SUMMARY
To provide a detailed analysis of the molecular components and underlying mechanisms associated with ovarian cancer, we performed a comprehensive mass spectrometry-based proteomic characterization of 174 ovarian tumors previously analyzed by The Cancer Genome Atlas (TCGA), of which 169 were high-grade serous carcinomas (HGSC). Integrating our proteomic measurements with the genomic data yielded a number of insights into disease such as how different copy number alternations influence the proteome, the proteins associated with chromosomal instability, the sets of signaling pathways that diverse genome rearrangements converge on, as well as the ones most associated with short overall survival. Specific protein acetylations associated with homologous recombination deficiency suggest a potential means for stratifying patients for therapy. In addition to providing a valuable resource, these findings provide a view of how the somatic genome drives the cancer proteome and associations between protein and post-translational modification levels and clinical outcomes in HGSC.
China is one of the few countries with some of the highest particulate matter levels in the world. However, only a small number of particulate matter health studies have been conducted in China. The study objective was to examine the association of particulate matter with an aerodynamic diameter of less than 10 μm (PM(10)) with daily mortality in 16 Chinese cities between 1996 and 2008. Two-stage Bayesian hierarchical models were applied to obtain city-specific and national average estimates. Poisson regression models incorporating natural spline smoothing functions were used to adjust for long-term and seasonal trends of mortality, as well as other time-varying covariates. The averaged daily concentrations of PM(10) in the 16 Chinese cities ranged from 52 μg/m(3) to 156 μg/m(3). The 16-city combined analysis showed significant associations of PM(10) with mortality: A 10-μg/m(3) increase in 2-day moving-average PM(10) was associated with a 0.35% (95% posterior interval (PI): 0.18, 0.52) increase of total mortality, 0.44% (95% PI: 0.23, 0.64) increase of cardiovascular mortality, and 0.56% (95% PI: 0.31, 0.81) increase of respiratory mortality. Females, older people, and residents with low educational attainment appeared to be more vulnerable to PM(10) exposure. Conclusively, this largest epidemiologic study of particulate air pollution in China suggests that short-term exposure to PM(10) is associated with increased mortality risk.
AMP-activated protein kinase (AMPK) is a metabolic sensor in mammals that is activated when ATP levels in the cell decrease. AMPK is a heterotrimeric protein that comprises 3 subunits, each of which has multiple phosphorylation sites that play critical roles in the regulation of either anabolism or catabolism by directly phosphorylating proteins or modulating gene transcription in multiple pathways, such as synthesis, oxidation and lipolysis of lipid. Research focused on the phosphorylation sites that are involved in lipid metabolism will lead to a better recognition of the role of AMPK in therapeutics for several common diseases. In this review, close attention is paid to the recent research on the structure, and multisite phosphorylation of AMPK subunits, as well as AMPK regulation of lipid metabolism via phosphorylation of related molecules.
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