Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east Asians

We conducted a meta-analysis of genome-wide association studies of systolic (SBP) and diastolic (DBP) blood pressure in 19,608 subjects of east Asian ancestry from the AGEN-BP consortium followed up with de novo genotyping (n = 10,518) and further replication (n = 20,247) in east Asian samples. We identified genome-wide significant (P < 5 × 10(-8)) associations with SBP or DBP, which included variants at four new loci (ST7L-CAPZA1, FIGN-GRB14, ENPEP and NPR3) and a newly discovered variant near TBX3. Among the five newly discovered variants, we obtained significant replication in the independent samples for all of these loci except NPR3. We also confirmed seven loci previously identified in populations of European descent. Moreover, at 12q24.13 near ALDH2, we observed strong association signals (P = 7.9 × 10(-31) and P = 1.3 × 10(-35) for SBP and DBP, respectively) with ethnic specificity. These findings provide new insights into blood pressure regulation and potential targets for intervention.     

Spatial and temporal evolutions of groundwater arsenic approximately along the flow path in the Hetao basin, Inner Mongolia

Patchy distribution of high As groundwater has normally been observed in As-affected areas. Spatial and temporal evolutions help in better understanding mechanisms of As mobilization and in developing effective strategies for ensuring drinking water safety. Four multilevel samplers were installed approximately along the groundwater flow path to investigate spatial and temporal variations in groundwater As in the Hetao basin, Inner Mongolia. Both water chemistry and groundwater level were monitored for about two years. Groundwater As concentration generally showed increasing trends, and Eh values showed decreasing trends along the flow path, indicating that As was mobilized via reductive dissolution of Fe oxides. However, in evaporation discharge area, shallow groundwater As was generally lower than those upstream and downstream. In addition to evaporation, siderite and pyrite precipitations controlled groundwater As concentrations. The negative correlations between As concentration and SIpyrite (or SIsiderite) implied that siderite and pyrite precipitations wold scavenge groundwater As and lower As concentration. Temporal variation showed different trends in different locations. It may reflect replenishment of high/low As groundwater for the increase/decrease in As concentrations, resulting from water level fluctuation. The increase trends in groundwater As concentrations at depth around 15m in the discharge areas would result from the increase in the recharge of underlying groundwater (20m) with high As concentration due to enhanced evaporation in the seasons with high water levels. The investigation suggested that monitoring of groundwater As should be routinely carried out to ensure the drinking water safety in the As-affected areas.     

Prediction of Essential Proteins Using Topological Properties in GO-Pruned PPI Network Based on Machine Learning Methods

The prediction of essential proteins, the minimal set required for a living cell to support cellular life, is an important task to understand the cellular processes of an organism. Fast progress in high-throughput technologies and the production of large amounts of data enable the discovery of essential proteins at the system level by analyzing Protein-Protein Interaction (PPI) networks, and replacing biological or chemical experiments. Furthermore, additional gene-level annotation information, such as Gene Ontology (GO) terms, helps to detect essential proteins with higher accuracy. Various centrality algorithms have been used to determine essential proteins in a PPI network, and, recently motif centrality GO, which is based on network motifs and GO terms, works best in detecting essential proteins in a Baker’s yeast Saccharomyces cerevisiae PPI network, compared to other centrality algorithms. However, each centrality algorithm contributes to the detection of essential proteins with different properties, which makes the integration of them a logical next step. In this paper, we construct a new feature space, named CENT-ING-GO consisting of various centrality measures and GO terms, and provide a computational approach to predict essential proteins with various machine learning techniques. The experimental results show that CENT-ING-GO feature space improves performance over the INT-GO feature space in previous work by Acencio and Lemke in 2009. We also demonstrate that pruning a PPI with informative GO terms can improve the prediction performance further.     

Neuroprotection against hypoxia/ischemia: δ-opioid receptor-mediated cellular/molecular events

Hypoxic/ischemic injury remains the most dreaded cause of neurological disability and mortality. Despite the humbling experiences due to lack of promising therapy, our understanding of the complex cascades underlying the neuronal insult has led to advances in basic science research. One of the most noteworthy has been the effect of opioid receptors, especially the delta-opioid receptor (DOR), on hypoxic/ischemic neurons. Our recent studies, and those of others worldwide, present strong evidence that sheds light on DOR-mediated neuroprotection in the brain, especially in the cortex. The mechanisms of DOR neuroprotection are broadly categorized as: (1) stabilization of the ionic homeostasis, (2) inhibition of excitatory transmitter release, (3) attenuation of disrupted neuronal transmission, (4) increase in antioxidant capacity, (5) regulation of intracellular pathways—inhibition of apoptotic signals and activation of pro-survival signaling, (6) regulation of specific gene and protein expression, and (7) up-regulation of endogenous opioid release and/or DOR expression. Depending upon the severity and duration of hypoxic/ischemic insult, the release of endogenous opioids and DOR expression are regulated in response to the stress, and DOR signaling acts at multiple levels to confer neuronal tolerance to harmful insult. The phenomenon of DOR neuroprotection offers a potential clue for a promising target that may have significant clinical implications in our quest for neurotherapeutics.     

Duplication of the MYB oncogene in T cell acute lymphoblastic leukemia

We identified a duplication of the MYB oncogene in 8.4% of individuals with T cell acute lymphoblastic leukemia (T-ALL) and in five T-ALL cell lines. The duplication is associated with a threefold increase in MYB expression, and knockdown of MYB expression initiates T cell differentiation. Our results identify duplication of MYB as an oncogenic event and suggest that MYB could be a therapeutic target in human T-ALL.     

采用BDMA从硫酸溶液中液–液萃取分离磷

This study addresses the liquid-liquid extraction behavior of phosphorus from a sulfuric acid solution using benzyl dimethyl amine (BDMA) in kerosene. The extraction equilibria investigated with varied BDMA concentrations could reveal the formation of3[BDMA]·[H3PO4]complex in the organic phase. The thermodynamic properties determined at various temperatures indicated that the pro-cess was exothermic with a calculated enthalpy (△H(〇)) of ?24.0 kJ·mol?1. The organic-to-aqueous phase (O/A) volume ratio was varied to elu-cidate the quantitative extraction of phosphorus. The McCabe-Thiele diagram plotted for the extraction isotherm was validated for the require-ment of three counter-current stages in the extraction at an O/A volume ratio of 2.0/3.5. The back-extraction of phosphorus from the loaded or-ganic phase was quantitatively achieved by contacting 4.0 mol·L?1 H2SO4 solution in three stages of counter-current contact at an O/A volume ratio of 3/2. This study can be applied to remove phosphorus from the sulfuric acid leach solutions of monazite processing, and many other solutions.     

大气环境影响评价AirEIA软件开发

针对大气环境影响评价过程巨量的计算和繁琐的绘图,利用Visual C .NET开发出具有良好界面,能够快速进行数据处理、浓度预测、图形制作等功能为一体的系统软件AirEIA.介绍了该软件的框架及软件各部分的功能,以工程实例说明了该软件的运行效果并分析总结了该软件的特点.     

The Shigella flexneri effector OspI deamidates UBC13 to dampen the inflammatory response

Many bacterial pathogens can enter various host cells and then survive intracellularly, transiently evade humoral immunity, and further disseminate to other cells and tissues. When bacteria enter host cells and replicate intracellularly, the host cells sense the invading bacteria as damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) by way of various pattern recognition receptors. As a result, the host cells induce alarm signals that activate the innate immune system. Therefore, bacteria must modulate host inflammatory signalling and dampen these alarm signals. How pathogens do this after invading epithelial cells remains unclear, however. Here we show that OspI, a Shigella flexneri effector encoded by ORF169b on the large plasmid and delivered by the type ΙΙΙ secretion system, dampens acute inflammatory responses during bacterial invasion by suppressing the tumour-necrosis factor (TNF)-receptor-associated factor 6 (TRAF6)-mediated signalling pathway. OspI is a glutamine deamidase that selectively deamidates the glutamine residue at position 100 in UBC13 to a glutamic acid residue. Consequently, the E2 ubiquitin-conjugating activity required for TRAF6 activation is inhibited, allowing S. flexneri OspI to modulate the diacylglycerol-CBM (CARD-BCL10-MALT1) complex-TRAF6-nuclear-factor-κB signalling pathway. We determined the 2.0 ? crystal structure of OspI, which contains a putative cysteine-histidine-aspartic acid catalytic triad. A mutational analysis showed this catalytic triad to be essential for the deamidation of UBC13. Our results suggest that S. flexneri inhibits acute inflammatory responses in the initial stage of infection by targeting the UBC13-TRAF6 complex.     

A new atmospherically relevant oxidant of sulphur dioxide

Atmospheric oxidation is a key phenomenon that connects atmospheric chemistry with globally challenging environmental issues, such as climate change, stratospheric ozone loss, acidification of soils and water, and health effects of air quality. Ozone, the hydroxyl radical and the nitrate radical are generally considered to be the dominant oxidants that initiate the removal of trace gases, including pollutants, from the atmosphere. Here we present atmospheric observations from a boreal forest region in Finland, supported by laboratory experiments and theoretical considerations, that allow us to identify another compound, probably a stabilized Criegee intermediate (a carbonyl oxide with two free-radical sites) or its derivative, which has a significant capacity to oxidize sulphur dioxide and potentially other trace gases. This compound probably enhances the reactivity of the atmosphere, particularly with regard to the production of sulphuric acid, and consequently atmospheric aerosol formation. Our findings suggest that this new atmospherically relevant oxidation route is important relative to oxidation by the hydroxyl radical, at least at moderate concentrations of that radical. We also find that the oxidation chemistry of this compound seems to be tightly linked to the presence of alkenes of biogenic origin.