205 research outputs found

    ZnO-based film bulk acoustic resonator for high sensitivity biosensor applications

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    Author name used in this publication: G. K. H. Pang2006-2007 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

    Actin Dynamics Regulate Multiple Endosomal Steps during Kaposi's Sarcoma-Associated Herpesvirus Entry and Trafficking in Endothelial Cells

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    The role of actin dynamics in clathrin-mediated endocytosis in mammalian cells is unclear. In this study, we define the role of actin cytoskeleton in Kaposi's sarcoma-associated herpesvirus (KSHV) entry and trafficking in endothelial cells using an immunofluorescence-based assay to visualize viral capsids and the associated cellular components. In contrast to infectivity or reporter assays, this method does not rely on the expression of any viral and reporter genes, but instead directly tracks the accumulation of individual viral particles at the nuclear membrane as an indicator of successful viral entry and trafficking in cells. Inhibitors of endosomal acidification reduced both the percentage of nuclei with viral particles and the total number of viral particles docking at the perinuclear region, indicating endocytosis, rather than plasma membrane fusion, as the primary route for KSHV entry into endothelial cells. Accordingly, a viral envelope protein was only detected on internalized KSHV particles at the early but not late stage of infection. Inhibitors of clathrin- but not caveolae/lipid raft-mediated endocytosis blocked KSHV entry, indicating that clathrin-mediated endocytosis is the major route of KSHV entry into endothelial cells. KSHV particles were colocalized not only with markers of early and recycling endosomes, and lysosomes, but also with actin filaments at the early time points of infection. Consistent with these observations, transferrin, which enters cells by clathrin-mediated endocytosis, was found to be associated with actin filaments together with early and recycling endosomes, and to a lesser degree, with late endosomes and lysosomes. KSHV infection induced dynamic actin cytoskeleton rearrangements. Disruption of the actin cytoskeleton and inhibition of regulators of actin nucleation such as Rho GTPases and Arp2/3 complex profoundly blocked KSHV entry and trafficking. Together, these results indicate an important role for actin dynamics in the internalization and endosomal sorting/trafficking of KSHV and clathrin-mediated endocytosis in endothelial cells

    Molecular Mechanisms Associated with Nicotine Pharmacology and Dependence.

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    Tobacco dependence is a leading cause of preventable disease and death worldwide. Nicotine, the main psychoactive component in tobacco cigarettes, has also been garnering increased popularity in its vaporized form, as derived from e-cigarette devices. Thus, an understanding of the molecular mechanisms underlying nicotine pharmacology and dependence is required to ascertain novel approaches to treat drug dependence. In this chapter, we review the field's current understanding of nicotine's actions in the brain, the neurocircuitry underlying drug dependence, factors that modulate the function of nicotinic acetylcholine receptors, and the role of specific genes in mitigating the vulnerability to develop nicotine dependence. In addition to nicotine's direct actions in the brain, other constituents in nicotine and tobacco products have also been found to alter drug use, and thus, evidence is provided to highlight this issue. Finally, currently available pharmacotherapeutic strategies are discussed, along with an outlook for future therapeutic directions to achieve to the goal of long-term nicotine cessation

    Postulated Vasoactive Neuropeptide Autoimmunity in Fatigue-Related Conditions: A Brief Review and Hypothesis

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    Disorders such as chronic fatigue syndrome (CFS) and gulf war syndrome (GWS) are characterised by prolonged fatigue and a range of debilitating symptoms of pain, intellectual and emotional impairment, chemical sensitivities and immunological dysfunction. Sudden infant death syndrome (SIDS) surprisingly may have certain features in common with these conditions. Post-infection sequelae may be possible contributing factors although ongoing infection is unproven. Immunological aberration may prove to be associated with certain vasoactive neuropeptides (VN) in the context of molecular mimicry, inappropriate immunological memory and autoimmunity

    Study of the ZZ\gamma and Z\gamma\gamma Couplings in Z(\nu\nu)\gamma Production

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    We have measured the ZZ-gamma and Z-gamma-gamma couplings by studying p-bar p -> (missing ET) gamma + X events at sqrt(s)=1.8 TeV with the D0 detector at the Fermilab Tevatron Collider. This first study of hadronic Z-gamma production in the neutrino decay channel gives the most stringent limits on anomalous couplings available. A fit to the transverse energy spectrum of the photon in the candidate event sample, based on a data set corresponding to an integrated luminosity of 13.1 pb^(-1), yields 95% CL limits on the anomalous CP-conserving ZZ-gamma couplings of |h^Z_(30)|<0.9, |h^Z_(40)|<0.21, for a form-factor scale Lambda = 500 GeV. Combining these results with our previous measurement using Z -> ee and mu-mu yields the limits:|h^Z_(30)|<0.8, |h^Z_(40)|<0.19 (Lambda = 500 GeV) and |h^Z_(30)|<0.4, |h^Z_(40)|<0.06 (Lambda = 750 GeV).Comment: 10 pages, 2 figures, 2 table

    Studies of Gauge Boson Pair Production and Trilinear Couplings

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    The gauge boson pair production processes Wg, WW, WZ, and Zg were studied using pbarp collisions corresponding to an integrated luminosity of ~14 pb-1 at a center-of-mass energy of sqrt(s) = 1.8 TeV. Analysis of Wg prod with subsequent W boson decay to lv (l=e,mu) is reported, including a fit to the pT spectrum of the photons which leads to limits on anomalous WWg couplings. A search for WW prod with subsequent decay to l-lbar-v-vbar (l=e,mu) is presented leading to an upper limit on the WW prod cross section and limits on anomalous WWg and WWZ couplings. A search for high pT W bosons in WW and WZ prod is described, where one W boson decays to an ev and the second W boson or the Z boson decays to two jets. A maximum likelihood fit to the pT spectrum of W bosons resulted in limits on anomalous WWg and WWZ couplings. A combined fit to the three data sets which provided the tightest limits on anomalous WWg and WWZ couplings is also described. Limits on anomalous ZZg and Zgg couplings are presented from an analysis of the photon ET spectrum in Zg events in the decay channels (ee, mu-mu, and v-vbar) of the Z boson.Comment: 77 Pages including 40 Figures. Submitted to PR
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