“Although evolutionary theories predict functional diverge

“Although evolutionary theories predict functional divergence between duplicate genes, many old duplicates still maintain a high degree of functional similarity and are synthetically lethal or sick, an observation that has puzzled many geneticists. We propose that expression reduction, a special type of subfunctionalization, facilitates the retention of duplicates

and the conservation of their ancestral functions. Consistent with this hypothesis, gene expression data from both yeasts and mammals show a substantial decrease in the level of gene expression after duplication. Whereas the majority of the expression reductions are likely to be neutral, some are apparently beneficial to rebalancing gene dosage after duplication.”
“Increased anxiety is commonly observed in individuals who illicitly administer Alvespimycin nmr anabolic androgenic steroids (AAS). Behavioral effects of steroid abuse have become an increasing concern in adults and adolescents of both sexes. The dorsolateral bed nucleus of the stria terminalis (dlBnST) has a critical

role in the expression of diffuse anxiety Nirogacestat clinical trial and is a key site of action for the anxiogenic neuromodulator, corticotropin releasing factor (CRF). Here we demonstrate that chronic, but not acute, exposure of female mice during adolescence to AAS augments anxiety-like behaviors; effects that were blocked by central infusion of the CRF receptor type 1 antagonist, antalarmin. AAS treatment

selectively increased action potential (AP) firing in neurons of the central amygdala (CeA) that project to the dlBnST, increased the frequency of GABA(A) receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) in dlBnST target neurons, and decreased both c-FOS immunoreactivity (IR) and AP frequency in these postsynaptic cells. Acute application of antalarmin abrogated the enhancement of GABAergic inhibition induced by chronic AAS exposure whereas application of CRF to brain slices of naive mice mimicked the actions of this treatment. These results, in concert with previous data demonstrating that chronic AAS treatment results in enhanced levels of CRF mRNA in the CeA and increased CRF-IR in the dlBnST neuropil, are consistent most with a mechanism in which the enhanced anxiety elicited by chronic AAS exposure involves augmented inhibitory activity of CeA afferents to the dlBnST and CRF-dependent enhancement of GABAergic inhibition in this brain region. Neuropsychopharmacology (2012) 37, 1483-1499; doi: 10.1038/npp.2011.334; published online 1 February 2012″
“Background Although most cardiovascular disease occurs in low-income and middle-income countries, little is known about the use of effective secondary prevention medications in these communities.

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