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61.
Dr. Adarshi P. Welegedara Dr. Ansis Maleckis Ruchira Bandara Dr. Mithun C. Mahawaththa Iresha Dilhani Herath Yi Jiun Tan Dr. Angeliki Giannoulis Prof. Daniella Goldfarb Prof. Gottfried Otting Prof. Thomas Huber 《Chembiochem : a European journal of chemical biology》2021,22(8):1480-1486
The selenol group of selenocysteine is much more nucleophilic than the thiol group of cysteine. Selenocysteine residues in proteins thus offer reactive points for rapid post-translational modification. Herein, we show that selenoproteins can be expressed in high yield and purity by cell-free protein synthesis by global substitution of cysteine by selenocysteine. Complete alkylation of solvent-exposed selenocysteine residues was achieved in 10 minutes with 4-chloromethylene dipicolinic acid (4Cl-MDPA) under conditions that left cysteine residues unchanged even after overnight incubation. GdIII−GdIII distances measured by double electron–electron resonance (DEER) experiments of maltose binding protein (MBP) containing two selenocysteine residues tagged with 4Cl-MDPA-GdIII were indistinguishable from GdIII−GdIII distances measured of MBP containing cysteine reacted with 4Br-MDPA tags. 相似文献
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Nicholas Caffes David B. Kurland Volodymyr Gerzanich J. Marc Simard 《International journal of molecular sciences》2015,16(3):4973-4984
Ischemic and hemorrhagic strokes are associated with severe functional disability and high mortality. Except for recombinant tissue plasminogen activator, therapies targeting the underlying pathophysiology of central nervous system (CNS) ischemia and hemorrhage are strikingly lacking. Sur1-regulated channels play essential roles in necrotic cell death and cerebral edema following ischemic insults, and in neuroinflammation after hemorrhagic injuries. Inhibiting endothelial, neuronal, astrocytic and oligodendroglial sulfonylurea receptor 1–transient receptor potential melastatin 4 (Sur1–Trpm4) channels and, in some cases, microglial KATP (Sur1–Kir6.2) channels, with glibenclamide is protective in a variety of contexts. Robust preclinical studies have shown that glibenclamide and other sulfonylurea agents reduce infarct volumes, edema and hemorrhagic conversion, and improve outcomes in rodent models of ischemic stroke. Retrospective studies suggest that diabetic patients on sulfonylurea drugs at stroke presentation fare better if they continue on drug. Additional laboratory investigations have implicated Sur1 in the pathophysiology of hemorrhagic CNS insults. In clinically relevant models of subarachnoid hemorrhage, glibenclamide reduces adverse neuroinflammatory and behavioral outcomes. Here, we provide an overview of the preclinical studies of glibenclamide therapy for CNS ischemia and hemorrhage, discuss the available data from clinical investigations, and conclude with promising preclinical results that suggest glibenclamide may be an effective therapeutic option for ischemic and hemorrhagic stroke. 相似文献
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Muntasir Hashim Farnoosh Farhad David Smyth‐Boyle Robert Akid Xiang Zhang Philip J. Withers 《工业材料与腐蚀》2019,70(11):2009-2019
The environmental performance of 316L grade stainless steel, in the form of tensile specimens containing a single corrosion pit with various aspect ratios, under cyclic loading in aerated chloride solutions is investigated in this study. Results from environmental tests were compared and contrasted with those obtained using finite element analysis (FEA). Fractography of the failed specimens obtained from experiments revealed that fatigue crack initiation took place at the base of the shallow pit. The crack initiation shifted towards the shoulder and the mouth of the pit for pits of increasing depth. This process is well predicted by FEA, as the strain contour maps show that strain is the highest around the centric strip of the pit. However, for shallow pits, local strain is uniformly distributed around that strip but begins to concentrate more towards the shoulder and the mouth region for increasingly deep pits. 相似文献
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