21) to 65 (FIO(2) = 0 5) to 140 s (FIO(2) = 1 0) Conclusions:

21) to 65 (FIO(2) = 0.5) to 140 s (FIO(2) = 1.0).\n\nConclusions: Findings from this swine hemorrhagic shock model confirm that FIO(2) and the level of hemorrhagic shock, but not fluid resuscitation, influence the rate of apneic desaturation. A five-fold increase in time until critical oxygen desaturation occurs can be achieved when preoxygenating with 100% oxygen compared with room air, underscoring the importance of adequate preoxygenation

before emergent airway management.”
“Treatment with sigma1 receptor (Sigma1) ligands can inhibit cell proliferation in vitro and tumor growth in vivo. However, the cellular pathways engaged in response to Sigma1 ligand treatment that contribute to these outcomes remain largely undefined. Here, we show that treatment with putative antagonists buy PF-00299804 of Sigma1 decreases cell mass. This effect corresponds with repressed Bafilomycin A1 mouse cap-dependent translation initiation in multiple breast and prostate cancer cell lines. Sigma1 antagonist treatment suppresses phosphorylation of translational regulator proteins p70S6K, 56, and 4E-BP1. RNAi-mediated knockdown of Sigma1 also results in translational repression, consistent with the effects of antagonist treatment. Sigma1 antagonist mediated

translational repression and decreased cell size are both reversible. Together, these data reveal a role for Sigma1 in tumor cell protein synthesis, and demonstrate that small molecule Sigma1 ligands can be used as modulators of protein translation. (c) 2012 Elsevier selleck Inc. All rights reserved.”
“Ca2+/calmodulin-dependent protein kinase kinases (CaMKKs) phosphorylate and activate specific downstream protein kinases, including CaMKI, CaMKIV, and 5′-AMP-activated protein kinase, which mediates a variety of Ca2+ signaling cascades. CaMKKs have been shown to undergo autophosphorylation, although their role in enzymatic regulation remains unclear. Here, we found that CaMKK alpha and beta isoforms expressed in nonstimulated transfected COS-7 cells, as well as recombinant CaMKKs expressed in and purified

from Escherichia coli, were phosphorylated at Thr residues. Introduction of a kinase-dead mutation completely impaired the Thr phosphorylation of these recombinant CaMKK isoforms. In addition, wild-type recombinant CaMKKs were unable to transphosphorylate the kinase-dead mutants, suggesting that CaMKK isoforms undergo Ca2+/CaM-independent autophosphorylation in an intramolecular manner. Liquid chromatography tandem mass spectrometry analysis identified Thr(482) in the autoinhibitory domain as one of the autophosphorylation sites in GaMKK beta, but phosphorylation of the equivalent Thr residue (Thr(446)) in the alpha isoforrn was not observed. Unlike CaMKK alpha that has high Ca2+/CaM-dependent activity, wild-type CaMKK beta displays enhanced autonomous activity (Ca2+/CaM-independent activity, 71% of total activity).

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