11 research outputs found

    Mice lacking integrin β3 expression exhibit altered response to chronic stress

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    Recent studies indicate multiple roles for integrin αvβ3 in adult neurons, including response to pharmacological agents such as cocaine and selective serotonin reuptake inhibitors. In this study, we examined the role of the integrin β3 gene (Itgb3) in the response to environmental stimuli by subjecting Itgb3+/+ and Itgb3−/− mice to unpredictable chronic mild stressors. We found that genetic abrogation of integrin β3 expression elicits an exaggerated vulnerability to chronic unpredictable stress in the open field test. In this test, chronic stress elicited significant decreases in stereotypic behavior and horizontal locomotor activity, including increases in anxiety behaviors. Mild chronic stress led to reductions in dopamine turnover in midbrains of Itgb3+/+, but not Itgb3−/− mice, suggesting a disruption of stress-dependent regulation of DA homeostasis. Chronic stress elicited altered synaptic expression of syntaxin and synaptophysin in midbrains of Itgb3−/− mice, when compared to Itgb3+/+. Semi-quantitative Western blot studies revealed that the synaptic expression, but not total tissue expression, of multiple signaling proteins is correlated with integrin αv levels in the midbrain. Moreover, loss of integrin β3 expression modifies this correlation network. Together, these findings demonstrate that Itgb3−/− mice display a pattern of changes indicating disrupted regulation of midbrain synaptic systems involved in conferring resilience to mild stressors

    Generation and characterization of point defects in SrTiO3 and Y3Al5O12

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    Positron annihilation lifetime spectroscopy (PALS) was applied to characterize point defects in single crystals of Y3Al5O12 and SrTiO3 after populating different types of defects by relevant thermal treatments. In SrTiO3, PALS measurements identified Sr vacancy, Ti vacancy, vacancy complexes of Ti–O (vacancy) and hydrogen complex defects. In Y3Al5O12 single crystals the measurements showed the presence of Al-vacancy, (Al–O) vacancy and Al-vacancy passivated by hydrogen. These defects are shown to play the major role in defining the electronic and optical properties of these complex oxides

    A Polymorphism in the HLA-DPB1 Gene Is Associated with Susceptibility to Multiple Sclerosis

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    We conducted an association study across the human leukocyte antigen (HLA) complex to identify loci associated with multiple sclerosis (MS). Comparing 1927 SNPs in 1618 MS cases and 3413 controls of European ancestry, we identified seven SNPs that were independently associated with MS conditional on the others (each ). All associations were significant in an independent replication cohort of 2212 cases and 2251 controls () and were highly significant in the combined dataset (). The associated SNPs included proxies for HLA-DRB1*15:01 and HLA-DRB1*03:01, and SNPs in moderate linkage disequilibrium (LD) with HLA-A*02:01, HLA-DRB1*04:01 and HLA-DRB1*13:03. We also found a strong association with rs9277535 in the class II gene HLA-DPB1 (discovery set , replication set , combined ). HLA-DPB1 is located centromeric of the more commonly typed class II genes HLA-DRB1, -DQA1 and -DQB1. It is separated from these genes by a recombination hotspot, and the association is not affected by conditioning on genotypes at DRB1, DQA1 and DQB1. Hence rs9277535 represents an independent MS-susceptibility locus of genome-wide significance. It is correlated with the HLA-DPB1*03:01 allele, which has been implicated previously in MS in smaller studies. Further genotyping in large datasets is required to confirm and resolve this association

    Organic solvents and hearing loss: The challenge for audiology

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    Organic solvents have been reported to adversely affect human health, including hearing health. Animal models have demonstrated that solvents may induce auditory damage, especially to the outer hair cells. Research on workers exposed to solvents has suggested that these chemicals may also induce auditory damage through effects on the central auditory pathways. Studies conducted with both animals and humans demonstrate that the hearing frequencies affected by solvent exposure are different to those affected by noise, and that solvents may interact synergistically with noise. The present article aims to review the contemporary literature of solventinduced hearing loss, and consider the implications of solvent-induced auditory damage for clinical audiologists. Possible audiological tests that may be used when auditory damage due to solvent exposure is suspected are discussed

    Methods of peri-annulation of five- and six-membered carbocyclic and nitrogen containing heterocyclic fragments

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    Cytokines. 3. Cytokines in asthma.

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