Lipid Membrane Structure and Dynamics Studied by All-Atom Molecular Dynamics Simulations of Hydrated Phospholipid Bilayers

Abstract

The structure and dynamics of phosphatidylcholine bilayers are examined by reviewing the results of several nanoseconds of molecular dynamics simulations on a number of bilayer and monolayer models. The lengths of these simulations, the longest single one of which was 2 nanoseconds, were sufficiently long to effectively sample many of the longer-scale motions governing the behaviour of biomembranes. These simulations reproduce many experimental observables well and provide a degree of resolution currently unavailable experimentally.     

Redox-sensitive stimulation of type-1 ryanodine receptors by the scorpion toxin maurocalcine

The scorpion toxin maurocalcine acts as a high affinity agonist of the type-1 ryanodine receptor expressed in skeletal muscle. Here, we investigated the effects of the reducing agent dithiothreitol or the oxidizing reagent thimerosal on type-1 ryanodine receptor stimulation by maurocalcine. Maurocalcine addition to sarcoplasmic reticulum vesicles actively loaded with calcium elicited Ca²⁺ release from native vesicles and from vesicles pre-incubated with dithiothreitol; thimerosal addition to native vesicles after Ca²⁺ uptake completion prevented this response. Maurocalcine enhanced equilibrium [³H]-ryanodine binding to native and to dithiothreitol-treated reticulum vesicles, and increased 5-fold the apparent K_i for Mg²⁺ inhibition of [³H]-ryanodine binding to native vesicles. Single calcium release channels incorporated in planar lipid bilayers displayed a long-lived open sub-conductance state after maurocalcine addition. The fractional time spent in this sub-conductance state decreased when lowering cytoplasmic [Ca²⁺] from 10 μM to 0.1 μM or at cytoplasmic [Mg²⁺] ≥ 30 μM. At 0.1 μM [Ca²⁺], only channels that displayed poor activation by Ca²⁺ were readily activated by 5 nM maurocalcine; subsequent incubation with thimerosal abolished the sub-conductance state induced by maurocalcine. We interpret these results as an indication that maurocalcine acts as a more effective type-1 ryanodine receptor channel agonist under reducing conditions.     

崇明东滩鸟类栖息地优化区越冬水鸟的栖息地利用及影响因子

阐明水鸟栖息地利用与环境因子的关系有助于制定针对性的水鸟保护对策。本研究在2012~2013年冬季对崇明东滩鸟类栖息地优化区内越冬水鸟的种类、数量以及6种环境因子(植被面积比例、裸地面积比例、水深、地形变异、栖息地结构多样性和干扰)进行调查,以了解水鸟对人工湿地的栖息地利用及其影响因子。野外调查共记录到水鸟24种9 018只,其中优势种为斑嘴鸭(Anas poecilorhyncha)和绿头鸭(A.platyrhynchos);栖息地优化区内水鸟休息的个体数量占总数量的79.2%,这表明优化区是大多数水鸟的休息地,而小(Tachybaptus ruficollis)、白骨顶(Fulica atra)、黑水鸡(Gallinula chloropus)、白琵鹭(Platalea leucorodia)和黑脸琵鹭(P.minor)的觅食个体数量超过60%,说明优化区也为这些鸟类提供了觅食地。逐步回归分析表明,裸地面积比例是影响越冬水鸟种类分布的最主要因子;尽管游禽在地形变异较大、植被面积比例较低的区域数量较多,但在休息时游禽更偏好于裸地面积比例较高的区域,而涉禽休息时偏好于地形变异较大的区域。为增加栖息地优化区内的水鸟多样性,建议在优化区内种植水鸟可食的沉水植物以增加水鸟的食物资源,同时增加裸地面积比例和地形变异程度,更好地为水鸟提供栖息地。     

人工髋关节置换术发生股骨假体周围骨折的影响因素分析

目的:探讨人工髋关节置换术患者发生股骨假体周围骨折的相关危险因素,为临床预防和治疗提供参考资料。方法:回顾性分析2012年5月~2015年5月在我院接受人工髋关节置换术的92例患者的临床资料。根据是否发生股骨假体周围骨折将所选患者分为研究组和对照组,每组46例,比较两组患者的性别分布、年龄、骨折类型及假体固定方式等,分析影响患者发生股骨假体周围骨折的危险因素。结果:研究组患者骨折类型多为A2型,患者平均年龄、女性患者数及使用生物假体的比例均高于对照组,差异具有统计学意义(P0.05)。患者性别、年龄、骨折类型及假体固定方式是人工髋关节置换术患者发生股骨假体周围骨折的危险因素(OR=1.993、2.012和2.363,P0.05)。结论:高龄女性患者是发生股骨周围假体骨折的高危人群,骨质疏松及骨量减少是引发该并发症的主要危险因素。     

Molecular insights into cell toxicity of a novel familial amyloidogenic variant of β2‐microglobulin

The first genetic variant of β₂‐microglobulin (b2M) associated with a familial form of systemic amyloidosis has been recently described. The mutated protein, carrying a substitution of Asp at position 76 with an Asn (D76N b2M), exhibits a strongly enhanced amyloidogenic tendency to aggregate with respect to the wild‐type protein. In this study, we characterized the D76N b2M aggregation path and performed an unprecedented analysis of the biochemical mechanisms underlying aggregate cytotoxicity. We showed that, contrarily to what expected from other amyloid studies, early aggregates of the mutant are not the most toxic species, despite their higher surface hydrophobicity. By modulating ganglioside GM1 content in cell membrane or synthetic lipid bilayers, we confirmed the pivotal role of this lipid as aggregate recruiter favouring their cytotoxicity. We finally observed that the aggregates bind to the cell membrane inducing an alteration of its elasticity (with possible functional unbalance and cytotoxicity) in GM1‐enriched domains only, thus establishing a link between aggregate‐membrane contact and cell damage.     

基于机器学习的医学影像分析在药物研发和精准医疗方面的应用

MRI,PET,和CT等医学影像在新药研发和精准医疗中起着越来越重要的作用。影像技术可以被用来诊断疾病,评估药效,选择适应患者,或者确定用药剂量。 随着人工智能技术的发展,特别是机器学习以及深度学习技术在医学影像中的应用,使得我们可以用更短的时间,更少的放射剂量获取更高质量的影像。这些技术还可以帮助放射科医生缩短读片时间,提高诊断准确率。除此之外,机器学习技术还可以提高量化分析的可行性和精度,帮助建立影像与基因以及疾病的临床表现之间的关系。首先根据不同形态的医学影像,简单介绍他们在药物研发和精准医疗中的应用。并对机器学习在医学影像中的功能作一概括总结。最后讨论这个领域的挑战和机遇。     

The enhanced effect of supplemented lighting on nutrient removal by an aquatic vegetables (lettuce) purification system from rural domestic sewage

Abstract

Aquatic plant treatment system (APTS) is a widely used sewage purification technique; however, it requires a large area of land due to its long hydraulic retention time. In order to improve the economic value of APTS in the treatment of rural sewage, an aquatic vegetables (lettuce) purification system strengthened with a set of supplemented lighting was evaluated. The effect of supplemented lighting of blue and red light on lettuce growth and sewage purification was studied by batch experiments. The results showed that the lettuce growth and the removal rates of pollutants were enhanced by supplemented lighting, of which red light is superior to blue light, and the increase of red light intensity further promoted the growth of lettuce and the removal rate of pollutants. Supplementary light is a suitable method which could improve the purification effect of APTS in most weather conditions especially in countries where day-night light patterns change substantially between winter and summer. The results would be useful for the APTS design for treating rural domestic sewage.     

Proposing a Radial Basis Function and CSDM Indices to Predict the Traumatic Brain Injury Risk

BackgroundMany head injury indices and finite element (FE) head models have been proposed to predict traumatic brain injury (TBI). Although FE head models are suitable methods with high accuracy, they are computationally intensive. Head motion-based brain injury criteria are usually fast tools with lower accuracy. So, the objective of this study is to propose new criteria along with an artificial neural network model to predict TBI risks, which can be fast and accurate.MethodsFor this purpose, 250 FE head simulations have been carried out at 5 magnitudes and 50 rotational impact directions using the SIMon model. The effects of directions and magnitudes of rotational impacts were assessed for cumulative strain damage measure (CSDM) values. Next, statistical analysis and neural network were applied to predict CSDM values.ResultsThe results of the present research showed that the direction of rotation in the sagittal and frontal planes had a considerable effect on the CSDM values. Furthermore, new brain injury indices and a radial basis function neural network have been proposed to predict CSDM values which having high correlation coefficients with SIMon responses.ConclusionsThe results of this research demonstrated that rotational impact directions should be used to develop new head injury criteria being able to predict CSDM values. However, findings of present research proved that head motion-based brain injury criteria and RBF network can be used to predict FE head model responses with high speed and accuracy.     

Rapid adaptation to a novel host in a seed beetle (Callosobruchus maculatus): the role of sexual selection

Rapid diversification is common among herbivorous insects and is often the result of host shifts, leading to the exploitation of novel food sources. This, in turn, is associated with adaptive evolution of female oviposition behavior and larval feeding biology. Although natural selection is the typical driver of such adaptation, the role of sexual selection is less clear. In theory, sexual selection can either accelerate or impede adaptation. To assess the independent effects of natural and sexual selection on the rate of adaptation, we performed a laboratory natural selection experiment in a herbivorous bruchid beetle (Callosobruchus maculatus). We established replicated selection lines where we varied natural (food type) and sexual (mating system) selection in a 2 x 2 orthogonal design, and propagated our lines for 35 generations. In half of the lines, we induced a host shift whereas the other half was kept on the ancestral host. We experimentally enforced monogamy in half of the lines, whereas the other half remained polygamous. The beetles rapidly adapted to the novel host, which primarily involved increased host acceptance by females and an accelerated rate of larval development. We also found that our mating system treatment affected the rate of adaptation, but that this effect was contingent upon food type. As beetles adapted to the novel host, sexual selection reinforced natural selection whereas populations residing close to their adaptive peak (i.e., those using their ancestral host) exhibited higher fitness in the absence of sexual selection. We discuss our findings in light of current sexual selection theory and suggest that the net evolutionary effect of reproductive competition may critically depend on natural selection. Sexual selection may commonly accelerate adaptation under directional natural selection whereas sexual selection, and the associated load brought by sexual conflict, may tend to depress population fitness under stabilizing natural selection.     

24例人工全膝关节置换术患者手术前后的护理

目的：观察2000年3月至2003年4月人工全膝关节置换术（TKR）患者围手术期进行系统康复训练的护理.方法：选择接受TKR的患者24例30个膝关节,入院后进行术前康复教育和肢体的康复训练（包括肌肉、关节训练及步态训练等）,术后护理包括有针对性的心理护理及系统规范的康复训练.结果：本组术后随访6-12周,效果满意,优良率达95.8%,未发生并发症.结论：TKP患者围手术期间进行系统康复训练,可以减少膝关节并发症,增强膝关节活动范围,满足日常生活所需的关节活动,提高生活质量.