7,511 research outputs found

    Representations in Density Dependent Hadronic Field Theory and compatibility with QCD sum-rules

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    Different representations of an effective, covariant theory of the hadronic interaction are examined. For this purpose we have introduced nucleon-meson vertices parametrized in terms of scalar combinations of hadronic fields, extending the conceptual frame of the Density Dependent Hadronic Field Theory. Nuclear matter properties at zero temperature are examined in the Mean Field Approximation, including the equation of state, the Landau parameters, and collective modes. The treatment of isospin channels in terms of QCD sum rules inputs is outlined.Comment: 23 pages, 6 PostScript figures, Revtex4 clas

    Electroretinography in Veterinary Ophthalmology

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    Autoinhibition and Activation of Parkin

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    Mutations in the gene encoding parkin, an E3-ubiquitin ligase, result in 50% of Autosomal Recessive Juvenile Parkinsonism cases. Parkin has been identified as a key mediator of mitochondrial regeneration following oxidative stress, and pathogenic mutations have been shown to impair its ubiquitin ligase activity. Neurodegeneration of dopamine-producing neurons appears to be a downstream consequence of parkin loss-of-function, resulting in early-onset forms of Parkinson’s disease. Although ubiquitination activity is essential for its neuroprotective function, parkin is autoinhibited in its native state by various mechanisms, including its N-terminal ubiquitin-like (UBL) domain. Therefore, the overarching objective of this thesis was to structurally characterize the autoinhibited state of parkin and determine how this inactive structure is modified to a catalytically-competent form. It was determined that autoinhibited parkin maintains a compact tertiary structure mediated by a tight intramolecular association between the UBL and C-terminal region. A high-resolution NMR strategy was developed and used to identify the binding site of the UBL domain that further revealed allosteric structural changes associated with UBL binding and displacement. Recently, multiple reports emerged identifying serine 65 phosphorylation of both ubiquitin and parkin’s UBL domain as key inducers of parkin activity. To examine the roles of these phosphorylation signals, several methods were used to generate homogenous S65-phosphorylated ubiquitin and UBL including: chemical modification, orthogonal translation, and phosphorylation by a catalytically-active kinase. Thermodynamic parameters of ubiquitin and UBL binding to parkin were measured and it was demonstrated how these are significantly altered upon S65 phosphorylation to promote a loss of autoinhibition. To understand the structural consequences of S65 phosphorylation, the three-dimensional structure of the phosphorylated parkin UBL was solved. Phosphorylation impacts the structure, stability and autoinhibitory association of the UBL domain in parkin. Further, cooperative roles of phospho-ubiquitin and phospho-UBL were established in reorganizing the parkin to an extended structure, allowing its engagement in the ubiquitination cascade. Finally, to investigate a chemical mechanism of catalysis in activated parkin, a detailed characterization of active site atoms in parkin was performed. Chemical biology approaches were used to generate an activated parkin~ubiquitin intermediate that will provide further mechanistic insight into ubiquitin transfer onto mitochondrial substrates

    Wide Angle: Eadweard Muybridge, the Pacific Coast, and Trans-Indigenous Representation

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    Eadweard Muybridge's Pacific Coast photographs provide an important site for investigating Victorian visual practices and their relationship to imperial control. This essay's analysis of critical spatiality engages with the familiar temporal dimension of the "long nineteenth century" through discussions of periodicity and the representation of timescales in nineteenth-century media

    Window Into Retinal Studies

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    Professor Gustavo Aguirre discusses the context of his research studies at the University of Pennsylvania, which are currently concentrating on the degenerative disease, retinitis pigmentosa

    Pigmentary Uveitis

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    The recent report by Townsend and Gornik aims to provide more reliable data on the prevalence of two common but poorly understood ocular conditions of Golden Retrievers: uveal cysts and pigmentary uveitis (PU). The study is well designed in terms of patient selection and examination methods, and high degree of disease ascertainment and diagnostic consistency was obtained by having all examinations performed by a single board-certified veterinary ophthalmologist. Even though this and two other studies suggest that these two conditions may perhaps be part of a broader disease complex, there is, as yet, no conclusive evidence of such an association

    Concepts and Strategies in Retinal Gene Therapy

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    Genetic defects of the retina or retinal pigment epithelium (RPE) cause a substantial number of sight-impairing or blinding disorders, many of which eventually cause the degeneration and death of the visual cells. Previously considered incurable, some of these retinal diseases can now be treated, at least experimentally, by gene therapy

    Electroretinography - Are We Misusing an Excellent Diagnostic Tool?

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