Unique assignment of inter-subunit association in GABAA α1β3γ2 receptors determined by molecular modeling

Recent publications defined requirements for inter-subunit contacts in a benzodiazepine-sensitive GABA_A receptor (GABA_ARα1β3γ2). There is strong evidence that the heteropentameric receptor contains two α1, two β3, and one γ2 subunit. However, the available data do not distinguish two possibilities: When viewed clockwise from an extracellular viewpoint the subunits could be arranged in either γ2β3α1β3α1 or γ2α1β3α1β3 configurations. Here we use molecular modeling to thread the relevant GABA_AR subunit sequences onto a template of homopentameric subunits in the crystal structure of the acetylcholine binding protein (AChBP). The GABA_A sequences are known to have 15-18% identity with the acetylcholine binding protein and nearly all residues that are conserved within the nAChR family are present in AChBP. The correctly aligned GABA_A sequences were threaded onto the AChBP template in the γ2β3α1β3α1 or γ2α1β3α1β3  arrangements. Only the γ2α1β3α1β3 arrangement satisfied three known criteria: (1) α1 His¹⁰² binds at the γ2 subunit interface in proximity to γ2 residues Thr¹⁴², Phe⁷⁷, and Met¹³⁰; (2) α1 residues 80-100 bind near γ2 residues 91-104; and (3) α1 residues 58-67 bind near the β3 subunit interface. In addition to predicting the most likely inter-subunit arrangement, the model predicts which residues form the GABA and benzodiazepine binding sites.     

Mapping palm extractivism in Ecuador using pair-wise comparisons and bioclimatic modeling

The native palm flora of Ecuador consists of 129 taxa, including at least 69 species used by rural people, 19 of which are exploited commercially. This paper integrates bioclimatic modeling of palm distribution and quantitative ranking through pair-wise comparisons of species as a tool to evaluate and map the importance of 14 taxa of commercially exploited palms in Ecuador based on criteria of harvest values, sustainability, vegetation cover and population density. The ranking procedure could find broad application within ethnobotany and economic botany. Results show that extraction of palm products, economically speaking, is most important in the heavily deforested and populated coastal lowland.     

Modeling the hydrochemistry of the Choptank River basin using GWLF and Arc/Info: 2. Model Validation and Application

We used the hydrochemical model GWLF to estimate terrestrial diffuse fluxes from ungauged areas of a coastal plain catchment, the Choptank River basin. The gauged area of the basin is 17% of the land surface, and we divided the remaining ungauged area into 21 subbasins. Three comparative approaches were used: (1) application of area yield coefficients based on 11 years of observations from the gauged area to extrapolate over ungauged subbasins without modeling, (2) application of GWLF to estimate export from all subbasins using model parameters calibrated in the gauged subbasin, and (3) application of GWLF with parameter adjustments based on the local characteristics in each subbasin. Comparison of the predicted export from 6 selected subbasins with observed export data showed that application of GWLF with local adjustments reduced model errors of N export from 43% to 27%. With only one adjustment for sediment P, application of GWLF alone reduced errors of P export from 92%to 40–45%, with or without local adjustments for flow and sediment retention. The data supported the hypothesis that significant spatial variations in N and P yields introduce large errors when extrapolating from gauged to ungauged subbasins, and estimated TN and TP yield coefficients varied over 1–21 kg N and 0.1–0.5 kg P ha^–1 y^–1 in ungauged areas due to varying human population densities, soil drainage characteristics, and amounts of agriculture. The most accurate estimates of terrestrial diffuse sources were combined with point source discharges and wet atmospheric inputs to estimate annual average inputs of 2.5 × 10⁶ kg N and 5.8 × 10⁴ kg P y^–1 to the Choptank estuary during 1980–1996. These results illustrate the problems of spatial extrapolation from gauged to ungauged areas and emphasize the need for application of local characteristics for accurate assessment of watershed export.     

Soil-air exchange of nitric oxide: An overview of processes, environmental factors, and modeling studies

Terrestrial ecosystems with their main elements soil and plants may act, in principle, as both source and sink for atmospheric nitric oxide (NO). The net exchange between ecosystems and the atmosphere, however, is globally dominated by biogenic emissions of NO from soils. Consequently the soil–air exchange of NO is the focus of the following overview. Particular emphasis is placed on the major processes that are responsible for NO production in soils (nitrification, denitrification) and their regulation by environmental factors (nitrogen availability, soil water content, soil temperature, ambient NO concentration). It is shown that interactions of these factors are a major reason for the broad range that exists in published data on NO fluxes. This variability makes it difficult to predict the magnitude of NO fluxes on relevant spatial and temporal scales. To overcome the problem various generalization procedures for scaling up in space and time have been developed, and the potential and limitations of the different approaches is discussed.     

Boron adsorption by maize cell walls

Boron adsorption by cell walls isolated from corn (Zea mays) roots was investigated as a function of solution pH and ionic strength. Adsorption increased with increasing solution pH from pH 4.5 to 10, exhibited an adsorption maximum at pH 10–10.5, and decreased with increases in pH above 10.5. Boron adsorption increased with increasing solution ionic strength indicating the formation of strong inner-sphere surface complexes. A surface complexation model, the constant capacitance model was well able to describe the B adsorption data, optimizing two B surface complexes and the dissociation constant for the surface functional group, XOH. The large absolute value of the dissociation constant is consistent with phenolic functional groups.     

用距离几何算法和同源建模法对水稻类金属硫蛋白（rgMT）的三维结构建模

水稻类金属硫蛋白(rgMT)的两端是高度保守的半胱氨酸富含区的结构域(CR区),中间是不含半胱氨酸的间隔区,呈典型的三段式结构。本研究分别采用距离几何算法和同源建模相结合的方法对水稻类金属硫蛋白进行三级结构建模。在排列出CR区的所有可能的半胱氨酸-金属硫络合的组合方式,并对每一种组合方式给出一定的限制条件后各生成20个随机构象。根据生成的随机构象足否能形成金属硫络合结构,从900个随机构象中最终选出6个构象(N端4种,C端2种组合)作为可能的结构模型。另一方面,采用GOR方法对间隔区进行了二级结构预测,随后用同源建模法对其建模。将上述建成的三部分模型连接起来后形成rgMT的整体三维构象。结果表明rgMT能像哺乳动物MT蛋白一样,可形成两个独立的、在结构和能量上均没有障碍的金属-硫络合结构。介于所有植物类金属硫蛋白都具有典型的三段式结构,其中的一部分还具有与rgMT相同的半胱氨酸排列方式,所以rgMT三维结构模型的建立对于其他植物类金属硫蛋白的结构研究具有重要的参考价值。     

Two-dimensional growth of a root system modelled as a diffusion process. I. Analytical solutions

For functioning of a root system, the temporal development of distribution of roots in the soil is important. For example, for computing uptake of water and nutrients the root length density distribution might be required. A way to describe root proliferation is to consider it as a diffusion process with a first-order sink term accounting for decay. In this paper, analytical solutions are derived for two-dimensional diffusion of roots both in a rectangular area, and in a cylindrical volume. The source of root dry matter is located at the surface. Root dry matter enters the soil domain through a part of the soil surface. It is shown that different distribution patterns are obtained, with different ratios of the diffusion coefficients in horizontal and vertical direction. From the solutions obtained it can be shown that for the situation where the dry matter enters through the complete surface eventually a steady-state occurs where root length density decreases exponentially with depth, as often is found in experiments.     

The consequences of uncertainties in land use, climate and vegetation responses on the terrestrial carbon

The IPCC SRES narratives were implemented in IMAGE 2.2 to evaluate thefuture condition of the climate system (including the biosphere). A series of scenario experiments was used to assess possible ranges in emissions and concentrations of greenhouse gases, climate change and impacts. These experiments focussed on the role of the terrestrial carbon cycle. The experiments show that the SRES narratives dominate human emissions and not natural processes. In contrary, atmospheric CO2 concentration strongly differs between the experiments. Atmospheric CO2 concentrations range for A1B from 714 to 1009 ppmv CO2 in 2100. The spread of this range is comparable with the full SRES range as implemented in IMAGE 2.2 (515-895 μmol/mol CO2). The most important negative and positive feedback processes in IMAGE 2.2 on the build-up of CO2 concentrations are CO2 fertilisation and soil respiration respectively. Indirect effects of these processes furtherchange land-use patterns, deforestation rates and alter the natural C fluxes. The cumulative effects of these changes have a pronounced influence on the final CO2 concentrations. Our scenario experiments highlight the importance of a proper parameterisation of feedback processes, C-cycle and land use in determining the future states of the climate system.     

人脯氨肽酶活性中心结构的计算机模拟

氨酰基脯氨酸二肽酶 (脯氨肽酶 )为广泛分布于生物界的细胞内二肽水解酶 .它特异性地水解以脯氨酸或羟脯氨酸为羧基端的二肽 (X Pro) ,而且只对反式肽键有催化活性 .此酶与脯氨酸代谢、胶原蛋白合成及细胞生长有密切关系 .文献报道 ,从Alteromonas细菌中提取的脯氨肽酶有水解梭曼的活性 ,其有机磷酸酐水解酶也有脯氨肽酶活性 .用重组基因表达的人肝脯氨肽酶也同时具有脯氨肽酶活性和水解梭曼的活性 .研究脯氨肽酶活性中心的结构具有重要理论意义和潜在实用价值 .但目前尚无人脯氨肽酶晶体结构的报道 .本文采用蛋白质结构模式识别 (threading)方法对脯氨肽酶的高级结构进行模拟 ,以大肠杆菌甲硫氨酸氨肽酶 (1MAT)为模板 ,模建了人脯氨肽酶C端结构域的空间结构 .通过对模建结构的 3D评估及电荷分布分析 ,对人脯氨肽酶活力中心结构进行了预测 .模建的人脯氨肽酶活性中心位于C端结构域 ,为 6条β折叠围成的一个疏水性口袋 ,外面被 5条α螺旋及一些loop包围 ,活力中心位于疏水结构中央 ,其中有 5个保守氨基酸 ,形成 1个较强的负电荷区 ,周围有 3个较弱的正电荷区域 .实验还发现 ,虽然Mn2 + 或Co2 + 对酶的活性极其重要 ,但对酶蛋白结构的贡献很小 .提示它们可能是在催化反应的电荷转移过程中发挥着重要作用     

Improving Risk Assessment: Priorities for Epidemiologic Research

The Epidemiology Work Group at the Workshop on Future Research for Improving Risk Assessment Methods, Of Mice, Men, and Models, held August 16 to 18, 2000, at Snowmass Village, Aspen, Colorado, concluded that in order to improve the utility of epidemiologic studies for risk assessment, methodologic research is needed in the following areas: (1) aspects of epidemiologic study designs that affect doseresponse estimation; (2) alternative methods for estimating dose in human studies; and (3) refined methods for dose-response modeling for epidemiologic data. Needed research in aspects of epidemiologic study design includes recognition and control of study biases, identification of susceptible subpopulations, choice of exposure metrics, and choice of epidemiologic risk parameters. Much of this research can be done with existing data. Research needed to improve determinants of dose in human studies includes additional individual-level data (e.g., diet, co-morbidity), development of more extensive human data for physiologically based pharmacokinetic (PBPK) dose modeling, tissue registries to increase the availability of tissue for studies of exposure/dose and susceptibility biomarkers, and biomarker data to assess exposures in humans and animals. Research needed on dose-response modeling of human studies includes more widespread application of flexible statistical methods (e.g., general additive models), development of methods to compensate for epidemiologic bias in dose-response models, improved biological models using human data, and evaluation of the benchmark dose using human data. There was consensus among the Work Group that, whereas most prior risk assessments have focused on cancer, there is a growing need for applications to other health outcomes. Developmental and reproductive effects, injuries, respiratory disease, and cardiovascular disease were identified as especially high priorities for research. It was also a consensus view that epidemiologists, industrial hygienists, and other scientists focusing on human data need to play a stronger role throughout the risk assessment process. Finally, the group agreed that there was a need to improve risk communication, particularly on uncertainty inherent in risk assessments that use epidemiologic data.