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.

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Agricultural activities, especially reclamation, are considered major threats to the wetland ecosystems in Sanjiang Plain, the largest concentrated area of the freshwater wetlands in China. In the past decades, the area of the cultivated land and its grain production have been increased at the cost of wetlands shrinkage. The large-scale land reclamation severely affected the ecosystems in this region. However, such effects at the regional scale are seldom evaluated quantitatively. We used three datasets of LANDSAT MSS and/or TM imagery to estimate the area changes and the transition of land use types from 1980 to 2000. We also valued changes in ecosystem services delivered by each land category using value coefficients published by Costanza et al. Sensitivity analysis suggested that these estimates were relatively robust. Finally, the contribution of various ecosystem functions was ranked to the overall value of the ecosystem services in this study. According to our estimates, the total annual ecosystem service values in Sanjiang Plain have declined by about 40% between 1980 and 2000 (156284-182572.18 million US dollars in total over 20 years). This substantial decline is largely attributed to the 53.4% loss of wetlands. For individual ecosystem functions, waste treatment, water supply and disturbance regulation account for more than 60% to the total ecological values. During those two decades, the contribution of disturbance regulation, cultural and recreation decreased, while the contribution of water regulation, nutrient cycling, food production, raw materials and climate regulation increased during the same period. We also put forward a few proposals concerning the future land use policy formulation and sustainable ecosystems. They are adjusting the 'food first' agricultural policy, establishing more nature reserves for wetlands, creating systems for the rational use of water, harnessing the degraded cultivated land and encouraging eco-tourism.

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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.

Although the relationship between asthma and exposure to fine particulate matter (PM2.5) has been frequently measured, reported conclusions have not been consistent. As emergency department (ED) visits are an effective way to estimate health outcomes for people with asthma and short-term exposure to PM2.5, this review systematically searched five databases without language or geographical restrictions from inception to January 13, 2015 to study the impact of PM2.5 on asthma ED visits. A random-effects model was used to calculate the pooled risk ratio (RR) and 95% confidence intervals (CI). With respect to short-term effects, asthma ED visits increased at higher PM2.5 concentrations (RR 1.5% per 10 μg/m(3); 95% CI 1.2-1.7%), and children were more susceptible (3.6% per 10 μg/m(3); 95% CI 1.8, 5.3%) than adults (1.7, 95% CI 0.7%, 2.8%) to increased PM2.5; the ED visits increased during the warm season by 3.7% (95% CI 0.5, 6.9%) per 10 μg/m(3) increase in PM2.5, which was higher than the corresponding increase during the cold season (2.6, 95% CI 0.7-4.6%). This demonstrates that ambient PM2.5 has an adverse impact on asthma ED visits after short-term exposure and that children are a high-risk population when PM2.5 concentrations are high, particularly in warm seasons, during which measures should be taken to prevent PM2.5.

Background After myocardial infarction (MI), the left ventricle (LV) undergoes a wound healing response that includes the robust infiltration of neutrophils and macrophages to facilitate removal of dead myocytes as well as turnover of the extracellular matrix (ECM). Matrix metalloproteinase (MMP)-9 is a key enzyme that regulates post-MI LV remodeling. Methods and Results Infarct regions from wild type and MMP-9 null mice (n=8/group) analyzed by glycoproteomics showed that of 541 N-glycosylated proteins quantified, 45 proteins were at least two-fold up- or down-regulated with MMP-9 deletion (all p<0.05). Cartilage intermediate layer protein (CILP) and platelet glycoprotein 4 (CD36) were identified as having the highest fold increase in MMP-9 null mice. By immunoblotting, CD36 but not CILP decreased steadily over the time course post-MI, which identified CD36 as a candidate MMP-9 substrate. MMP-9 was confirmed in vitro and in vivo to proteolytically degrade CD36. In vitro stimulation of day 7 post-MI macrophages with MMP-9 or a CD36 blocking peptide reduced phagocytic capacity. Dual immunofluorescence revealed concomitant accumulation of apoptotic neutrophils in the MMP-9 null group compared to WT. In vitro stimulation of isolated neutrophils with MMP-9 decreased neutrophil apoptosis, indicated by reduced caspase-9 expression. Conclusions Our data reveals a new cell signaling role for MMP-9 through CD36 degradation to regulate macrophage phagocytosis and neutrophil apoptosis.