996 resultados para NETTRA-P2.


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Bibliography: p. 209-212.

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"UILU-ENG 77 1743."

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Thesis (M. S.)--University of Illinois at Urbana-Champaign.

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"Work supported in part by the National Science Foundation under Grant no. GJ-40221."

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Phosphoinositides are signalling lipids that are crucial for major signalling events as well as established regulators of membrane trafficking. Control of endosomal sorting and endosomal homeostasis requires phosphatidylinositol-3-phosphate (PI(3)P) and phosphatidylinositol-3,5-bisphosphate (PI(3,5)P2), the latter a lipid of low abundance but significant physiological relevance. PI(3,5)P2 is formed by phosphorylation of PI(3)P by the PIKfyve complex which is crucial for maintaining endosomal homeostasis. Interestingly, loss of PIKfyve function results in dramatic neurodegeneration. Despite the significance of PIKfyve, its regulation is still poorly understood. Here we show that the Amyloid Precursor Protein (APP), a central molecule in Alzheimer’s disease, associates with the PIKfyve complex (consisting of Vac14, PIKfyve and Fig4) and that the APP intracellular domain directly binds purified Vac14. We also show that the closely related APP paralogues, APLP1 and 2 associate with the PIKfyve complex. Whether APP family proteins can additionally form direct protein–protein interaction with PIKfyve or Fig4 remains to be explored. We show that APP binding to the PIKfyve complex drives formation of PI(3,5)P2 positive vesicles and that APP gene family members are required for supporting PIKfyve function. Interestingly, the PIKfyve complex is required for APP trafficking, suggesting a feedback loop in which APP, by binding to and stimulating PI(3,5)P2 vesicle formation may control its own trafficking. These data suggest that altered APP processing, as observed in Alzheimer’s disease, may disrupt PI(3,5)P2 metabolism, endosomal sorting and homeostasis with important implications for our understanding of the mechanism of neurodegeneration in Alzheimer’s disease.

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A 415cm thick permafrost peat section from the Verkhoyansk Mountains was radiocarbon-dated and studied using palaeobotanical and sedimentological approaches. Accumulation of organic-rich sediment commenced in a former oxbow lake, detached from a Dyanushka River meander during the Younger Dryas stadial, at ~12.5 kyr BP. Pollen data indicate that larch trees, shrub alder and dwarf birch were abundant in the vegetation at that time. Local presence of larch during the Younger Dryas is documented by well-preserved and radiocarbon-dated needles and cones. The early Holocene pollen assemblages reveal high percentages of Artemisia pollen, suggesting the presence of steppe-like communities around the site, possibly in response to a relatively warm and dry climate ~11.4-11.2 kyr BP. Both pollen and plant macrofossil data demonstrate that larch woods were common in the river valley. Remains of charcoal and pollen of Epilobium indicate fire events and mark a hiatus ~11.0-8.7 kyr BP. Changes in peat properties, C31/C27 alkane ratios and radiocarbon dates suggest that two other hiatuses occurred ~8.2-6.9 and ~6.7-0.6 kyr BP. Prior to 0.6 kyr BP, a major fire destroyed the mire surface. The upper 60 cm of the studied section is composed of aeolian sands modified in the uppermost part by the modern soil formation. For the first time, local growth of larch during the Younger Dryas has been verified in the western foreland of the Verkhoyansk Mountains (~170km south of the Arctic Circle), thus increasing our understanding of the quick reforestation of northern Eurasia by the early Holocene.

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Universidade Estadual de Campinas . Faculdade de Educação Física

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Universidade Estadual de Campinas . Faculdade de Educação Física

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Universidade Estadual de Campinas. Faculdade de Educação Física