The TSC complex is a critical negative regulator of the small GTPase Rheb and mTORC1 in cellular stress signaling. The TSC2 subunit contains a catalytic GTPase activating protein domain and interacts with multiple regulators, while the precise function of TSC1 is unknown. Here we provide a structural characterization of TSC1 and define three domains: a C-terminal coiled-coil that interacts with TSC2, a central helical domain that mediates TSC1 oligomerization, and an N-terminal HEAT repeat domain that interacts with membrane phosphatidylinositol phosphates (PIPs).
View Article and Find Full Text PDFThe TSC complex is the cognate GTPase-activating protein (GAP) for the small GTPase Rheb and a crucial regulator of the mechanistic target of rapamycin complex 1 (mTORC1). Mutations in the TSC1 and TSC2 subunits of the complex cause tuberous sclerosis complex (TSC). We present the crystal structure of the catalytic asparagine-thumb GAP domain of TSC2.
View Article and Find Full Text PDFObjective: To determine the housing situation among people seeking psychiatric treatment in relation to morbidity and service utilisation.
Design: Cross-sectional patient survey.
Setting: Psychiatric centre with a defined catchment area in Berlin, Germany, March-September 2016.
Objective: Contrast-induced nephropathy (CIN) is a complication which may develop after exposure to iodinated contrast media. The resulting acute kidney injury (AKI) is associated with an increase in both short- and long-term morbidity and mortality, increased hospital length of stay, and greater health care costs. The pathophysiological mechanism associated with the development of CIN remains unknown.
View Article and Find Full Text PDFBackground: Erythropoietin stimulating agents (ESAs) are high-cost medications that have a significant impact on many pharmacy budgets. Recently, ESAs have received stronger safety warnings and reimbursement has been curtailed by third-party payers including the Centers for Medicare and Medicaid Services. For these reasons, many hospitals are developing strategies to optimize their use.
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