受体功能区结构与环境内分泌干扰效应生物差异的关系

环境中存在的多种内分泌干扰物能够与生物体内的天然激素受体选择性结合并产生多种生物效应,由于受体功能区三维结构的不同,其内分泌干扰活性存在着种间、种内、组织间等的种种差异,限制了不同物种间毒性效应的外推研究,增加了环境内分泌干扰物筛选和风险评价的难度.论文综述了基于受体介导的环境内分泌干扰物生物活性与相应受体选择性及受体功能区结构关系的研究进展,并利用分子模拟方法分析探讨了雌激素受体与部分化合物结合作用模式,讨论了目前存在的问题,对以后有关方面的研究提出了建议.     

多溴联苯醚和全氟烷基酸的分子毒理机制研究

多溴联苯醚(PBDEs)和全氟烷基酸(PFAAs)是两类使用量大、环境污染广泛、人体暴露严重的新型有机污染物,2009年已纳入《斯德哥尔摩公约》持久性有机污染物(POPs)名单,但其毒性效应及作用机制并不明确.本文综述了本课题组近几年针对多溴联苯醚PBDEs和全氟烷基酸PFAAs的分子毒理机制研究工作,主要集中在这两类污染物对甲状腺系统、雌激素系统和肝脏脂肪酸代谢系统干扰效应的分子机制研究.本文分别从分子、细胞和活体三个层面,研究了污染物与核受体的直接结合作用、结合后受体的构象变化、细胞内受体的转录活性、以及活体暴露后受体调控基因的表达变化,由此阐明了污染物通过与受体直接作用导致细胞和活体生物功能改变的分子机制.同时结合计算模拟,探讨了污染物生物效应与其化学结构之间的关系,发现污染物的受体活性取决于它们与受体结合的空间构型,而其活性强度基本与二者的结合能力一致,主要受疏水作用和氢键的影响.此外,还通过研究污染物与天然配体转运蛋白的相互作用,明确了各个污染物与转运蛋白的结合能力,探讨了其构效关系,并评估了污染物对天然配体在体内转运过程的潜在干扰效应.通过上述研究工作,提出了多层面、多靶点研究环境污染物分子毒理机制的新思路,建立和引进了研究污染物与生物靶分子相互作用的新方法,发现了PBDEs、PFAAs与TR、ER、PPARγ核受体结合的新模式,为深入了解这些污染物的分子毒理机制提供了有用的信息和有效的研究手段.     

多溴二苯醚类化合物干扰人雌激素受体alpha活性机理的理论研究

基于分子对接方法探讨了多溴二苯醚(PBDEs)类化合物与人雌激素受体α亚型间的分子作用机理.对多溴二苯醚类化合物是否具有拟雌激素功能的研究得出:可通过对接打分值和化合物结构特征来推测PBDEs母体化合物是否具有拟雌激素活性;对HO-PBDEs,与氨基酸残基GLU53和/或ARG394形成氢键可能是影响其拟雌激素活性的重要因素;对MeO-PBDEs,疏水MeO-位于结合腔的疏水中部有利于拟雌激素活性.从结构及构象分析得出,邻位疏水基(Br-、MeO-)有利于PBDEs类化合物的拟雌激素活性.同时对多溴二苯醚类化合物是否具有抗雌激素功能的结合特征研究发现,表现出抗雌激素活性的部分PBDEs类化合物伸进通常被雌激素受体拮抗剂雷洛昔芬和4-羟基它莫西芬的烷基胺侧链占据的通道,而大多数未表现出抗雌激素活性的PBDEs类化合物的结合模式类似雌激素受体激动剂17β-雌二醇,位于结合腔,没有伸进通道.本研究从化合物结构及化合物在受体内结合的构象特征上解释化合物活性不同的原因,以期能够利用构象分析得到的结果进行筛选.     

内分泌干扰物对核受体二聚化影响的研究进展

环境内分泌干扰物(endocrine disrupting chemicals,EDCs)可模仿或拮抗天然激素与核受体结合,干扰核受体的同源或异源二聚,进而通过共调节因子的招募调控转录活性,最终引起内分泌干扰效应.目前研究主要针对EDCs与核受体的结合过程,忽视了其对核受体二聚化过程的影响,而该过程的阻断可直接导致转录失活.EDCs对于不同核受体二聚化的影响不同,只有激动剂EDCs能够促进雄激素受体(androgen receptor,AR)的同源二聚化,而雌激素受体(estrogen receptor,ER)在与具有激动或拮抗活性的EDCs结合后都可诱导ER二聚体的形成,但二聚化类型不同.通过检索ToxCast和Tox21数据库发现多达227种EDCs可以诱导ER二聚化,相比于ERα-ERα同源二聚体(6.09％ ～7.38％的活性率),EDCs更易诱导ERα-ERβ异源二聚体(11.25％ ～12.22％的活性率)和ERβ-ERβ同源二聚体(10.02％ ～11.69％的活性率).EDCs也能够差异性诱导其他核受体如维生素D受体(vitamin D receptor,VDR)与维甲酸X受体(retinoid X receptor,RXR)形成的异源二聚体,不同类型的二聚体对于研究EDCs转录活性的生理学相关性具有重要意义.基于经济合作与发展组织(Organization for Economic Co-operation and Development,OECD)报告的参考化学品研究发现,相比于配受体结合活性,二聚活性与转录活性之间有着更好的相关关系.本文从EDCs介导的核受体二聚化转录机制、二聚化与转录活性间的关系以及二聚化研究方法三方面,总结EDCs对核受体二聚化的影响,以期为深入理解EDCs的分子作用机制,推进化合物的内分泌干扰风险评估提供参考.     

对特辛基苯酚干扰雌激素受体作用的分子基础及其对ERβ亚型选择性结合的理论研究

对特辛基苯酚(4-tert-octylphenol,PTOP)是一种环境内分泌干扰物。已有研究发现虽然其能够直接与雌激素受体(estrogen receptor,ER)的两种亚型(ERα,ERβ)结合并产生干扰效应,但其结合能力却各不相同,PTOP对ERβ表现出更强的结合活性。为了探究PTOP与ER结合的分子机制及其对ER两种亚型的选择性机制,本文采用分子动力学模拟对PTOP-ER复合物进行了研究,并利用MM-GBSA方法计算了结合自由能。结果表明,范德华作用是维持PTOP与ER结合的主要驱动力;而极性相互作用的差异是导致PTOP对ERα和ERβ产生选择性结合的重要因素,PTOP与ERα之间的极性溶剂化作用阻碍了两者的结合。将PTOP与ER的天然底物雌二醇进行比较,发现PTOP与ER口袋之间缺乏氢键稳定二者结合,因此PTOP的结合活性较低。计算模拟亦指出了PTOP结合过程中发挥重要作用的关键氨基酸。以上计算结果将有助于我们进一步理解PTOP影响ER介导生理过程的干扰机制。     

高职院校科技创新能力结构及其评价指标体系的研究

阐述了高职院校科技创新能力、结构及其评价指标体系与综合测评方法研究的价值与意义,探讨分析了高职院校科技创新能力的内涵及其基本特征与基本结构,并在此基础上论述了高职院校科技创新能力结构要素之间的相互关系.并以系统学的理论为指导,将高职院校科技创新能力结构要素进行系统深入分析,构建了一套评价高职院校科技创新能力结构的指标体系,并提出了高职院校科技创新能力的综合测评方法.表1,参6.     

卤代苯甲醚正辛醇/水分配系数(lgKow)的QSPR研究

基于卤代苯甲醚类化合物的定量结构与性质关系,对其中有正辛醇/水分配系数(lgKow)数据的43个卤代苯甲醚进行了HF/6-31G·水平上的结构优化,并在优化结构的基础上进行了分子静电势及其导出参数的计算.选取其中的27个化合物作为训练集,应用多元线性回归方法对卤代苯甲醚的lgKow与分子结构参数进行了关联,其余16个化合物作为测试集.结果表明:分子静电势参数结合分子最低空轨道能级可以很好地表达卤代苯甲醚的lgKow与其分子结构间的定量关系,所建立的QSPR模型具有较强的稳健性和预测能力,同时也证明了分子静电势参数在卤代苯甲醚类化合物QSPR研究中的适用性.     

应用受体学说模型研究硝基苯类化合物的致毒机理

应用受体学说推出的定量结构活性相关(QSAR)模型研究了硝基苯类化合物的致毒机理,结果表明,硝基苯类化合物的主要致毒机理是化合物亲电中心与受体分子亲核活性中心发生反应．并引入硝基数目和位置指示变量I,分析表明,苯环上硝基的数目和位置的差别引起化合物的最低未占轨道能ELUMO的变化,即化合物亲电结合能的变化,从而影响了化合物的生物活性．     

细胞膜结合的雌激素受体的特异性标记

细胞膜结合的雌激素受体(Cell membrane-bound estrogen receptor,cmER)介导了雌激素的非基因组作用,参与了乳腺癌等诸多疾病的发生,但是作用机制研究受限于能够有效区分cmER和细胞质内ER(Estrogen receptor)的标记手段.为了实现cmER的特异性标记,首先在体外分别表达含有A1、S6和ybbR三个不同短肽的谷胱甘肽S转移酶融合蛋白,比较磷酸泛酰巯基乙胺基转移酶(Phosphopantetheinyl transferase,PPTase)-AcpS和Sfp对其的识别选择性.选取识别效率较高和特异性较好的A1短肽,将其构建到雌激素受体ERα的C端(ERα-A1),结果表明该偶联并不影响ERα的蛋白质表达及其在雌激素作用下的转录.进一步研究表明,来源于大肠杆菌的PPTase-AcpS可以以辅酶A-生物素(Coenzyme A-biotin)为底物,将生物素特异性标记到ERα-A1.这些结果为进一步研究雌激素及cmER介导的非基因组调控机制提供了新的方法.     

简析分子对接模拟中雌激素受体的柔性

根据刚性雌激素受体模型的原位和交叉对接的情况,探讨了配体诱导的受体结构差异或晶体本身的缺陷,导致模拟产生偏差的原因;总结了受体结构和残基位置对模拟的影响,并由此提出部分柔性多重受体构象(PFMRC)对接体系,考虑受体的部分柔性以达到同时提高对接精度和速率的目的.     

Achieving Open Access to Conservation Science

Conservation science is a crisis discipline in which the results of scientific enquiry must be made available quickly to those implementing management. We assessed the extent to which scientific research published since the year 2000 in 20 conservation science journals is publicly available. Of the 19,207 papers published, 1,667 (8.68%) are freely downloadable from an official repository. Moreover, only 938 papers (4.88%) meet the standard definition of open access in which material can be freely reused providing attribution to the authors is given. This compares poorly with a comparable set of 20 evolutionary biology journals, where 31.93% of papers are freely downloadable and 7.49% are open access. Seventeen of the 20 conservation journals offer an open access option, but fewer than 5% of the papers are available through open access. The cost of accessing the full body of conservation science runs into tens of thousands of dollars per year for institutional subscribers, and many conservation practitioners cannot access pay‐per‐view science through their workplace. However, important initiatives such as Research4Life are making science available to organizations in developing countries. We urge authors of conservation science to pay for open access on a per‐article basis or to choose publication in open access journals, taking care to ensure the license allows reuse for any purpose providing attribution is given. Currently, it would cost $51 million to make all conservation science published since 2000 freely available by paying the open access fees currently levied to authors. Publishers of conservation journals might consider more cost effective models for open access and conservation‐oriented organizations running journals could consider a broader range of options for open access to nonmembers such as sponsorship of open access via membership fees. Obtención de Acceso Abierto a la Ciencia de la Conservación     

Rapid,recurring, structured survey versus bioblitz for generating biodiversity data and analysis with a multispecies abundance model

A bioblitz inexpensively and quickly generates biodiversity data, but bioblitzes are often conducted with haphazard, unreplicated sampling. Results tend to be taxonomically, geographically, or temporally biased, lack metadata, and consist of lists of observed taxa that do not enable further analyses or correction for imperfect detection. A rapid, recurring, structured survey (RRSS) uses a structured sampling design and temporal and spatial replication to survey randomly selected sites on a conservation property. We participated in a loosely structured bioblitz and a subsequent RRSS at Big Canoe Creek Nature Preserve in Springville (St. Clair County), Alabama (USA) to compare observed richness derived from the 2 survey approaches. The RRSS data structure enabled us to fit models that accounted for imperfect detection to estimate abundances, occupancy probabilities, and habitat associations. The loosely structured bioblitz data could not be used in such models. We present a new integrated multispecies abundance model that we applied to avian RRSS data. Our model extension enables estimation for the community, employs data augmentation to estimate the number of undetected species, and incorporates covariates. The RRSS generated a more comprehensive and less biased list of observed taxonomic richness than the loosely structured bioblitz (e.g., 73 vs. 45 bird species and 104 vs. 63 insect families from the RRSS vs. loosely structured bioblitz, respectively). Models fit to the RRSS data identified seasonal patterns in avian community composition and allowed for estimation of habitat–occupancy relationships for insect taxa. The RRSS protocol has potential for broad transferability as a standardized, quick, and inexpensive way to inventory biodiversity and estimate ecological parameters while providing an outreach opportunity.     

Compliance with and ecosystem function of biodiversity offsets in North American and European freshwaters

Land-use change via human development is a major driver of biodiversity loss. To reduce these impacts, billions of dollars are spent on biodiversity offsets. However, studies evaluating offset project effectiveness that examine components such as the overall compliance and function of projects remain rare. We reviewed 577 offsetting projects in freshwater ecosystems that included the metrics project size, type of aquatic system (e.g., wetland and creek), offsetting measure (e.g., enhancement, restoration, and creation), and an assessment of the projects’ compliance and functional success. Project information was obtained from scientific and government databases and gray literature. Despite considerable investment in offsetting projects, crucial problems persisted. Although compliance and function were related to each other, a high level of compliance did not guarantee a high degree of function. However, large projects relative to area had better function than small projects. Function improved when projects targeted productivity or specific ecosystem features and when multiple complementary management targets were in place. Restorative measures were more likely to achieve targets than creating entirely new ecosystems. Altogether the relationships we found highlight specific ecological processes that may help improve offsetting outcomes.     

Some polyphagous Homoptera gain protection from their natural enemies by feeding on the toxic plantsSpartium junceum andErythrina corallodendrum (Leguminosae)

Summary Interactions were studied among alkaloid-containing legumes (Erythrina corallodendrum andSpartium junceum) and non-toxic plants (Citrus sinensis, Cucurbita moschata andEuphorbia tirucalli), several polyphagous homopterans,Aphis craccivora (Aphididae),Icerya purchasi, I. aegyptiaca (Margarodidae),Lepidosaphes ulmi (Diaspididae) andPlanococcus citri (Pseudococcidae), and some major natural enemies of these homopterans. Significant reductions in survival due to negative effects of alkaloid containing as compared with non-alkaloidal plants were recorded for the predatorsRodolia cardinalis andChilocorus bipustulatus, but not forCryptolaemus montrouzieri (Coleoptera: Coccinellidae),Chrysoperla carnea (Neuroptera: Chrysopidae) andSympherobius sanctus (Neuroptera: Sympherobiidae). The development time of the larvae or pupae ofR. cardinalis, C. carnea andS. sanctus was longer on the toxic plants than on the non-toxic ones. The percentage of parasitism ofA. craccivora collected from the non-alkaloidal plantsVicia palaestina andMelilotus albus was much higher than that onS. junceum. The parasitoid complexes ofA. craccivora differed between both plant groups. The nutritive value of honeydew ofI. purchasi andA. craccivora, as expressed by the life span ofEncyrtus infelix (Hymenoptera: Encyrtidae) adults, was also investigated. Life spans were significantly longer when the wasps fed on honeydew produced on non-alkaloidal plants (C. sinensis andPittosporum tobira) than on alkaloid containing plants whenI. purchasi — but notA. craccivora — was the producer. It is suggested that the chemical defense ofE. corallodendrum andS. junceum is exploited by polyphagous phytophages to reduce predation. In nature, population growth and density of four of the investigated homopterans are conspicuously high when they developed on the alkaloid containing plant species, and very low on non-alkaloid plants. The efficiency of their natural enemies may be reduced by sequestration of alkaloids (or other toxic plant compounds) or their transfer into excreted honeydew. Therefore it is assumed that a generalist phytophagous homopteran may be protected from its natural enemies, although at different rates of efficiency, if it can safely sequester the host allelochemical when it develops on toxic species within its host range.     

A palaeo-hydrogeological model for arsenic contamination in southern and south-east Asia

An argument is presented in which areas of natural arsenic contamination of modern groundwaters throughout Asia have a common origin. Arsenic originally accumulated in oceanic ferro-manganoan sediments of the eastern Palaeo-Tethys. This was further concentrated through oceanic crustal extinction in what later became the south-east Chinese accreted mineralised terrain. Proto-Himalayan uplift of this area created the palaeo-drainage systems of the Ganges – Brahmaputra, Irrawaddy, Mekong, and Red Rivers, with consequent headwater erosion of arsenic-rich sediments. Their downstream deposition as immature and easily redistributed Neogene sandstones, silts, and iron-rich clays has created secondary and tertiary reservoirs of adsorbed and authigenic arsenic, from which the current arsenic-rich groundwaters have evolved. Considering river basins within the above palaeo-hydrogeological framework provides a basis for assessing the risk of arsenic in groundwater basins of south and south-eastern Asia.     

Sequestration of cucurbitacin analogs by New and Old World chrysomelid leaf beetles in the tribe Luperini

Summary Two South American polyphagous leaf beetles,Diabrotica speciosa andCerotoma arcuata, selectively accumulated the bitter tasting compound 23,24-dihydrocucurbitacin D in their body after ingesting root tissues of cucurbit plants. Similarly, three Asian Cucurbitaceae-feeding specialists in the genusAulacophora were found to sequester the same compound. Cucurbitacin analogs were shown to deter feeding by a bird predator, indicating an allomonal role for these compounds in cucurbitacin-associated chrysomelid leaf beetles both of New and Old Worlds. The strong affinity to cucurbitacins, selective sequestration of the analogs and consequent protection from predators suggested an ecological adaptation mechanism developed in common among these two geographically isolated subtribes in the Luperini.     

Threats to intact tropical peatlands and opportunities for their conservation

Large, intact areas of tropical peatland are highly threatened at a global scale by the expansion of commercial agriculture and other forms of economic development. Conserving peatlands on a landscape scale, with their hydrology intact, is of international conservation importance to preserve their distinctive biodiversity and ecosystem services and maintain their resilience to future environmental change. We explored threats to and opportunities for conserving remaining intact tropical peatlands; thus, we excluded peatlands of Indonesia and Malaysia, where extensive deforestation, drainage, and conversion to plantations means conservation in this region can protect only small fragments of the original ecosystem. We focused on a case study, the Pastaza‐Marañón Foreland Basin (PMFB) in Peru, which is among the largest known intact tropical peatland landscapes in the world and is representative of peatland vulnerability. Maintenance of the hydrological conditions critical for carbon storage and ecosystem function of peatlands is, in the PMFB, primarily threatened by expansion of commercial agriculture linked to new transport infrastructure that is facilitating access to remote areas. There remain opportunities in the PMFB and elsewhere to develop alternative, more sustainable land‐use practices. Although some of the peatlands in the PMFB fall within existing legally protected areas, this protection does not include the most carbon‐dense (domed pole forest) areas. New carbon‐based conservation instruments (e.g., REDD+, Green Climate Fund), developing markets for sustainable peatland products, transferring land title to local communities, and expanding protected areas offer pathways to increased protection for intact tropical peatlands in Amazonia and elsewhere, such as those in New Guinea and Central Africa which remain, for the moment, broadly beyond the frontier of commercial development.     

Effects of Controlled Fire and Livestock Grazing on Bird Communities in East African Savannas

Abstract: In East Africa fire and grazing by wild and domestic ungulates maintain savannas, and pastoralists historically set fires and herded livestock through the use of temporary corrals called bomas. In recent decades traditional pastoral practices have declined, and this may be affecting biodiversity. We investigated the effects of prescribed fires and bomas on savanna bird communities in East Africa during the first and second dry seasons of the year (respectively before and after the rains that mark the onset of breeding for most birds). We compared abundance, richness, and community composition on 9‐ha burned plots, recently abandoned bomas, and control plots in the undisturbed matrix habitat over a 3‐year period. Generally, recently burned areas and abandoned bomas attracted greater densities of birds and had different community assemblages than the surrounding matrix. The effects of disturbances were influenced by interactions between primary productivity, represented by the normalized difference vegetation index, and time. Bird densities were highest and a greater proportion of species was observed on burned plots in the months following the fires. Drought conditions equalized bird densities across treatments within 1 year, and individuals from a greater proportion of species were more commonly observed on abandoned bomas. Yearly fluctuations in abundance were less pronounced on bomas than on burns, which indicate that although fire may benefit birds in the short term, bomas may have a more‐lasting positive effect and provide resources during droughts. Several Palearctic migrants were attracted to burned plots regardless of rainfall, which indicates continued fire suppression may threaten their already‐declining populations. Most notably, the paucity of birds observed on the controls suggests that the current structure of the matrix developed as a result of fire suppression. Traditional pastoralism appears critical to the maintenance of avian diversity in these savannas.     

Cost‐effective conservation of an endangered frog under uncertainty

How should managers choose among conservation options when resources are scarce and there is uncertainty regarding the effectiveness of actions? Well‐developed tools exist for prioritizing areas for one‐time and binary actions (e.g., protect vs. not protect), but methods for prioritizing incremental or ongoing actions (such as habitat creation and maintenance) remain uncommon. We devised an approach that combines metapopulation viability and cost‐effectiveness analyses to select among alternative conservation actions while accounting for uncertainty. In our study, cost‐effectiveness is the ratio between the benefit of an action and its economic cost, where benefit is the change in metapopulation viability. We applied the approach to the case of the endangered growling grass frog (Litoria raniformis), which is threatened by urban development. We extended a Bayesian model to predict metapopulation viability under 9 urbanization and management scenarios and incorporated the full probability distribution of possible outcomes for each scenario into the cost‐effectiveness analysis. This allowed us to discern between cost‐effective alternatives that were robust to uncertainty and those with a relatively high risk of failure. We found a relatively high risk of extinction following urbanization if the only action was reservation of core habitat; habitat creation actions performed better than enhancement actions; and cost‐effectiveness ranking changed depending on the consideration of uncertainty. Our results suggest that creation and maintenance of wetlands dedicated to L. raniformis is the only cost‐effective action likely to result in a sufficiently low risk of extinction. To our knowledge we are the first study to use Bayesian metapopulation viability analysis to explicitly incorporate parametric and demographic uncertainty into a cost‐effective evaluation of conservation actions. The approach offers guidance to decision makers aiming to achieve cost‐effective conservation under uncertainty.