27,843 research outputs found

    Axonal stress kinase activation and tau misbehavior induced by kinesin-1 transport defects

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    Many neurodegenerative diseases exhibit axonal pathology, transport defects, and aberrant phosphorylation and aggregation of the microtubule binding protein tau. While mutant tau protein in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP17) causes aberrant microtubule binding and assembly of tau into filaments, the pathways leading to tau-mediated neurotoxicity in Alzheimer's disease and other neurodegenerative disorders in which tau protein is not genetically modified remain unknown. To test the hypothesis that axonal transport defects alone can cause pathological abnormalities in tau protein and neurodegeneration in the absence of mutant tau or amyloid β deposits, we induced transport defects by deletion of the kinesin light chain 1 (KLC1) subunit of the anterograde motor kinesin-1. We found that upon aging, early selective axonal transport defects in mice lacking the KLC1 protein (KLC1-/-) led to axonopathies with cytoskeletal disorganization and abnormal cargo accumulation. In addition, increased c-jun N-terminal stress kinase activation colocalized with aberrant tau in dystrophic axons. Surprisingly, swollen dystrophic axons exhibited abnormal tau hyperphosphorylation and accumulation. Thus, directly interfering with axonal transport is sufficient to activate stress kinase pathways initiating a biochemical cascade that drives normal tau protein into a pathological state found in a variety of neurodegenerative disorders including Alzheimer's disease.Fil: Falzone, Tomas Luis. Howard Hughes Medical Institute; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Stokin, Gorazd B.. University Psychiatric Hospital; EsloveniaFil: Lillo, Concepción. University of California at San Diego; Estados UnidosFil: Rodrigues, Elizabeth M.. Howard Hughes Medical Institute; Estados UnidosFil: Westerman, Eileen L.. Howard Hughes Medical Institute; Estados UnidosFil: Williams, David S.. University of California at San Diego; Estados UnidosFil: Goldstein, Lawrence S. B.. Howard Hughes Medical Institute; Estados Unido

    Climatically driven loss of calcium in steppe soil as a sink for atmospheric carbon

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    During the last several thousand years the semi‐arid, cold climate of the Russian steppe formed highly fertile soils rich in organic carbon and calcium (classified as Chernozems in the Russian system). Analysis of archived soil samples collected in Kemannaya Steppe Preserve in 1920, 1947, 1970, and fresh samples collected in 1998 indicated that the native steppe Chernozems, however, lost 17–28 kg m−2 of calcium in the form of carbonates in 1970–1998. Here we demonstrate that the loss of calcium was caused by fundamental shift in the steppe hydrologic balance. Previously unleached soils where precipitation was less than potential evapotranspiration are now being leached due to increased precipitation and, possibly, due to decreased actual evapotranspiration. Because this region receives low levels of acidic deposition, the dissolution of carbonates involves the consumption of atmospheric CO2. Our estimates indicate that this climatically driven terrestrial sink of atmospheric CO2 is ∼2.1–7.4 g C m−2 a−1. In addition to the net sink of atmospheric carbon, leaching of pedogenic carbonates significantly amplified seasonal amplitude of CO2 exchange between atmosphere and steppe soil

    Overcoming the boundary layer turbulence at Dome C: ground-layer adaptive optics versus tower

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    The unique atmospheric conditions present at sites such as Dome C on the Antarctic plateau are very favorable for high spatial resolution astronomy. At Dome C, the majority of the optical turbulence is confined to a 30 to 40 m thick stable boundary layer that results from the strong temperature inversion created by the heat exchange between the air and the ice-covered ground. To fully realize the potential of the exceptionally calm free atmosphere, this boundary layer must be overcome. In this article we compare the performance of two methods proposed to beat the boundary layer: mounting a telescope on a tower that physically puts it above the turbulent layer, and installing a telescope at ground level with a ground-layer adaptive optics system. A case is also made to combine these two methods to further improve the image quality

    A global, collaborative, E-learning ecosystem: An academic/industry partnership in action

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    A number of apparent failures in the use of education technology should provide a warning as universities and training institutes progress their strategy and management plans for elearning. Fundamental problems in the academic environment relate to the lack of training in new technologies available to academics responsible for elearning. No less importantly the synergies among commercial providers of Asynchronous Learning Network (ALN) software, pedagogical knowledge and experiential learning requirements have not been addressed in the vision and strategy statements provided by senior management. The requisite solution is seen to be a framework for all stakeholders to evaluate e-learning proposals to ensure the effectiveness and value propositions are based in reality. What can we learn from the e-business environment and, in particular, the Cisco Network Academy Program (Academy Connection) that would inform the structure and deliverables required to support the proposed framework? This proposed framework also needs to accommodate value propositions for the diverse student cohorts involved in e-learning, having particular regard to professional practical requirements

    Kinesin Light Chains Are Essential for Axonal Transport in Drosophila

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    Kinesin is a heterotetramer composed of two 115-kD heavy chains and two 58-kD light chains. The microtubule motor activity of kinesin is performed by the heavy chains, but the functions of the light chains are poorly understood. Mutations were generated in the Drosophila gene Kinesin light chain (Klc), and the phenotypic consequences of loss of Klc function were analyzed at the behavioral and cellular levels. Loss of Klc function results in progressive lethargy, crawling defects, and paralysis followed by death at the end of the second larval instar. Klc mutant axons contain large aggregates of membranous organelles in segmental nerve axons. These aggregates, or organelle jams (Hurd, D.D., and W.M. Saxton. 1996. Genetics. 144: 1075-1085), contain synaptic vesicle precursors as well as organelles that may be transported by kinesin, kinesin-like protein 68D, and cytoplasmic dynein, thus providing evidence that the loss of Klc function blocks multiple pathways of axonal transport. The similarity of the Klc and Khc ((Saxton et al. Cell 64:1093-1102; Hurd, D.D., and W.M. Saxton. 1996. Genetics 144: 1075-1085) mutant phenotypes indicates that KLC is essential for kinesin function, perhaps by tethering KHC to intracellular cargos or by activating the kinesin motor

    Teaching and Learning Issues in the Disciplines: Leisure Studies

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    This report is submitted to the Higher Education Academy (HEA) on behalf of the Leisure Studies Association (LSA). The LSA aims to foster research in Leisure Studies; to promote interest in Leisure Studies and advance education in this field; to encourage debate through publications, and an international journal Leisure Studies; to stimulate the exchange of ideas on contemporary leisure issues; to disseminate knowledge of Leisure Studies to create the conditions for better-informed decisions by policy makers. The LSA is a member society of the Academy of Social Sciences

    Seeking Common Ground in Nuclear Complexity

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    Biot-Savart correlations in layered superconductors

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    We discuss the superconductor to normal phase transition in an infinite-layered type-II superconductor in the limit where the Josephson coupling between layers is negligible. We model each layer as a neutral gas of thermally excited pancake vortices. We assume the dominant interaction between vortices in the same and in different layers is the electromagnetic interaction between the screening currents induced by these vortices. Our main result, obtained by exactly solving the leading order renormalization group flow, is that the phase transition in this model is a Kosterlitz--Thouless transition despite being a three--dimensional system. While the transition itself is driven by the unbinding of two-dimensional pancake vortices, an RG analysis of the low temperature phase and a mean-field theory of the high temperature phase reveal that both phases possess three-dimensional correlations. An experimental consequence of this is that the jump in the measured in-plane superfluid stiffness, which is a universal quantity in 2d Kosterlitz-Thouless theory, will receive a small non--universal correction (of order 1% in Bi2_2Sr2_2CaCu2_2O8+x_{8+x}). This overall picture places some claims expressed in the literature on a more secure analytical footing and also resolves some conflicting views.Comment: 16 pages, 2 figures; minor typos corrected, references adde
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