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Start Over Author "CIS BIOINTERNATIONAL" Topic 030304 developmental biology
5 results on '"CIS BIOINTERNATIONAL"'

1. Functioning of the dimeric GABAB receptor extracellular domain revealed by glycan wedge scanning

Author

Fanny Malhaire, Jianfeng Liu, Carine Monnier, Jean-Philippe Pin, Philippe Rondard, Bertrand Blanchard, Eric Trinquet, Ying Li, Nadia Oueslati, Gilles Labesse, Siluo Huang, Haijun Tu, Rondard, Philippe, Institut de Génomique Fonctionnelle (IGF), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sino-France Laboratory for Drug Screening, Huazhong University of Science and Technology [Wuhan] (HUST), Cisbio, Research Department, CIS BIOINTERNATIONAL, 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), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Models, Molecular, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Plasma protein binding, Protein Structure, Secondary, 0302 clinical medicine, Chlorocebus aethiops, Fluorescence Resonance Energy Transfer, Receptor, gamma-Aminobutyric Acid, 0303 health sciences, General Neuroscience, Transmembrane domain, Biochemistry, COS Cells, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurons and Cognition (q-bio.NC), Dimerization, Protein Binding, Agonist, G protein, medicine.drug_class, Blotting, Western, Allosteric regulation, Enzyme-Linked Immunosorbent Assay, Biology, GABAB receptor, Transfection, Article, General Biochemistry, Genetics and Molecular Biology, Cell Line, Structure-Activity Relationship, 03 medical and health sciences, Allosteric Regulation, Polysaccharides, medicine, Animals, Humans, Immunoprecipitation, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Molecular Biology, 030304 developmental biology, G protein-coupled receptor, Binding Sites, General Immunology and Microbiology, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Computational Biology, Biomolecules (q-bio.BM), Protein Structure, Tertiary, Receptors, GABA-B, nervous system, Quantitative Biology - Biomolecules, FOS: Biological sciences, Quantitative Biology - Neurons and Cognition, Biophysics, 030217 neurology & neurosurgery
Abstract

International audience; The G-protein-coupled receptor (GPCR) activated by the neurotransmitter GABA is made up of two subunits, GABA(B1) and GABA(B2). GABA(B1) binds agonists, whereas GABA(B2) is required for trafficking GABA(B1) to the cell surface, increasing agonist affinity to GABA(B1), and activating associated G proteins. These subunits each comprise two domains, a Venus flytrap domain (VFT) and a heptahelical transmembrane domain (7TM). How agonist binding to the GABA(B1) VFT leads to GABA(B2) 7TM activation remains unknown. Here, we used a glycan wedge scanning approach to investigate how the GABA(B) VFT dimer controls receptor activity. We first identified the dimerization interface using a bioinformatics approach and then showed that introducing an N-glycan at this interface prevents the association of the two subunits and abolishes all activities of GABA(B2), including agonist activation of the G protein. We also identified a second region in the VFT where insertion of an N-glycan does not prevent dimerization, but blocks agonist activation of the receptor. These data provide new insight into the function of this prototypical GPCR and demonstrate that a change in the dimerization interface is required for receptor activation.

Published
2008
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2. In Vitro Models for the Study of the Intracellular Activity of Antibiotics

Author

Julien M. Buyck, Cristina Seral, Sandrine Lemaire, Paul M. Tulkens, Ahalieyah Anantharajah, Frédéric Peyrusson, Françoise Van Bambeke, Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe de recherche Achac (ACHAC), Aix Marseille Université (AMU)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Lausanne (UNIL)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National des Langues et Civilisations Orientales (Inalco)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Université Sorbonne Nouvelle - Paris 3-Université de Lorraine (UL)-Université libre de Bruxelles (ULB), University of Zaragoza - Universidad de Zaragoza [Zaragoza], Cisbio, Research Department, CIS BIOINTERNATIONAL, Pharmacologie Cellulaire et Moléculaire [Brussels], Louvain Drug Research Institute [Bruxelles, Belgique] (LDRI), Université Catholique de Louvain = Catholic University of Louvain (UCL)-Université Catholique de Louvain = Catholic University of Louvain (UCL), Université Catholique de Louvain = Catholic University of Louvain (UCL), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Sorbonne Nouvelle - Paris 3-Université de Lausanne = University of Lausanne (UNIL)-Université de Rennes (UR)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Aix Marseille Université (AMU)-Université de Bordeaux (UB)-Institut National des Langues et Civilisations Orientales (Inalco)-Université libre de Bruxelles (ULB)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)

Subjects
0301 basic medicine, 0303 health sciences, medicine.drug_class, 030306 microbiology, Intracellular parasite, Phagocytosis, 030106 microbiology, Antibiotics, Biology, medicine.disease_cause, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, In vitro, Microbiology, 3. Good health, 03 medical and health sciences, Staphylococcus aureus, medicine, Gentamicin, Intracellular, Bacteria, ComputingMilieux_MISCELLANEOUS, medicine.drug, 030304 developmental biology
Abstract

Intracellular bacteria are poorly responsive to antibiotic treatment. Pharmacological studies are thus needed to determine which antibiotics are most potent or effective against intracellular bacteria as well as to explore the reasons for poor bacterial responsiveness. An in vitro pharmacodynamic model is described, consisting of (1) phagocytosis of pre-opsonized bacteria by eukaryotic cells; (2) elimination of non-internalized bacteria with gentamicin; (3) incubation of infected cells with antibiotics; and (4) determination of surviving bacteria by viable cell counting and normalization of the counts based on sample protein content.

Published
2016
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3. RX-P873, a Novel Protein Synthesis Inhibitor, Accumulates in Human THP-1 Monocytes and Is Active against Intracellular Infections by Gram-Positive (Staphylococcus aureus) and Gram-Negative (Pseudomonas aeruginosa) Bacteria

Author

Julien M. Buyck, Frédéric Peyrusson, Paul M. Tulkens, Françoise Van Bambeke, Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Cisbio, Research Department, CIS BIOINTERNATIONAL, Pharmacologie Cellulaire et Moléculaire [Brussels], Louvain Drug Research Institute [Bruxelles, Belgique] (LDRI), Université Catholique de Louvain = Catholic University of Louvain (UCL)-Université Catholique de Louvain = Catholic University of Louvain (UCL), and Université Catholique de Louvain = Catholic University of Louvain (UCL)

Subjects
Staphylococcus aureus, medicine.drug_class, Antibiotics, Moxifloxacin, Ceftazidime, Microbial Sensitivity Tests, Pyrimidinones, Staphylococcal infections, medicine.disease_cause, Guanidines, Monocytes, Microbiology, 03 medical and health sciences, Daptomycin, Ciprofloxacin, Vancomycin, Drug Resistance, Multiple, Bacterial, medicine, Humans, Pharmacology (medical), Pseudomonas Infections, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Pharmacology, Protein Synthesis Inhibitors, 0303 health sciences, biology, 030306 microbiology, Pseudomonas aeruginosa, Staphylococcal Infections, medicine.disease, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Anti-Bacterial Agents, Infectious Diseases, Bacteria, medicine.drug, Fluoroquinolones
Abstract

The pyrrolocytosine RX-P873, a new broad-spectrum antibiotic in preclinical development, inhibits protein synthesis at the translation step. The aims of this work were to study RX-P873's ability to accumulate in eukaryotic cells, together with its activity against extracellular and intracellular forms of infection by Staphylococcus aureus and Pseudomonas aeruginosa , using a pharmacodynamic approach allowing the determination of maximal relative efficacies ( E max values) and bacteriostatic concentrations ( C s values) on the basis of Hill equations of the concentration-response curves. RX-P873's apparent concentration in human THP-1 monocytes was about 6-fold higher than the extracellular one. In broth, MICs ranged from 0.125 to 0.5 mg/liter ( S. aureus ) and 2 to 8 mg/liter ( P. aeruginosa ), with no significant shift in these values against strains resistant to currently used antibiotics being noted. In concentration-dependent experiments, the pharmacodynamic profile of RX-P873 was not influenced by the resistance phenotype of the strains. E max values (expressed as the decrease in the number of CFU from that in the initial inoculum) against S. aureus and P. aeruginosa reached more than 4 log units and 5 log units in broth, respectively, and 0.7 log unit and 2.7 log units in infected THP-1 cells, respectively, after 24 h. C s values remained close to the MIC in all cases, making RX-P873 more potent than antibiotics to which the strains were resistant (moxifloxacin, vancomycin, and daptomycin for S. aureus ; ciprofloxacin and ceftazidime for P. aeruginosa ). Kill curves in broth showed that RX-P873 was more rapidly bactericidal against P. aeruginosa than against S. aureus . Taken together, these data suggest that RX-P873 may constitute a useful alternative for infections involving intracellular bacteria, especially Gram-negative species.

Published
2015
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4. Homogeneous Two-Site Immunometric Assay Kinetics as a Theoretical Tool for Data Analysis

Author

Jean-Pierre Flandrois, Emmanuel Zuber, Gérard Mathis, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Cisbio, Research Department, CIS BIOINTERNATIONAL, Bioinformatique, phylogénie et génomique évolutive (BPGE), Département PEGASE [LBBE] (PEGASE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE)

Subjects
Fluoroimmunoassay, Kinetics, Combined use, Biophysics, Analytical chemistry, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, 01 natural sciences, Biochemistry, Antigen-Antibody Reactions, 03 medical and health sciences, [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, medicine, Animals, Humans, Antigens, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Chromatography, medicine.diagnostic_test, Chemistry, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], 010401 analytical chemistry, Reproducibility of Results, Cell Biology, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Prolactin, 0104 chemical sciences, Models, Chemical, Nonlinear Dynamics, Evaluation Studies as Topic, Inflection point, Homogeneous, Data Interpretation, Statistical, Immunoassay, Data reduction
Abstract

The easily accessible kinetics of a new homogeneous two-site fluorometric immunoassay for prolactin was studied, in order to determine its usefulness for assay data reduction and optimization. The combined use of a simple descriptive model fitted to experimental data and a mechanistic model to simulate the kinetics revealed that (i) the kinetics curve presented an early inflexion point. Its time of occurrence was constant as long as the antigen concentration was below the smallest antibody concentration and decreased to zero for higher concentrations. It may therefore be used as an indicator of hooked samples. (ii) The kinetics steepest slope was correlated with antigen concentration. Its use as a dose–response curve variable would allow higher concentrations to be assayed than with the classical end-point dose–response curve. The results suggest that control and exploitation of kinetic parameters could help to improve the rapidity, analytical range, and reliability of homogeneous two-site immunometric assays.

Published
1997
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5. A Descriptive Model for the Kinetics of a Homogeneous Fluorometric Immunoassay

Author

Bruno Darbouret, Emmanuel Zuber, Francoise Socquet, Laurent Rosso, Gérard Mathis, Jean-Pierre Flandrois, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre Technique Interprofessionnel des Fruits et Légumes (CTIFL), Thermo Fisher Scientific [Nimes], Cisbio, Research Department, CIS BIOINTERNATIONAL, Bioinformatique, phylogénie et génomique évolutive (BPGE), Département PEGASE [LBBE] (PEGASE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE)

Subjects
Immunology, Gompertz function, Kinetics, Analytical chemistry, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, 01 natural sciences, 03 medical and health sciences, [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, medicine, Range (statistics), Statistical analysis, Fluorometry, Antigens, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Pharmacology, Immunoassay, 0303 health sciences, medicine.diagnostic_test, Chemistry, Kinetic information, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], 010401 analytical chemistry, Models, Immunological, Reproducibility of Results, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 0104 chemical sciences, Prolactin, Homogeneous, Regression Analysis, Biological system
Abstract

A descriptive mathematical model was chosen to fit the antigen-antibody association kinetics of a new homogeneous immunometric assay for prolactin, involving time-resolved fluorescence detection (TRACE® technology, Time Resolved Amplified Cryptate Emission). We paid special attention to the methodology and criteria applied, to yield a convenient and statistically valid model, designed to allow potential exploitation of kinetic information in the data processing of the assay. We compared specific parameterizations of an hyperbolic model, the Gompertz, and the monomolecular models on the basis of morphological considerations, a statistical analysis of fit, and an assessment of the parameters estimation quality, over a wide range of antigen concentrations. The monomolecular model gave the best fit, and the most precise and stable estimation of its parameters. The study of parameter properties confirmed this choice.

Published
1997
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