Numerous human diseases are associated with the chronic expression of misfolded and aggregation-prone proteins. The expansion of polyglutamine residues in unrelated proteins is associated with the early onset of neurodegenerative disease. To understand how the presence of misfolded proteins leads to cellular dysfunction, we employed Caenorhabditis elegans polyglutamine aggregation models. Here, we find that polyglutamine expansions disrupted the global balance of protein folding quality control, resulting in the loss of function of diverse metastable proteins with destabilizing temperature-sensitive mutations. In turn, these proteins, although innocuous under normal physiological conditions, enhanced the aggregation of polyglutamine proteins. Thus, weak folding mutations throughout the genome can function as modifiers of polyglutamine phenotypes and toxicity.
A number of studies have reported associations between sleep disorders and adverse outcomes in both elderly and younger populations, but because few included pregnant women it is unclear whether sleep abnormalities during pregnancy are associated with adverse health consequences. Previous reports on sleep and pregnancy have focused only on specific sleep disturbances such as snoring, and most have studied a very heterogeneous population and included
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