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“There is a pressing need for new therapies to treat pancreatic cancer. In principle, this could

be achieved by taking advantage of signaling pathways that are active in tumor, but not normal, cells. The work described in this study set out to determine whether the activities of three enhancers, which have been reported to be highly responsive to activated ras, differ in pancreatic tumor cells that express wild-type versus constitutively active Kinase Inhibitor Library nmr mutant forms of K-ras. Surprisingly, the three enhancers are active in four different pancreatic tumor cell lines that express either normal K-ras gene or mutant K-ras. Moreover, reducing the concentration of serum in the growth medium from 10% to 0.5% had relatively little effect on the strength of any of the enhancers, although it drastically affected cell growth. importantly, our studies also indicate that MEK is active in pancreatic tumor cells that possess wild-type as well as mutant K-ras, even when cultured in medium that severely limits cell growth. These findings support the hypothesis that the Ras/Raf/Mek/Erk pathway may be constitutively active even in pancreatic tumor cells that express wild-type K-ras. (C) 2009 Elsevier Inc. All rights reserved.”
“We describe a general mass spectrometry approach to determine subunit stoichiometry and lipid binding in intact membrane protein complexes. By exploring conditions for preserving interactions

during transmission into the gas phase and for optimally stripping away detergent, by subjecting the complex to multiple collisions, we released the intact complex largely devoid of detergent. This enabled PP2 nmr us to characterize both subunit stoichiometry and lipid binding in 4 membrane protein complexes.”
“Rationale The common methionine (met) for valine (val) at codon 158 (val(158)met) polymorphism in

the catechol-O-methyltransferase (COMT) gene has been associated with nicotine dependence, alterations in executive cognitive function, and abstinence-induced working memory deficits in smokers.\n\nObjectives We sought GSK3326595 in vitro to replicate the association of the COMT val allele with abstinence-induced alterations in working memory-related activity in task-positive (executive control) and task-negative (default mode network) regions.\n\nMethods Forty smokers (20 val/val and 20 met/met) performed an N-back task while undergoing blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) on two separate occasions: following 72 h of confirmed abstinence and during smoking as usual. An independent sample of 48 smokers who completed the identical N-back task during fMRI in smoking vs. abstinence for another study was used as a validation sample.\n\nResults Contrary to expectations, genotype by session interactions on BOLD signal in executive control regions (dorsolateral prefrontal cortex and dorsal cingulate/medial prefrontal cortex) revealed significant abstinence-induced reductions in the met/met group, but not the val/val group.