29 research outputs found

    Allosteric Regulation of Fibronectin/α5β1 Interaction by Fibronectin-Binding MSCRAMMs

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    Citation: Liang, X. W., Garcia, B. L., Visai, L., Prabhakaran, S., Meenan, N. A. G., Potts, J. R., . . . Hook, M. (2016). Allosteric Regulation of Fibronectin/alpha(5)beta(1) Interaction by Fibronectin-Binding MSCRAMMs. Plos One, 11(7), 17. doi:10.1371/journal.pone.0159118Adherence ofmicrobes to host tissues is a hallmark of infectious disease and is often mediated by a class of adhesins termed MSCRAMMs (Microbial Surface Components Recognizing Adhesive Matrix Molecules). Numerous pathogens express MSCRAMMs that specifically bind the heterodimeric human glycoprotein fibronectin (Fn). In addition to roles in adhesion, Fn-binding MSCRAMMs exploit physiological Fn functions. For example, several pathogens can invade host cells by a mechanism whereby MSCRAMM-bound Fn bridges interaction with alpha(5)beta(1) integrin. Here, we investigate two Fn-binding MSCRAMMs, FnBPA (Staphylococcus aureus) and BBK32 (Borrelia burgdorferi) to probe structure-activity relationships of MSCRAMM-induced Fn/alpha(5)beta(1) integrin activation. Circular dichroism, fluorescence resonance energy transfer, and dynamic light scattering techniques uncover a conformational rearrangement of Fn involving domains distant from the MSCRAMM binding site. Surface plasmon resonance experiments demonstrate a significant enhancement of Fn/alpha(5)beta(1) integrin affinity in the presence of FnBPA or BBK32. Detailed kinetic analysis of these interactions reveal that this change in affinity can be attributed solely to an increase in the initial Fn/alpha(5)beta(1) on-rate and that this rate-enhancement is dependent on high-affinity Fn-binding by MSCRAMMs. These data implicate MSCRAMM-induced perturbation of specific intramolecular contacts within the Fn heterodimer resulting in activation by exposing previously cryptic alpha(5)beta(1) interaction motifs. By correlating structural changes in Fn to a direct measurement of increased Fn/alpha(5)beta(1) affinity, this work significantly advances our understanding of the structural basis for the modulation of integrin function by Fn-binding MSCRAMMs

    SILICA AEROGELS PREPARED BY HYPERCRITICAL ACETONE EVACUATION

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    Le tétraméthoxysilane est le précurseur utilisé. La réaction d'hydrolyse, effectuée en milieu acétone, conduit à des gels monolithiques dans un grand domaine de compositions. Le séchage hypercritique est directement réalisé sur les gels tels qu'ils ont été obtenus. Les conditions permettant d'élaborer des aérogels monolithiques sont précisées. L'analyse structurale des aérogels montre qu'ils sont similaires à ceux obtenus dans des conditions d'évacuation hypercritique de solvants alcooliques. Cependant, la distribution des groupements hydroxyles est fortement affectée par la nature du solvant employé. L'évolution de la structure des aérogels en fonction de la température est étudiée. Le frittage s'effectue à des températures supérieures à 1000°C et l'aérogel se transforme en verre.Tetramethoxysilane is used as the silica source. The hydrolysis reaction, carried out in acetone, leads to gels which are monolithic in a large domain of compositions. The hypercritical drying is directly performed on the gels as obtained. Conditions to prepare monolithic aerogels are reported. The structural analysis of the aerogels shows that they are similar to those obtained from hypercritical drying in alcoholic medium. However, the hydroxyl group distribution is strongly affected by the nature of the solvent. The evolution of the structure of the aerogels as a function of temperature is investigated. Sintering occurs above 1000°C and the aerogel transforms into glass

    On-line characterization of silica gels by acoustic near field

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    Composite & hybrid (bio)materials based on bioactive glass: toward optimised substitute for bone bio-engineering

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    Evolution of the porous volume during the aerogel-glass transformation

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    The evolution of the texture of a silica aerogel during sintering is studied by thermoporometry. During the first stages of the densification the macroporous volume drops strongly while the mesoporous volume seems to be constant. This behavior is in contradiction with sintering models which predict that the sintering rate is faster for bodies with smaller particles or pores. In fact the analysis of the micropore size distribution shows that the sintering of the mesopores is responsible for macropore decrease
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