The investigation of the secondary structure propensities and free-energy landscapes of peptide ligands by replica exchange molecular dynamics simulations

The conformational states of two peptide sequences that bind to staphylococcal enterotoxin B are sampled by replica exchange molecular dynamic (REMD) simulations in explicit water. REMD simulations were treated with 52 replicas in the range of 280–501 K for both peptides. The conformational ensembles of both peptides are dominated by random coil, bend and turn structures with a small amount of helical structures for each temperature. In addition, while an insignificant presence of β-bridge structures were observed for both peptides, the β-sheet structure was observed only for peptide 3. The results obtained from simulations at 300 K are consistent with the experimental results obtained from circular dichroism spectroscopy. From the analysis of REMD results, we also calculated hydrophobic and hydrophilic solvent accessible surface areas for both peptides, and it was observed that the hydrophobic segments of the peptides tend to form bend or turn structures. Moreover, the free-energy landscapes of both peptides were obtained by principal component analysis to understand how the secondary structural properties change according to their complex space. From the free-energy analysis, we have found several minima for both peptides at decreased temperature. For these obvious minima of both peptides, it was observed that the random coil, bend and turn structures are still dominant and the helix, β-bridge or β-sheet structures can appear or disappear with respect to minima. On the other hand, when we compare the results of REMD with conventional MD simulations for these peptides, the configurations of peptide 3 might be trapped in energy minima during the conventional MD simulations. Hence, it can be said that the REMD simulations have provided a sufficiently high sampling efficiency.     

基于方证相关探讨茵陈蒿汤调控库普弗细胞功能及MAPK通路抗肝纤维化的作用机制

目的：基于前期茵陈蒿汤类方抗肝硬化的方证病理基础结果,围绕“方-证相关”的学术内涵,提出了“方证相关时,方剂对机体基因的调控遵循‘无差错修复’原则”的假说;并探讨茵陈蒿汤对DMN诱导大鼠肝纤维化形成阶段肝组织库普弗细胞（Kupffer Cells,KCs）相关基因表达及对丝裂原活化蛋白激酶（MAPK）通路的影响。方法：采用wistar大鼠,于每周前3天连续腹腔注射0．5％二甲基亚硝胺（Dimethylnitrosamine,DMN）制备大鼠肝纤维化模型,2周末取模型组6只做动态观察。第3周初开始,在持续造模的同时给予茵陈蒿汤干预治疗到4周末,正常组与模型对照组给予等量生理盐水。4周末在3％戊巴比妥钠腹腔注射麻醉情况下,杀鼠取材,检测肝功能、肝组织病理、肝组织羟脯氨酸含量、胶原半定量,并采用基因芯片检测分析茵陈蒿汤对模型大鼠肝组织基因表达谱的影响。结果：与正常组比较,造模4周大鼠血清肝功能水平明显升高（P＜0．01）;病理观察肝组织炎细胞显著浸润,胶原显著沉积（P＜0．01）,肝组织白介素1（IL-1 b）、Cd68、肿瘤坏死因子受体超家族成员14（Tnfrsf14）、肿瘤坏死因子受体超家族成员9（Tnfrsf9）、TNF受体超家族成员6（Fas）、Cd14、结缔组织生长因子（Ctgf）、Ⅰ型胶原α2（Col1 a2）、胰岛素样生长因子结合蛋白（Igfals）、胰岛素样生长因子1（Igf1）、胰岛素样生长因子结合蛋白1（Igfbp1）、基质金属蛋白酶12（Mmp12）、基质金属蛋白酶2（Mmp2）、基质金属蛋白酶23（Mmp23）、趋化因子配体21（Ccl21）、蛋白激酶Cβ（Prkcb）基因表达明显上调,MAPK通路被激活。经2周治疗后茵陈蒿汤能显著降低DMN诱导的大鼠血清肝功能水平,抑制组织炎细胞的浸润与坏死,胶原沉积,并下调了肝组织IL-1 b、Cd68、Tnfrsf14、Tn-frsf9、Fas、Cd14、Ctgf、Col1 a2、Igfals、Igf1、Igfbp1、Mmp12、Mmp2、Mmp23、Ccl21、Prkcb 基因的表达,抑制了MAPK通路的活化。通过全基因芯片的分析,在茵陈蒿汤干预治疗后基因表达得到了不同程度的修复。结论：验证了“方证相关时,方剂对机体基因的调控遵循‘无差错修复’原则”的假说;茵陈蒿汤显著抑制DMN 诱导肝纤维化形成,其机制可能是调控了KCs,抑制相关炎症因子的释放,同时可能参与调控MAPK通路,从而达到抗肝纤维化的作用。     

姜黄素对阿尔茨海默病小鼠海马InR和IGF1R表达的影响

目的观察姜黄素对阿尔茨海默病（Alzheimer＇sdisease,AD）模型APP／PS1双转基因小鼠胰岛素受体（insulinreceptor,InR）和胰岛素样生长因子1受体（insulin·likegrowthfactor1receptor,IGF1R）表达的影响。方法将3月龄的APP／PS1双转基因小鼠随机分为模型组、阳性罗格列酮对照组（每日10ms／kg）、姜黄素大（每日400mg／kg）、中（每日200mg／kg）、小剂量组（100mg／kg）,正常组为相同背景非转基因小鼠。灌胃3个月后,应用免疫组织化学和Westernblot方法进行检测。结果InR和IGF1R免疫组化染色,模型组小鼠大脑海马CA1区较正常对照组InR阳性细胞明显增加（P〈0．01）,姜黄素干预组有所恢复;而模型组小鼠大脑海马CA1区较正常对照组IGF1R阳性细胞明显减少（P〈0．01）,姜黄素干预组有所恢复。Western blot检测海马InR和IGF1R的蛋白表达结果与免疫组织化学检测结果一致。结论姜黄素可以使APP／PS1双转基因小鼠海马增加的InR和减少的IGF1R得以恢复,改善APP／PS1双转基因小鼠胰岛素信号转导。     

鸡马立克氏病毒抗性相关基因研究进展

马立克氏病（MD）对养禽业危害极大,可导致鸡群的免疫抑制,引起继发感染和免疫失败。然而,不同品系鸡对马立克氏病毒（MDV）抗性差异较大,呈现出较高的遗传相关性。近年来,随着MDV抗性研究的不断深入,与MDV抗性相关基因的研究已成为研究热点,本文就其研究进展作一综述。     

参数序列比对算法研究

序列比对是生物信息学中的一项重要任务,通过序列比对可以发现生物序列中的功能、结构和进化的信息。序列比对结果的生物学意义与所选择的匹配、不匹配、插入和删除以及空隙的罚分函数密切相关。现介绍一种参数序列比对方法,该方法把最佳比对作为权值和罚分的函数,可以系统地得到参数的选择对最佳比对结果的影响。然后将其应用于RNA序列比对,分析不同的参数选择对序列比对结果的影响。最后指出参数序列比对算法的应用以及未来的发展方向。     

基于分布式水文模型的水源涵养不同功能评估方法——以渭河涵养区为例

为了实现水源涵养量计算和不同功能的综合评估,基于分布式水文模型(WEP-L)提出了一种新方法,即利用WEP-L模型计算次降水过程中降水量和地表产流、冠层截留量的差值作为水源涵养量,并分别评估削洪(地表径流量)、补枯(地下径流量)、维持植被生态系统用水(植被蒸腾量)等不同水源涵养功能的评估方法。为了验证该方法的合理性,以渭河流域咸阳站以上区域为例,对比了该方法和InVEST模型方法的计算结果,由于两种方法在评估内容和使用模型上都存在差异,为了保证计算结果的可比性,先对比了基于相同评价内容的WEP-L模型法I和InVEST模型方法,再对比了基于不同评价内容的WEP-L模型法I和WEP-L模型法II,结论如下:基于相同评价内容的WEP模型法I和InVEST模型法计算结果数值接近,研究区2000-2018年水源涵养量年均值分别为12.43 mm(5.76亿m³)和12.08 mm(5.6亿m³),两种方法所得结果空间分布特征相似,稍有差异之处与InVEST模型的参数没有经过本地化处理有关;基于不同评价内容的WEP-L模型法Ⅰ和WEP-L模型法II计算结果数值相差较大,研究区2000-2018年水源涵养量均值分别为12.43 mm和432.57 mm,空间分布特征上有差异的地方分布于研究区的北部、东部及东北部,主要与两种方法评价时是否考虑蒸散发有关。WEP-L模型法II评估结果中削洪、补枯、维持植被生态系统用水等功能多年变化趋势分别为:2006-2010年期间增加、2012年以后下降以及增加。2012年后补枯功能和维持植被生态系统用水功能之间可能存在权衡关系。通过不同方法计算结果差异原因分析,证明了基于WEP-L模型的不同涵养功能评估方法的合理性,其结果也可为渭河涵养区水资源和生态保护策略的制定提供更多依据。     

A Thermodynamic Perspective on Natural Selection

A novel thermodynamic perspective on natural selection is presented. In the case that life continuity is optimized in an ideal system, where relatively constant and homogeneous selective pressures favour a given competing species, natural selection leads that system to a stationary state of maximum genotypic uniformity of life and maximum sustainable consumption of available energy by life (competitive equilibrium). Structurally and functionally, this optimizing tendency towards competitive equilibrium looks similar to the optimizing tendency towards thermodynamic equilibrium of classical thermodynamics (maximum energetic uniformity and maximum degradation of available energy). The principle of competitive exclusion may thus be conceptually viewed as an ecological manifestation of the second law of (classical) thermodynamics. On the other hand, the novel thermodynamic perspective on natural selection is discussed with regard to the open and nonequilibrium system of nature, where selective pressures vary in space and time. In this case, natural selection can induce diversity instead of uniformity, though an optimizing tendendcy towards maximum sustainable consumption of resources (optimization of life continuity) always remains. Overall, it is concluded that the action of natural selection favours the maximization of the sustainable consumption of energy at the level of individual organism.     

Larval food affects oviposition preference,female fecundity and offspring survival in Yponomeuta evonymellus

1. Yponomeuta evonymellus is a monophagous moth that feeds on Prunus padus which is native to Europe. In recent years, larval feeding and egg clusters have also been observed on non‐native Prunus serotina plants; however, survival of larvae on this new host is very low. 2. The objective of the present study was to determine how the feeding of larvae on each of the two host plants impacts oviposition, offspring survival and fecundity in Y. evonymellus. Our hypothesis was that, under controlled conditions, females will lay eggs on the host on which they fed as larvae. We also hypothesised that the lower survival of young larvae feeding on P. serotina was due to the smaller buds and leaves present in this species, relative to those of P. padus. 3. A dual‐choice experiment conducted under laboratory conditions demonstrated that females preferentially chose to oviposit on the plant species on which they fed as larvae. In the experiment, potential fecundity and offspring survival were significantly higher on P. padus than on P. serotina. The reduced performance of Y. evonymellus on P. serotina was correlated with a smaller bud mass and volume, lower leaf mass and surface area, and difficulty in constructing a protective tent against unfavourable weather conditions. 4. In summary, the identity of the host plant species during larval feeding determines adult oviposition preference for that host species. The survival of larvae on P. serotina growing in the nature is low, but for phenology‐related reasons.     

Measuring the relationship between dietary quality and body size in primates

The feeding niche and the body size of any species are fundamental parameters that constrain the evolution of many other phenotypic characters. Moreover, previous work has shown that body size and diet are correlated, as a consequence of the negative allometry of metabolic rate. Unfortunately, the precise form of the association between body size and diet has never been specified, principally because no suitable cross-species measure of diet has been advanced. Here we develop a measure of diet that is sensitive over the whole spectrum of primate feeding niches, and use this measure to define the relationship between body size and diet for a sample of 72 primate species. Subsequently, we present several examples of how behavioral and ecological hypotheses can be tested by examining the extent to which particular species deviate from the general diet-body size pattern.