Acute Mn exposure via intranasal instillation of 2-200 mu g MnCl2 solution caused a dose-dependent reduction in odorant-evoked neurotransmitter release, with significant effects at as little as 2 mu g MnCl2 and a 90% reduction compared to vehicle controls with a 200 mu g exposure. This reduction was also observed in response to direct electrical stimulation of the olfactory nerve layer in the olfactory bulb, demonstrating that Mn’s action is occurring centrally, not peripherally. This is the selleck screening library first direct evidence that Mn intoxication can disrupt neurotransmitter release, and is consistent with previous work suggesting that chronic Mn exposure limits amphetamine-induced dopamine increases

in the basal ganglia despite normal levels

of dopamine synthesis (Guilarte et al., J Neurochem 2008). The commonality of Mn’s action between glutamatergic neurons in the olfactory bulb and dopaminergic neurons in the basal ganglia suggests that a disruption of neurotransmitter release may be a general consequence wherever Mn accumulates in the brain and could underlie its pleiotropic effects. (c) 2012 Elsevier Inc. All rights reserved.”
“Ribonuclease U2, secreted by the smut fungus Ustilago sphaerogena, is a cyclizing ribonuclease that displays a rather unusual specificity selleck within the group of microbial extracellular RNases, best represented by RNase T1. Superposition of the three-dimensional oxyclozanide structures of RNases T1 and U2 suggests that the RNase U2 His 101 would be the residue equivalent to the RNase T1 catalytically essential His 92. RNase U2 contains three disulfide bridges but only two of them are conserved among the family of fungal extracellular RNases. The non-conserved disulfide bond is established between Cys residues 1 and 54. Mispairing of the disulfide network due to the presence of two consecutive Cys residues

(54 and 55) has been invoked to explain the presence of wrongly folded RNase U2 species when produced in Pichia pastoris. In order to study both hypotheses, the RNase U2 H101Q and C1/54S variants have been produced, purified, and characterized. The results obtained support the major conclusion that His 10 1 is required for proper protein folding when secreted by the yeast A pastoris. On the other hand, substitution of the first Cys residue for Set results in a mutant version which is more efficiently processed in terms of a more complete removal of the yeast a-factor signal peptide. In addition, it has been shown that elimination of the Cys 1-Cys 54 disulfide bridge does not interfere with RNase U2 proper folding, generating a natively folded but much less stable protein. (C) 2009 Elsevier Inc. All rights reserved.”
“Objective: The aim of this study was to determine if statin therapy improves clinical outcomes after endovascular intervention in patients with critical limb ischemia (CLI).