Virtual screening pipeline and ligand modelling for H5N1 neuraminidase

The H5N1 virus neuraminidase structure was solved in two different conformations depending on the inhibitor concentration. In the absence of oseltamivir or at a low concentration, the neuraminidase structure assumes an open form that closes at a high oseltamivir concentration due to the shift of the so-called 150-loop near the active site. Although the close conformation is similar to all the other structurally known neuraminidase types, it doesn’t appear to be the most likely physiological condition for N1.To investigate the specific ligand binding properties of the open form, we screened by docking simulation, a large dataset of ligands and compared the results with closed form. The virtual screening procedure was implemented in a docking pipeline that also performs a step-by-step, target specific, filtering approach for data reduction. The selected ligands display binding ability involving multiple sites of interaction including the active site and an adjacent cavity made available by the 150-loop shift. Two ligands are especially interesting and are proposed as substituents to design oseltamivir derivatives specifically suited for the open conformation.     

不同滤波方法对超声图像分割的影响

采用各向异性滤波方法以及Gabor滤波方法对乳腺肿瘤超声图像进行处理,再使用snake方法以及levelset方法在设置相同参数的条件下,对过滤的图像分别进行分割。试验结果表明,不同的滤波方法在分害4目标图像的收敛度,边缘圆滑度及整体轮廓提取效果都有较大影响,为分割图像选取适当的滤波器提供了参考。     

Insights into succession processes using temporally repeated habitat models: results from a long‐term study in a post‐mining landscape

Questions: The early phases of primary succession are governed by chance events and dispersal‐related processes in an environment that is largely free of competition. Thus, the predictability of vegetation patterns using environmental site factors can be expected to be low and spatial autocorrelation to be high. We asked whether the match between vegetation and environment becomes better in the course of succession, and whether vegetation types shift their realized niche with time. Location: Lignite mining region in Central Germany, the post‐mining landscape “Goitzsche” (Saxony‐Anhalt). Methods: Vegetation types were mapped in a 10‐m grid (total area 4.8 ha), starting in 1995, at 3‐year intervals until 2007. We used a temporal comparison of habitat models. We applied: GLS regression to partition the variation in coverage of vegetation types into environmental (soil pH) and spatial components; logistic regression to model the presence/absence of vegetation types along a soil acidity gradient; and autologistic regression allowing for soil acidity and neighbourhood effects. Results: For most vegetation types, the proportion of variation explained by space was high but declined during succession. The outcome of autologistic models suggests that soil acidity often plays a minor role compared to neighbourhood effects in the earlier phase of succession than 12 years later. For four vegetation types, the pH range in which the type was expected to be dominant clearly became smaller with time. These trends support the view that the role of processes related to chance and dispersal decrease with time, while those related to environmental filtering mediated by biotic interactions increase. Conclusions: We conclude that temporal comparisons of spatially explicit habitat models provide insights into changing biotic community processes and their effects on habitat specificity of species or their communities. Thus, this approach may be particularly important for analysis of ecological systems that are not in equilibrium with their environmental drivers.     

蛋白质-蛋白质分子对接方法研究进展

蛋白质分子间相互作用与识别是21世纪生命科学研究的前沿和热点.分子对接方法是研究这一课题有效的计算机模拟手段.通常,蛋白质-蛋白质分子对接包括四个阶段:搜索受体与配体分子间的结合模式,过滤对接结构以排除不合理的结合模式,优化结构,用精细的打分函数评价、排序对接模式并挑选近天然构象.结合国内外研究蛋白质-蛋白质分子对接方法进展和本研究小组的工作,对以上四个环节做了详细的综述.另外,还分析了目前存在的主要问题,并提出对未来工作的展望.     

Trait similarity, shared ancestry and the structure of neighbourhood interactions in a subtropical wet forest: implications for community assembly

Ecology Letters (2010) 13: 1503-1514 ABSTRACT: The phylogenetic structure and distribution of functional traits in a community can provide insights into community assembly processes. However, these insights are sensitive to the spatial scale of analysis. Here, we use spatially explicit, neighbourhood models of tree growth and survival for 19 tree species, a highly resolved molecular phylogeny and information on eight functional traits to quantify the relative efficacy of functional similarity and shared ancestry in describing the effects of spatial interactions between tree species on demographic rates. We also assess the congruence of these results with observed phylogenetic and functional structure in the neighbourhoods of live and dead trees. We found strong support for models in which the effects of spatial neighbourhood interactions on tree growth and survival were scaled to species-specific mean functional trait values (e.g., wood specific gravity, leaf succulence and maximum height) but not to phylogenetic distance. The weak phylogenetic signal in functional trait data allowed us to independently interpret the static neighbourhood functional and phylogenetic patterns. We observed greater functional trait similarity in the neighbourhoods of live trees relative to those of dead trees suggesting that environmental filtering is the major force structuring this tree community at this scale while competitive interactions play a lesser role.     

Ultra scaledown to predict filtering centrifugation of secreted antibody fragments from fungal broth

Extracellularly expressed anti-hen egg lysozyme single-chain antibody fragments (scFv) produced by Aspergillus awamori were recovered using filtering centrifugation. Two filtering centrifuges with 0.5- and 30-L capacities were used to represent laboratory- and pilot-scale equipment, respectively. Critical regime analysis using the computational fluid dynamics (CFD) technique provided information about the local energy dissipation rates in both units. Experimental data indicated loss of scFv activity for energy dissipation rates above about 2.0 x 10(4) W kg(-1). This loss of activity increased in the presence of gas-liquid interfaces during filtering centrifugation. An ultra scaledown filtering centrifuge with a maximum working volume of 35 mL was designed to mimic the operating conditions identified by the critical regime analysis for the laboratory- and pilot-plant-scale units. The recovered scFv activity levels and the separation performance of the three units were comparable when operated at equal maximum energy dissipation rates.     

视觉系统初级信息处理的时变通带滤波模型

通过分析在视觉初级信息处理过程中时间、空间信息的依存关系,提出了随时间变化的方差σ＾２（ｔ）因子表示的时变通带高斯滤波函数模型,从数学上证明了时变带通高斯函数的微分正好实现了空间域中的滤波,由此分别讨论了零交叉检测滤波器和典型的ｏｎ－ｏｆｆ感受野的关系,计算了各特征频率通道的峰值频率,该值在一定程度上与以往的研究结果基本吻合。本文从数学上具体描述了视觉信息的提取过程是一个分时分频的提取过程的思想,     

Global net biome CO2 exchange predicted comparably well using parameter–environment relationships and plant functional types

Accurate estimation and forecasts of net biome CO₂ exchange (NBE) are vital for understanding the role of terrestrial ecosystems in a changing climate. Prior efforts to improve NBE predictions have predominantly focused on increasing models' structural realism (and thus complexity), but parametric error and uncertainty are also key determinants of model skill. Here, we investigate how different parameterization assumptions propagate into NBE prediction errors across the globe, pitting the traditional plant functional type (PFT)-based approach against a novel top-down, machine learning-based “environmental filtering” (EF) approach. To do so, we simulate these contrasting methods for parameter assignment within a flexible model–data fusion framework of the terrestrial carbon cycle (CARDAMOM) at a global scale. In the PFT-based approach, model parameters from a small number of select locations are applied uniformly within regions sharing similar land cover characteristics. In the EF-based approach, a pixel's parameters are predicted based on underlying relationships with climate, soil, and canopy properties. To isolate the role of parametric from structural uncertainty in our analysis, we benchmark the resulting PFT-based and EF-based NBE predictions with estimates from CARDAMOM's Bayesian optimization approach (whereby “true” parameters consistent with a suite of data constraints are retrieved on a pixel-by-pixel basis). When considering the mean absolute error of NBE predictions across time, we find that the EF-based approach matches or outperforms the PFT-based approach at 55% of pixels—a narrow majority. However, NBE estimates from the EF-based approach are susceptible to compensation between errors in component flux predictions and predicted parameters can align poorly with the assumed “true” values. Overall, though, the EF-based approach is comparable to conventional approaches and merits further investigation to better understand and resolve these limitations. This work provides insight into the relationship between terrestrial biosphere model performance and parametric uncertainty, informing efforts to improve model parameterization via PFT-free and trait-based approaches.     

Investigation of the early mineralisation on collagen in dentine of rat incisors by quantitative electron spectroscopic diffraction (ESD)

The earliest crystallites in dentine appear as chains of dots in ultra-thin sections viewed by transmission electron microscopy. These dots rapidly coalesce along the longitudinal directions of the collagen microfibrils to form needle-like structures that coalesce preferentially in lateral directions to form ribbon-like or plate-like crystallites. This morphological interpretation is supported by line-scans of the corresponding zero-loss filtered electron spectroscopic diffraction patterns, which demonstrate the crystalline structure of the dentine mineral (apatite). The intensity ratio of the Debye-Scherrer rings of the characteristic Bragg-reflections (002 to 300, together with 1 or 2 unresolved reflections) shows a maximum in the region of early chain-like and needle-like crystallites, decreasing with maturation of the dentine mineral to the ribbon-plate-like crystallites. Detailed investigations using line-scans of the zero-loss filtered electron spectroscopic diffraction patterns through the dentine zone show that the intensity ratio found near the mineralisation front is repeated 3–5 times at distances of about 10–20 m. This may represent a circadian pattern of mineralisation corresponding to light microscopically visible incremental lines in dentine.     

Communication in the weakly electric fish Sternopygus macrurus

Summary A classical conditioning paradigm was used to test the ability of Sternopygus macrurus to detect EOD-like stimuli (sine waves) of different frequencies. The behavioral tuning curves were quite close in shape to tuning curves based on single-unit recordings of T units, although the sensitivity at all frequencies was much greater. The behavioral curves showed notches of greatly reduced sensitivity when the test frequency was equal to, or twice the EOD frequency. The EOD of each of the fish was eliminated by lesioning the medullary pacemaker nucleus, and the fish were retested. The resulting tuning curves were nearly the same in shape as those of the EOD-intact individuals, but the PMN-lesioned fish showed an overall reduction of sensitivity of 30 dB. The EOD appears to enhance sensitivity by placing the summed stimulus (test stimulus + fish's EOD) at an amplitude where T units are maximally sensitive to small temporal modulations in the fish's own EOD. Peripheral tuning appears to limit the ability of males to detect the EOD of females, since these are, on average, an octave higher in frequency than the male EOD, while the peak sensitivity of the male occurs 5–10 Hz above its own EOD frequency.Abbreviations EOD electric organ discharge - PMN pacemaker nucleus - BF best frequency - DF difference frequency