Hedgehog信号通路与脂肪细胞发育育

TGFβ、Wnt、FGF和Hedgehog（Hh)等信号通路是参与胚胎发育的关键信号通路.从果蝇到人类,Hh信号通路广泛存在并高度保守,在多种器官的发育过程中发挥重要作用. 脂肪细胞发育的过程包括多潜能干细胞向前脂肪细胞定向和脂肪细胞终末分化两个阶段.近年来,Hh信号通路在脂肪细胞发育过程中的作用逐渐成为研究热点.越来越多的研究表明,Hh信号通路抑制脂肪细胞发育.本文将对Hh信号通路抑制脂肪细胞发育的作用以及其发挥作用的阶段进行综述,并分析将该信号通路作为靶点治疗肥胖症及相关疾病的可行性.     

十五肽 BPC-157通过 p38 MAPK 信号通路途径调节人脐静脉内皮细胞的功能

目的:初步探究十五肽 BPC-157调节人脐静脉内皮细胞(HUVEC)功能的信号通路作用机制.方法:首先利用生物芯片筛选 BPC-157参与激活的细胞信号转导通路途径,进而通过 real-time PCR 证实 BPC-157对候选信号通路中相关基的 mRNA 表达水平的影响,最后采用 Western 印迹观察 BPC-157对候选信号通路中相关蛋白的磷酸化水平影响.结果:10μg/mL BPC-157作用 HUVEC 24 h 后,信号转导通路发现者芯片结果显示,与18条信号转导通路相关的96个关键基中分别有4个基的 mRNA 表达水平上调和下调,其中与 MAPK 信号通路相关的3个关键基 c-Fos、c-Jun 和 Egr-1的 mRNA 表达水平显著性上调;低剂量 BPC-157(1μg/mL)作用 HUVEC 12 h 后,能够促进早期即刻基 c-Fos、c-Jun 和 Egr-1的 mRNA 表达水平;10μg/mL BPC-157作用 HUVEC 30 min 后,可明显促进 ERK1/2、p38蛋白磷酸化.结论:BPC-157可能通过活化 MAPK 信号转导通路途径后,激活下游早期即刻基转录,启动靶基的表达,从而发挥促进 HUVEC 增殖、迁移等功能.     

POMP与SuFu相互作用调控Hedgehog信号通路的活性

Hedgehog信号通路在胚胎发育、组织再生中发挥重要的作用,且与癌症发生发展密切相关. 其胞内调控组分Suppressor of Fused（SuFu）蛋白通过结合转录因子Gli(s),负调控该信号通路,但其作用的分子机制仍不甚清楚. 在本项研究中,以人SuFu作为诱饵蛋白,利用酵母双杂交技术成功地筛选到1个新的相互作用因子-蛋白酶体成熟蛋白（POMP）. 通过免疫共沉淀、体外GST pull-down和免疫细胞化学实验验证其相互作用. 为了探究POMP与SuFu的相互作用对Hedgehog信号通路的影响,构建了POMP的过表达质粒和干扰质粒（miR-RNAi）以及转录因子Gli活性检测系统,即荧光素酶报告基因法,结果显示,过表达SuFu蛋白时POMP正调控Hedgehog信号通路,而下调POMP的表达则抑制Gli的活性. 该研究结果揭示了POMP新的生物学功能,为阐明Hedgehog信号通路的具体分子机制提供了新的线索.     

心肌分化过程中经典Wnt信号促进Isl1表达北大核心CSCD

ISL1是第二生心区的分子标志,在心血管发育中发挥重要作用.在心脏发育过程中,Isl1的表达具有鲜明的时空特异性.本研究利用P19CL6畸胎瘤干细胞作为心肌分化模型,探讨了Isl1在心肌诱导分化过程中的时间特异性表达及经典Wnt信号通路对其的调控.研究发现,Isl1在心肌分化早期高表达,于诱导第4 d到达高峰,随后快速下调.其表达趋势与经典Wnt通路的激活模式具有时间上的同步性.通过加入Wnt3a蛋白及Li Cl激活经典Wnt通路,能够促进Isl1基因的表达,而Wnt通路抑制分子Frizzled-4/Fc和DKK1能够下调Isl1表达.β-catenin过表达及RNAi实验也获得相似的结果.染色质免疫共沉淀实验证实,Wnt通路效应分子LEF1,在细胞分化第4 d与其在Isl1基因启动子上游-2 300 bp处的结合增强,因而促进了Isl1基因的表达.本研究表明,经典Wnt信号能够通过LEF1/β-catenin与Isl1启动子特异结合,调控Isl1基因在心肌早期分化阶段的表达.     

心肌分化过程中经典Wnt信号促进Isl1表达

ISL1是第二生心区的分子标志,在心血管发育中发挥重要作用.在心脏发育过程中,Isl1的表达具有鲜明的时空特异性.本研究利用P19CL6畸胎瘤干细胞作为心肌分化模型,探讨了Isl1在心肌诱导分化过程中的时间特异性表达及经典Wnt信号通路对其的调控.研究发现,Isl1在心肌分化早期高表达,于诱导第4 d到达高峰,随后快速下调.其表达趋势与经典Wnt通路的激活模式具有时间上的同步性.通过加入Wnt3a蛋白及Li Cl激活经典Wnt通路,能够促进Isl1基因的表达,而Wnt通路抑制分子Frizzled-4/Fc和DKK1能够下调Isl1表达.β-catenin过表达及RNAi实验也获得相似的结果.染色质免疫共沉淀实验证实,Wnt通路效应分子LEF1,在细胞分化第4 d与其在Isl1基因启动子上游-2 300 bp处的结合增强,因而促进了Isl1基因的表达.本研究表明,经典Wnt信号能够通过LEF1/β-catenin与Isl1启动子特异结合,调控Isl1基因在心肌早期分化阶段的表达.     

microRNAs与TP53基因调控网络研究进展

TP53基因(编码p53蛋白)作为一个重要的抑瘤基因,通过调控一系列信号转导通路广泛参与了多种恶性肿瘤的发生发展,一直是肿瘤分子生物学研究领域的热点.最近的研究发现,microRNAs(miRNAs)参与了TP53的信号通路,它们之间存在着复杂的调控网络.一方面,p53通过调控一些miRNAs的转录及转录后成熟,促进细胞周期阻滞、诱导细胞凋亡和衰老,抑制肿瘤发生.另一方面,许多miRNAs,如miR-25、miR-30d、miR-125b和miR-504等可直接调控p53的表达与活性,参与TP53信号通路的调节,还有一些miRNAs则通过调节p53上下游基因,发挥重要的生物学功能.其中,最具有代表性的是miR-34家族,它们受p53直接调控并参与TP53信号通路,通过靶向抑制多个TP53信号通路关键分子的表达,发挥抑瘤作用.此外,它们还可以通过抑制沉默信息调节子,增强p53的活性,反馈调节TP53信号通路.miRNAs与TP53之间调控网络的研究,是对TP53抑瘤机制的重要补充.     

TRAF6对BMP经典通路中Smad1的调控作用研究

BMP经典的Smad通路和非经典信号的MAPK通路调控中胚层形成、骨骼发育和肿瘤形成等许多生物学过程.TRAF6作为BMP非经典信号通路中的重要组成部分,在非经典通路激活中有重要的调节作用.对于TRAF6与BMP经典信号通路的关系未见相关报道.本研究发现,过表达TRAF6后Smad1的表达被抑制;反之,敲低TRAF6后Smad1的表达上升.进一步的研究表明,TRAF6对Smad1的调节作用发生在mRNA水平.这些研究揭示了TRAF6在协调BMP经典通路和非经典通路中发挥着重要作用.     

MAPK信号通路基因在小鼠肝再生中的表达谱变化

为了分析丝裂原活化蛋白激酶(Mitogen-Activated Protein Kinases,MAPK)信号通路基因在肝再生中的表达图谱,以及探讨MAPK信号通路在肝再生中的作用,文章利用四氯化碳(Carbon Tetrachloride,CCl4)诱导的小鼠肝损伤再生模型对MAPK信号通路基因的表达进行检测.首先,采用CCl4腹腔注射的方法建立小鼠肝损伤再生模型,通过肝脏切片HE染色和测定血清中谷丙转氨酶活性确认模型的质量,然后,在注射CCl4后的第0、0.5、1.5、4.5、7 d分别采集小鼠肝脏样本,应用Affymetrix公司的小鼠基因表达芯片,检测MAPK信号通路中93个基因的差异表达图谱,并用荧光实时定量PCR法验证芯片检测的结果.结果表明,在芯片检测到的93个MAPK信号通路基因中,有31个在肝再生中有不同程度差异表达,且经荧光实时定量RT-PCR检测的结果与基因芯片的结果相符合.基因表达谱芯片技术可以筛选出肝再生中差异表达的基因,在小鼠肝再生中的第0.5和1.5 d,MAPK信号通路中表达水平上调的基因增多,而在第4.5和7 d,则表达水平下调的基因明显增多.这一结果表明MAPK信号通路对肝再生不同阶段的双重调控作用.     

进食障碍数据库的建立及其在识别与进食障碍相关的扩展脂肪细胞因子信号通路中的应用

进食障碍是一种生理和心理上的进食失调,影响了世界范围近1%的女性人群.尽管已广泛开展了针对此疾病遗传角度的流行病学研究,但其分子机制仍需进一步阐释.近期,高通量技术被广泛应用于发现复杂疾病中可能的致病基因以及其潜在的致病机理.本研究首次收集了大量文献报道的与进食障碍有关的基因,建立了进食障碍相关的数据库,以期对进食障碍的分子机制进行初步了解.EDdb数据库包括了从发表的文献中收集的有实验验证的与进食障碍有关的59个基因,并将这些基因作为核心数据集.根据核心数据集,利用蛋白-蛋白相互作用信息、基因共享的染色体条带信息及疾病相关信息扩展出其他4个数据集,这4个数据集包括了2824个潜在的进食障碍相关基因,这些基因分布在601个基因组区间.根据人的蛋白-蛋白相互作用数据,重建了可能的与进食障碍相关的分子相互作用网络.进一步,利用代谢通路富集性分析方法,识别出EDdb中的3个基因ADIPO,TNF和NR3C1可以将KEGG中的＂脂肪细胞因子信号通路＂和BioCarta中的＂内脏脂肪沉着和代谢综合征＂2个通路结合在一起,得到一个与进食障碍相关的扩展的脂肪细胞因子信号通路.在这个扩展通路中共包括43个基因,其中39个基因与进食障碍有关.本研究构建了第一个进食障碍相关的基因数据库,其中的各种数据信息将有助于对进食障碍的研究,揭示其中的基因和疾病关系.通过初步的统计分析,发现进食障碍引起的体重失调和肥胖可能与本研究发现的扩展通路的调节障碍有关,并且这个扩展通路也可能与不健康的生活习惯引起的体重失调等复杂疾病有关.     

SIK2参与TGFβ信号通路的调节

SIK2是调节糖脂代谢最重要的激酶之一.前期研究表明SIK2的同源家族成员SIK1可调控TGFβ信号通路的活性,但SIK2对TGFβ信号通路的调控作用尚无报导.本研究中我们检测了TGFβ通路对SIK2的调节作用以及SIK2对该通路活性的调控.结果表明,TGF β刺激可诱导SIK2的mRNA表达上调|转染结合报告酶活性分析显示,SIK2可反式激活含TGFβ信号通路反应元件（CAGA）的人工启动子驱动的Luc报告基因的表达|在有TGFβ存在时甚至增强其表达|Western印迹分析表明TGFβ1诱导下敲低SIK2 使p21蛋白表达水平下降.本研究结果显示SIK2可被TGFβ诱导表达,是一个新的TGFβ信号通路正调控因子.     

Numerical approaches towards life cycle interpretation five examples

The ISO-standard for LCA distinguishes four phases, of which the last one, the interpretation, is the least elaborated. It can be regarded as containing procedural steps (like a completeness check) as well as numerical steps (like a sensitivity check). This paper provides five examples of techniques that can be used for the numerical steps. These are the contribution analysis, the perturbation analysis, the uncertainty analysis, the comparative analysis, and the discernibility analysis. All five techniques are described at a non-technical level with respect to basic concept, possibilities, tabular and graphical representation, restriction and warnings, and all are illustrated with a simple example.     

影响水稻光合日变化的酶和相关因素的分析

水稻叶片的最大光合速率出现在上午１０：００时,Ｒｕｂｉｓｃｏ初始活力也在此时达到最大,然后逐渐降低,下午１４：００时略上升后又下降．Ｒｕｂｉｓｃｏ初始活力与光合速率之间极显著相关,相关系数为 ０．９４７４．运用相关性分析、回归分析、通径分析,对晴（有时有云）天气水稻叶片的光合速度、光合关键酶及有关因素的日变化进行综合评估,结果发现中午光合下降主要来自气孔限制,同时Ｒｕｂｉｓｃｏ活性也下降;Ｒｕｂｉｓｃｏ活性是影响光合日变化的又一重要生化因子．体内Ｒｕｂｉｓｃｏ活性受Ｒｕｂｉｓｃｏ活化酶的调节．     

Discrimination of higher plant calluses based on embryogenic capacity and taxonomic classification by pyrolysis mass spectrometry

Pyrolysis mass spectrometry (PyMS) is a rapid, simple, high-resolution analytical method based on thermal degradation of complex material in a vacuum, and has been widely applied to the discrimination of closely related microbial strains. Minimally prepared samples of embryogenic and non-embryogenic calluses derived from various higher plants (sweet potato, morning glory, Korean ginseng, Siberian ginseng, and balloon flower) were subjected to PyMS for spectral fingerprinting. A dendrogram based on the unweighted pair group method, with arithmetic mean of pyrolysis mass spectra, divided the calluses into Siberian ginseng embryogenic callus and the others, which were subsequently divided into embryogenic and non-embryogenic callus groups, regardless of plant species from which the calluses were derived. In the non-embryogenic callus group, the dendrogram was in agreement with the known taxonomy of the plants. These results indicate that PyMS analysis could be applied for discriminating plant calluses based on embryogenic capacity and taxonomic classification.     

Intraspecific variation in Licuala glabra Griff. (Palmae) in Peninsular Malaysia– a morphometric analysis

We studied vegetative and reproductive characters of 74 herbarium specimens of Licuala glabra Griff. (Palmae) collected from 22 localities throughout Peninsular Malaysia. To test the null hypothesis that there are no distinct groups within the species, cluster analysis (nearest neighbour), principal coordinates and principal components analyses were performed on the set of 43 qualitative and quantitative characters. The results obtained suggested that: (1) there are three infraspeciflc groups within the species, viz., the two published varieties glabra and selangorensis as well as a possible third novel taxon; (2) there is clustering of individuals corresponding to their geographic localities; (3) clusters generated using only reproductive characters indicate a biogeographic distribution of populations correlated with the mountain ranges in the peninsula.     

Fish ecoregions of Kansas: stream fish assemblage patterns and associated environmental correlates

Synopsis Principal components analysis was performed on fish presence/absence data for 39 common fish species from 410 stream sites in Kansas. The analysis confirmed ten ecologically meaningful fish assemblages, based on species associations. Factor scores based on these assemblages were then clustered into six geographic areas or fish ecoregions. Canonical discriminant analysis identified environmental variables that distinguished the derived fish ecoregions. Mean annual runoff, mean annual growing season, and discharge appear most important. Mean width, mean depth, chloride concentration, water temperature, substrate type, gradient, and percent of pool habitat were less important. Correspondence exists between these fish ecoregions and the patterns of physiographic regions, river basins, geology, soil, and potential natural vegetation in Kansas. The multivariate statistical approach used to classify fish ecoregions should have considerable potential value for fish assessment and management purposes in areas other than the state of Kansas.     

Normal Approximations of Exact Tests in Configural Frequency Analysis

The most common tests for types and antitypes in configural frequency analysis are normal approximations of exact tests. In the paper such statistics under the complete independence model and under the fixed margins model are discussed. It turns out that these test statistics are not acceptable when the number of simultaneously performed tests is large or when the expected frequencies are small. In these cases, the use of exact tests is advocated and some existing computer programs for such tests are indicated. A normal approximation based on the strong version of the De Moivre-Laplace limit theorem is also discussed. Empirical examples are given from longitudinal data describing psychological development of boys.     

Some remarks about the analysis of active control studies

In an active-controlled trial, the experimental treatment can be declared to be non-inferior to the control if the confidence interval for the difference excludes a fixed pre-specified margin. Recently, some articles have discussed an alternative method where the data from the current study and placebo-controlled studies for the active control are combined together into a single test statistic to test whether a fixed fraction of the effect of the active control is preserved. It has been shown that, conditional on nuisance parameters from the active-controlled study, a fixed margin can be defined that will be operationally equivalent to this latter method. In this article, we will discuss statistical properties associated with these approaches. Specifically, the interim monitoring boundaries and level of evidence will be considered.     

Phenotypic evaluation of genetic variability and selection of yield contributing traits in chickpea recombinant inbred line population under high temperature stress

Heat is a major abiotic stress that drastically reduces chickpea yield. This study aimed to identify heat-responsive traits to sustain crop productivity by screening a recombinant inbred line (RILs) population at two locations in India (Ludhiana and Faridkot). The RIL population was derived from an inter-specific cross between heat-tolerant genotype GPF 2 (C. arietinum L.) and heat sensitive accession ILWC 292 (C. reticulatum). The pooled analysis of variance showed highly significant differences for all the traits in RILs and most of the traits were significantly affected by heat stress at both locations. High values of genotypic coefficient of variation (19.52–38.53%), phenotypic coefficient of variation (20.29–39.85%), heritability (92.50–93.90%), and genetic advance as a percentage of mean (38.68–76.74%) have been observed for plant height, number of pods per plant, biomass, yield, and hundred seed weight across the heat stress environments. Association studies and principal component analysis showed a significant positive correlation of plant height, number of pods per plant, biomass, hundred seed weight, harvest index, relative leaf water content, and pollen viability with yield under both timely-sown and late-sown conditions. Path analysis revealed that biomass followed by harvest index was the major contributor to yield among the environments. Both step-wise and multiple regression analyses concluded that number of pods per plant, biomass and harvest index consistently showed high level of contribution to the total variation in yield under both timely-sown and late-sown conditions. Thus, the holistic approach of these analyses illustrated that the promising traits provide a framework for developing heat-tolerant cultivars in chickpea.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12298-021-00977-5.     

分子水平的遗传多样性及其测量方法

遗传多样性水平是一项很重要的数据。目前从分子水平量化遗传多样性的方法以等位酶分析、ＲＦＬＰ分析和ＲＡＰＤ分析为代表。遗传变异在基因组中并非随机分布,所以取样方式对分析结果的影响不容忽视。本文叙述了遗传变异的产生和分布,并以此为基础比较了上述３种分析方法的理论与实践。     

凡纳滨对虾各月龄性状的主成分与判别分析

为了研究凡纳滨对虾各性状增长规律和判定最佳生长季节凡纳滨对虾的体格与月龄的关系,选择1～6月龄凡纳滨对虾各1000只,选择全长、体长、第一腹节背高、第三腹节背高、第一腹节背宽、头胸甲长和体重共7个性状,进行主成分与判别分析.结果表明:各月龄凡纳滨对虾性状之间均呈现显著的正相关(P<0.01), 其中以全长与体长的相关性最为明显,1月龄凡纳滨对虾体重与形态性状的相关系数较小.各月龄凡纳滨对虾的主成分有所不同,1～2月龄凡纳滨对虾的第一主成分为长度因子,第二主成分为宽度因子,第三主成分为高度因子;3月龄凡纳滨对虾的第一主成分与1～2月龄凡纳滨对虾一致,但第二主成分为高度因子,第三主成分为体重因子;4～6月龄凡纳滨对虾的第一主成分为体重因子,第二主成分为高度因子,第三主成分为宽度因子.1～3月龄凡纳滨对虾形态性状的增长优先于体重, 4～6月龄凡纳滨对虾体重优先于形态性状的增长.错过最佳生长季节的凡纳滨对虾的与体格大小相符的月龄可通过建立的判别式来判断,总的判别准确率为98.98%,其中2～4月龄凡纳滨对虾的判别准确率为100%.