89 research outputs found

    Preparation, structural characterisation and antibacterial properties of Ga-doped sol-gel phosphate-based glass

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    A sol-gel preparation of Ga-doped phosphate-based glass with potential application in antimicrobial devices has been developed. Samples of composition (CaO)(0.30)(Na2O)(0.20-x) (Ga2O3) (x) (P2O5)(0.50) where x = 0 and 0.03 were prepared, and the structure and properties of the gallium-doped sample compared with those of the sample containing no gallium. Analysis of the P-31 MAS NMR data demonstrated that addition of gallium to the sol-gel reaction increases the connectivity of the phosphate network at the expense of hydroxyl groups. This premise is supported by the results of the elemental analysis, which showed that the gallium-free sample contains significantly more hydrogen and by FTIR spectroscopy, which revealed a higher concentration of -OH groups in that sample. Ga K-edge extended X-ray absorption fine structure and X-ray absorption near-edge structure data revealed that the gallium ions are coordinated by six oxygen atoms. In agreement with the X-ray absorption data, the high-energy XRD results also suggest that the Ga3+ ions are octahedrally coordinated with respect to oxygen. Antimicrobial studies demonstrated that the sample containing Ga3+ ions had significant activity against Staphylococcus aureus compared to the control

    Rescuing Loading Induced Bone Formation at Senescence

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    The increasing incidence of osteoporosis worldwide requires anabolic treatments that are safe, effective, and, critically, inexpensive given the prevailing overburdened health care systems. While vigorous skeletal loading is anabolic and holds promise, deficits in mechanotransduction accrued with age markedly diminish the efficacy of readily complied, exercise-based strategies to combat osteoporosis in the elderly. Our approach to explore and counteract these age-related deficits was guided by cellular signaling patterns across hierarchical scales and by the insight that cell responses initiated during transient, rare events hold potential to exert high-fidelity control over temporally and spatially distant tissue adaptation. Here, we present an agent-based model of real-time Ca2+/NFAT signaling amongst bone cells that fully described periosteal bone formation induced by a wide variety of loading stimuli in young and aged animals. The model predicted age-related pathway alterations underlying the diminished bone formation at senescence, and hence identified critical deficits that were promising targets for therapy. Based upon model predictions, we implemented an in vivo intervention and show for the first time that supplementing mechanical stimuli with low-dose Cyclosporin A can completely rescue loading induced bone formation in the senescent skeleton. These pre-clinical data provide the rationale to consider this approved pharmaceutical alongside mild physical exercise as an inexpensive, yet potent therapy to augment bone mass in the elderly. Our analyses suggested that real-time cellular signaling strongly influences downstream bone adaptation to mechanical stimuli, and quantification of these otherwise inaccessible, transient events in silico yielded a novel intervention with clinical potential

    Structural difference between heteromeric somatic and homomeric axonal glycine receptors in the hypothalamo-neurohypophysial system

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    Glycine receptors are ionotropic receptors formed by either the homomeric assembly of ligand-binding alpha subunits or the heteromeric combination of an alpha subunit and the auxiliary beta subunit. Glycine receptors in the brain are found at either pre- or post-synaptic sites. Rat supraoptic nucleus neurons express glycine receptors on the membrane of both their soma and dendrites within the supraoptic nucleus, and their axon terminals in the neurohypophysis. Taking advantage of the well-separated cellular compartments of this system, we correlated the structural properties of the receptors to their subcellular localization. Immunohistochemical study using the generic mAb4a antibody revealed that somatodendritic receptors were clustered, whereas axonal glycine receptors showed a more diffuse distribution. This was paralleled by the presence of clusters of the glycine receptor aggregating protein gephyrin in the supraoptic nucleus and its complete absence in the neurohypophysis. Moreover, another antibody recognizing the alpha1/alpha2 subunits similarly labeled the axonal glycine receptors, but did not recognize the somatodendritic receptor clusters of supraoptic nucleus neurons, indicative of structural differences between somatic and axonal glycine receptors. Furthermore, the subunits composing the somatic and axonal receptors have different molecular weight. Functional study further differentiated the two types of glycine receptors on the basis of their sensitivity to picrotoxin, identifying somatic receptors as alpha/beta heteromers, and axonal receptors as alpha homomers. These results indicate that targeting of glycine receptors to axonal or somatodendritic compartment is directly related to their subunit composition, and set the hypothalamo-neurohypophysial system as an excellent model to study the mechanisms of targeting of proteins to various neuronal cellular compartments

    Palladium-Catalyzed Functionalization of Olefins and Alkynes: From Oxyalkynylation to Tethered Dynamic Kinetic Asymmetric Transformations (DYKAT)

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    This review presents an account of the palladium-catalyzed functionalizations of alkenes and alkynes developed at the Laboratory of Catalysis and Organic Synthesis (LCSO). Starting from the intramolecular oxy- and aminoalkynylation of alkenes, tethered methods were then developed to functionalize allylic amines and alcohols, as well as propargylic amines. Finally, a new dynamic kinetic asymmetric transformation was developed based on the use of a 'one-arm' Trost-type ligand, giving access to enantiopure amino alcohols. Each section is a personal account by the researcher(s) who performed the work. 1 Introduction, 2 Oxy- and Aminoalkynylation of Olefins, 3 In Situ Tethering Strategies for the Synthesis of Vicinal Amino Alcohols and Diamines, 4 Carboamination of Allylic Alcohols, 5 Carbooxygenation of Propargylic Amines, 6 Enantioselective Carboetherification/Hydrogenation via a Catalytically Formed Chiral Auxiliary, 7 Conclusio
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