Determinants for High Maternal Mortality in Multiethnic Populations in Western China

Our purpose of this study was to investigate determinants and patterns of associations with high maternal mortality in poor and multiethnic populations from the Xinjiang Uigur autonomous region of Western China. The researcher found that the maternal mortality ratio of Xinjiang was very high; almost half of the participants delivered at home without clean delivery, and nearly one-fifth of the participants had not received any medical treatment. Eighty-seven percent of maternal deaths were among ethnic minority groups. In multiethnic areas in Xinjiang, social–culture factors, lack of health resources, and low health services utilization were related to high maternal mortality.     

Mutant methionyl-tRNA synthetase from bacteria enables site-selective N-terminal labeling of proteins expressed in mammalian cells

Newly synthesized cellular proteins can be tagged with a variety of metabolic labels that distinguish them from preexisting proteins and allow them to be identified and tracked. Many such labels are incorporated into proteins via the endogenous cellular machinery and can be used in numerous cell types and organisms. Though broad applicability has advantages, we aimed to develop a strategy to restrict protein labeling to specified mammalian cells that express a transgene. Here we report that heterologous expression of a mutant methionyl-tRNA synthetase from Escherichia coli permits incorporation of azidonorleucine (Anl) into proteins made in mammalian (HEK293) cells. Anl is incorporated site-selectively at N-terminal positions (in competition with initiator methionines) and is not found at internal sites. Site selectivity is enabled by the fact that the bacterial synthetase aminoacylates mammalian initiator tRNA, but not elongator tRNA. N-terminally labeled proteins can be selectively conjugated to a variety of useful probes; here we demonstrate use of this system in enrichment and visualization of proteins made during various stages of the cell cycle. N-terminal incorporation of Anl may also be used to engineer modified proteins for therapeutic and other applications.     

Histone deacetylase inhibitor induces DNA damage,which normal but not transformed cells can repair

Histone deacetylase inhibitors (HDACi) developed as anti-cancer agents have a high degree of selectivity for killing cancer cells. HDACi induce acetylation of histones and nonhistone proteins, which affect gene expression, cell cycle progression, cell migration, and cell death. The mechanism of the tumor selective action of HDACi is unclear. Here, we show that the HDACi, vorinostat (Suberoylanilide hydroxamic acid, SAHA), induces DNA double-strand breaks (DSBs) in normal (HFS) and cancer (LNCaP, A549) cells. Normal cells in contrast to cancer cells repair the DSBs despite continued culture with vorinostat. In transformed cells, phosphorylated H2AX (γH2AX), a marker of DNA DSBs, levels increased with continued culture with vorinostat, whereas in normal cells, this marker decreased with time. Vorinostat induced the accumulation of acetylated histones within 30 min, which could alter chromatin structure-exposing DNA to damage. After a 24-h culture of cells with vorinostat, and reculture without the HDACi, γH2AX was undetectable by 2 h in normal cells, while persisting in transformed cells for the duration of culture. Further, we found that vorinostat suppressed DNA DSB repair proteins, e.g., RAD50, MRE11, in cancer but not normal cells. Thus, the HDACi, vorinostat, induces DNA damage which normal but not cancer cells can repair. This DNA damage is associated with cancer cell death. These findings can explain, in part, the selectivity of vorinostat in causing cancer cell death at concentrations that cause little or no normal cell death.     

Physical activity attenuates the effect of increased left ventricular mass on the risk of ischemic stroke: The Northern Manhattan Stroke Study

OBJECTIVES: The goal of this study was to determine whether the risk of ischemic stroke associated with increased left ventricular mass (LVM) is modified by physical activity (PA). BACKGROUND: Increased LVM is associated with an increased risk for stroke. Physical activity can decrease the risk of stroke and may have variable effects on LVM. METHODS: We used a case-control study design in a multiethnic population in northern Manhattan, New York, to study 394 case subjects who had a first ischemic stroke and 413 stroke-free control subjects. All subjects were interviewed and two-dimensional echocardiograms obtained to determine LVM. RESULTS: A sharp increase in risk of ischemic stroke was seen in the highest quartile of LVM (odds ratio [OR]: 6.14 [95% confidence interval [CI]: 3.04 to 12.38]). Thus, increased LVM was defined by the highest quartile of LVM. In multivariate analysis, the effect of increased LVM on the risk of stroke was significantly decreased by the presence of any level of PA versus no PA (OR: 1.59 [95% CI: 0.99 to 2.57] p < 0.07 vs. 3.53 [95% CI: 1.94 to 6.42] p < 0.0001). Although PA decreased the risk of stroke in all patients, the effect was stronger in subjects with increased LVM than among those without increased LVM (p = 0.033). CONCLUSIONS: Increased LVM is associated with an increased risk of stroke, especially among sedentary patients. Physical activity decreases the risk of stroke among patients with increased LVM to a level comparable to that of patients without increased LVM. Recommending PA may be a nonpharmacologic tool to reduce the stroke risk, especially among patients with increased LVM.