A small molecule Smac mimic potentiates TRAIL- and TNFalpha-mediated cell death

We describe the synthesis and properties of a small molecule mimic of Smac, a pro-apoptotic protein that functions by relieving inhibitor-of-apoptosis protein (IAP)-mediated suppression of caspase activity. The compound binds to X chromosome- encoded IAP (XIAP), cellular IAP 1 (cIAP-1), and cellular IAP 2 (cIAP-2) and synergizes with both tumor necrosis factor alpha (TNFalpha) and TNF-related apoptosis-inducing ligand (TRAIL) to potently induce caspase activation and apoptosis in human cancer cells. The molecule has allowed a temporal, unbiased evaluation of the roles that IAP proteins play during signaling from TRAIL and TNF receptors. The compound is also a lead structure for the development of IAP antagonists potentially useful as therapy for cancer and inflammatory diseases.     

8个碗莲品种的DNA指纹鉴定

利用RAPD标记技术,对8个碗莲品种进行了遗传多态性分析,从70个10碱基随机引物中,筛选出多态性频率较高的引物4个:S87、S110、S130、S473,扩增后共得到14条多态性条带,平均多态性为70%.选择6条清晰度高的多态性条带绘制8个碗莲品种的指纹图谱,在该图谱中每个品种均有各自特异的DNA指纹.研究结果为碗莲品种的鉴定和保护提供了一种有效的方法.     

小分子有机酸对纳米颗粒CNTs和SBA-15在多孔介质中迁移的影响

【目的】了解有机酸对硅酸盐纳米颗粒(SBA-15)和碳纳米管(CNTs)在多孔介质中迁移行为的影响差异。【方法】采用恒定流速柱迁移试验,探讨不同浓度(0,1,2.5和5 mmol/L)乙酸、酒石酸、柠檬酸对CNTs和SBA-15纳米颗粒在多孔介质(石英砂)中穿透曲线的影响。【结果】平衡对流-弥散方程能描述多孔介质中CNTs和SBA-15迁移过程的穿透曲线。在石英砂多孔介质中,CNTs的迁移能力强于SBA-15。体系不含有机酸时,CNTs、SBA-15流出液中的纳米颗粒浓度(C)与纳米悬液进入砂柱前的初始浓度(C_0)比值(C/C_0)的峰值分别为0.74和0.25,最远迁移距离L_(max)分别为221.2和45.1cm。3种有机酸对CNTs和SBA-15在多孔介质中的迁移具有类似的抑制作用,随着介质中3种有机酸浓度的增加,CNTs和SBA-15纳米颗粒的C/C_0减小,C/C_0平台峰值对应空隙体积(PV)倍数增大,迁移阻滞因子R和不可逆吸附系数μ增大,最远迁移距离L_(max)减小。柠檬酸对CNTs和SBA-15迁移的抑制作用强于乙酸和酒石酸。Zeta电位分析表明,当体系中引入有机酸后,随着有机酸浓度的增加,石英砂、CNTs和SBA-15纳米颗粒悬液的Zeta电位均逐渐增大。【结论】有机酸会改变多孔介质和CNTs、SBA-15这2种纳米颗粒的表面电荷特征,从而使得纳米颗粒悬液在多孔介质中的迁移行为更容易受团聚、滞留和沉积作用的影响。不管在何种有机酸中,CNTs的迁移能力均强于SBA-15。     

From knowing to controlling: a path from genomics to drugs using small molecule probes

The National Cancer Institute Initiative in Chemical Genetics is designed to encourage the development of small molecular probes. The probes are useful for activating or inactivating protein functions, thereby providing resources that help discern the functions of gene products in normal and disease cells, as well as in tissues. This initiative includes "ChemBank," a suite of informatics tools and databases aimed at promoting the development and use of chemical genetics by scientists worldwide. The information generated with such tools should provide a critical link from genomic discovery to drug development.     

不同类型猪小肠组织差异EST的鉴定及其SNPs分析

采用DDRT-PCR技术,对中国地方猪种和杜长大（大白×长白×杜洛克）猪的小肠组织进行差异EST分析。试验提取了地方猪和杜长大猪小肠组织的总mRNA,反转录成cDNA,利用3条锚定引物和6条随机引物组成18个引物对其进行PCR扩增,对特异性差异条带进行测序分析和鉴定其EST;针对EST序列特征,在不同产脂能力猪种中开展SNPs分析。结果表明,18个引物对共得到180多条EST序列,其中地方猪种个体间差异EST为6条,杜长大猪个体间差异EST为12条,地方猪与杜长大猪间差异EST为8条。选取具有代表性的3条种群间差异EST进行序列研究,结果显示,G24-300在种群之间的表达量存在明显的差异,是在杜长大猪群中高表达的EST;G01-360具有丰富的SNPs,并且其基因频率分布在不同类型猪群中存在明显的差异。     

石斛药理作用研究进展

目的筛选合适的DNA条形码序列并建立高效准确鉴定药用石斛(Dendrobium)的方法。方法以12种药用石斛的82个样品为材料,提取样品总DNA,对核基因片段ITS和ITS2、叶绿体基因片段psbA-trnH和matK序列进行扩增和测序;利用生物信息学软件进行序列特征、DNA条形码序列间隔(barcoding gap)和系统发育分析。结果4条序列扩增成功率均为100%,其中ITS和ITS2测序成功率最高,均为97.6%,其次是matK为96.3%,psbA-trnH为95.1%;ITS和ITS2序列与其他序列相比,种内和种间存在重叠的部分较少,具有条形码序列间隔。系统发育树表明：ITS和ITS2序列能够成功区分12种药用石斛及混伪品,psbA-trnH序列未能把叠鞘石斛(D. aurantiacum Rchb. f. var. denneanum)、双斑叠鞘石斛(D. aurantiacum Rchb. f. var. zhaojuense)和流苏石斛(D. fimbriatum)以及混伪品全部区分开,matK序列未能把叠鞘石斛和流苏石斛区分开;4条序列联合构建的系统发育树与ITS和ITS2单序列构建的系统发育树相似。结论以ITS和ITS2序列为主,psbA-trnH和matK序列为辅的DNA条形码鉴定方法能够对药用石斛及其混伪品进行快速准确的鉴定。     

Generation of an LFA-1 antagonist by the transfer of the ICAM-1 immunoregulatory epitope to a small molecule

The protein-protein interaction between leukocyte functional antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) is critical to lymphocyte and immune system function. Here, we report on the transfer of the contiguous, nonlinear epitope of ICAM-1, responsible for its association with LFA-1, to a small-molecule framework. These LFA-1 antagonists bound LFA-1, blocked binding of ICAM-1, and inhibited a mixed lymphocyte reaction (MLR) with potency significantly greater than that of cyclosporine A. Furthermore, in comparison to an antibody to LFA-1, they exhibited significant anti-inflammatory effects in vivo. These results demonstrate the utility of small-molecule mimics of nonlinear protein epitopes and the protein epitopes themselves as leads in the identification of novel pharmaceutical agents.     

不同活化剂对磷矿粉的活化作用

以沸石、膨润土、糠醛渣为活化剂，研究了不同活化剂对磷矿粉的活化作用，结果表明：沸石产地不同进对同一磷矿粉的增效作用不同，且沸石对磷矿粉的活化作用随土壤性质而异，在北方含Ｎa^ 较高的盐化潮土上速效磷增加了１８２．９％，膨润土、糠醛渣作为活化剂也可提高磷矿粉中磷的释放。     

A molecule carrier

We found that anthraquinone diffuses along a straight line across a flat, highly symmetric Cu111 surface. It can also reversibly attach one or two CO2 molecules as "cargo" and act as a "molecule carrier," thereby transforming the diffusive behavior of the CO2 molecules from isotropic to linear. Density functional theory calculations indicated a substrate-mediated attraction of approximately 0.12 electron volt (eV). Scanning tunneling microscopy revealed individual steps of the molecular complex on its diffusion pathway, with increases of approximately 0.03 and approximately 0.02 eV in the diffusion barrier upon attachment of the first and second CO2 molecule, respectively.     

小麦小分子RNA TaMIR1129介导植株抵御低氮逆境功能研究

本研究针对迄今有关小麦小分子RNA(miRNA)家族成员介导植株氮素吸收和利用机理尚少见报道的现状,对TaMIR1129的表达特征和介导植株抵御低氮逆境功能进行了研究。结果表明,TaMIR1129呈低氮胁迫诱导表达,表现为随氮浓度降低(0.02~6mmol/L)和处理时间延长(0~48h)表达水平不断增高特征。此外,低氮诱导的高表达水平在恢复供氮后表达下调。表明该miRNA对介质中氮素应答呈典型的时间及浓度依赖特征。TaMIR1129作用2个靶基因,包括Molybdenum cofactor sulfurase(TaMCS)和Major facilitator family transporter(TaMFFT),上述基因应答低氮特征与TaMIR1129相反。遗传转化结果表明,超表达TaMIR1129具有显著增强植株抵御低氮逆境的能力。表现为与野生型对照相比,转基因系Sen 1和Sen 2低氮处理后植株形态增大,干质量增加,氮累积量增多。表明TaMIR1129与作用靶基因构建miRNA/target模块在介导植株抵御低氮逆境中发挥重要作用。     

Allosteric activators of glucokinase: potential role in diabetes therapy

Glucokinase (GK) plays a key role in whole-body glucose homeostasis by catalyzing the phosphorylation of glucose in cells that express this enzyme, such as pancreatic beta cells and hepatocytes. We describe a class of antidiabetic agents that act as nonessential, mixed-type GK activators (GKAs) that increase the glucose affinity and maximum velocity (Vmax) of GK. GKAs augment both hepatic glucose metabolism and glucose-induced insulin secretion from isolated rodent pancreatic islets, consistent with the expression and function of GK in both cell types. In several rodent models of type 2 diabetes mellitus, GKAs lowered blood glucose levels, improved the results of glucose tolerance tests, and increased hepatic glucose uptake. These findings may lead to the development of new drug therapies for diabetes.     

Synthesis beyond the molecule

Weak, noncovalent interactions between molecules control many biological functions. In chemistry, noncovalent interactions are now exploited for the synthesis in solution of large supramolecular aggregates. The aim of these syntheses is not only the creation of a particular structure, but also the introduction of specific chemical functions in these supramolecules.     

Probing single molecule dynamics

The room temperature dynamics of single sulforhodamine 101 molecules dispersed on a glass surface are investigated on two different time scales with near-field optics. On the 10(-2)- to 10(2)-second time scale, intensity fluctuations in the emission from single molecules are examined with polarization measurements, providing insight into their spectroscopic properties. On the nanosecond time scale, the fluorescence lifetimes of single molecules are measured, and their excited-state energy transfer to the aluminum coating of the near-field probe is characterized. A movie of the time-resolved emission demonstrates the feasibility of fluorescence lifetime imaging with single molecule sensitivity, picosecond temporal resolution, and a spatial resolving power beyond the diffraction limit.