546 research outputs found

    Preservation of glaciochemical time-series in snow and ice from the Penny Ice Cap, Baffin Island

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    A detailed investigation of major ion concentrations of snow and ice in the summit region of Penny Ice Cap (PIC) was performed to determine the effects of summer melt on the glaciochemical time-series. While ion migration due to meltwater percolation makes it difficult to confidently count annual layers in the glaciochemical profiles, time-series of these parameters do show good structure and a strong one year spectral component, suggesting that annual to biannual signals are preserved in PIC glaciochemical records

    ABBA regulates plasma-membrane and actin dynamics to promote radial glia extension

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    Radial glia play key roles in neuronal migration, axon guidance, and neurogenesis during development of the central nervous system. However, the molecular mechanisms regulating growth and morphology of these extended cells are unknown. We show that ABBA, a novel member of the IRSp53-MIM protein family, is enriched in different types of radial glia. ABBA binds ATP-actin monomers with high affinity and deforms PtdIns(4,5)P2-rich membranes in vitro through its WH2 and IM domains, respectively. In radial-glia-like C6-R cells, ABBA localises to the interface between the actin cytoskeleton and plasma membrane, and its depletion by RNAi led to defects in lamellipodial dynamics and process extension. Together, this study identifies ABBA as a novel regulator of actin and plasma membrane dynamics in radial glial cells, and provides evidence that membrane binding and deformation activity is critical for the cellular functions of IRSp53-MIM-ABBA family proteins

    Nr-CAM and neurofascin interactions regulate ankyrin G and sodium channel clustering at the node of Ranvier

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    AbstractVoltage-dependent sodium (Na+) channels are highly concentrated at nodes of Ranvier in myelinated axons and play a key role in promoting rapid and efficient conduction of action potentials by saltatory conduction. The molecular mechanisms that direct their localization to the node are not well understood but are believed to involve contact-dependent signals from myelinating Schwann cells [1] and interactions of Na+ channels with the cytoskeletal protein, ankyrin G [2]. Two cell adhesion molecules (CAMs) expressed at the axon surface, Nr-CAM and neurofascin, are also linked to ankyrin G and accumulate at early stages of node formation, suggesting that they mediate contact-dependent Schwann cell signals to initiate node development [3]. To examine the potential role of Nr-CAM in this process, we treated myelinating cocultures of DRG (dorsal root ganglion) neurons and Schwann cells with an Nr-CAM-Fc (Nr-Fc) fusion protein. Nr-Fc had no effect on initial axon-Schwann cell interactions, including Schwann cell proliferation, or on the extent of myelination, but it strikingly and specifically inhibited Na+ channel and ankyrin G accumulation at the node. Nr-Fc bound directly to neurons and clustered and coprecipitated neurofascin expressed on axons. These results provide the first evidence that neurofascin plays a major role in the formation of nodes, possibly via interactions with Nr-CAM

    Challenges of Population-based Measurement of Suicide Prevention Activities Across Multiple Health Systems

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    Suicide is a preventable public health problem. Zero Suicide (ZS) is a suicide prevention framework currently being evaluated by Mental Health Research Network investigators embedded in six Health Care Systems Research Network (HCSRN) member health systems implementing ZS. This paper describes ongoing collaboration to develop population-based process improvement metrics for use in, and comparison across, these and other health systems. Robust process improvement metrics are sorely needed by the hundreds of health systems across the country preparing to implement their own best practices in suicide care. Here we articulate three examples of challenges in using health system data to assess suicide prevention activities, each in ascending order of complexity: 1) Mapping and reconciling different versions of suicide risk assessment instruments across health systems; 2) Deciding what should count as adequate suicide prevention follow-up care and how to count it in different health systems with different care processes; and 3) Trying to determine whether a safety planning discussion took place between a clinician and a patient, and if so, what actually happened. To develop broadly applicable metrics, we have advocated for standardization of care processes and their documentation, encouraged standardized screening tools and urged they be recorded as discrete electronic health record (EHR) variables, and engaged with our clinical partners and health system data architects to identify all relevant care processes and the ways they are recorded in the EHR so we are not systematically missing important data. Serving as embedded research partners in our local ZS implementation teams has facilitated this work
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