and health sciences, Internal medicine, medicine.artery, medicine, Animals, Rats, Wistar, 030304 developmental biology, Hypertrophy, Right Ventricular, business.industry, Hypoxia (medical), medicine.disease, Pulmonary hypertension, Myocardial Contraction, Cardiovascular biology, Rats, Circulation, Disease Models, Animal, Blood pressure, Pulmonary artery, Ventricular Function, Right, business
Abstract: Pulmonary hypertension (PH) initially results in compensatory right ventricular (RV) hypertrophy, but eventually in RV failure. This transition is poorly understood, but may be triggered by hypoxia. Measurements of RV oxygen tension (pO2) in PH are lacking. We hypothesized that RV hypoxia occurs in monocrotaline-induced PH in rats and that myo-inositol trispyrophosphate (ITPP), facilitating oxygen dissociation from hemoglobin, can relieve it. Rats received monocrotaline (PH) or saline (control) and 24 days later echocardiograms, pressure–volume loops were obtained and myocardial pO2 was measured using a fluorescent probe. In PH mean pulmonary artery pressure more than doubled (35 ± 5 vs. 15 ± 2 in control), RV was hypertrophied, though its contractility was augmented. RV and LV pO2 was 32 ± 5 and 15 ± 8 mmHg, respectively, in control rats. In PH RV pO2 was reduced to 18 ± 9 mmHg, while LV pO2 was unchanged. RV pO2 correlated with RV diastolic wall stress (negatively) and LV systolic pressure (positively). Acute ITPP administration did not affect RV or LV pO2 in control animals, but increased RV pO2 to 26 ± 5 mmHg without affecting LV pO2 in PH. RV oxygen balance is impaired in PH and as such can be an important target for PH therapy. ITPP may be one of such potential therapies.
Published: 2021

34. Monitoring Human Neutrophil Activation by a Proteinase 3 Near-Infrared Fluorescence Substrate-Based Probe

Author: Vincent Aucagne, Mylène Wartenberg, Gilles Lalmanach, Jean-Baptiste Madinier, Seda Seren, Fabien Lecaille, Guy Ilango, Ahlame Saidi, Brice Korkmaz, Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Plateforme IBISA de Microscopie Electronique [CHRU de Tours] (UNIV Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT), Aucagne, Vincent, and Lalmanach, Gilles
Subjects: Proteinase 3, Spectrophotometry, Infrared, Cell Survival, Neutrophils, Myeloblastin, Biomedical Engineering, Pharmaceutical Science, Bioengineering, Near-infrared fluorescence (NIRF), Cathepsin G, Gene Expression Regulation, Enzymologic, Neutrophil Activation, Cathepsin, law.invention, chemistry.chemical_compound, Confocal microscopy, law, Elastase, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Dark quencher, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Fluorescent Dyes, Pharmacology, Microscopy, Confocal, Molecular Structure, biology, Neutrophil serine protease (NSP), Ionomycin, Organic Chemistry, Fluorescence, Förster resonance energy transfer, chemistry, Neutrophil elastase, biology.protein, Biophysics, Norvaline, Biotechnology
Abstract: International audience; A near-infrared fluorescent (NIRF) substrate-based probe (SBP) was conceived to monitor secreted human proteinase 3 (hPR3) activity. This probe, called pro3-SBP, is shaped by a fused peptide hairpin loop structure, which associates a hPR3 recognition domain (Val-Ala-Asp-Nva-Ala-Asp-Tyr-Gln, where Nva is norvaline) and an electrostatic zipper (consisting of complementary polyanionic (d-Glu)5 and polycationic (d-Arg)5 sequences) in close vicinity of the N- and C-terminal FRET couple (fluorescent donor, sulfoCy5.5; dark quencher, QSY21). Besides its subsequent stability, no intermolecular fluorescence quenching was detected following its complete hydrolysis by hPR3, advocating that pro3-SBP could further afford unbiased imaging. Pro3-SBP was specifically hydrolyzed by hPR3 (kcat/Km= 440 000 ± 5500 M-1·s-1) and displayed a sensitive detection threshold for hPR3 (subnanomolar concentration range), while neutrophil elastase showed a weaker potency. Conversely, pro3-SBP was not cleaved by cathepsin G. Pro3-SBP was successfully hydrolyzed by conditioned media of activated human neutrophils but not by quiescent neutrophils. Moreover, unlike unstimulated neutrophils, a strong NIRF signal was specifically detected by confocal microscopy following neutrophil ionomycin-induced degranulation. Fluorescence release was abolished in the presence of a selective hPR3 inhibitor, indicating that pro3-SBP is selectively cleaved by extracellular hPR3. Taken together, the present data support that pro3-SBP could be a convenient tool, allowing straightforward monitoring of human neutrophil activation.
Published: 2021

35. Sedimentary and stratigraphic observations at the Jezero western delta front using Perseverance cameras: initial constraints on palaeoenvironments

Author: Gupta, Sanjeev, Bell, Jim F., Kanine, Oak, Tate, Christian, Caravaca, Gwénaël, Núñez, Jorge, Mangold, Nicolas, Dromart, Gilles, Le Mouélic, Stéphane, Annex, Andrew, Paar, Gerhard, Holm-Alwmark, Sanna, Rice, Melissa S., Rice, Jim, Horgan, Briony, Grotzinger, John, Maki, Justin, Hickman Lewis, Keyron, Kah, Lindah, Shuster, David L., Simon, Justin I., Gasnault, Olivier, Wiens, Roger, Maurice, Sylvestre, Stack, Kathryn, Farley, Kenneth A., Department of Earth Science and Engineering [Imperial College London], Imperial College London, Arizona State University [Tempe] (ASU), Division of Geological and Planetary Sciences [Pasadena], California Institute of Technology (CALTECH), Institut de recherche en astrophysique et planétologie (IRAP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Johns Hopkins University Applied Physics Laboratory [Laurel, MD] (APL), Laboratoire de Planétologie et Géosciences [UMR_C 6112] (LPG), Université d'Angers (UA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Laboratoire de Géologie de Lyon - Terre, Planètes, Environnement (LGL-TPE), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut national des sciences de l'Univers (INSU - CNRS)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Joanneum Research, Department of Earth, Atmospheric, and Planetary Sciences, Purdue University, Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), The University of Tennessee [Knoxville], Berkeley Geochronology Center (BGC), Center for Isotope Cosmochemistry and Geochronology, NASA Johnson Space, and Europlanet
Subjects: [SDU.STU.PL]Sciences of the Universe [physics]/Earth Sciences/Planetology, [SDU]Sciences of the Universe [physics], [SDU.STU.ST]Sciences of the Universe [physics]/Earth Sciences/Stratigraphy, [SDU.STU]Sciences of the Universe [physics]/Earth Sciences
Abstract: International audience; NASA’s Mars 2020 Perseverance rover mission is seeking signs of ancient life in Jezero crater and is collecting a cache of Martian rock and soil samples for planned return to Earth by a future mission. A key exploration target for the mission is a prominent sedimentary fan deposit at the western margin of Jezero crater that has been interpretated to be a river delta that built into an ancient lake basin during the Late Noachian-Early Hesperian epochs on Mars (~3.6-3.8 Ga) [1, 2]. Long distance observations of a remnant butte (informally named Kodiak) related to the western fan demonstrated that it comprised two distinct Gilbert-type delta units [2, 3].In her approach to the western fan, Perseverance drove alongside the east-facing scarp of the western fan and arrived at a key location called Three Forks - a setting off point for delta exploration - in April 2022. Images from the Mastcam-Z and SuperCam Remote Micro-Imager instrumentsprovide new views of the stratigraphy exposed in the erosional front of the western Jezero delta; in particular, showing sections of the delta previously not visible from long distance observations and at much higher resolution. These observations provide the first direct evidence of delta geometries in the main western fan deposit. Here, we report its stratigraphy and sedimentology, which providenew constraints on the nature of the fan deposits, and therefore paleoenvironmental implications.
Published: 2022

36. A scalable framework for the discovery of functional helicase substrates and helicase-driven regulatory switches

Author: Mildred Delaleau, Eric Eveno, Isabelle Simon, Annie Schwartz, Marc Boudvillain, Boudvillain, Marc, Toward an Integrated View of Transcription Terminator Rho Functions and Mechanisms - - IntegRhoMe2015 - ANR-15-CE11-0024 - AAPG2015 - VALID, Exploiter l'activité ARN hélicase à des fins de (ribo)régulation synthétique - - HELISWITCH2019 - ANR-19-CE44-0009 - AAPG2019 - VALID, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), ANR-15-CE11-0024,IntegRhoMe,Toward an Integrated View of Transcription Terminator Rho Functions and Mechanisms(2015), and ANR-19-CE44-0009,HELISWITCH,Exploiter l'activité ARN hélicase à des fins de (ribo)régulation synthétique(2019)
Subjects: riboswitches, Binding Sites, Multidisciplinary, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], helicases, SELEX Aptamer Technique, DNA Helicases, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Ligands, Substrate Specificity, Rho, Riboswitch, Transcription Termination, Genetic, Escherichia coli, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], transcription termination
Abstract: Helicases are ubiquitous motor enzymes that remodel nucleic acids (NA) and NA–protein complexes in key cellular processes. To explore the functional repertoire and specificity landscape of helicases, we devised a screening scheme—Helicase-SELEX (Systematic Evolution of Ligands by EXponential enrichment)—that enzymatically probes substrate and cofactor requirements at global scale. Using the transcription termination Rho helicase of Escherichia coli as a prototype for Helicase-SELEX, we generated a genome-wide map of Rho utilization ( Rut ) sites. The map reveals many features, including promoter- and intrinsic terminator-associated Rut sites, bidirectional Rut tandems, and cofactor-dependent Rut sites with inverted G > C skewed compositions. We also implemented an H-SELEX variant where we used a model ligand, serotonin, to evolve synthetic Rut sites operating in vitro and in vivo in a ligand-dependent manner. Altogether, our data illustrate the power and flexibility of Helicase-SELEX to seek constitutive or conditional helicase substrates in natural or synthetic NA libraries for fundamental or synthetic biology discovery.
Published: 2022

37. Science in the digital era

Author: Hinsen, Konrad, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), and Hinsen, Konrad
Subjects: [PHYS.PHYS.PHYS-COMP-PH]Physics [physics]/Physics [physics]/Computational Physics [physics.comp-ph], [SHS.HISPHILSO]Humanities and Social Sciences/History, Philosophy and Sociology of Sciences, [INFO.INFO-CY] Computer Science [cs]/Computers and Society [cs.CY], [INFO.INFO-CY]Computer Science [cs]/Computers and Society [cs.CY], [SHS.HISPHILSO] Humanities and Social Sciences/History, Philosophy and Sociology of Sciences, [INFO.INFO-CE]Computer Science [cs]/Computational Engineering, Finance, and Science [cs.CE], [PHYS.PHYS.PHYS-COMP-PH] Physics [physics]/Physics [physics]/Computational Physics [physics.comp-ph], [INFO.INFO-CE] Computer Science [cs]/Computational Engineering, Finance, and Science [cs.CE], [INFO.INFO-MO] Computer Science [cs]/Modeling and Simulation, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation
Abstract: This digital garden contains essays, thoughts, random ideas, and references that relate to the practice of scientific research in the digital era, characterized by computers (personal, high-performance, cloud, . . . ), software, the Internet, global collaborations, social networks, and more. They represent exclusively my personal views and in particular not those of my employer. There are many empty pages in this collection, and you may wonder why.
Published: 2022

38. Insights into the Responding Modes of Highly Potent Gadolinium-Based Magnetic Resonance Imaging Probes Sensitive to Zinc Ions

Author: Gaoji Wang, Harlei Martin, Susana Amézqueta, Clara Ràfols, Célia S. Bonnet, Goran Angelovski, Bonnet, Célia, Max Planck Institute for Biological Cybernetics, Max-Planck-Gesellschaft, JiangSu University, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Universitat de Barcelona (UB)
Subjects: Ions, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Carboxylic Acids, Contrast Media, Tricarboxylic Acids, Water, Esters, Gadolinium, Serum Albumin, Human, [CHIM.COOR] Chemical Sciences/Coordination chemistry, Magnetic Resonance Imaging, Inorganic Chemistry, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, [CHIM.THEO] Chemical Sciences/Theoretical and/or physical chemistry, Zinc, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Humans, Tyrosine, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Physical and Theoretical Chemistry, Amines, Chelating Agents
Abstract: International audience; Zinc ions (Zn 2+) play an important biological role in many diseases, hence an imaging method for monitoring the Zn 2+ distribution in tissues could provide important clinical insights. Recently, we reported a potent Zn-sensitive probe based on the Gd-DO3A (DO3A-1,4,7,10-tetraazacyclododecane-1,4,7-tricarboxylic acid), modified tyrosine and DPA (di-(2-picolyl)amine) chelator for this metal cation, which generates outstanding magnetic resonance imaging (MRI) response. Here we further explored the origin of this unprecedented response and expanded the choice of the potential MRI probes by preparing the free acid version of the initial MRI sensor. We report a detailed investigation of the 1 H nuclear magnetic relaxation dispersion (NMRD), 17 O NMR and isothermal titration calorimetry properties of these two MRI probes upon interacting with Zn 2+. The performed experiments confirm the selective interaction of the MRI probes and the target metal cation, which causes substantial changes in the coordination sphere of the paramagnetic center. It also evidenced some aggregation which enhances the relaxivity response. Interestingly, conversion of the methyl ester to the free carboxylic acid of tyrosine moiety changes the nature of the aggregates and leads to a smaller relaxivity response. The probes interact with human serum albumin (HSA) in the absence of Zn 2+ , which leads to a possible modification of the coordination sphere of Gd 3+ or a substantial change in the exchange rate of second sphere water molecules. In the presence of Zn 2+ , the interaction with HSA is very weak, demonstrating the importance of the Zn 2+ coordination sphere in the behavior of these systems.
Published: 2022

39. A single run LC-MS/MS method for phospholipidomics

Author: Jean-Marie Schmitter, Corinne Buré, Eric Testet, Sophie Ayciriex, Université Paris Descartes - Faculté de Pharmacie de Paris ( UPD5 Pharmacie ), Université Paris Descartes - Paris 5 ( UPD5 ), Max Planck Institute for Cell Biology and Genetics, Max-Planck-Institut, Institut des Sciences Analytiques ( ISA ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon, Centre de biophysique moléculaire ( CBM ), Université d'Orléans ( UO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), UMR5200, Laboratoire de biogenèse membranaire (LBM), Université de Bordeaux ( UB ), Chimie et Biologie des Membranes et des Nanoobjets ( CBMN ), Université Sciences et Technologies - Bordeaux 1-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux ( ENITAB ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Faculté de Pharmacie de Paris (UPD5 Pharmacie), Université Paris Descartes - Paris 5 (UPD5), Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Max-Planck-Gesellschaft, Institut des Sciences Analytiques (ISA), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Laboratoire de biogenèse membranaire (LBM), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), French Agence Nationale de la Recherche [NT09_517917], Region Aquitaine, platforms Proteome, Centre National de la Recherche Scientifique, Conseil Regional d'Aquitaine, Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École normale supérieure - Lyon (ENS Lyon), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université Sciences et Technologies - Bordeaux 1-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Centre National de la Recherche Scientifique (CNRS)
Subjects: ELECTROSPRAY-IONIZATION, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MECHANISTIC PROPOSAL, Tandem mass spectrometry, Phosphatidylinositols, 01 natural sciences, Biochemistry, ENERGY COLLISIONAL ACTIVATION, Analytical Chemistry, DATA-DEPENDENT ACQUISITION, chemistry.chemical_compound, [ SDV.BBM.BC ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Tandem Mass Spectrometry, BIOLOGICAL SAMPLES, [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Chromatography, High Pressure Liquid, Phospholipids, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, 0303 health sciences, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Hydrophilic interaction chromatography, Phosphatidylglycerols, Phosphatidic acid, Phosphatidylserine, QUANTITATIVE-ANALYSIS, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Lipids, [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], [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, DRIVEN FRAGMENTATION PROCESSES, Phosphatidylcholines, Shotgun, Phospholipid, Liquid chromatography, Phosphatidic Acids, Phosphatidylserines, Chemistry Techniques, Analytical, 03 medical and health sciences, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Phosphatidylcholine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], TANDEM MASS-SPECTROMETRY, MULTIPLE PRECURSOR, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], 030304 developmental biology, Phosphatidylethanolamine, Chromatography, Mass spectrometry, Phosphatidylethanolamines, 010401 analytical chemistry, Fungi, Fatty acid, Reproducibility of Results, Carbon, 0104 chemical sciences, chemistry, SHOTGUN LIPIDOMICS, [ CHIM.ANAL ] Chemical Sciences/Analytical chemistry, Acyltransferases, Chromatography, Liquid, [ SDV.BBM.BS ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
Abstract: International audience; Liquid chromatography coupled to tandem mass spectrometry has been compared to shotgun analysis with the objective of finding the best compromise for a single run analysis of whole cell phospholipids. Hydrophilic interaction liquid chromatography (HILIC), normal phase (NP), and reversed phase (RP) liquid chromatography were evaluated with reference phospholipids belonging to phosphatidic acid (PA), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylinositol (PI), and phosphatidylserine (PS) classes. NP-HPLC- and RP-HPLC-ESI-MS/MS were applied to yeast phospholipidome analysis, using a wild-type strain and two strains defective for acyltransferases that are known to be involved in de novo phospholipid synthesis or phospholipid remodeling. The MRM mode was used for relative quantitation of individual compounds based on reference phospholipids bearing fatty acid chains with an odd number of carbon atoms. Combined LC-MS/MS was found superior to shotgun analysis, leading to a larger number of quantified species than shotgun analysis. Finally, RP-HPLC-MS/MS was the preferred method for its higher selectivity, robustness, and better repeatability.
Published: 2013

40. Structural insights into the regulation of the human E2∼SUMO conjugate through analysis of its stable mimetic

Author: Stéphane Goffinont, Franck Coste, Pierre Prieu-Serandon, Lucija Mance, Virginie Gaudon, Norbert Garnier, Bertrand Castaing, Marcin Józef Suskiewicz, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and European Project: 101078837,SUMOwriteNread
Subjects: Cell Biology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Molecular Biology, Biochemistry
Abstract: International audience; Protein SUMOylation is a ubiquitylation-like post-translational modification (PTM) that is synthesised through an enzymatic cascade involving an E1 (SAE1:SAE2), an E2 (UBC9), and various E3 enzymes. In the final step of this process, the small ubiquitin-like modifier (SUMO) is transferred from the UBC9∼SUMO thioester onto a lysine residue of a protein substrate. This reaction can be accelerated by an E3 ligase. As the UBC9∼SUMO thioester is chemically unstable, a stable mimetic is desirable for structural studies of UBC9∼SUMO alone and in complex with a substrate and/or an E3 ligase. Recently, a strategy for generating a mimetic of the yeast E2∼SUMO thioester by mutating alanine 129 of Ubc9 to a lysine has been reported. Here, we reproduce and further investigate this approach using the human SUMOylation system and characterise the resulting mimetic of human UBC9∼SUMO1. We show that substituting lysine for alanine 129, but not for other active-site UBC9 residues, results in a UBC9 variant that is efficiently auto-SUMOylated. The auto-modification is dependent on cysteine 93 of UBC9, suggesting that it proceeds via this residue, through the same pathway as that for SUMOylation of substrates. The process is also partially dependent on aspartate 127 of UBC9 and accelerated by high pH, highlighting the importance of the substrate lysine protonation state for efficient SUMOylation. Finally, we present the crystal structure of the UBC9–SUMO1 molecule, which reveals the mimetic in an open conformation and its polymerisation via the noncovalent SUMO-binding site on UBC9. Similar interactions could regulate UBC9∼SUMO in some cellular contexts.
Published: 2023

41. Supporting Mars exploration: BIOMEX in Low Earth Orbit and further astrobiological studies on the Moon using Raman and PanCam technology

Author: Thomas Leya, Ulrich Szewzyk, Mickael Baqué, Elke Rabbow, Jörg Fritz, René Demets, Pascale Ehrenfreund, Laura Zucconi, Laura Selbmann, Jean-Pierre de Vera, Paloma Serrano, Björn Huwe, C. Meyer, Andreas Elsaesser, Heinz-Wilhelm Hübers, Caroline Lange, Ralf Möller, F. J. Sánchez, Silvano Onofri, Daniela Billi, J. Meessen, Dana Grunow, Jochen Jänchen, Frances Westall, Nicole Schmitz, N. Feyh, Natalia Kozyrovska, Bernard Foing, Maria Bohmeier, Rosa de la Torre Noetzel, Ralf Jaumann, Tilman Spohn, Petra Rettberg, Thomas Berger, Sieglinde Ott, Charles S. Cockell, Dirk Wagner, Ute Boettger, Howell G. M. Edwards, Günther Reitz, Casey Bryce, Jasmin Joshi, Gerda Horneck, DLR Institut für Planetenforschung, Deutsches Zentrum für Luft- und Raumfahrt [Berlin] ( DLR ), Instituto Nacional de Técnica Aeroespacial ( INTA ), Technische Universität Berlin ( TUB ), Università degli Studi di Roma Tor Vergata [Roma], Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] ( IBMM ), Ecole Nationale Supérieure de Chimie de Montpellier ( ENSCM ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Deutsches Zentrum für Luft- und Raumfahrt [Köln] ( DLR ), Centre de biophysique moléculaire ( CBM ), Université d'Orléans ( UO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Technische Hochschule Wildau ( TH Wildau ), Centre Pluridisciplinaire Textes et Cultures ( CPTC ), Université de Bourgogne ( UB ), Museum für Naturkunde [Berlin], Università degli studi della Tuscia [Viterbo], National Academy of Sciences of Ukraine ( NASU ), Fraunhofer - Institut für Biomedizinische Technik ( IBMT ), European Space Research and Technology Centre ( ESTEC ), European Space Agency ( ESA ), School of Physics and Astronomy [Edinburgh], University of Edinburgh, Design of Distributed Operating Systems ( SOLIDOR ), Institut de Recherche en Informatique et Systèmes Aléatoires ( IRISA ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ) -INRIA Rennes, Institut National de Recherche en Informatique et en Automatique ( Inria ), GeoForschungsZentrum - Helmholtz-Zentrum Potsdam ( GFZ ), Joint Center for Structural Genomics ( JCSG ), Stanford University [Stanford], Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung ( AWI ), University of Sheffield [Sheffield], University of Bradford, Universität Potsdam, Leiden Observatory [Leiden], Universiteit Leiden [Leiden], Space Policy Institute [Washington], George Washington University ( GW ), Heinrich-Heine-Universität Düsseldorf [Düsseldorf], DLR Institute of Planetary Research, German Aerospace Center ( DLR ), Deutsches Zentrum für Luft- und Raumfahrt [Berlin] (DLR), Instituto Nacional de Técnica Aeroespacial (INTA), Technische Universität Berlin (TU), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Deutsches Zentrum für Luft- und Raumfahrt [Köln] (DLR), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Technische Hochschule Wildau (TH Wildau), Centre Pluridisciplinaire Textes et Cultures (CPTC), Université de Bourgogne (UB), National Academy of Sciences of Ukraine (NASU), Fraunhofer Institute for Biomedical Engineering [Sulzbach] (Fraunhofer IBMT), Fraunhofer (Fraunhofer-Gesellschaft), European Space Research and Technology Centre (ESTEC), European Space Agency (ESA), SUPA School of Physics and Astronomy [Edinburgh], GeoForschungsZentrum - Helmholtz-Zentrum Potsdam (GFZ), Joint Center for Structural Genomics (JCSG), Stanford University, Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung (AWI), The George Washington University (GW), Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], German Aerospace Center (DLR), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Design of Distributed Operating Systems (SOLIDOR), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-INRIA Rennes, Institut National de Recherche en Informatique et en Automatique (Inria), and Publica
Subjects: BIOMEX, Settore BIO/01, Mars, 550 - Earth sciences, Life on Mars, Exploration of Mars, 01 natural sciences, 7. Clean energy, Space exploration, Astrobiology, Lunar Lander, 03 medical and health sciences, 0103 physical sciences, International Space Station, Low Earth Orbit, Biosignature, Space research, Moon, 010303 astronomy & astrophysics, Lunar lander, Instrumentation, Spectroscopy, 030304 developmental biology, 0303 health sciences, Institut für Physik und Astronomie, Astronomy and Astrophysics, Mars Exploration Program, Lithopanspermia, 13. Climate action, Space and Planetary Science, [SDU]Sciences of the Universe [physics], Environmental science, Extraterrestrial Environment, Exploration, [ SDU ] Sciences of the Universe [physics]
Abstract: International audience; The Low Earth Orbit (LEO) experiment Biology and Mars Experiment (BIOMEX) is an interdisciplinary and international space research project selected by ESA. The experiment will be accommodated on the space exposure facility EXPOSE-R2 on the International Space Station (ISS) and is foreseen to be launched in 2013. The prime objective of BIOMEX is to measure to what extent biomolecules, such as pigments and cellular components, are resistant to and able to maintain their stability under space and Mars-like conditions. The results of BIOMEX will be relevant for space proven biosignature definition and for building a biosignature data base (e.g. the proposed creation of an international Raman library). The library will be highly relevant for future space missions such as the search for life on Mars. The secondary scientific objective is to analyze to what extent terrestrial extremophiles are able to survive in space and to determine which interactions between biological samples and selected minerals (including terrestrial, Moon- and Mars analogs) can be observed under space and Mars-like conditions. In this context, the Moon will be an additional platform for performing similar experiments with negligible magnetic shielding and higher solar and galactic irradiation compared to LEO. Using the Moon as an additional astrobiological exposure platform to complement ongoing astrobiological LEO investigations could thus enhance the chances of detecting organic traces of life on Mars. We present a lunar lander mission with two related objectives: a lunar lander equipped with Raman and PanCam instruments which can analyze the lunar surface and survey an astrobiological exposure platform. This dual use of testing mission technology together with geo- and astrobiological analyses will significantly increase the science return, and support the human preparation objectives. It will provide knowledge about the Moon′s surface itself and, in addition, monitor the stability of life-markers, such as cells, cell components and pigments, in an extraterrestrial environment with much closer radiation properties to the surface of Mars. The combination of a Raman data base of these data together with data from LEO and space simulation experiments, will lead to further progress on the analysis and interpretation of data that we will obtain from future Moon and Mars exploration missions.
Published: 2012

42. Ultrasound and microbubble-assisted gene delivery: recent advances and ongoing challenges

Author: Michiel Postema, Anthony Delalande, Chantal Pichon, Patrick Midoux, Nathalie Mignet, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Unité de pharmacologie chimique et génétique et d'imagerie (UPCGI - UMR 8151 / UMR_S 1022 ), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC), Centre de biophysique moléculaire ( CBM ), Université d'Orléans ( UO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Unité de pharmacologie chimique et génétique et d'imagerie ( UPCGI - UMR 8151 / UMR_S 1022 ), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Postema, Michiel, BLANC - Formulations originales de liposomes acoustiques pour une délivrance assistée par des ultrasons - - MEDDU2011 - ANR-11-BSV5-0026 - BLANC - VALID, Department of Physics and Technology [Bergen] (UiB), University of Bergen (UiB), Haukeland University Hospital, Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-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 d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Region Centre (Nanodeliv project), Norwegian research cluster MedViz, and ANR-11-BSV5-0026,MEDDU,Formulations originales de liposomes acoustiques pour une délivrance assistée par des ultrasons(2011)
Subjects: Cell Membrane Permeability, MESH : Sonication, Cell membrane permeability, Membrane permeability, Pharmaceutical Science, Ultrasound exposure, Nanotechnology, MESH: Gene Transfer Techniques, Gene delivery, 01 natural sciences, Sonication, 03 medical and health sciences, MESH : Genetic Therapy, 0103 physical sciences, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, Medicine, MESH: Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Cell Membrane Permeability, MESH : Gene Transfer Techniques, MESH: Sonication, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 010301 acoustics, Ultrasonography, 030304 developmental biology, MESH : Microbubbles, MESH: Genetic Therapy, MESH : Ultrasonography, 0303 health sciences, Microbubbles, MESH: Humans, business.industry, MESH : Humans, Ultrasound, Gene Transfer Techniques, Genetic Therapy, 3. Good health, MESH : Cell Membrane Permeability, Ultrasound imaging, MESH : Animals, business, Sonoporation, Neuroscience, MESH: Microbubbles, MESH: Ultrasonography
Abstract: International audience; Having first been developed for ultrasound imaging, nowadays, microbubbles are proposed as tools for ultrasound-assisted gene delivery, too. Their behavior during ultrasound exposure causes transient membrane permeability of surrounding cells, facilitating targeted local delivery. The increased cell uptake of extracellular compounds by ultrasound in the presence of microbubbles is attributed to a phenomenon called sonoporation. Sonoporation has been successfully applied to deliver nucleic acids in vitro and in vivo in a variety of therapeutic applications. However, the biological and physical mechanisms of sonoporation are still not fully understood. In this review, we discuss recent data concerning microbubble--cell interactions leading to sonoporation and we report on the progress in ultrasound-assisted therapeutic gene delivery in different organs. In addition, we outline ongoing challenges of this novel delivery method for its clinical use.
Published: 2012

43. DNA nuclear targeting sequences for enhanced non-viral gene transfer: An in vitro and in vivo study

Author: Tristan Montier, Philippe Guégan, Sandrine Quemener, Kévin Pluchon, Juliette Ropars, Chantal Pichon, Tanguy Haute, Yann Thierry Le Guen, Tony Le Gall, Patrick Midoux, Gestionnaire, Hal Sorbonne Université, monopDNA-Nanoparticules Virus-Inspirées pour transfert de gènes. - - VINP2017 - ANR-17-CE18-0015 - AAPG2017 - VALID, Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Parisien de Chimie Moléculaire (IPCM), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Chimie des polymères (LCP), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut Parisien de Chimie Moléculaire (IPCM), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Chimie Moléculaire de Paris Centre (FR 2769), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires (RNMCD - U1011), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), This work was funded by grants from the AFM – Association Française contre les Myopathies (project no. AFM2017#20609, AFM, Evry, France), the ANR – Agence Nationale de la Recherche (project no. ANR-17-CE18-0015-03, 'monopDNA-Nanoparticules Virus-Inspirées pour transfert de gènes', ANR, Paris, France), the Association de Transfusion Sanguine et de Biogénétique Gaétan Saleün (Brest, France), and the Région Bretagne (France). The Service Général des Plateformes, Animalerie Commune (Brest, France) and SynNanoVect (Brest-Rennes, France) are also acknowledged. Y.T.L.G. was a recipient of a PhD fellowship from the French Ministry of Higher Education, Research and Innovation., ANR-17-CE18-0015,VINP,monopDNA-Nanoparticules Virus-Inspirées pour transfert de gènes.(2017), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Chimie Moléculaire de Paris Centre (FR 2769), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), and Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD)
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], RM1-950, NF-κB, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, plasmid DNA, In vivo, Drug Discovery, skeletal muscle, Transcription factor, hydrodynamic limb vein injection, Transfection, nuclear import, In vitro, Cell biology, [SDV] Life Sciences [q-bio], 030104 developmental biology, chemistry, transfection, Cell culture, 030220 oncology & carcinogenesis, Nucleic acid, Molecular Medicine, Therapeutics. Pharmacology, Nuclear transport, DNA
Abstract: International audience; An important bottleneck for non-viral gene transfer commonly relates to translocation of nucleic acids into the nuclear compartment of target cells. So-called 3NFs are optimized short nucleotide sequences able to interact with the transcription factor nuclear factor κB (NF-κB), which can enhance the nuclear import of plasmid DNA (pDNA) carrying such motifs. In this work, we first designed a consistent set of six pDNAs featuring a common backbone and only varying in their 3NF sequences. These constructions were then transfected under various experimental settings. In vitro, cationic polymer-assisted pDNA delivery in five human-derived cell lines showed the potential advantage of 3NF carrying pDNA in diverse cellular contexts. In vivo, naked pDNAs were hydrodynamically delivered to muscle hindlimbs in healthy mice; this direct accurate comparative (in the absence of any gene carrier) revealed modest but consistent trends in favor of the pDNAs equipped with 3NF. In summary, the results reported emphasize the implications of various parameters on NF-κB-mediated pDNA nuclear import; under specific conditions, 3NF can provide modest to substantial advantages for pDNA gene transfer, in vitro as well as in vivo. This study thus further underscores the potential of optimized nuclear import for more efficient non-viral gene transfer applications.
Published: 2021

44. Three‐dimensional structures of avian beta‐microseminoproteins: insight from the chicken egg‐specific beta‐microseminoprotein 3 paralog

Author: Bertrand Castaing, Mégane Bregeon, Valérie Labas, Magali Chessé, Karine Loth, Nicolas Guyot, Hervé Meudal, Thierry Moreau, Sophie Réhault-Godbert, Franck Coste, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Biologie des Oiseaux et Aviculture (BOA), Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Plate-forme Phénotypage par imagerie in/ex vivo de l'Animal à la Molécule (Plate-forme PIXANIM), Université de Tours-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université d'Orléans (UO), Région Centre Val de Loire : MUSE Project (Grant No. 2014-00094512) and Grant No. 2013-00082978, European Regional Development Fund (ERDF): SMHART Project, 35069, Conseil Régional du Centre, INRAE, INSERM, ANR-11-BSV5-0020,SPOREPAIR,Caractérisation d'une enzyme radicalaire de réparation de l'ADN : la lyase du photoproduit des spores(2011), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Tours (UT)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), REHAULT-GODBERT, Sophie, BLANC - Caractérisation d'une enzyme radicalaire de réparation de l'ADN : la lyase du photoproduit des spores - - SPOREPAIR2011 - ANR-11-BSV5-0020 - BLANC - VALID, Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Models, Molecular, 0301 basic medicine, crystal structure, animal structures, QH301-705.5, Eggs, [SDV]Life Sciences [q-bio], Crystallography, X-Ray, Proteomics, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Affinity chromatography, Animals, MSMB, Amino Acid Sequence, paralogs, Biology (General), Research Articles, biology, Phylogenetic tree, Embryogenesis, Prostatic Secretory Proteins, biology.organism_classification, [SDV] Life Sciences [q-bio], 030104 developmental biology, Biochemistry, 030220 oncology & carcinogenesis, Neognathae, birds, beta‐microseminoproteins, egg, Chickens, Sequence Alignment, MSMB3, Function (biology), Research Article, Egg white
Abstract: Beta‐microseminoproteins (MSMBs) are small disulfide‐rich proteins that are conserved among vertebrates. These proteins exhibit diverse biological activities and were mainly reported to play a role in male fertility, immunity, and embryogenesis. In this work, we focused on the chicken MSMB3 protein that was previously depicted as an egg antibacterial protein. We report that MSMB3 protein is exclusively expressed in the reproductive tissues of laying hens (in contrast to chicken MSMB1 and MSMB2 paralogs), to be incorporated in the egg white during the process of egg formation. We also showed that chicken MSMB3 possesses highly conserved orthologs in bird species, including Neognathae and Palaeognathae. Chicken MSMB3 was purified from egg white using heparin affinity chromatography and was analyzed by top‐down and bottom‐up proteomics. Several proteoforms could be characterized, and a homodimer was further evidenced by NMR spectroscopy. The X‐ray structure of chicken MSMB3 was solved for the first time, revealing that this protein adopts a novel dimeric arrangement. The highly cationic MSMB3 protein exhibits a distinct electrostatic distribution compared with chicken MSMB1 and MSMB2 structural models, and with published mammalian MSMB structures. The specific incorporation of MSMB3 paralog in the egg, and its phylogenetic conservation in birds together with its peculiar homodimer arrangement and physicochemical properties, suggests that the MSMB3 protein has evolved to play a critical role during the embryonic development of avian species. These new data are likely to stimulate research to elucidate the structure/function relationships of MSMB paralogs and orthologs in the animal kingdom., Beta‐microseminoproteins (MSMBs) are small proteins conserved among vertebrates. The chicken genome contains three MSMB paralogs, which exhibit distinct tissue expression profiles, with chicken beta‐MSMB 3 (MSMB3) protein being egg‐specific. Collectively, results from protein sequence analysis, mass spectrometry analysis, and 3D structure data highlight that chicken MSMB3 possesses specific features that may be related to its presumed role in avian reproduction.
Published: 2021

45. Molecular Aspects concerning the Use of the SARS-CoV-2 Receptor Binding Domain as a Target for Preventive Vaccines

Author: Yury Valdés-Balbín, Fabrizio Chiodo, Lila Castellanos-Serra, Françoise Paquet, Belinda Sánchez Ramírez, Yanet Climent, Sonsire Fernández, Laura Rodriguez, Kalet León, Vicente Verez-Bencomo, Daniel G. Rivera, Guang-Wu Chen, Darielys Santana-Mederos, Raine Garrido, Dagmar García-Rivera, Tays Hernández, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Molecular cell biology and Immunology, and Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: General Chemical Engineering, [SDV]Life Sciences [q-bio], Biology, 010402 general chemistry, 01 natural sciences, Epitope, Neutralization, Virus, law.invention, Immune system, Antigen, law, Neutralizing antibody, QD1-999, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, 010405 organic chemistry, General Chemistry, Virology, 3. Good health, 0104 chemical sciences, Chemistry, chemistry, Recombinant DNA, biology.protein, Glycoprotein, Outlook
Abstract: The development of recombinant COVID-19 vaccines has resulted from scientific progress made at an unprecedented speed during 2020. The recombinant spike glycoprotein monomer, its trimer, and its recombinant receptor-binding domain (RBD) induce a potent anti-RBD neutralizing antibody response in animals. In COVID-19 convalescent sera, there is a good correlation between the antibody response and potent neutralization. In this review, we summarize with a critical view the molecular aspects associated with the interaction of SARS-CoV-2 RBD with its receptor in human cells, the angiotensin-converting enzyme 2 (ACE2), the epitopes involved in the neutralizing activity, and the impact of virus mutations thereof. Recent trends in RBD-based vaccines are analyzed, providing detailed insights into the role of antigen display and multivalence in the immune response of vaccines under development., SARS-CoV-2 receptor-binding domain (RBD)-specific antibodies are crucial for neutralizing efficacy. Emerging mutations, the quality of the IgG response, and the benefit of multivalent display are analyzed here for RBD subunit vaccines.
Published: 2021

46. Reproducibility and accuracy of microscale thermophoresis in the NanoTemper Monolith: a multi laboratory benchmark study

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

47. Metal-based environment-sensitive MRI contrast agents

Author: Éva Tóth, Célia S. Bonnet, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Bonnet, Célia, and Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
Subjects: 0301 basic medicine, Materials science, medicine.diagnostic_test, Cation detection, [SDV]Life Sciences [q-bio], Responsive probes, Contrast Media, Transition metal, Magnetic resonance imaging, Nanotechnology, 010402 general chemistry, Magnetic Resonance Imaging, 01 natural sciences, Biochemistry, 0104 chemical sciences, Analytical Chemistry, [SDV] Life Sciences [q-bio], 03 medical and health sciences, Preclinical research, 030104 developmental biology, Metal complexes, medicine, Molecular mri, MRI
Abstract: International audience; Interactions of paramagnetic metal complexes with their biological environment can modulate their magnetic resonance imaging (MRI) contrast-enhancing properties in different ways, and this has been widely exploited to create responsive probes that can provide biochemical information. We survey progress in two rapidly growing areas: the MRI detection of biologically important metal ions, such as calcium, zinc, and copper, and the use of transition metal complexes as smart MRI agents. In both fields, new imaging technologies, which take advantage of other nuclei (19F) and/or paramagnetic contact shift effects, emerge beyond classical, relaxation-based applications. Most importantly, in vivo imaging is gaining ground, and the promise of molecular MRI is becoming reality, at least for preclinical research.
Published: 2021

48. Functionalized single-walled carbon nanotubes containing traces of iron as new negative MRI contrast agents for in vivo imaging

Author: Doan , Bich-Thuy, Seguin , Johanne, Breton , Marie, Le Beherec , Ronan, Bessodes , Michel, Rodríguez-Manzo , Julio A, Banhart , Florian, Beloeil , Jean-Claude, Scherman , Daniel, Richard , Cyrille, Unité de pharmacologie chimique et génétique et d'imagerie (UPCGI - UMR 8151 / UMR_S 1022 ), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Institut de Physique et Chimie des Matériaux de Strasbourg (IPCMS), Université de Strasbourg (UNISTRA)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-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)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-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)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-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), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de physique et de chimie des matériaux (IPCM), Unité de pharmacologie chimique et génétique et d'imagerie ( UPCGI - UMR 8151 / UMR_S 1022 ), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de biophysique moléculaire ( CBM ), Université d'Orléans ( UO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), and Institut de physique et de chimie des matériaux ( IPCM )
Subjects: MESH: Cell Death, Contrast Media, MESH : Iron, TOXICITY, MESH: Magnetic Resonance Imaging, X-Ray Diffraction, BIODISTRIBUTION, MAGNETIC-RESONANCE, MRI contrast agents, NANOPARTICLES, MESH: Animals, Lung, MESH: Iron, Cell Death, MESH : Hep G2 Cells, MESH: X-Ray Diffraction, Hep G2 Cells, Magnetic Resonance Imaging, CANCER, in vivo, Liver, MESH: Nanotubes, Carbon, MESH : Imaging, Three-Dimensional, functionalization, TOXICOLOGY, MESH : Lung, Iron, MESH: Hep G2 Cells, MESH: Imaging, Three-Dimensional, MESH : X-Ray Diffraction, Imaging, Three-Dimensional, MESH : Magnetic Resonance Imaging, MESH: Contrast Media, MESH : Mice, Animals, Humans, MESH: Lung, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, MESH : Contrast Media, MESH: Humans, carbon nanotubes, Nanotubes, Carbon, MESH : Humans, MESH : Liver, TRANSPORTERS, GADONANOTUBES, MICE, MESH : Cell Death, traces of iron, ENHANCED MRI, MESH : Nanotubes, Carbon, MESH : Animals, MESH: Liver
Abstract: International audience; Single-walled carbon nanotubes (SWCNTs) containing traces of iron oxide were functionalized by noncovalent lipid-PEG or covalent carboxylic acid function to supply new efficient MRI contrast agents for in vitro and in vivo applications. Longitudinal (r(1)) and transversal (r(2)) water proton relaxivities were measured at 300 MHz, showing a stronger T(2) feature as an MRI contrast agent (r(2)/r(1) = 190 for CO(2) H functionalisation). The r(2) relaxivity was demonstrated to be correlated to the presence of iron oxide in the SWNT-carboxylic function COOH, in comparison to iron-free ones. Biodistribution studies on mice after a systemic injection showed a negative MRI contrast in liver, suggesting the presence of the nanotubes in this organ until 48 h after i.v. injection. The presence of carbon nanotubes in liver was confirmed after ex vivo carbon extraction. Finally, cytotoxicity studies showed no apparent effect owing to the presence of the carbon nanotubes. The functionalized carbon nanotubes were well tolerated by the animals at the dose of 10 µg g(-1) body weight.
Published: 2012

49. Synthesis and Structure-Activity Relationships of Constrained Heterocyclic Analogues of Combretastatin A4

Author: Lionel Quentin, Luc Morin-Allory, Renée Pontikis, Jean-Claude Florent, Stéphane Bourg, Johanne Seguin, Guy G. Chabot, Martin Arthuis, Institut Curie [Paris], Conception, synthèse et vectorisation de biomolécules. (CSVB), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris], Unité de pharmacologie chimique et génétique et d'imagerie (UPCGI - UMR 8151 / UMR_S 1022 ), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC), Institut de Chimie Organique et Analytique (ICOA), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Orléans (UO)-Institut de Chimie du CNRS (INC), Compartimentation et dynamique cellulaires (CDC), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut Curie, Institut Curie-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Curie-Université Pierre et Marie Curie - Paris 6 (UPMC), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-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 d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Conception, synthèse et vectorisation de biomolécules. ( CSVB ), INSTITUT CURIE-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ), Unité de pharmacologie chimique et génétique et d'imagerie ( UPCGI - UMR 8151 / UMR_S 1022 ), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de biophysique moléculaire ( CBM ), Université d'Orléans ( UO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Chimie Organique et Analytique ( ICOA ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université d'Orléans ( UO ), Compartimentation et dynamique cellulaires ( CDC ), and Centre National de la Recherche Scientifique ( CNRS ) -INSTITUT CURIE-Université Pierre et Marie Curie - Paris 6 ( UPMC )
Subjects: Angiogenesis Inhibitors, MESH: Tubulin, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, MESH : Palladium, 01 natural sciences, Biochemistry, Mice, chemistry.chemical_compound, 0302 clinical medicine, MESH: Structure-Activity Relationship, Heterocyclic Compounds, Tubulin, MESH: Stilbenes, MESH : Structure-Activity Relationship, Stilbenes, Drug Discovery, MESH : Catalysis, Moiety, MESH: Animals, MESH: Endothelial Cells, General Pharmacology, Toxicology and Pharmaceutics, ComputingMilieux_MISCELLANEOUS, MESH: Angiogenesis Inhibitors, chemistry.chemical_classification, Biological activity, MESH : Tubulin, MESH : Antineoplastic Agents, 030220 oncology & carcinogenesis, Lactam, Molecular Medicine, MESH: Palladium, Palladium, Lactone, MESH: Cell Line, Tumor, MESH: Heterocyclic Compounds, Stereochemistry, Antineoplastic Agents, Ring (chemistry), Catalysis, MESH : Stilbenes, Structure-Activity Relationship, 03 medical and health sciences, Cell Line, Tumor, MESH : Mice, MESH : Angiogenesis Inhibitors, Animals, Humans, Structure–activity relationship, Oxindole, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, Pharmacology, Combretastatin, MESH: Humans, MESH : Cell Line, Tumor, MESH : Endothelial Cells, 010405 organic chemistry, MESH : Humans, Organic Chemistry, Endothelial Cells, MESH: Catalysis, 0104 chemical sciences, MESH : Heterocyclic Compounds, chemistry, MESH: Antineoplastic Agents, MESH : Animals
Abstract: International audience; A series of combretastatin A4 (CA4) analogues with a lactam or lactone ring fused to the trimethoxyphenyl or the B-phenyl moiety were synthesized in an efficient and stereoselective manner by using a domino Heck-Suzuki-Miyaura coupling reaction. The vascular-disrupting potential of these conformationally restricted CA4 analogues was assessed by various in vitro assays: inhibition of tubulin polymerization, modification of endothelial cell morphology, and disruption of endothelial cell cords. Compounds were also evaluated for their growth inhibitory effects against murine and human tumor cells. B-ring-constrained derivatives that contain an oxindole ring (in contrast to compounds with a benzofuranone ring) as well as analogues bearing a six-membered lactone core fused to the trimethoxyphenyl ring are endowed with significant biological activity. The most potent compound of this series (oxindole 9 b) is of particular interest, as it combines chemical stability and a biological activity profile characteristic of a vascular-disrupting agent.
Published: 2011

50. The Sm-like RNA chaperone Hfq mediates transcription antitermination at Rho-dependent terminators

Author: Rabhi, Makhlouf, Espéli, Olivier, Schwartz, Annie, Cayrol, Bastien, Rahmouni, a Rachid, Arluison, Véronique, Boudvillain, Marc, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Laboratoire Bioénergétique Membranaire et Stress (LBMS), Département Biochimie, Biophysique et Biologie Structurale (B3S), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre de biophysique moléculaire ( CBM ), Université d'Orléans ( UO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Bioénergétique, Métalloprotéines et Stress ( LBMS ), Département Biochimie, Biophysique et Biologie Structurale ( B3S ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), and Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH : Escherichia coli, MESH : Molecular Sequence Data, Transcription, Genetic, MESH : Transcription Factors, MESH: Peptide Elongation Factors, Molecular Sequence Data, Electrophoretic Mobility Shift Assay, MESH: Terminator Regions, Genetic, MESH: Escherichia coli Proteins, MESH: Host Factor 1 Protein, Host Factor 1 Protein, MESH: Base Sequence, Article, Escherichia coli, MESH: Adenosine Triphosphatases, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Peptide Elongation Factors, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Adenosine Triphosphatases, Terminator Regions, Genetic, MESH: Gene Expression Regulation, Bacterial, MESH: Molecular Sequence Data, Base Sequence, MESH : Adenosine Triphosphatases, MESH : Terminator Regions, Genetic, MESH: RNA Helicases, MESH: Escherichia coli, Escherichia coli Proteins, MESH : Escherichia coli Proteins, MESH: Transcription, Genetic, MESH : Host Factor 1 Protein, MESH : Molecular Chaperones, MESH : Transcription, Genetic, Gene Expression Regulation, Bacterial, MESH: Transcription Factors, MESH : RNA, Bacterial, Peptide Elongation Factors, MESH : RNA Helicases, RNA, Bacterial, MESH : Electrophoretic Mobility Shift Assay, MESH: Electrophoretic Mobility Shift Assay, MESH : Base Sequence, MESH: Molecular Chaperones, MESH: RNA, Bacterial, RNA Helicases, Molecular Chaperones, Transcription Factors, MESH : Gene Expression Regulation, Bacterial
Abstract: International audience; In Escherichia coli, the essential motor protein Rho promotes transcription termination in a tightly controlled manner that is not fully understood. Here, we show that the general post-transcriptional regulatory protein Hfq associates with Rho to regulate Rho function. The Hfq:Rho complex can be further stabilized by RNA bridging both factors in a configuration that inhibits the ATP hydrolysis and duplex unwinding activities of Rho and that mediates transcription antitermination at Rho-dependent terminators in vitro and in vivo. Antitermination at a prototypical terminator (λtR1) requires Hfq binding to an A/U-rich transcript region directly upstream from the terminator. Antitermination is modulated by trans-acting factors (NusG or nucleic acid competitors) that affect Hfq association with Rho or RNA. These data unveil a new Hfq function and a novel transcription regulatory mechanism with potentially important implications for bacterial RNA metabolism, gene silencing, and pathogenicity.
Published: 2011

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2,625 results on '"Centre de biophysique moléculaire (CBM)"'

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