Small molecule approach to studying protein tyrosine phosphatase

Understanding the function of protein tyrosine phosphatases (PTPs) is crucial to deciphering cellular signaling in higher organisms. Of the 100 putative PTPs in human genome, only a little is known about their precise biological functions. Thus establishing novel ways to study PTP function remains a top priority among researchers. Classical genetics and more recently the use of RNA interference (RNAi) for gene silencing remains a popular choice to study function. However, the one gene-one function hypothesis is now recognized as an oversimplified scenario, especially among the signaling proteins such as PTPs. Therefore, there is a need to understand gene function in an appropriate cellular context. Since proteins are the work horses of the cell, alteration of protein function by various means is a particularly attractive strategy. In this context, the chemical approach, where a small molecule is used to affect the function of the desired protein is increasingly being recognized as a method of choice. In this review, we describe how small molecules can be used to study the function of a prototypical PTP, PTP1B, which is a negative regulator in insulin signaling. This includes our initial strategies for finding the most potent and specific PTP1B inhibitor to date, synthesizing cell permeable analogues suitable for cellular studies, and using them to dissect the role of PTP1B in the insulin signaling pathway. This approach is potentially general and thus could be utilized to study the function of other PTPs.     

新疆阿勒泰地区草地资源可持续管理分析

通过分析新疆阿勒泰地区草地资源的利用现状,草地类型的生产性能、生态服务价值和在区域发展中的主导功能,指出分类经营是该区草地资源可持续管理的有效途径。研究表明,阿勒泰地区的草地资源在空间上可划分为生态功能区(高寒草甸和草原、沼泽、山地荒漠草原、山地草原化荒漠和部分平原荒漠),经济功能区(山地草甸,低地草甸和草甸草原)和混合功能区(山地草原、平原荒漠草原和大部分平原荒漠),在时间上可采取不同的经营策略。生态功能区经营策略是禁牧和封育,经济功能区的经营策略是通过施肥、灌溉等手段,集约化管理,提高单位面积产值I混合功能区的经营策略是以草定畜,合理轮牧。     

Effect of Selection on the Failure Rate Function

Effect of selection procedures such as truncation and genotypic selection, are studied using selection differentials. These studies are mainly restricted to the study of mean or percentiles of the characteristics of interest. However, in situations where improvement on longetivity is itself of interest, in addition to studying mean or percentiles, one may study the reliability characteristics such as Failure Rate, Mean Residual Life etc., of the lifetimes of individuals. In this paper, we study the effect of genotypic selection when the distribution function of the lifetime is governed by a single locus with 2 alleles. We compute the difference in the failure rate function from one generation to the next generation for different values of n, the number of generations. We also obtain the limiting values of the failure rate function as n and compute the number of generations required for the failure rate to reach a value close enough to the limiting failure rate function. We also consider an example in a two-loci case and study the effect of selection on the failure rate function.     

功能性电刺激联合循环运动系统对老年脑卒中后肌肉衰减综合征患者肢体功能、平衡能力以及认知功能的影响

摘要 目的：研究功能性电刺激联合循环运动系统对老年脑卒中后肌肉衰减综合征患者肢体功能、平衡能力以及认知功能的影响。方法：选择2020年6月到2021年6月在我院进行康复治疗的老年脑卒中后肌肉衰减综合征患者64例,据其治疗方式的不同分为对照组和研究组,两组患者均给予常规康复治疗,对照组患者在常规治疗的基础上加用功能性电刺激治疗,而研究组在对照组基础上加用脑循环系统治疗仪进行治疗,比较两组患者临床治疗疗效。使用运动功能评分法（FMA）和上肢功能评定（STEF）评价肢体患者功能,使用平衡量表（BBS）和Fuglg-Meyer平衡量表（FM-B）评价患者平衡能力,使用自拟认知量表评价患者认知功能。结果：（1）研究组患者临床治疗总有效率较对照组高（93.75 % vs 75.00 %,P<0.05）;（2）两组患者治疗后FMA和STEF评分均显著增高（P<0.05）,并且研究组患者治疗后BBS和FM-B评分显著高于对照组患者（P<0.05）;（3）两组患者治疗后BBS和FM-B评分均显著增高,并且研究组患者治疗后BBS和FM-B评分显著高于对照组患者（P<0.05）;（4）两组患者治疗后认知功能评分均升高,并且研究组患者较对照组患者高（P<0.05）。结论：功能性电刺激联合循环运动系统对老年脑卒中后肌肉衰减综合征患者具有显著的临床治疗效果,可显著改善患者肢体功能、平衡能力和认知功能。     

水生态功能区划流程:双关系树框架与概念模型

水生态区划和水生态功能区划是流域水环境管理与水生态系统合理利用的重要基础,国内已经研究十年有余.本文针对该领域的一些共性问题,通过对水生态区划分与水生态功能类型划分的系统分析,探讨了水生态区划与水生态功能区划的关联性,提出了基于双树结构的RFCH流程和钻石概念模型;并以辽河流域为例,参照其他研究者的区划方案,开展了以水生态三级区为基础的水生态功能分类,为流域水生态功能区划提供了一种可借鉴的流程框架.     

市县级限制开发区环境功能区划研究——以河北省张家口市为例

限制开发地区是我国主体功能区划中划定的提供重要生态功能和农产品的地区,对其进行环境功能区划对于推动环境功能区划制度落地与实施,以及限制开发区的保护与发展有着重要意义。当前国家及省级的环境功能区划研究已经相对成熟,而市县尺度的限制开发地区环境功能区划相关研究较少。在总结现有环境功能区划研究方法的基础上,以河北省张家口市为例,探讨了市县级限制开发地区环境功能区划体系设计和技术方法,提出了以公里格网作为分析单元,结合县域行政边界,基于环境功能综合评价的结果,从自然生态安全、维护人群健康和区域环境支撑能力等3个方面,开展环境功能区划。基于该方法,将张家口市分为自然生态保留区、生态功能保持区、生态功能恢复区、农产品安全保障区、环境开发准入区、聚居发展维护区6类环境功能区,并根据各环境功能区的主要功能及生态环境特点提出相应的发展建议,以期为该区域管理提供可行的操作手段。本文提出的方法也可为其他限制开发地区的环境功能区划提供参考。     

基于景观生态学“源-汇”理论的市域尺度生态功能分区——以内蒙古通辽市为例

市域尺度的生态功能分区对于市域生态资源的有效保护和合理利用起着不可替代的指导作用。现阶段较为被动而静态的功能分区研究忽视了市域生态资源在城镇化发展中的剧烈变化。而景观生态学的"源-汇"概念和相关手段,将区域生态功能空间格局与不断变化的生态过程之间建立了联系,在生态功能分区科学理性的研究实践中运用前景广阔。运用景观生态学"源-汇"理论,以内蒙古通辽市为例,通过对于研究区域中"源"景观的划分,设定不同景观要素的阻力值,构建基于"源"动态特征的最小累计阻力模型,计算得出阻力面。并进一步通过寻找阻力面突变点来确定分区阈值,最终确定通辽市域尺度生态功能的5大分区,最后提出有针对性的分区管控措施与指引。研究将市域生态要素在城市化下的动态演变与生态安全格局进行有机关联并制定科学的分区策略,为市域生态空间的优化及管理提供了理论依据。     

低频重复经颅磁刺激联合Bobath疗法对脑卒中偏瘫患者神经功能、运动功能及平衡能力的影响

摘要 目的：观察Bobath疗法联合低频重复经颅磁刺激对脑卒中偏瘫患者运动功能、神经功能、平衡能力的影响。方法：研究对象为我院2020年05月-2022年05月期间收治的脑卒中偏瘫患者148例。按照随机数字表法分为对照组（Bobath疗法,74例）和研究组（低频重复经颅磁刺激联合Bobath疗法,74例）。观察两组平衡能力[Berg平衡量表（BBS）]、神经功能[美国国立卫生研究院卒中量表（NIHSS）]、日常生活自理能力[改良Barthel指数（mBI）]、运动功能[Fugl-Meyer上肢运动功能评定量表（FMA-UE）、Fugl-Meyer下肢运动功能评定量表（FMA-LE）]、凝血功能[凝血酶原时间（PT）、纤维蛋白原（FIB）、D- 二聚体（D-D）、活化部分凝血活酶时间（APTT）]的变化情况。结果：两组治疗20 d后NIHSS评分下降, mBI评分升高,且研究组变化程度大于对照组（P<0.05）。两组治疗20 d后FMA-UE、FMA-LE评分升高,且研究组高于对照组（P<0.05）。两组治疗20 d后BBS评分升高,且研究组高于对照组（P<0.05）。两组治疗20 d后FIB、APTT、D-D、PT均下降,且研究组低于对照组（P<0.05）。结论：低频重复经颅磁刺激联合Bobath疗法用于脑卒中偏瘫患者,可改善其凝血功能,恢复神经功能,进而改善运动功能,提高其日常生活活动能力。     

糖脂转运蛋白家族新成员人类GLTPD2的生物信息学分析

人类糖脂转运结构域2蛋白(Glycolipid transfer protein domain containing 2,GLTPD2)是糖脂转运蛋白(Glycolipid trans-fer protein,GLTP)家族的一个新成员,其功能目前尚不清楚.研究的目的在于通过生物信息学分析,预测人类GLTPD2的结构、...     

生物信息学及其在环境微生物研究中的应用

生物信息学的快速发展,推动了微生物信息学的建立。模式微生物基因组学的研究,极大地丰富了生物信息学的内容。微生物结构基因组学和功能基因组学研究试图揭示基因结构与功能的内在联系,绘制出基因调控网络图。基因组功能注释是功能基因组学研究的主要目的。基因芯片技术的运用,成为环境微生物生态研究和功能酶基因定位的有力工具。生物信息学为环境微生物的研究和发展提供了一个崭新的信息平台和技术手段。介绍了一些相关数据库和专业网站。     

Structure,function, and mechanism of action of Calmodulin

The structure, function, and mechanism of action of plant calmodulins have been the subject of intense study for plant scientists during the past several years. While precedents in animal biochemistry and physiology have suggested logical starting points for studies of how calmodulin is involved in higher plant and algal cell function, recent biochemical studies have demonstrated unique structural characteristics for this highly conserved protein. Enzym‐ological analyses have demonstrated novel functional properties and provided limited insight into the molecular mechanisms of calmodulin action. This review will summarize much of the early work, but will concern itself mainly with the methods and approaches that are used to study plant and animal calmodulins as well as models for how calmodulin may be involved in plant cell function.     

点格局研究过程中K-函数的累积效应

植物种群空间格局是生态学研究的基本问题之一, 点格局分析已成为植物种群空间格局研究的重要方法之一, 其中, Ripley's K函数是点格局常用分析方法。然而, 由于Ripley's K函数具有累积效应, 这种累积效应可能会导致特定的格局特征。为了探讨Ripley's K函数的累积效应如何影响种群格局研究结果, 以大针茅种群数据为基础, 通过R软件模拟聚集分布、随机分布和均匀分布3种格局类型, 对比使用具有累积效应的Ripley's K函数和不具有累积效应的成对相关函数进行分析。结果表明: 对于聚集分布和均匀分布, Ripley's K函数的累积效应表现在2个方面: 一方面增加了聚集分布(或均匀分布)的尺度, 另一方面能够检测到聚块或负相互作用范围在取样空间的分布差异而表现出不同的格局特征。而对于随机分布, Ripley's K函数没有累积效应。因此, 在种群格局研究过程中, 通过重复取样且Ripley's K 函数与成对相关函数相结合的方法探讨种群格局, 更能揭示空间格局的本质特征。     

东亚飞蝗羧酸酯酶基因的克隆和原核表达

羧酸酯酶是昆虫体内重要的代谢解毒酶系,其主要功能是水解和结合内源性和外源性含有酯键的有毒物质,减缓其到达靶标部位的时间。东亚飞蝗Locusta migratoria manilensis(Meyen)是我国重要的农业害虫,对其羧酸酯酶基因克隆和表达有助于深入探索杀虫剂代谢毒理机制。本研究首先对羧酸酯酶基因(CarE4)进行了克隆,并将其插入到pCold TF DNA Vector中,在大肠杆菌中进行了原核表达,最后用疏水层析和离子交换层析方法对目的蛋白进行了纯化。本文成功建立了羧酸酯酶蛋白原核表达和纯化技术体系,为进一步研究东亚飞蝗羧酸酯酶的生理功能、结构特点和作用原理提供了基础资料。     

Semiparametric estimation of marginal hazard function from case-control family studies

Estimating marginal hazard function from the correlated failure time data arising from case-control family studies is complicated by noncohort study design and risk heterogeneity due to unmeasured, shared risk factors among the family members. Accounting for both factors in this article, we propose a two-stage estimation procedure. At the first stage, we estimate the dependence parameter in the distribution for the risk heterogeneity without obtaining the marginal distribution first or simultaneously. Assuming that the dependence parameter is known, at the second stage we estimate the marginal hazard function by iterating between estimation of the risk heterogeneity (frailty) for each family and maximization of the partial likelihood function with an offset to account for the risk heterogeneity. We also propose an iterative procedure to improve the efficiency of the dependence parameter estimate. The simulation study shows that both methods perform well under finite sample sizes. We illustrate the method with a case-control family study of early onset breast cancer.     

Mental practice-based rehabilitation training to improve arm function and daily activity performance in stroke patients: a randomized clinical trial

Background  

Over 50% of patients with upper limb paresis resulting from stroke face long-term impaired arm function and ensuing disability in daily life. Unfortunately, the number of effective treatments aimed at improving arm function due to stroke is still low. This study aims to evaluate a new therapy for improving arm function in sub-acute stroke patients based on mental practice theories and functional task-oriented training, and to study the predictors for a positive treatment result. It is hypothesized that a six-week, mental practice-based training program (additional to regular therapy) targeting the specific upper extremity skills important to the individual patient will significantly improve both arm function and daily activity performance, as well as being cost effective.     

酵母菌中谷胱甘肽的主要生理功能及其代谢调控

谷胱甘肽是生物体内一种重要的三肽小分子 ,具有广泛的生理功能。对谷胱甘肽在酵母细胞中的作用及其代谢调控机制 ,做了较为详细的介绍。这一带有基础性研究的内容 ,对于以酵母为生产菌的谷胱甘肽的生产 ,或是酵母的其他工业化生产 ,具有重要的启示。     

Family-Based Association Study of Pulmonary Function in a Population in Northeast Asia

The spirometric measurement of pulmonary function by measuring the forced expiratory volume in one second (FEV₁) is a heritable trait that reflects the physiological condition of the lung and airways. Genome-wide linkage and association studies have identified a number of genes and genetic loci associated with pulmonary function. However, limited numbers of studies have been reported for Asian populations. In this study, we aimed to investigate genetic evidence of pulmonary function in a population in northeast Asia. We conducted a family-based association test with 706 GENDISCAN study participants from 72 Mongolian families to determine candidate genetic determinants of pulmonary function. For the replication, we chose seven candidate single nucleotide polymorphisms (SNPs) from the 5 loci, and tested 1062 SNPs for association with FEV₁ from 2,729 subjects of the Korea Healthy Twin study. We identified TMEM132C as a potential candidate gene at 12q24.3, which is a previously reported locus of asthma and spirometric indices. We also found two adjacent candidate genes (UNC93A and TTLL2) in the 6q27 region, which has been previously identified as a pulmonary function locus in the Framingham cohort study. Our findings suggest that novel candidate genes (TMEM132C, UNC93A and TTLL2) in two different regions are associated with pulmonary function in a population in northeast Asia.     

猪主要组织相容性复合体研究进展

主要组织相容性复合体（major histocompatibility complex,MHC）分子首先作为主要组织相容性抗原被发现,进而以此命名。随着其抗原结合分子及T细胞信使生物学功能本质的揭示,关于MHC结构与功能的研究就进入了一个崭新时代,并在这一领域中取得了许多可喜的成果。论述了近年来猪MHC（SLA）结构与功能方面的研究进展,包括SLA的分类及多态性、SLA分子结构特点、SLA分子功能及SLA分子相关领域的最新研究进展。     

Intravital multi-photon microscopy reveals several levels of heterogeneity in endocytic uptake by mouse renal proximal tubules

Understanding renal function requires one to integrate the structural complexity of kidney nephrons and the dynamic nature of their cellular processes. Multi-photon fluorescence microscopy is a state-of-the-art imaging technique for in vivo analysis of kidney tubules structure and function in real time. This study presents visual evidence for several levels of heterogeneity of proximal tubular endocytic uptake in the superficial renal mouse cortex and illustrates the potential of multi-photon microscopy for providing a comprehensive and dynamic portrayal of renal function.     

Generality versus specificity: a comparison of dynamic and isometric measures of strength and speed-strength

Considerable debate exists as to whether the qualities of muscle function exist as general or specific physiological capacities. If there is a generality of muscle function then strong relationships would exist between various measures of function for the same muscle(s), independent of the test contraction, mode or velocity. The purpose of this study was to examine the relationship between isometric and dynamic measures of muscle function to determine the existence of generality or specificity. A group of 22 men, experienced in weight training, were tested for lower and upper body dynamic and isometric measures of strength and speed-strength. The changes in these measures consequent to a resistance training programme were also investigated. The results of this study indicated that whilst isometric and dynamic measures of strength did significantly correlate (r=0.57-0.61), the relationship was below that required to denote statistical generality. More important, the changes in isometric and dynamic strength consequent to a dynamic heavy resistance training programme were unrelated (r=0.12-0.15). Thus the mechanisms that contribute to enhanced dynamic strength appearred unrelated to the mechanisms that contribute to enhanced isometric strength. Measures of dynamic and isometric speed-strength were unrelated, as were the changes in these measures resulting from training. The results of this study demonstrated that a generality of muscle function did not exist and that modality specific results were observed. Consequently this study calls into question the validity of isometric tests to monitor dynamically induced training adaptations.