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Perot S.,University Paris Diderot | Sperandio O.,University Paris Diderot | Sperandio O.,Igm Web Inc. | Miteva M.A.,University Paris Diderot | And 3 more authors.
Drug Discovery Today | Year: 2010

Detection, comparison and analyses of binding pockets are pivotal to structure-based drug design endeavors, from hit identification, screening of exosites and de-orphanization of protein functions to the anticipation of specific and non-specific binding to off- and anti-targets. Here, we analyze protein-ligand complexes and discuss methods that assist binding site identification, prediction of druggability and binding site comparison. The full potential of pockets is yet to be harnessed, and we envision that better understanding of the pocket space will have far-reaching implications in the field of drug discovery, such as the design of pocket-specific compound libraries and scoring functions. © 2010 Elsevier Ltd.

Chalabaev S.,Institute Pasteur Paris | Chauhan A.,Institute Pasteur Paris | Novikov A.,University Paris - Sud | Novikov A.,Igm Web Inc. | And 5 more authors.
mBio | Year: 2014

Bacterial biofilm communities are associated with profound physiological changes that lead to novel properties compared to the properties of individual (planktonic) bacteria. The study of biofilm-associated phenotypes is an essential step toward control of deleterious effects of pathogenic biofilms. Here we investigated lipopolysaccharide (LPS) structural modifications in Escherichia coli biofilm bacteria, and we showed that all tested commensal and pathogenic E. coli biofilm bacteria display LPS modifications corresponding to an increased level of incorporation of palmitate acyl chain (palmitoylation) into lipid A compared to planktonic bacteria. Genetic analysis showed that lipid A palmitoylation in biofilms is mediated by the PagP enzyme, which is regulated by the histone-like protein repressor H-NS and the SlyA regulator. While lipid A palmitoylation does not influence bacterial adhesion, it weakens inflammatory response and enhances resistance to some antimicrobial peptides. Moreover, we showed that lipid A palmitoylation increases in vivo survival of biofilm bacteria in a clinically relevant model of catheter infection, potentially contributing to biofilm tolerance to host immune defenses. The widespread occurrence of increased lipid A palmitoylation in biofilms formed by all tested bacteria suggests that it constitutes a new biofilm-associated phenotype in Gram-negative bacteria.Importance Bacterial communities called biofilms display characteristic properties compared to isolated (planktonic) bacteria, suggesting that some molecules could be more particularly produced under biofilm conditions. We investigated biofilmassociated modifications occurring in the lipopolysaccharide (LPS), a major component of all Gram-negative bacterial outer membrane. We showed that all tested commensal and pathogenic biofilm bacteria display high incorporation of a palmitate acyl chain into the lipid A part of LPS. This lipid A palmitoylation is mediated by the PagP enzyme, whose expression in biofilm is controlled by the regulatory proteins H-NS and SlyA. We also showed that lipid A palmitoylation in biofilm bacteria reduces host inflammatory response and enhances their survival in an animal model of biofilm infections. While these results provide new insights into the biofilm lifestyle, they also suggest that the level of lipid A palmitoylation could be used as an indicator to monitor the development of biofilm infections on medical surfaces. © 2014 Chalabaev et al.

Basantes-Serrano R.,University Grenoble Alpes | Basantes-Serrano R.,French National Center for Scientific Research | Rabatel A.,University Grenoble Alpes | Rabatel A.,French National Center for Scientific Research | And 9 more authors.
Journal of Glaciology | Year: 2016

In this paper, we reanalyze the glacier mass balance on Glaciar Antisana 15α over the 1995-2012 period. Annual glacier mass balances were quantified on the basis of monthly glaciological measurements using an adaptation of Lliboutry's statistical approach. The geodetic mass balance was computed between 1997 and 2009 giving a cumulative balance of -1.39 ± 1.97 m w.e. and a slightly negative adjusted annual glaciological mass balance (-0.12 ± 0.16 m w.e. a-1). Despite a careful analysis of uncertainties, we found a large discrepancy between the cumulative glaciological and the geodetic mass balances over the common period, of 4.66 m w.e. This discrepancy can mainly be explained by underestimated net accumulation in the glacier upper reaches, which could be due to the peculiar climate conditions of the equatorial zone with year round accumulation, thereby preventing clear identification of annual layers. An increase of ∼70% in measured rates of net accumulation would be needed to balance the glaciological and geodetic mass balances; a hypothesis confirmed by estimated ice flux in the vicinity of the ELA. Consequently, the vertical gradient of precipitation may be higher than previously estimated and the accumulation processes (including the role of frost deposition) need to be carefully analyzed. © The Author(s) 2016.

Novikov A.,University Paris - Sud | Novikov A.,Igm Web Inc. | Shah N.R.,University of British Columbia | Albitar-Nehme S.,University Paris - Sud | And 10 more authors.
Innate Immunity | Year: 2014

Endotoxin is recognized as one of the virulence factors of the Bordetella avium bird pathogen, and characterization of its structure and corresponding genomic features are important for an understanding of its role in pathogenicity and for an improved general knowledge of Bordetella spp virulence factors. The structure of the biologically active part of B. avium LPS, lipid A, is described and compared to those of another bird pathogen, opportunistic in humans, Bordetella hinzii, and to that of Bordetella trematum, a human pathogen. Sequence analyses showed that the three strains have homologues of acyl-chain modifying enzymes PagL, PagP and LpxO, of the 1-phosphatase LpxE, in addition to LgmA, LgmB and LgmC, which are required for the glucosamine modification. MALDI mass spectrometry identified a high amount of glucosamine substituting the phosphate groups of B. avium lipid A; this modification was absent from B. hinzii and B. trematum. The acylation patterns of the three lipid As were similar, but they differed from those of Bordetella pertussis and Bordetella parapertussis. They were also found to be close to the lipid A structure of Bordetella bronchiseptica, a mammalian pathogen, only differing from the latter by the degree of hydroxylation of the branched fatty acid. © The Author(s) 2013.

Mathew K.T.,Cochin University of Science and Technology | Kalappura U.G.,Cochin University of Science and Technology | Augustine R.,Igm Web Inc. | Jean-Marc L.,Igm Web Inc. | Lakshmi K.,Cochin University of Science and Technology
Microwave and Optical Technology Letters | Year: 2010

Conducting polymers have found significant applications in the past decade in industrial, scientific, and medical (ISM) fields. The characteristic features of conducting polymers like reversible proton doping, variable conductivity, facile synthesis, and low cost make them potential candidates in various microelectronic applications. Conventional microwave absorbing materials such as carbon and graphite in the powder form were blended with polyaniline as base at different proportions and microwave properties such as transmission, reflection, and shielding efficiency (SE) were evaluated from S parameter measurements using HP 8714ET network analyzer. The newly developed polyaniline blend exhibits high-electromagnetic interference shielding efficiency when compared with previously developed materials and is a promising candidate for shielding applications. © 2009 Wiley Periodicals, Inc.

Frassetto A.,University of Trieste | Navarra C.O.,University of Trieste | Marchesi G.,University of Trieste | Turco G.,University of Trieste | And 5 more authors.
Dental Materials | Year: 2012

Objectives: The aim of the study was to evaluate the contraction stress, microhardness and polymerization kinetics of three self-adhesive cements vs. conventional dual-cure resin cement. Methods: Cements tested were: RelyX Unicem (3M ESPE, St. Paul, MN, USA), MaxCem Elite (Kerr, Orange, CA, USA), Clearfil SA Cement (Kuraray, Tokyo, Japan) and Duolink (Bisco Inc., Schaumburg, IL, USA). Cements were irradiated with a LED-curing unit (bluephase, IvoclarVivadent) for 20 or 40 s and the contraction forces (N) generated during polymerization were continuously recorded for 6 h with a universal testing machine. Polymerization kinetics were monitored using micro-Raman spectroscopy and degree of conversion was calculated. Vickers microhardness was also recorded. All measurements were performed at 10 min and 6 h. Data were statistically analyzed by three-way ANOVA with repeated measures and Tukey's post hoc test (α = 0.05). Results: Irrespective of exposure time, stress analysis ranked in the following order: Clearfil SA Cement < MaxCem < RelyX Unicem ≤ Duolink (p < 0.05). Stress was correlated with microhardness values (p < 0.05). Kinetic curves showed that maximum degree of conversion was attained more quickly than maximum stress after light activation. Significance: The conventional resin-based cement showed higher stress values than the self-adhesive cements. The results were material-dependent and probably correlated to the composition of each material. © 2012 Academy of Dental Materials.

Colonna M.,University of Bologna | Breschi M.,University of Bologna | Mazzoni A.,University of Bologna | Mazzoni A.,Rizzoli Orthopaedic Institute | And 8 more authors.
Dental Materials | Year: 2011

Objectives: The application of an electric field has been shown to positively influence the bonding of dentin bonding systems (DBS) by improving adhesive impregnation into dentin. However, the mechanism responsible for this phenomenon has not been completely elucidated. The aim of this study was to clarify the effects of pH, matrix ionic strength, and applied voltage on the migration of commonly used DBS monomers in a model matrix (agarose gel). Methods: Some common monomers examined were bis-GMA (2,2-bis[4-(2-hydroxy-3- methacryloyloxy propoxy) phenyl] propane); HEMA (2-hydroxyethyl methacrylate); 2-MP (bis[2-(methacryloyloxy) ethyl] phosphate); TCDM [di(hydroxyethyl methacrylate) ester of 5-(2,5,-dioxo tetrahydrofurfuryl)-3-methyl-3- cyclohexenyl-1,2-dicarboxylic acid]; and TEGDMA (triethylene glycol dimethacrylate). Agarose gels poured into a horizontal 10-well electrophoretic cell were used to mimic the collagen fibrils of the dentin organic matrix. The role of pH, matrix ionic strength, and voltage on monomer migration was assayed by modifying the experimental conditions. Results: Results of experiments performed at pH 3.1, 6.3, 8.5, and 12.3; at low, medium, and high ionic strength; and at 50 and 100 V clearly showed that DBA monomer migration toward both the anode and the cathode can be affected by each of these parameters. Significance: Migration of acrylic monomers toward the anode or cathode can be achieved as desired by selective choice of pH, ionic strength, and applied voltage. Additional studies are needed to evaluate the synergistic effects of DBS monomer blends on migration in an electric field. © 2011 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Molina A.,French Institute of Health and Medical Research | Molina A.,French National Center for Scientific Research | Molina A.,University of Paris Descartes | Velot L.,French Institute of Health and Medical Research | And 42 more authors.
Cancer Research | Year: 2013

Metastasis, a fatal complication of breast cancer, does not fully benefit from available therapies. In this study, we investigated whether ATIP3, the major product of 8p22 MTUS1 gene, may be a novel biomarker and therapeutic target for metastatic breast tumors. We show that ATIP3 is a prognostic marker for overall survival among patients with breast cancer. Notably, among metastatic tumors, low ATIP3 levels associate with decreased survival of the patients. By using a well-defined experimental mouse model of cancer metastasis, we show that ATIP3 expression delays the time-course of metastatic progression and limits the number and size of metastases in vivo. In functional studies, ATIP3 silencing increases breast cancer cell migration, whereas ATIP3 expression significantly reduces cell motility and directionality. We report here that ATIP3 is a potent microtubule-stabilizing protein whose depletion increases microtubule dynamics. Our data support the notion that by decreasing microtubule dynamics, ATIP3 controls the ability of microtubule tips to reach the cell cortex during migration, a mechanism that may account for reduced cancer cell motility and metastasis. Of interest, we identify a functional ATIP3 domain that associates with microtubules and recapitulates the effects of ATIP3 on microtubule dynamics, cell proliferation, and migration. Our study is a major step toward the development of new personalized treatments against metastatic breast tumors that have lost ATIP3 expression. Cancer Res; 73(9); 2905-15. © 2013 AACR.

Saro C.,University of León | Ranilla M.J.,University of León | Ranilla M.J.,Igm Web Inc. | Cifuentes A.,CSIC - Mediterranean Institute for Advanced Studies | And 2 more authors.
Journal of Animal Science | Year: 2014

The aim of this study was to compare automated ribosomal intergenic spacer analysis (ARISA) and denaturing gradient gel electrophoresis (DGGE) techniques to assess bacterial diversity in the rumen of sheep. Sheep were fed 2 diets with 70% of either alfalfa hay or grass hay, and the solid (SOL) and liquid (LIQ) phases of the rumen were sampled immediately before feeding (0 h) and at 4 and 8 h postfeeding. Both techniques detected similar differences between forages, with alfalfa hay promoting greater (P < 0.05) bacterial diversity than grass hay. In contrast, whereas ARISA analysis showed a decrease (P < 0.05) of bacterial diversity in SOL at 4 h postfeeding compared with 0 and 8 h samplings, no variations (P > 0.05) over the postfeeding period were detected by DGGE. The ARISA technique showed lower (P < 0.05) bacterial diversity in SOL than in LIQ samples at 4 h postfeeding, but no differences (P > 0.05) in bacterial diversity between both rumen phases were detected by DGGE. Under the conditions of this study, the DGGE was not sensitive enough to detect some changes in ruminal bacterial communities, and therefore ARISA was considered more accurate for assessing bacterial diversity of ruminal samples. The results highlight the influence of the fingerprinting technique used to draw conclusions on factors affecting ruminal bacterial diversity. © 2014 American Society of Animal Science. All rights reserved.

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