Modulating α-synuclein fibril formation using DNA tetrahedron nanostructures

The small presynaptic protein α-synuclein (α-syn) is involved in the etiology of Parkinson's disease owing to its abnormal misfolding. To date, little information is known on the role of DNA nanostructures in the formation of α-syn amyloid fibrils. Here, the effects of DNA tetrahedrons on the formation of α-syn amyloid fibrils were investigated using various biochemical and biophysical methods such as thioflavin T fluorescence assay, atomic force microscopy, light scattering, transmission electron microscopy, and cell-based cytotoxicity assay. It has been shown that DNA tetrahedrons decreased the level of oligomers and increased the level of amyloid fibrils, which corresponded to decreased cellular toxicity. The ability of DNA tetrahedron to facilitate the formation of α-syn amyloid fibrils demonstrated that structured nucleic acids such as DNA tetrahedrons could modulate the process of amyloid fibril formation. Our study suggests that DNA tetrahedrons could be used as an important facilitator toward amyloid fibril formation of α-synuclein, which may be of significance in finding therapeutic approaches to Parkinson's disease and related synucleinopathies.     

DNA–DNA kissing complexes as a new tool for the assembly of DNA nanostructures

Kissing-loop annealing of nucleic acids occurs in nature in several viruses and in prokaryotic replication, among other circumstances. Nucleobases of two nucleic acid strands (loops) interact with each other, although the two strands cannot wrap around each other completely because of the adjacent double-stranded regions (stems). In this study, we exploited DNA kissing-loop interaction for nanotechnological application. We functionalized the vertices of DNA tetrahedrons with DNA stem-loop sequences. The complementary loop sequence design allowed the hybridization of different tetrahedrons via kissing-loop interaction, which might be further exploited for nanotechnology applications like cargo transport and logical elements. Importantly, we were able to manipulate the stability of those kissing-loop complexes based on the choice and concentration of cations, the temperature and the number of complementary loops per tetrahedron either at the same or at different vertices. Moreover, variations in loop sequences allowed the characterization of necessary sequences within the loop as well as additional stability control of the kissing complexes. Therefore, the properties of the presented nanostructures make them an important tool for DNA nanotechnology.     

The modelling of interactions between organs and medical tools: a volumetric mass-spring chain algorithm

This paper adds volume deformation capability to the mass-spring chain method using tetrahedral elements in order to obtain more realistic deformations, which occur during the interactions between medical tools and soft tissues. The mass-spring chain method originally does not consider volume information and performs deformation by moving and deforming individual springs of a deformable model. However, most of the applications in computer graphics require volume modelling using tetrahedrons. In the proposed method, the deformation algorithm loops through tetrahedrons and performs deformation based on defined rules similar to those of the original mass-spring chain method. This method can handle not only ordinary deformation applications but also those with topology changes, such as cutting and tearing, as it does not rely on any pre-computed quantities. A method to preserve the volume and the shape of the tetrahedral elements is also developed. In order to speed up the new version of the algorithm, a tetrahedral propagation for deformation is developed. The detailed implementation of the algorithm and the various applications of the organ–surgery tool interactions are presented. The paper also provides the animations of the different models obtained by the proposed method.     

In vitro and in silico characterization of open-cell structures of trabecular bone

This work aimed to perform a detailed in vitro and in silico characterization of open-cell structures, which resemble trabecular bone, to elucidate osteoporosis failure mechanisms. Experimental and image-based computational methods were used to estimate Young′s modulus and porosities of different open-cell structures (Sawbones; Malmö, Sweden). Three different open-cell structures with different porosities were characterized. Additionally, some open-cell structures were scanned using a microcomputed tomography system (μCT) to non-destructively predict specimen Young′s modulus of the structures by developing voxel-based and tetrahedral finite element (FE) models. A 3D reconstruction and FE analyses were used. The experimental and computational results with different element types (linear and quadratic tetrahedrons and voxel-based meshes) were compared with Sawbones data (Sawbones; Malmö, Sweden) revealing important differences in Young′s modulus and porosities. The specimens with high and low volume fractions were best represented by linear and quadratic tetrahedrons, respectively. These results could be used to develop new osteoporosis-prevention strategies.     

Phosphofructokinase-1 from Saccharomyces cerevisiae: analysis of molecular structure and function by electron microscopy and self-catalysed affinity labelling

Conventional and cryoelectron microscopy portray native octameric yeast phosphofructokinase-1 (PFK) as consisting of two identical heterotetrameric tetrahedron-like moieties being rotated relative to each other. Immunoelectron microscopy employing subunit-specific IgG identifies alpha-type subunits in the contact zone of the two tetrahedrons, while beta-chains are recognized exclusively at the tips of the octamer. The chemical reaction of phosphofructokinase with analogues of fructose 6-phosphate followed by autocatalytic phosphoryl transfer from [gamma-32P]-ATP results in a specific labelling of the alpha-subunit. AMP and fructose 2,6-bisphosphate affect labelling by stimulating the binding of substrate analogue; AMP additionally promotes phosphoryl transfer. No stimulation of labelling is observed with proteolytically modified tetrameric 12-S phosphofructokinase.     

构建基于患者个体化的Stanford B型主动脉夹层计算流体力学数值模拟分析模型（英文）

目的：探索简便、高效、精确的构建基于真实人体解剖形态结构的Stanford B型主动脉夹层计算流体力学数值模拟分析模型的方法。方法：利用Siemens Sensation Cardiac64层螺旋CT薄层扫描技术,基于1mm层厚获取6例Stanford B型主动脉夹层连续断层DICOM格式图像,导入Materialise MIMICS v12.11软件,界定目标区域后生成三维动脉模型,经网格优化处理去除低质量及相交面网格,保存结果输出,导入TGrid5.0软件,对主动脉面网格模型进行几何修复,使面网格扭曲率〈0.75,采用自由分网方式生成Stanford B型主动脉夹层计算流体力学分析体网格模型,并对所构建模型进行血流属性、流场边界等界定,初步验证模型的有效性。结果：通过初步计算求解,确定所构建的6例Stanford B型主动脉夹层计算流体力学分析模型分别包含1857030,1820501,1844181,1849651,1858246及1814914个四面体单元。结论：利用64层螺旋CT薄层扫描技术获取DICOM格式连续断层CT图像可快速、准确地构建Stanford B型主动脉夹层计算流体力学数值模拟分析模型,为进一步的计算流体力学分析奠定了良好的基础。     

构建基于患者个体化的Stanford B型主动脉夹层计算流体力学数值模拟分析模型

目的:探索简便、高效、精确的构建基于真实人体解剖形态结构的Stanford B型主动脉夹层计算流体力学数值模拟分析模型的方法.方法:利用Siemens Sensation Cardiac 64层螺旋CT薄层扫描技术,基于1mm层厚获取6例Stanford B型主动脉夹层连续断层DICOM格式图像,导入Materialise MIMICS v12.11软件,界定目标区域后生成三维动脉模型,经网格优化处理去除低质量及相交面网格,保存结果输出,导入TGrid 5.0软件,对主动脉面网格模型进行几何修复,使面网格扭曲率<0.75,采用自由分网方式生成Stanford B型主动脉夹层计算流体力学分析体网格模型,并对所构建模型进行血流属性、流场边界等界定,初步验证模型的有效性.结果:通过初步计算求解,确定所构建的6例Stanford B型主动脉夹层计算流体力学分析模型分别包含1857030,1820501,1844181,1849651,1858246及1814914个四面体单元.结论:利用64层螺旋CT薄层扫描技术获取DICOM格式连续断层CT图像可快速、准确地构建Stanford B型主动脉夹层计算流体力学数值模拟分析模型,为进一步的计算流体力学分析奠定了良好的基础.     

Experimental validation of intact and implanted distal femur finite element models

Four finite element (FE) models of intact and distal femur of knee replacements were validated relative to measured bone strains. FE models of linear tetrahedrons were used. Femoral replacements with cemented stemless, cemented and noncemented femoral stems of the PFC Sigma Modular Knee System were analyzed. Bone strains were recorded at ten locations on the cortex. The magnitude of the FE bone strains corresponded to the mean measured strains, with an overall agreement of 10%. Linear regression between the FE and mean experimental strains produced slopes between 0.94 and 1.06 and R(2) values between 0.92 and 0.99. RSME values were less than 12%. The FE models were able to adequately replicate the mechanical behavior of distal femur reconstructions.     

Structures and formation mechanisms of aquo/hydroxo oligomeric beryllium in aqueous solution: a density functional theory study

The structures and formation mechanisms of a wide variety of aquo/hydroxo oligomeric beryllium clusters were investigated using density functional theory. The structural parameters of beryllium clusters were found to vary regularly with the stepwise substitution of bound water molecules in the inner coordination sphere by hydroxyl groups. According to the Gibbs free energies deduced from SMD solvation model computations, unhydrolyzed oligomeric beryllium species are the most favorable products of polymerization, independent of the degrees of hydrolysis of the reactants. Simulation of the formation processes of oligomeric beryllium showed that polymerization, in essence, involves the nucleophilic attack of a terminal hydroxyl group in one BeO₄ tetrahedron on the beryllium center in another BeO₄ tetrahedron, leading to the bridging of two BeO₄ tetrahedrons by a hydroxyl group.     

Rampant False Detection of Adaptive Phenotypic Optimization by ParTI-Based Pareto Front Inference

Organisms face tradeoffs in performing multiple tasks. Identifying the optimal phenotypes maximizing the organismal fitness (or Pareto front) and inferring the relevant tasks allow testing phenotypic adaptations and help delineate evolutionary constraints, tradeoffs, and critical fitness components, so are of broad interest. It has been proposed that Pareto fronts can be identified from high-dimensional phenotypic data, including molecular phenotypes such as gene expression levels, by fitting polytopes (lines, triangles, tetrahedrons, and so on), and a program named ParTI was recently introduced for this purpose. ParTI has identified Pareto fronts and inferred phenotypes best for individual tasks (or archetypes) from numerous data sets such as the beak morphologies of Darwin’s finches and mRNA concentrations in human tumors, implying evolutionary optimizations of the involved traits. Nevertheless, the reliabilities of these findings are unknown. Using real and simulated data that lack evolutionary optimization, we here report extremely high false-positive rates of ParTI. The errors arise from phylogenetic relationships or population structures of the organisms analyzed and the flexibility of data analysis in ParTI that is equivalent to p-hacking. Because these problems are virtually universal, our findings cast doubt on almost all ParTI-based results and suggest that reliably identifying Pareto fronts and archetypes from high-dimensional phenotypic data are currently generally difficult.     

Pyrococcus horikoshii TET2 Peptidase Assembling Process and Associated Functional Regulation

Tetrahedral (TET) aminopeptidases are large polypeptide destruction machines present in prokaryotes and eukaryotes. Here, the rules governing their assembly into hollow 12-subunit tetrahedrons are addressed by using TET2 from Pyrococcus horikoshii (PhTET2) as a model. Point mutations allowed the capture of a stable, catalytically active precursor. Small angle x-ray scattering revealed that it is a dimer whose architecture in solution is identical to that determined by x-ray crystallography within the fully assembled TET particle. Small angle x-ray scattering also showed that the reconstituted PhTET2 dodecameric particle displayed the same quaternary structure and thermal stability as the wild-type complex. The PhTET2 assembly intermediates were characterized by analytical ultracentrifugation, native gel electrophoresis, and electron microscopy. They revealed that PhTET2 assembling is a highly ordered process in which hexamers represent the main intermediate. Peptide degradation assays demonstrated that oligomerization triggers the activity of the TET enzyme toward large polypeptidic substrates. Fractionation experiments in Pyrococcus and Halobacterium cells revealed that, in vivo, the dimeric precursor co-exists together with assembled TET complexes. Taken together, our observations explain the biological significance of TET oligomerization and suggest the existence of a functional regulation of the dimer-dodecamer equilibrium in vivo.     

Structural alignment of proteins by a novel TOPOFIT method, as a superimposition of common volumes at a topomax point

Similarity of protein structures has been analyzed using three-dimensional Delaunay triangulation patterns derived from the backbone representation. It has been found that structurally related proteins have a common spatial invariant part, a set of tetrahedrons, mathematically described as a common spatial subgraph volume of the three-dimensional contact graph derived from Delaunay tessellation (DT). Based on this property of protein structures, we present a novel common volume superimposition (TOPOFIT) method to produce structural alignments. Structural alignments usually evaluated by a number of equivalent (aligned) positions (N(e)) with corresponding root mean square deviation (RMSD). The superimposition of the DT patterns allows one to uniquely identify a maximal common number of equivalent residues in the structural alignment. In other words, TOPOFIT identifies a feature point on the RMSD N(e) curve, a topomax point, until which the topologies of two structures correspond to each other, including backbone and interresidue contacts, whereas the growing number of mismatches between the DT patterns occurs at larger RMSD (N(e)) after the topomax point. It has been found that the topomax point is present in all alignments from different protein structural classes; therefore, the TOPOFIT method identifies common, invariant structural parts between proteins. The alignments produced by the TOPOFIT method have a good correlation with alignments produced by other current methods. This novel method opens new opportunities for the comparative analysis of protein structures and for more detailed studies on understanding the molecular principles of tertiary structure organization and functionality. The TOPOFIT method also helps to detect conformational changes, topological differences in variable parts, which are particularly important for studies of variations in active/ binding sites and protein classification.     

基于ISSR分子标记的孑遗濒危植物四合木遗传结构分析

为阐明中国西北干旱区单属种孑遗濒危植物四合木(Tetraena mongolica)种群间的遗传分化和基因流。利用6个不同地理分布的四合木种群作为试验材料,从30条UBC引物中筛选出6条引物,并且对ISSR扩增反应体系和扩增程序进行了合理的优化,6个引物扩增出370个条带,多态性条带占71%。分析结果如下:①Nei’s基因多样性指数(He)为0. 316 8,Shannon’s多态性信息指数(I)为0. 458 6。表明四合木在不同种源间的遗传多样性水平差异较小;②群体多态性位点百分率在70. 00%~83. 33%,Nei’s基因多样性指数范围0. 286 5~0. 350 8,Shannon’s多态性信息指数在0. 423 6~0. 504 9。6个群体间的遗传分化系数Gst为0. 125 3,表明群体间具有一定程度的遗传分化;③6个种群的基因流(Nm)为3. 491 5>1,说明6个种群间存在一定的基因流,可以防止遗传漂变引起的遗传分化;④通过聚类分析,将6个不同地理种群的四合木分为3类,千里沟种群、伊克布拉格种群和巴拉贡种群先聚成第一大类,再与磴口—桃司兔种群聚成第二大类,而四合木自然保护区种群和甘德尔山种群则组成第大三类,这说明距离因素是影响四合木种群间遗传分化的主要原因,但不同生境条件也对四合木种群的遗传分化产生了影响。     

Large-scale molecular dynamics modeling of boron-doped amorphous SiCO ceramics

At high temperature, silicon oxycarbide (SiCO) exhibits excellent mechanical properties and thermal stability. The incorporation of boron in SiCO results in improved performance in creep temperatures. In this work, large-scale molecular dynamics calculations were applied to obtain amorphous SiCO structures containing boron. Phase separation of C–C, B–C and Si–O was achieved for three compositions, and silicon-centered mixed-bond tetrahedrons were reproduced successfully. As the boron content increases, the boron atoms tend to form B–C and B–Si bonds in the voids, which stretches the free carbon network in some instances, causing a increase in C–C distance. Young’s modulus remains stable at high temperature for the high-carbon case, which indicates that the free carbon network plays a critical role in the structural and thermal stability of SiBCO.

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Graphical Abstract Three major typical structures in the cooling down process for silicon boron oxycarbide (Si₅BC₂O₈). Bonds: red Si–O, blue Si–C, black C–C, green B–C, purple Si–B

     

湖南土家族的体质特征

以20至69岁的湖南土家族人为观察测量对象,根据1392人(男896,女496)的身高,1038人(男668,女370)的头部测量,364人(男235,女129)的五官测量和观察结果,分析该民族的体质特征,并与国内其他民族相比较。     

维吾尔族的体质特征研究

１９９１年５月,对新疆伊梨维吾尔族５２９人（男２７１,女２５８）进行了活体观察和测量。观察２９项,测量９２项。维吾尔族的主要特征是：黑直发,黑褐色眼,眉毛较浓密,大都有上眼脸皱褶,鼻根中等偏高,大多为直形鼻,鼻尖向前,鼻基部下垂,大多有达尔文结节,耳垢湿型。头面部指数分型,属于特短头型,阔头型和高头型。身材中等偏高,平均身高男１６８．６毫米,女１５７８．８毫米。     

草基-鱼塘生态系统的能量转化与养分循环研究

应用模拟试验的方法,研究了“草基-鱼塘”系统中的能量转化与养分循环.结果表明,该系统中饲草对太阳能的利用率为0.83%,鱼对饲料能的转化率为7.3%.与以粮食作为鱼饲料比较,单位面积草地的产鱼当量是粮食作物的1.6倍.鱼对饲料N、P、K的转化率分别为16.8%、32.3%和2.0%.塘泥沉积的N、P分别占饲料的23.4%和56.1%;猪对饲料N、P、K的转化率分别为20.5%、33.7%和4.6%,猪粪尿回收饲料N为36.4%、P为63.8%、K为39.4%.猪-草-鱼结合的基塘系统其能量和养分转化效率均高于单一的养鱼系统.     

草基—鱼塘生态系统的能量转化与养分循环研究

应用模拟试验的方法,研究了“草基-鱼塘”系统中的能量转化与养分循环．结果 表明,该系统中饲草对太阳能的利用率为 ０． ８３％,鱼对饲料能的转化率为 ７． ３％．与以粮 食作为鱼饲料比较,单位面积草地的产鱼当量是粮食作物的１．６倍．鱼对饲料Ｎ、Ｐ、Ｋ的 转化率分别为１６．８％、３２．３％和２．０％．塘泥沉积的Ｎ、Ｐ分别占饲料的２３．４％和５６．１％; 猪对饲料 Ｎ、 Ｐ、 Ｋ的转化率分别为 ２０． ５％、 ３３． ７％和 ４． ６％,猪粪尿回收饲料 Ｎ为 ３６． ４％、 Ｐ为 ６３． ８％、 Ｋ为 ３９． ４％．猪-草-鱼结合的基塘系统其能量和养分转化效率均高于单一的 养鱼系统．     

军标菌株生活史中各阶段生长发育时间的研究

为了更好地研究军标菌在其应用中的实验周期问题 ,采用插片培养法和载片培养法对军标中 5株实验菌的生活史中各阶段生长发育所需时间进行了研究。结果表明 ,5株菌的各时期生长发育所需时间有所不同。整个生活史最长的 4940min ,如AS 3 .42 5 4。最短的 3 888min ,如AS 3 .3 95 0。孢子萌发阶段所需时间也各不相同 ,最长的需 1 5 2 0min ,如AS 3 .3 885。最短的需 640min ,如AS 3 .3 95 0。这一研究为军标中霉菌试验周期 ,即 2 8d过长而且完全可缩短试验周期的观点 ,提供了有力的证据。     

成熟玉米秆组织结构切片方法的比较研究

于玉米成熟期选择健壮茎秆的基部第三节间为材料,采用徒手切片法、冰冻切片法、石蜡切片法、薄切片法等4种方法,比较不同方法的玉米茎秆组织结构切片质量,为研究玉米茎秆结构与其倒伏的关系奠定技术基础。结果表明:徒手切片法是获得成熟玉米秆组织结构切片较为方便、快速的方法,切片面积较大,适合大范围观察统计;冰冻切片法是获得成熟玉米秆组织结构较快的方法,切片面积较小,适合小范围观察;薄切片是获得高质量成熟玉米秆组织结构切片的最好方法,但切片面积太小,适合高倍数显微观察和小范围电镜扫描观察组织结构;石蜡切片不适合作为成熟玉米秆的组织切片方法。研究认为,徒手切片法是最适合成熟玉米秆组织结构观察研究的制片方法。