978 research outputs found

    Accessibility of Targeted DHPR Sites to Streptavidin and Functional Effects of Binding on EC Coupling

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    In skeletal muscle, the dihydropyridine receptor (DHPR) in the plasma membrane (PM) serves as a Ca2+ channel and as the voltage sensor for excitation–contraction (EC coupling), triggering Ca2+ release via the type 1 ryanodine receptor (RyR1) in the sarcoplasmic reticulum (SR) membrane. In addition to being functionally linked, these two proteins are also structurally linked to one another, but the identity of these links remains unknown. As an approach to address this issue, we have expressed DHPR α1S or β1a subunits, with a biotin acceptor domain fused to targeted sites, in myotubes null for the corresponding, endogenous DHPR subunit. After saponin permeabilization, the ∼60-kD streptavidin molecule had access to the β1a N and C termini and to the α1S N terminus and proximal II–III loop (residues 671–686). Steptavidin also had access to these sites after injection into living myotubes. However, sites of the α1S C terminus were either inaccessible or conditionally accessible in saponin- permeabilized myotubes, suggesting that these C-terminal regions may exist in conformations that are occluded by other proteins in PM/SR junction (e.g., RyR1). The binding of injected streptavidin to the β1a N or C terminus, or to the α1S N terminus, had no effect on electrically evoked contractions. By contrast, binding of streptavidin to the proximal α1S II–III loop abolished such contractions, without affecting agonist-induced Ca2+ release via RyR1. Moreover, the block of EC coupling did not appear to result from global distortion of the DHPR and supports the hypothesis that conformational changes of the α1S II–III loop are necessary for EC coupling in skeletal muscle

    Sub-Pixel Response Measurement of Near-Infrared Sensors

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    Wide-field survey instruments are used to efficiently observe large regions of the sky. To achieve the necessary field of view, and to provide a higher signal-to-noise ratio for faint sources, many modern instruments are undersampled. However, precision photometry with undersampled imagers requires a detailed understanding of the sensitivity variations on a scale much smaller than a pixel. To address this, a near-infrared spot projection system has been developed to precisely characterize near-infrared focal plane arrays and to study the effect of sub-pixel non uniformity on precision photometry. Measurements of large format near-infrared detectors demonstrate the power of this system for understanding sub-pixel response.Comment: 9 pages, 13 figures, submitted to PAS

    Surgical strategies for duodenal GISTs: benefits and limitations of minimal resections

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    Comment on Conservative surgery vs. duodeneopancreatectomy in primary duodenal gastrointestinal stromal tumors (GIST): a retrospective review of 114 patients from the French sarcoma group (FSG). [Eur J Surg Oncol. 2014
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