Helicobacter exploits integrin for type IV secretion and kinase activation

Integrins are important mammalian receptors involved in normal cellular functions as well as pathogenesis of chronic inflammation and cancer. We propose that integrins are exploited by the gastric pathogen and type-1 carcinogen Helicobacter pylori for injection of the bacterial oncoprotein cytotoxin-associated gene A (CagA) into gastric epithelial cells. Virulent H. pylori express a type-IV secretion pilus that injects CagA into the host cell; CagA then becomes tyrosine-phosphorylated by Src family kinases. However, the identity of the host cell receptor involved in this process has remained unknown. Here we show that the H. pylori CagL protein is a specialized adhesin that is targeted to the pilus surface, where it binds to and activates integrin alpha5beta1 receptor on gastric epithelial cells through an arginine-glycine-aspartate motif. This interaction triggers CagA delivery into target cells as well as activation of focal adhesion kinase and Src. Our findings provide insights into the role of integrins in H.-pylori-induced pathogenesis. CagL may be exploited as a new molecular tool for our further understanding of integrin signalling.     

Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2

Adipocyte fatty-acid-binding protein, aP2 (FABP4) is expressed in adipocytes and macrophages, and integrates inflammatory and metabolic responses. Studies in aP2-deficient mice have shown that this lipid chaperone has a significant role in several aspects of metabolic syndrome, including type 2 diabetes and atherosclerosis. Here we demonstrate that an orally active small-molecule inhibitor of aP2 is an effective therapeutic agent against severe atherosclerosis and type 2 diabetes in mouse models. In macrophage and adipocyte cell lines with or without aP2, we also show the target specificity of this chemical intervention and its mechanisms of action on metabolic and inflammatory pathways. Our findings demonstrate that targeting aP2 with small-molecule inhibitors is possible and can lead to a new class of powerful therapeutic agents to prevent and treat metabolic diseases such as type 2 diabetes and atherosclerosis.     

Gadd45a promotes epigenetic gene activation by repair-mediated DNA demethylation

DNA methylation is an epigenetic modification that is essential for gene silencing and genome stability in many organisms. Although methyltransferases that promote DNA methylation are well characterized, the molecular mechanism underlying active DNA demethylation is poorly understood and controversial. Here we show that Gadd45a (growth arrest and DNA-damage-inducible protein 45 alpha), a nuclear protein involved in maintenance of genomic stability, DNA repair and suppression of cell growth, has a key role in active DNA demethylation. Gadd45a overexpression activates methylation-silenced reporter plasmids and promotes global DNA demethylation. Gadd45a knockdown silences gene expression and leads to DNA hypermethylation. During active demethylation of oct4 in Xenopus laevis oocytes, Gadd45a is specifically recruited to the site of demethylation. Active demethylation occurs by DNA repair and Gadd45a interacts with and requires the DNA repair endonuclease XPG. We conclude that Gadd45a relieves epigenetic gene silencing by promoting DNA repair, which erases methylation marks.     

发射端信道信息对MIMO下行链路的影响

在MIMO(Multiple-Input Multiple-Output)多用户下行链路中,当发射端具有完全的信道状态信息(CSI:Channel State Information),则可以通过块对角化预编码完全消除用户间干扰(IUI:Inte-User Interfer-ence)。但是,不准确的发射端CSI会导致接收端有残留的IUI。针对最大比合并(MRC:Maximal Ratio Combi-ning)接收机,考察了不准确的发射端CSI对MRC接收机输出的信干噪比(SINR:Signal to Interference plusNoise Ratio)的影响。考虑两个用户的情况,其天线数均为N,而基站的天线数为N 1。推导了SINR的中断概率的上界和下界,且它们之间有简单的关系。仿真结果证明了理论推导的正确性。     

序批式移动床生物膜反应器脱氮除磷特性及机理

为研究生物膜系统脱氮除磷的相关特性及机理,采用序批式移动床生物膜反应器(SBMBBR)处理模拟生活污水。分析代表性周期内各种形态氮、磷等营养元素的变化特点,并与对照组序批式活性污泥反应器(SBR)进行比较。利用显微技术及分子生物学技术对相关特性进行分析。结果表明:SBMBBR在单位质量污泥的化学需用量(COD)负荷为0.8g/(g.d)的条件下对总氮(TN)、总磷(TP)的去除效率分别为91.4%、90.0%,均高于同等条件下的SBR系统。在好氧阶段,生物膜系统内有76.0%的TN损失,表明发生了明显的好氧反硝化过程。利用荧光原位杂交技术(FISH)以及对生物膜微观结构电镜观察的结果表明:微生物的群落结构是SBMBBR脱氮除磷的重要生物学条件,而生物膜内部非均质结构提供了不同氧浓度环境,既为不同习性功能菌的富集提供了良好条件又成为好氧条件下的反硝化过程的关键因素。     

Human embryonic stem cells-derived endothelial cell therapy facilitates kidney regeneration by stimulating renal resident stem cell proliferation in acute kidney injury

Endothelial cell therapy has been implicated to enhance tissue regeneration and vascularization in ischemic kidney. However, no published study has yet examined direct effects of endothelial cell treatment in kidney recovery. This study investigated the therapeutic efficacy of endothelial cells in a mouse model with acute kidney injury (AKI). Thus, human embryonic stem cells-derived endothelial cells (hESC-ECs) labeled with a reporter system encoding a double fusion reporter gene for firefly luciferase (Fluc) and green fluorescent protein (GFP) were characterized by Fluc imaging and immunofluoresence staining. Cultured hESC-ECs (1×106) were injected into ischemic kidney shortly after AKI. Survival of the transplanted hESC-ECs was monitored in vivo from day 1 to 14 after endothelial cell transplantation and potential impact of hESC-EC treatment on renal regeneration was assessed by histological analyses. We report that a substantial level of bioluminescence activity was detected 24 h after hESC-EC injection followed by a gradual decline from 1 to 14 d. Human ESC-ECs markedly accelerated kidney cell proliferation in response to ischaemia-induced damage, indicated by an elevated number of BrdU+ cells. Co-expression of Sca-1, a kidney stem cell proliferation marker, and BrdU further suggested that the observed stimulation in renal cell regeneration was, at least in part, due to increased proliferation of renal resident stem cells especially within the medullary cords and arteriole. Differentiation of hESC-ECs to smooth muscle cells was also observed at an early stage of kidney recovery. In summary, our results suggest that endothelial cell therapy facilitates kidney recovery by promoting vascularization, trans-differentiation and endogenous renal stem cell proliferation in AKI.     

ATHK1 acts downstream of hydrogen peroxide to mediate ABA signaling through regulation of calcium channel activity in Arabidopsis guard cells

Plants gradually develop their ability to tolerate environmental water deficit as part of the evolutionary process.Abscisic acid(ABA) plays a critical role during drought and osmotic stress.Several histidine protein kinases are regarded as osmotic sensors or regulators in the adaptive response of plants to water deficit.In this study,we report that ATHK1,which was previously shown to function as an osmotic regulator,is involved in ABA-induced stomatal signaling in Arabidopsis.Mutants null for ATHK1 expression were unable to transmit normal ABA responses in guard cells,including inducing stomatal closure,producing hydrogen peroxide and activating calcium influx.Moreover,patch clamp and confocal analysis demonstrated that ATHK1 may function downstream of hydrogen peroxide in ABA-induced stomatal closure,by regulating calcium channel activity and calcium oscillation in Arabidopsis guard cells.     

Optical characterization of single-crystal diamond grown by DC arc plasma jet CVD

Optical centers of single-crystal diamond grown by DC arc plasma jet chemical vapor deposition (CVD) were examined using a low-temperature photoluminescence (PL) technique. The results show that most of the nitrogen-vacancy (NV) complexes are present as NV-centers, although some H2 and H3 centers and B-aggregates are also present in the single-crystal diamond because of nitrogen aggregation resulting from high N₂ incorporation and the high mobility of vacancies under growth temperatures of 950-1000℃. Furthermore, emissions of radiation-induced defects were also detected at 389, 467.5, 550, and 588.6 nm in the PL spectra. The reason for the formation of these radiation-induced defects is not clear. Although a Ni-based alloy was used during the diamond growth, Ni-related emissions were not detected in the PL spectra. In addition, the silicon-vacancy (Si-V)-related emission line at 737 nm, which has been observed in the spectra of many previously reported microwave plasma chemical vapor deposition (MPCVD) synthetic diamonds, was absent in the PL spectra of the single-crystal diamond prepared in this work. The high density of NV- centers, along with the absence of Ni-related defects and Si-V centers, makes the single-crystal diamond grown by DC arc plasma jet CVD a promising material for applications in quantum computing.     

分布式阵列相参合成雷达技术研究

分布式阵列相参合成雷达是继多输入多输出(multiple input multiple output, MIMO)雷达之后的一种新体制雷达技术,在介绍其基本概念的基础上,建立了分布式阵列相参合成雷达的基本理论模型,提出了适用于分布式阵列相参合成雷达MIMO工作模式的正交波形设计方法,首次给出了分布式阵列相参合成雷达的部分实验结果,实验结果与理论分析一致,证明了理论模型的正确性。     

Theoretical study of N(C)―H…H―B multi-dihydrogen bonds

The optimized geometries, frequencies and interaction energy corrected with basis set superposition error (BSSE) of the multi-dihydrogen bond complexes C₄H₄NH…BH₄^–. and CH≡CH…BH₄^–. have been calculated at both the B3LYP/6-311++G** and the MP2/6-311++G** levels. The calculations were per-formed to study the nature of the N―H…H3―B and C―H…H2―B red shift multi dihydrogen bond in complex C4H4NH…BH^–₄ and CH≡CH…BH4–. The BSSE-corrected multi-dihydrogen bond interaction en-ergy of complex I (C₄H₄NH…BH₄^–.) and complexⅡ(CH≡CH…BH₄^–.) is -76.62 and -33.79 kJ/mol (MP2/6- 311++G**), respectively. From the natural bond orbital（NBO）analysis, we detailedly discussed the orbital interactions, electron density transfers, rehybridizations and the essential of the correlative bond length changes in the two complexes. In addition, solvent effect on the geometric structures, vibration frequencies and interaction energy of the monomer and complexes was studied in detail. It is relevant to the relatively dielectric constants (ε).