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The endogenous cannabinoid receptor agonist anandamide is a powerful vasodilator of isolated vascular preparations, but its mechanism of action is unclear. Here we show that the vasodilator response to anandamide in isolated arteries is capsaicin-sensitive and accompanied by release of calcitonin-gene-related peptide (CGRP). The selective CGRP-receptor(More)
N-terminal acetylation is ubiquitous among eukaryotic proteins and controls a myriad of biological processes. Of the N-terminal acetyltransferases (NATs) that facilitate this cotranslational modification, the heterodimeric NatA complex has the most diversity for substrate selection and modifies the majority of all N-terminally acetylated proteins. Here, we(More)
To study conformational transitions at the muscle nicotinic acetylcholine (ACh) receptor (nAChR), a rhodamine fluorophore was tethered to a Cys side chain introduced at the beta 19' position in the M2 region of the nAChR expressed in Xenopus oocytes. This procedure led to only minor changes in receptor function. During agonist application, fluorescence(More)
The binding of three distinct agonists-acetylcholine (ACh), nicotine, and epibatidine-to the nicotinic acetylcholine receptor has been probed using unnatural amino acid mutagenesis. ACh makes a cation-pi interaction with Trp alpha149, while nicotine employs a hydrogen bond to a backbone carbonyl in the same region of the agonist binding site. The nicotine(More)
The N -methyl-D-aspartate (NMDA) receptor plays a central role in learning and memory in the mammalian CNS. At normal neuronal resting membrane potentials, the pore of this glutamate-gated ion channel is blocked by a Mg(2+) ion. Previous work suggests that the Mg(2+) binding site is quite novel, involving several asparagine residues and a cation-pi(More)
We consider structural topology optimization problems including unilateral constraints arising from, for example, non-penetration conditions in contact mechanics or non-compression conditions for elastic ropes. To construct more realistic models and to hedge off possible failures or an inefficient behaviour of optimal structures, we allow parameters (for(More)
The caging of specific residues of proteins is a powerful tool. This discussion attempts to alert the reader to the considerations that must be made in preparing and analyzing a caged protein through nonsense suppression. Although the suppression methodology is conceptually straightforward, it not possible to provide a failsafe "cook book" method for using(More)
BACKGROUND Therapeutic hypothermia (TH) is a promising treatment of stroke, but limited data are available regarding the safety and effectiveness of cooling methodology. We investigated the safety of TH and compared the cooling capacity of two widely used cooling strategies - endovascular and surface cooling. METHODS COOLAID Oresund is a bicentre(More)
Otoferlin is a transmembrane protein consisting of six C2 domains, proposed to act as a calcium sensor for exocytosis. Although otoferlin is believed to bind calcium and lipids, the lipid specificity and identity of the calcium binding domains are controversial. Further, it is currently unclear whether the calcium binding affinity of otoferlin(More)
OBJECTIVES To evaluate the association between the hyperdense middle cerebral artery sign (HMCAS) and the functional outcome on one hand, and different predictors such as the National Institutes of Health Stroke Scale (NIHSS), infarct size, ASPECTS Score, intracerebral hemorrhage, and mortality on the other hand. MATERIAL AND METHODS Retrospective(More)