Community-wide assessment of protein-interface modeling suggests improvements to design methodology

The CAPRI (Critical Assessment of Predicted Interactions) and CASP (Critical Assessment of protein Structure Prediction) experiments have demonstrated the power of community-wide tests of methodology in assessing the current state of the art and spurring progress in the very challenging areas of protein docking and structure prediction. We sought to bring the power of community-wide experiments to bear on a very challenging protein design problem that provides a complementary but equally fundamental test of current understanding of protein-binding thermodynamics. We have generated a number of designed protein-protein interfaces with very favorable computed binding energies but which do not appear to be formed in experiments, suggesting that there may be important physical chemistry missing in the energy calculations. A total of 28 research groups took up the challenge of determining what is missing: we provided structures of 87 designed complexes and 120 naturally occurring complexes and asked participants to identify energetic contributions and/or structural features that distinguish between the two sets. The community found that electrostatics and solvation terms partially distinguish the designs from the natural complexes, largely due to the nonpolar character of the designed interactions. Beyond this polarity difference, the community found that the designed binding surfaces were, on average, structurally less embedded in the designed monomers, suggesting that backbone conformational rigidity at the designed surface is important for realization of the designed function. These results can be used to improve computational design strategies, but there is still much to be learned; for example, one designed complex, which does form in experiments, was classified by all metrics as a nonbinder.     

Prognostic molecular markers in pediatric liver disease – Are there any?

Pediatric liver disease (PLD) is a major cause of severe morbidity and prolonged hospitalizations in children. Stratifying patients in terms of prognosis remains challenging. The limited knowledge about molecular mechanisms causing and accompanying PLD remains the main obstacle in a search for reliable prognostic biomarkers. A systematic search of MEDLINE via PubMed and Embase via OVID was conducted on studies published between August 2007 and August 2017. Molecular markers with a prognostic potential in terms of survival, need for liver transplantation or disease progression/regression were selected. In general, identified studies were single center smaller case-control studies or case series with a low level of evidence and a high risk of bias. Only 23 studies comprising 898 patients could be included, mostly focusing on biliary atresia, non-alcoholic fatty liver disease, viral hepatitis, and LT; and markers related to morphogenesis and fibrosis. Furthermore, molecular markers in metabolic pathways and inflammation shown to be relevant, however requiring further validation. Hence, further biological and clinical studies are needed to gain greater molecular insight into PLD.     

蛋白质氯胺-T双相碘标法的建立及其应用

常规的蛋白质碘标方法易引起被标细胞因子的失活,是受体配基竞争结合实验失败的原因之一.试用氯胺-T双相碘标法标记rhG-CSF和rhEPO,并应用受体配基竞争结合分析法测定NFS-60细胞G-CSF受体及BET-2细胞EPO受体的特性.结果显示所获 ¹²⁵I-EPO和 ¹²⁵I-G-CSF放射比活度均较高;发现BET-2细胞有高、低两种亲和力的EPO受体,NFS-60细胞只有一种高亲和力的G-CSF受体,所获结果与文献资料相一致.说明氯胺-T双相碘标法是细胞因子同位素碘标记的理想方法之一.     

The utility of inflammation and platelet biomarkers in patients with acute coronary syndromes

Introduction

Thrombotic and inflammatory mechanisms are involved in the pathophysiology of acute coronary syndrome (ACS). The aim of the study was the evaluation of inflammation (white blood cells count/WBC, C-reactive protein/CRP, interleukin-6/IL-6) and platelet (platelet count/PLT, mean platelet volume/MPV, large platelet/LPLT, beta-thromboglobulin/β-TG) biomarkers in the groups of ACS patients depending on the severity of signs and symptoms and compared to controls without coronary artery disease.

种子脱水耐性及其与种子类型和发育阶段的相关性

种子脱水耐性是种子发育过程中获得的综合特性,是判断种子贮藏持性的一个重要依据。当种子获得脱水耐性时,生理,形态和结构会发生相应的变化,包括糖,蛋白质,脂类和抗氧化系统等保护性物质的合成,各种保护性物质不是单独作用的,而是协同调节种子的脱水耐性。不同的植物种子,其脱水耐性不同,并且随着种子的发育而变化。关于种子脱水耐性的获得,主要有2种观点,一种认为是数量性状,另一种认为是突变性状。种子库收集种子保存时,适时采集和适度脱水才能有效地延长种子的贮藏寿命。     

福建省直播稻根结线虫病的病原种类鉴定

[目的] 福建省福清市江镜镇与福安市潭溪镇水稻区直播稻苗期分别发生严重的根结线虫病,本研究对其病原物进行形态和分子鉴定,明确病原物种类,以期为福建省直播稻根结线虫病害防控提供理论依据。[方法] 通过根结线虫各虫态形态学特征进行观测;同时对其rDNA-ITS区进行测序,通过贝叶斯法与最大似然法构建了系统发育树来确定种类;利用拟禾本科根结线虫特异性引物Mg-F/Mg-R检测种群。[结果] 根结线虫的雌虫、雄虫和2龄幼虫的形态学特征与拟禾本科根结线虫原始描述种一致;rDNA-ITS区序列长度为576 bp,与GenBank拟禾本科根结线虫种群相似度均达99%以上;系统发育树明确了该根结线虫与拟禾本科根结线虫处于同一分支;特异性引物Mg-F/Mg-R检测进一步明确病原为拟禾本科根结线虫单一种群。[结论] 本研究通过形态与分子特征,明确了在福建直播稻上发现的根结线虫为拟禾本科根结线虫。拟禾本科根结线虫在福建省最早于2011年在政和县小范围水稻田发现,此后未在其他水稻种植区发现。本次在福建直播稻上首次发现大面积的根结线虫为害。随着直播稻的种植面积扩大,拟禾本根结线虫引起的水稻病害可能会成为制约其发展的新问题,应引起足够重视。     

弱背景噪声对大鼠听皮层神经元频率调谐的影响

在自然环境中,人和动物常在一定的背景噪声下感知信号声刺激,然而,关于低强度的弱背景噪声如何影响听皮层神经元对声刺激频率的编码尚不清楚.本研究以大鼠听皮层神经元的频率反应域为研究对象,测定了阈下背景噪声对79个神经元频率反应域的影响.结果表明,弱背景噪声对大鼠初级听皮层神经元的听反应既有抑制性影响、又有易化性影响.一般来说,抑制性影响使神经元的频率调谐范围和最佳频率反应域缩小,易化性影响使神经元的频率调谐范围和最佳频率反应域增大.对于少数神经元,弱背景噪声并未显著改变其频率调谐范围,但却改变了其最佳频率反应域范围.弱背景噪声对63.64%神经元的特征频率和55.84%神经元的最低阈值无显著影响.神经元频率调谐曲线的尖部比中部更容易受到弱背景噪声的影响.该研究结果有助于我们进一步理解复杂声环境下大脑听皮层对听觉信息的编码机制.     

不同砧木嫁接番茄光合特性的研究

采用LI-6400便携式光合作用系统对田间条件下嫁接番茄(珍红/砧木1号,珍红/桂砧1号)以及接穗(珍红)的光合作用特性进行了系统研究。结果表明:自根苗的光饱和点显著高于嫁接苗;自根苗和嫁接苗的光补偿点差异不显著,以珍红/桂砧1号最高(31.8μmolphotons·m-2·s-1),珍红/砧木1号最低(17.6μmolphotons·m-2·s-1);嫁接苗的CO2补偿点显著低于自根苗,且珍红/桂砧1号与自根苗的差异达极显著水平;表观量子效率变化范围为0.062~0.073;CO2饱和点在844~971μmolCO2·mol-1左右,CO2羧化效率变化范围为0.055~0.086molCO2·m-2·S-1;光合作用CO2补偿点珍红、珍红/砧木1号和珍红/桂砧1号分别为74.0、60.8和50μmolCO2·mol-1。嫁接苗的日平均光合速率和蒸腾速率高于自根苗,但两者的日进程曲线均为“单峰型”,其光合作用不存在“午休现象”。     

Combining multiple biomarker models in logistic regression

Summary .   In medical research, there is great interest in developing methods for combining biomarkers. We argue that selection of markers should also be considered in the process. Traditional model/variable selection procedures ignore the underlying uncertainty after model selection. In this work, we propose a novel model-combining algorithm for classification in biomarker studies. It works by considering weighted combinations of various logistic regression models; five different weighting schemes are considered in the article. The weights and algorithm are justified using decision theory and risk-bound results. Simulation studies are performed to assess the finite-sample properties of the proposed model-combining method. It is illustrated with an application to data from an immunohistochemical study in prostate cancer.     

新会区2004—2013年麻疹流行特征分析

目的了解新会区麻疹流行特征,为今后麻疹防控工作及全面实现消除麻疹提供依据。方法对2004—2008年(强化免疫前五年)和2009—2013年(强化免疫后五年)的数据采用EXCEL统计软件和SPSS17.0进行统计分析。结果 2004—2013年麻疹发病率在(0~27.59)/10万之间,平均发病率为7.45/10万;2004—2008年(强化免疫前五年)与2009—2013年(强化免疫后五年)的人群年龄分布、病例分类和流动性情况的差异存在统计学意义(χ2=62.870;917.254;19.170),而免疫史情况差异无统计学意义(χ2=0.949)。结论应加强麻疹防控工作,制定有效防控措施,实现全面消除麻疹。