In model systems,
pS6 is a specific marker for stress granules, and another stress granule protein, p54/Rck, was also found to be a component of GVD in the current study. Stress granules are transient, intracellular, dense aggregations of proteins and RNAs that accumulate as a stress response, protecting cells from apoptosis and inappropriate transcriptional activity, often described as a form of ‘molecular triage.’ The RNA oxidation modification 8-hydroxyguanosine (8OHG) is strikingly increased in AD, yet this study reports that those neurons with pS6 granules display reduced RNA oxidation demonstrated by lower levels of 8OHG. Since chronic oxidative stress Dehydrogenase inhibitor is central to AD pathogenesis, and RNA is a specific oxidative stress target and is intimately associated with stress granule biogenesis in model systems, we suggest that GVD in human brain parallel stress granules, and may in fact be more representative of early disease pathogenesis than traditionally believed. This proposed origin for GVD as a neuroprotective response, may represent a morphologic checkpoint between cell death
and reversible cellular stress that proceeds in the absence of other inclusions. Laboratory Crenolanib supplier Investigation (2011) 91, 1777-1786; doi:10.1038/labinvest.2011.149; published online 3 October 2011″
“Background. Little is known about factors that predict first lifetime episodes of major depression in middle-aged women. It is not known whether health-related factors and life stress pose more or less of a risk to the onset of clinical depression than does the menopausal transition.
Method. The Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) was used to
assess diagnoses of life-time, annual and current major depression in a community-based sample of premenopausal or early perimenopausal African American and White women. Menstrual cycle characteristics, psychosocial and health-related factors, and blood samples for assay of reproductive hormones were obtained annually. Two hundred and sixty-six women without a history of major depression all at baseline constituted the cohort for the current analyses.
Results. Over 7 years of follow-up, 42 (15.8%) women met criteria for a diagnosis of major depression. Frequent vasomotor symptoms (VMS; hot flashes and/or night sweats) (HR 2.14, p = 0.03) were a significant predictor of major depression in univariate analyses. After simultaneous adjustment for multiple predictors in Cox proportional hazards analyses, frequent VMS were no longer significant; lifetime history of an anxiety disorder (HR 2.20, p = 0.02) and role limitations due to physical health (HR 1.88, p = 0.07) at baseline and a very stressful life event (HR 2.25, p = 0.