Predicting kinetic constants of protein-protein interactions based on structural properties

Elucidating kinetic processes of protein–protein interactions (PPI) helps to understand how basic building blocks affect overall behavior of living systems. In this study, we used structure‐based properties to build predictive models for kinetic constants of PPI. A highly diverse PPI dataset, protein–protein kinetic interaction data and structures (PPKIDS), was built. PPKIDS contains 62 PPI with complex structures and kinetic constants measured experimentally. The influence of structural properties on kinetics of PPI was studied using 35 structure‐based features, describing different aspects of complex structures. Linear models for the prediction of kinetic constants were built by fitting with selected subsets of structure‐based features. The models gave correlation coefficients of 0.801, 0.732, and 0.770 for k_off, k_on, and K_d, respectively, in leave‐one‐out cross validations. The predictive models reported here use only protein complex structures as input and can be generally applied in PPI studies as well as systems biology modeling. Our study confirmed that different properties play different roles in the kinetic process of PPI. For example, k_on was affected by overall structural features of complexes, such as the composition of secondary structures, the change of translational and rotational entropy, and the electrostatic interaction; while k_off was determined by interfacial properties, such as number of contacted atom pairs per 100 Ų. This information provides useful hints for PPI design. Proteins 2010;79:720–734. © 2010 Wiley‐Liss, Inc.     

Novel pyrrolidine melanin-concentrating hormone receptor 1 antagonists with reduced hERG inhibition

We discovered novel pyrrolidine MCHR1 antagonist 1 possessing moderate potency. Profiling of pyrrolidine 1 demonstrated that it was an inhibitor of the hERG channel. Investigation of the structure-activity relationship of this class of pyrrolidines allowed us to optimize the MCHR1 potency and decrease the hERG inhibition. Increasing the acidity of the amide proton by converting the benzamide in lead 1 to an anilide provided single digit nanomolar MCHR1 antagonists while replacing the dimethoxyphenyl ring of 1 with alkyl groups possessing increased polarity dramatically reduced the hERG inhibition.     

Phylogenetic conservatism of environmental niches in mammals

Phylogenetic niche conservatism is the pattern where close relatives occupy similar niches, whereas distant relatives are more dissimilar. We suggest that niche conservatism will vary across clades in relation to their characteristics. Specifically, we investigate how conservatism of environmental niches varies among mammals according to their latitude, range size, body size and specialization. We use the Brownian rate parameter, σ(2), to measure the rate of evolution in key variables related to the ecological niche and define the more conserved group as the one with the slower rate of evolution. We find that tropical, small-ranged and specialized mammals have more conserved thermal niches than temperate, large-ranged or generalized mammals. Partitioning niche conservatism into its spatial and phylogenetic components, we find that spatial effects on niche variables are generally greater than phylogenetic effects. This suggests that recent evolution and dispersal have more influence on species' niches than more distant evolutionary events. These results have implications for our understanding of the role of niche conservatism in species richness patterns and for gauging the potential for species to adapt to global change.     

Remarkable morphological stasis in an extant vertebrate despite tens of millions of years of divergence

The relationship between genotypic and phenotypic divergence over evolutionary time varies widely, and cases of rapid phenotypic differentiation despite genetic similarity have attracted much attention. Here, we report an extreme case of the reverse pattern--morphological stasis in a tropical fish despite massive genetic divergence. We studied the enigmatic African freshwater butterfly fish (Pantodon buchholzi), whose distinctive morphology earns it recognition as a monotypic family. We sequenced the mitochondrial genome of Pantodon from the Congo basin and nine other osteoglossomorph taxa for comparison with previous mitogenomic profiles of Pantodon from the Niger basin and other related taxa. Pantodon populations form a monophyletic group, yet their mitochondrial coding sequences differ by 15.2 per cent between the Niger and Congo basins. The mitogenomic divergence time between these populations is estimated to be greater than 50 Myr, and deep genetic divergence was confirmed by nuclear sequence data. Among six sister-group comparisons of osteoglossomorphs, Pantodon exhibits the slowest rate of morphological divergence despite a level of genetic differentiation comparable to both species-rich (e.g. Mormyridae) and species-poor (e.g. Osteoglossidae) families. Morphological stasis in these two allopatric lineages of Pantodon offers a living vertebrate model for investigating phenotypic stability over millions of generations in the face of profound fluctuations in environmental conditions.     

The genome as a life-history character: why rate of molecular evolution varies between mammal species

DNA sequences evolve at different rates in different species. This rate variation has been most closely examined in mammals, revealing a large number of characteristics that can shape the rate of molecular evolution. Many of these traits are part of the mammalian life-history continuum: species with small body size, rapid generation turnover, high fecundity and short lifespans tend to have faster rates of molecular evolution. In addition, rate of molecular evolution in mammals might be influenced by behaviour (such as mating system), ecological factors (such as range restriction) and evolutionary history (such as diversification rate). I discuss the evidence for these patterns of rate variation, and the possible explanations of these correlations. I also consider the impact of these systematic patterns of rate variation on the reliability of the molecular date estimates that have been used to suggest a Cretaceous radiation of modern mammals, before the final extinction of the dinosaurs.     

UV-C irradiation as a tool to eradicate algae in caves

Algal proliferation has commonly been reported to occur on monuments, such as crypts, churches, and caves, as soon as artificial lighting is used. In this work we study the effects of UV-C irradiation on algae collected in different caves in Dordogne (southwest of France). First, the effect of UV-C irradiation was tested on algal cell suspensions during increasing exposure times. After treatment, the photosynthetic capacity was assayed using a polarometric method, and algal cell viability was then estimated using a Trypan blue test after a rest period of 15 h. UV-C irradiation was then studied on algal cells cultivated on a solid support consisting of pieces of calcareous stone. Drops of concentrated algal cells were inoculated on stone and exposed to UV-C radiation for 3, 6, or 9 h. After this irradiation, half of the samples were submitted to a high white light intensity (1400 ??mol m⁻² s⁻¹ of photosynthetically active radiation, PAR) for 6 h while the other half were incubated in the culture room. Subsequently, algal macroscopic parameters such as covering rate and colonized area were measured by macro photography. Both experiments led to the conclusion that UV-C irradiation has deleterious effects on photosynthetic parameters and growth of algal cells.     

光呼吸和谷氨酰胺合成酶抑制剂对水稻冠层NH3挥发的影响

在营养液培养条件下,对两个不同氮效率基因型水稻品种扬稻6号和武育粳3号采用光呼吸抑制剂异烟肼（INH）和谷氨酰胺合成酶（GS）抑制剂蛋氨酸亚砜亚胺（MSO）处理,研究其对水稻光合速率、光呼吸速率、GS酶活性及冠层的NH。挥发速率的影响。结果发现：（1）MSO导致剑叶光合速率下降,光呼吸速率升高;INH导致光呼吸速率显著下降,同时一定程度上引起光合速率降低。（2）MSO处理显著降低了GS酶活性,相应地引起NH。挥发速率增加;INH在一定程度上导致NH。挥发速率降低。（3）扬稻6号NH。挥发速率比武育粳3号低的生理原因是光呼吸速率较低和GS酶活性较高。     

紫柏山亚高山草甸群落的种间关联和相关分析

采用方差比率法、x2检验、Jaccard关联指数以及Pearson相关系数和Spearman秩相关系数研究了秦岭紫柏山亚高山草甸群落20个主要物种的种间关联与相关性.结果表明:种对间呈显著和极显著关联(相关)的种对较少,x2检验、Pearson相关系数检验和Spearman秩相关系数检验的正负关联(相关)比分别为0.85、0.61和1.02,群落总体上接近无关联,处于相对稳定状态;Spearman秩相关星座图将20个物种划分为4个生态种组,各生态种组内的物种具有相似的生态要求和资源利用方式,不同生态种组间呈现明显的演替转化趋势;种对间呈正关联或者正相关,主要是由于具有相近的生物学特性,对生境具有相似的生态适应性;种对间呈负关联或者负相关,主要由于彼此间具有不同的生物学特性,对生境具有不同的生态适应性和相互分离的生态位所致.     

带有饱和接触率和垂直传染的两病株病原体的共存性（英文）

讨论了带有饱和接触率和垂直传染的两病株病原体的共存性,获得了共存性存在的充要条件R_2（N_2~＊）〈R_1（N_2~＊）,R_1（N_1~＊）〈R_2（N_1~＊）,并且在共存平衡点存在的条件下证明得到其局部稳定.     

基于CLUE-S模型验证的海岸围垦区景观驱动因子贡献率

基于1990、2000、2009年TM影像、社会统计数据、野外调查数据,采用冗余分析和主成分分析方法对长江口奉贤段围垦区海岸带景观动态变化驱动力因子的贡献度进行分析,并利用Kappa指数对CLUE-S模型所选驱动力模拟效力进行验证.结果表明:海岸带围垦区景观动态变化的人为驱动因子贡献度(57.1％)大于自然驱动因子贡献度(42.9％).CLUE-S模型模拟的正确率达82％,研究区主要景观类型(耕地、未利用地和养殖塘)的Kappa指数均大于0.75,CLUE-S模型的模拟效果较理想,所选驱动力因子很好地模拟了规则景观突变的空间分布特征.