15 research outputs found

    Effects of environment on children\u27s motor scores, eligibility status, and administration times

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    Best practices for assessing developmental skills in young children focus on naturalistic observation in everyday settings, but the effects of environment on test scores, eligibility status and administration time have not been explored. The Peabody Developmental Motor Scales-Second Edition (PDMS-2) was administered to 34 children aged 18 to 59 months in natural and pull-out settings. PDMS-2 total, gross, and fine motor quotient (TMQ, GMQ, and FMQ) scores were significantly lower in the natural environment (p’s≀.014). Based on our results, more children would qualify for services when tested in natural environments using TMQ and GMQ scores. It also took significantly longer to test children in the natural environment (p=.044). Pediatric service providers should consider the impact environment may have on children’s scores and resource utilization when planning assessment. Further, use of standardized tests of discrete motor skills, such as the PDMS-2, may be more appropriate in pull-out settings

    APP controls the formation of PI(3,5)P2 vesicles through its binding of the PIKfyve complex

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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

    <i>Performative reading in the late Byzantine</i> theatron

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    Strangers in a Strange Land: the Position of the Foreign Prisoner in the UK Special Issue

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