Structural insights into human microsomal epoxide hydrolase by combined homology modeling,molecular dynamics simulations,and molecular docking calculations

A new homology model of human microsomal epoxide hydrolase was derived based on multiple templates. The model obtained was fully evaluated, including MD simulations and ensemble‐based docking, showing that the quality of the structure is better than that of only previously known model. Particularly, a catalytic triad was clearly identified, in agreement with the experimental information available. Analysis of intermediates in the enzymatic mechanism led to the identification of key residues for substrate binding, stereoselectivity, and intermediate stabilization during the reaction. In particular, we have confirmed the role of the oxyanion hole and the conserved motif (HGXP) in epoxide hydrolases, in excellent agreement with known experimental and computational data on similar systems. The model obtained is the first one that fully agrees with all the experimental observations on the system. Proteins 2017; 85:720–730. © 2016 Wiley Periodicals, Inc.     

Spatiotemporal Distribution of Black Bear-Human Conflicts in Colorado,USA

Abstract: Management and conservation of large carnivores increasingly includes conflicts with humans. Consequently, a greater understanding of spatiotemporal trends of conflicts is needed to efficiently allocate resources and apply targeted management. Therefore, we examined spatial and temporal distribution of American black bear (Ursus americanus; hereafter, bear)-human conflicts in Colorado, USA, related to 3 conflict types (agriculture operations, human development, and road kills). We used the Getis-Ord G_i* spatial clustering statistic to describe location and assess magnitude of bear-human conflicts in Colorado during 1986–2003 and investigated temporal trends of bear-human conflicts by type. Bear-human conflicts showed distinct spatial clustering by type, and areas of high clustering overlapped conflict types. Clustering for agriculture operations conflicts had the largest overall G_i* value and overlapped counties with high sheep production. Both human development and road-kill conflict clusters were high in areas of high-quality oak (Quercus spp.)—shrub habitat in the central and southern portions of Colorado's Front Range region and near the city of Durango in southwestern Colorado. Bear-human conflicts varied by year and type but overall increased during the 18 years. Summed across years, most conflicts were related to agriculture (32%), followed by road kills (27%) and human development (24%). The greatest proportion of agriculture operations-related conflicts (76%), human development-related conflicts (36%), and road kills (47%) occurred in 1988, 1999, and 2003, respectively. Considering that bear-human conflicts in Colorado increased over time and will likely continue to increase, we suggest wildlife managers improve data collection by obtaining detailed location data, categorizing conflict types uniformly, and applying conflict regulations consistently to strengthen inference of similar analyses. We also suggest that managers target efforts to mitigate damage by focusing on areas with high clustering of conflicts.     

应用聚类分析研究十字珊瑚亚科的分类并探讨其起源与演化

提要具分裂繁殖的十字珊瑚类在我国扬子区兰多维列统（Llandovery）分布广泛，属种繁多，有重要的地层意义．但长期以来关于该类群的分类位置及各属的定义和范围各家意见不一。文章应用Q型聚类分析研究十字珊瑚类的分类．提出十字珊瑚亚科可分为7属．即：Stauria Milne-Edwards et Haime, Cystostauria He et Li, Ceriaster Lindstrom. Eostauria He et Li. Paraceriaster Y. X. He. Parastauria He et Li. Massparaseriaster nora. provis. 对7个属分别给予简要定义。文中对十字珊瑚亚科的起源、演化及扩散进行探讨．并分析各属可能的演化亲缘关系。资料表明．最原始最早期的Eostauria属很可能起源于澳大利亚的新南威尔士晚奥陶世的Palaeophyllum的某一种群．后在早兰多维列世晚期扩散到扬子区．在中兰多维列世的爱隆期（Aeronian）迅速繁衍，产生许多新属种，因而扬子区在兰多维列世是十字珊瑚类的演化中心。除少数类群，如：Eostauria，Ceriaster．Stauria在晚兰多维列世或文洛克世（Wenlock）早期分别迁移到中亚地区和欧洲，多数类群在扬子区晚兰多维列世的早、中期因不适应环境巨变而快速衰亡。     

粪肠球菌精氨酸脱亚胺酶酶学性质研究

经硫酸铵分级沉淀、Q-Sepharose Fast Flow阴离子交换层析、SephadexG-75凝胶柱层析从NJ402自溶细胞超声破碎液中提纯得到精氨酸脱亚胺酶(ADI),纯化倍数为34.5,活力回收率为31.4%,经SDS-PAGE以及Native-PAGE测定结果表明,ADI亚基分子量约为46 kD,该酶非变性情况下的分子量约为190 kD左右,该酶为同四聚体结构.酶学,胜质研究结果表明:ADI催化最适温度和最适pH分别为50℃和6.5,在45℃以下和pH 5～8之间有很好的稳定性.ADI是L-型脱亚胺酶,具有严格的光学选择性,适当浓度的Mn2 、Mg2 、Co2 对ADI催化活力的促进作用较大,高浓度的Zn2 和Co2 对酶有一定程度的抑制作用,L-瓜氨酸对酶无抑制作用而L-鸟氨酸却表现出较强的抑制作用.ADI在最佳催化条件下作用于L-精氨酸的米氏常数为3.2686 mmol/L,最大反应速度为2.44 μmol/min.     

In-depth characterization of the GOTCAB saponins in seven cultivated Gypsophila L. species (Caryophyllaceae) by liquid chromatography coupled with quadrupole-Orbitrap mass spectrometer

Roots of Gypsophila L. (Caryophyllaceae) have been shown to accumulate bidesmosides of triterpenoid carboxylic acids, also called GOTCAB saponins (Glucuronide Oleanane-type Triterpenoid Carboxylic Acid 3, 28-Bidesmosides). The study aimed at in-depth characterization of GOTCABs from root extracts of cultivated Gypsophila scorzonerifolia Ser., G. acutifolia Stev. ex Spreng., G. altissima L., G. pacifica Kom., G. paniculata L., G. oldhamiana Miq. and G. zhegualensis Krasnova using ultra high-performance liquid chromatography coupled with hybrid quadrupol-Orbitrap high resolution mass spectrometry (UHPLC-HRMS). Based on the accurate mass measurements, elemental composition, isotopic peak profiles, fragmentation pattern in tandem mass spectrometry (MS/MS) and literature data, a total of 53 GOTCABs were tentatively identified. In addition, 29 core structures, forming between 2 and 12 isobaric isomers were described. They possess gypsogenin, quillaic and gypsogenic acid as sapogenin, substituted at C-3 with O-β-d-galactopyranosyl-(1 → 2)-[pentosyl-(1 → 3)]-β-d-glucuronopyranoside (β-chain). According to the C-28 ester-bonded oligosaccharide (α-chain) saponins were classified into four groups: GOTCABs with C-28 tetra- and pentasaccharide (type I), GOTCABs with C-28 oligosaccharide substituted with methoxycinnamoyl group (type II), GOTCABs with mono- and diacetylated C-28 oligosaccharide (type III) and GOTCABs with C-28 oligosaccharide substituted with both acetyl and methoxycinamoyl groups (type IV). The possible fragmentation pathways of saponins were proposed. Eleven core structures forming between 2 and 7 isobars are undescribed in the literature. To examine the differences between the assayed Gypsophila species at the same environmental conditions, the variation of saponins was estimated by hierarchical clustering on isobaric fingerprints of GOTCABs. The clustering of the studied species revealed three well-defined clusters. The first cluster comprises G. scorzonerifolia (G1) and G. altissima (G3), characterized by GOTCABs from type III. G. acutifolia (G2) and G. pacifica (G4) formed the second cluster accumulating saponins from types II and III. The third cluster grouped G. paniculata (G5), G. oldhamiana (G6) and G. zhegualensis (G7) sharing GOTCABs from types IV in addition to II and III. This is the first report on the saponins from G. scorzonerifolia and G. zhegualensis. An in-depth depiction of the GOTCAB saponin composition of seven cultivated Gypsophila species was achieved. Therefore, saponins are worth investigating for better understanding of the potential use of Gypsophila roots for pharmaceutical purposes.     

Elevated plasma vasopressin in cardiomyopathic hamsters

Hamsters of the BIO 14.6 strain characteristically develop cardiomyopathy as they age, and hamsters of this strain have overt signs of heart failure by 11 months of age. Plasma levels of the posterior pituitary hormone arginine-vasopressin (AVP) were found to be elevated (approximately 2-fold) in 11 month old BIO 14.6 hamsters, compared to age-matched hamsters of a control strain. AVP appeared inappropriately elevated in these animals, since they were neither hyperosmotic nor markedly hypotensive. The elevated levels of AVP observed in these animals appears to contribute to vasomotor tone, since intravenous adminstration of a specific antagonist of the vasoconstrictor action of AVP [d(CH₂)₅Ome(TYR)AVP] elicited a fall in arterial pressure (9±2 mm Hg, n=6, p<0.05). The AVP antagonist had no effect on arterial pressure in hamsters of a control strain, and vehicle administration had no effect on arterial pressure in either strain. These data indicate that inappropriately elevated levels of AVP contribute to the cardiovascular state of myopathic hamsters. Since elevated plasma AVP has been noted in human congestive heart failure, these results suggest that AVP may contribute to the cardiovascular status during congestive heart failure.     

Legacy effects and memory loss: how contingencies moderate the response of rocky intertidal biofilms to present and past extreme events

Understanding how historical processes modulate the response of ecosystems to perturbations is becoming increasingly important. In contrast to the growing interest in projecting biodiversity and ecosystem functioning under future climate scenarios, how legacy effects originating from historical conditions drive change in ecosystems remains largely unexplored. Using experiments in combination with stochastic antecedent modelling, we evaluated how extreme warming, sediment deposition and grazing events modulated the ecological memory of rocky intertidal epilithic microphytobenthos (EMPB). We found memory effects in the non‐clustered scenario of disturbance (60 days apart), where EMPB biomass fluctuated in time, but not under clustered disturbances (15 days apart), where EMPB biomass was consistently low. A massive grazing event impacted on EMPB biomass in a second run of the experiment, also muting ecological memory. Our results provide empirical support to the theoretical expectation that stochastic fluctuations promote ecological memory, but also show that contingencies may lead to memory loss.     

distruct: a program for the graphical display of population structure

In analysis of multilocus genotypes from structured populations, individual coefficients of membership in subpopulations are often estimated using programs such as structure . distruct provides a general method for visualizing these estimated membership coefficients. Subpopulations are represented as colours, and individuals are depicted as bars partitioned into coloured segments that correspond to membership coefficients in the subgroups. distruct , available at http://www.cmb.usc.edu/~noahr/distruct.html , can also be used to display subpopulation assignment probabilities when individuals are assumed to have ancestry in only one group.