The Effects of Thermal Disorder on the Solution-Scattering Profiles of Macromolecules

The solution-scattering profiles of macromolecules are significantly affected by the thermal motions of their atoms, especially at wide scattering angles, even when only a single conformational state is significantly populated in solution. Here it is shown that the impact thermal motions have on the molecular component of the solution-scattering profile of a single-state macromolecule can be predicted accurately if the variances and covariances of the thermal excursions of its atoms from their average positions are known.     

Influence of Thermal Annealing on PCDTBT:PCBM Composition Profiles

A variety of measurement techniques including photothermal deflection spectroscopy (PDS), auger electron spectroscopy (AES), (sub–bandgap) external quantum efficiency (EQE), and impedance spectroscopy are applied to poly[N‐900‐hepta‐decanyl‐2,7‐carbazole‐alt‐5,5‐(40,70‐di‐2‐thienyl‐20,10,30‐benzothiadiazole (PCDTBT)/[6,6]‐phenyl C₇₁ butyric acid methyl ester (PC₇₁BM) films and devices to probe the stability under thermal annealing. Upon annealing, solar cell performance is drastically decreased for temperatures higher than 140 °C. Detailed investigation indicate changes in polymer:fullerene interactions resulting in the formation of a polymer wetting layer upon annealing at temperatures higher than 140 °C. Upon device completion this wetting layer is located close to the metal electrode and therefore leads to an increase in recombination and a decrease in charge carrier extraction, providing an explanation for the reduced fill factor (FF) and power conversion efficiency (PCE).     

Effects of Charge on Osmotic Reflection Coefficients of Macromolecules in Fibrous Membranes

A model based on continuum hydrodynamics and electrostatics was developed to predict the combined effects of molecular charge and size on the osmotic reflection coefficient (σ_o) of a macromolecule in a fibrous membrane, such as a biological hydrogel. The macromolecule was represented as a sphere with a constant surface charge density, and the membrane was assumed to consist of an array of parallel fibers of like charge, also with a constant surface charge density. The flow was assumed to be parallel to the fiber axes. The effects of charge were included by computing the electrostatic free energy for a sphere interacting with an array of fibers. It was shown that this energy could be approximated using a pairwise additivity assumption. Results for σ_o were obtained for two types of negatively charged fibers, one with properties like those of glycosaminoglycan chains, and the other for thicker fibers having a range of charge densities. Using physiologically reasonable fiber spacings and charge densities, σ_o for bovine serum albumin in either type of fiber array was shown to be much larger than that for an uncharged system. Given the close correspondence between σ_o and the reflection coefficient for filtration, the results suggest that the negative charge of structures such as the endothelial surface glycocalyx is important in minimizing albumin loss from the circulation.     

Macromolecules and the origin of life

From our knonwledge of present day organisms, it is hard to imagine a living assembly, even at its most primitive stage, without macromolecules.In order to look for the macromolecules which possibly participated in the assembly of the primitive organisms, the reaction and formation of polymers in HCN under irradiation of ultraviolet ray of 184.9 nm. was studied.As a example of a simple way of producing an assembly of macromolecules, the mechanism of coacervation was studied by using gelatin as the material.     

蛋白质结晶的研究进展

概括了蛋白质结晶的基本过程,阐述了蛋白质结晶的早期发展历程,重点介绍了蛋白质结晶的近期研究状况,主要包括:形核机理的研究、结晶条件的筛选和结晶技术的优化以及基于结构的药物设计技术。特别是对离子液体在蛋白质结晶过程中的应用及发展前景进行了讨论。     

Computer Simulation of Macromolecules

Computer simulation techniques are now an essential part of modern structural molecular biology. They are used in many different ways in order to study the conformation, dynamics and interactions of proteins and nucleic acids. In this paper, I shall review several of these applications and then focus on three specific areas, namely the conformation and dynamics of proteins including the use of free energy perturbation methods to study mutant proteins, the conformation and dynamics of DNA and DNA-drug complexes, and the use of computers with parallel architectures. Although simulation of molecules as large and complex as proteins and nucleic acids may be considered a grand challenge in itself, there are even greater challenges for the future.     

The Effects of Birth Order and Birth Interval on the Phenotypic Expression of Autism Spectrum Disorder

A rise in the prevalence of diagnosed cases of autism spectrum disorder (ASD) has been reported in several studies in recent years. While this rise in ASD prevalence is at least partially related to increased awareness and broadened diagnostic criteria, the role of environmental factors cannot be ruled out, especially considering that the cause of most cases of ASD remains unknown. The study of families with multiple affected children can provide clues about ASD etiology. While the majority of research on ASD multiplex families has focused on identifying genetic anomalies that may underlie the disorder, the study of symptom severity across ASD birth order may provide evidence for environmental factors in ASD. We compared social and cognitive measures of behavior between over 300 first and second affected siblings within multiplex autism families obtained from the Autism Genetic Resource Exchange dataset. Measures included nonverbal IQ assessed with the Ravens Colored Progressive Matrices, verbal IQ assessed with the Peabody Picture Vocabulary Test, and autism severity assessed with the Social Responsiveness Scale (SRS), an instrument established as a quantitative measure of autism. The results indicated that females were more severely impacted by ASD than males, especially first affected siblings. When first and second affected siblings were compared, significant declines in nonverbal and verbal IQ scores were observed. In addition, SRS results demonstrated a significant increase in autism severity between first and second affected siblings consistent with an overall decline in function as indicated by the IQ data. These results remained significant after controlling for the age and sex of the siblings. Surprisingly, the SRS scores were found to only be significant when the age difference between siblings was less than 2 years. These results suggest that some cases of ASD are influenced by a dosage effect involving unknown epigenetic, environmental, and/or immunological factors.     

Hydrophobicity Density Profiles to Predict Thermal Stability Enhancement in Proteins

A hydrophobicity density is defined for a protein through its hydrophobicity tensor (similar to the inertia tensor), by using the Eisenberg hydrophobicity scale of the hydrophobic amino acids of a protein. This allows calculation of the radii of the corresponding hydrophobic ellipsoid of a protein and thus subsequently of its hydrophobic density. A hydrophobicity density profile is then obtained by simulating point mutations of each amino acid of a protein either to a high hydrophobicity value or to zero hydrophobicity. It is found that an increase in the hydrophobic density of the protein correlates with an increase of its mid-point transition temperature. From this profile it is possible to determine the amino acids or domain stretches in a protein that are most amenable to mutation in order to increase the thermal stability. The model is tested to predict the thermostabilisation effects of two mutations in a β-glucanase: M29G and M29F. This model is compared with other hydrophobicity-related profiles described by other authors.Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.     

Effects of Temperature on Transcriptome Profiles in Cardiocrinum cathayanum Leaves

Russian Journal of Plant Physiology - Cardiocrinum cathayanum (Endl.) Lindl. (Liliaceae) is a promising species for ornamental and pharmaceutical usage. However, genomic responses of C. cathayanum...     

Nonparametric Analysis of Thermal Proteome Profiles Reveals Novel Drug-binding Proteins*

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Highlights

• •Method for the analysis of response curves from thermal proteome profiling (TPP).
• •NPARC uses nonparametric statistics and provides false discovery-rate (FDR) control.
• •Increased proteome coverage and sensitivity to identify drug-binding proteins.

     

微重力环境对大鼠血浆蛋白质谱的影响

目的:探讨模拟失重环境下大鼠血浆蛋白质组变化特征.方法:健康成年雄性 Wistar 大鼠88只,按模拟失重时相随机分为11组,分别为6 h、12 h、1 d、2 d、3 d、5 d、1周、2周、3周、4周及0 h 组(对照组).采用尾悬吊法建立模拟失重动物模型,实验结束时取动物静脉血,利用表面增强激光解吸电离飞行时间质谱(SELDI-TOF-MS)技术及 MB-WCX 磁珠检测大鼠静脉血浆蛋白质谱,应用 Ciphergen Protein Chip Software 3.2.0和 Biomarker Wizard 3.1.0软件分析数据.结果:发现18个重力敏感蛋白,其中在模拟失重早期,相对分子质量较小的6个蛋白的表达呈上调趋势,而相对分子质量较大的12个蛋白的表达则逐渐下调;在模拟失重后期(悬尾2~3周后),上述蛋白的表达均呈回归趋势.结论:模拟失重环境对大鼠静脉血浆蛋白质谱产生明显影响,研究重力敏感蛋白对进一步揭示失重对机体的影响及机制具有重要意义,并对医监医保可能有一定的价值.     

磁休克治疗对重度抑郁症患者脑功能网络的影响

目的 磁休克治疗(MST)是一种新兴的神经调节干预技术,在重度抑郁症(MDD)治疗中得到广泛应用,然而其抗抑郁机制尚不清楚。探索MST对不同疗效MDD患者脑功能网络的调控作用,对MST治疗的抗抑郁作用机制研究具有重要意义。方法 本文对18例MDD患者MST作用前后的静息态脑电进行记录,基于皮尔逊相关方法构建脑功能网络;应用复杂网络理论对比分析脑功能网络拓扑结构的改变;根据HDRS-17评分变化率进一步区分治疗有效组和无效组,对网络特征进行二次比较。结果 MST后,MDD患者的脑功能网络平均节点度、平均聚类系数和平均全局效率值均比治疗前显著升高,平均路径长度值显著降低,小世界属性显著增大;相比于治疗无效组,治疗有效组的脑功能网络特征参数变化量更大。结论 MST显著改变了MDD患者脑功能网络拓扑结构,对患者的脑功能网络具有一定的调制作用,这些结果为MST治疗的抗抑郁机制研究提供了实验支持和理论依据。     

Alignment of Synaptic Vesicle Macromolecules with the Macromolecules in Active Zone Material that Direct Vesicle Docking

Synaptic vesicles dock at active zones on the presynaptic plasma membrane of a neuron’s axon terminals as a precondition for fusing with the membrane and releasing their neurotransmitter to mediate synaptic impulse transmission. Typically, docked vesicles are next to aggregates of plasma membrane-bound macromolecules called active zone material (AZM). Electron tomography on tissue sections from fixed and stained axon terminals of active and resting frog neuromuscular junctions has led to the conclusion that undocked vesicles are directed to and held at the docking sites by the successive formation of stable connections between vesicle membrane proteins and proteins in different classes of AZM macromolecules. Using the same nanometer scale 3D imaging technology on appropriately stained frog neuromuscular junctions, we found that ∼10% of a vesicle’s luminal volume is occupied by a radial assembly of elongate macromolecules attached by narrow projections, nubs, to the vesicle membrane at ∼25 sites. The assembly’s chiral, bilateral shape is nearly the same vesicle to vesicle, and nubs, at their sites of connection to the vesicle membrane, are linked to macromolecules that span the membrane. For docked vesicles, the orientation of the assembly’s shape relative to the AZM and the presynaptic membrane is the same vesicle to vesicle, whereas for undocked vesicles it is not. The connection sites of most nubs on the membrane of docked vesicles are paired with the connection sites of the different classes of AZM macromolecules that regulate docking, and the membrane spanning macromolecules linked to these nubs are also attached to the AZM macromolecules. We conclude that the luminal assembly of macromolecules anchors in a particular arrangement vesicle membrane macromolecules, which contain the proteins that connect the vesicles to AZM macromolecules during docking. Undocked vesicles must move in a way that aligns this arrangement with the AZM macromolecules for docking to proceed.     

A Statistical Mechanical Deconvolution of the Differential Scanning Calorimetric Profiles of the Thermal Denaturation of Cyanomethemoglobin

A differential scanning calorimetric study of the thermal unfolding of horse cyanomethemoglobin (as an irreversible protein system) was carried out in phosphate-EDTA buffer (20 mM phosphate, 1 mM EDTA) pH 7.2. The calorimetric rescanning of the protein solution was found to be irreversible and the process unfolded state → final state appears to follow first order kinetic. Assuming the system to be comprised of n reversible states and one irreversible final state, the number of particles participating in the reversible states changes with time because they ultimately transit to the final irreversible denatured state. Hence, we carried out the deconvolution analysis using the grand canonical ensembles instead of just the canonical ensembles. This change was effected by introducing a correction term into the related equations which determines the outlet share of those particles exiting from the reversible states and converting into the final irreversible state. This approach provided an improved interpretation of the experimental data, which supports the following two-step process for the thermal denaturation of cyanomethemoglobin: α₂β₂ → (α + αβ + β)^excited → α^melt + (αβ)^melt + (β^melt.     

Effects of Processing on the Release Profiles of Matrix Systems Containing 5-Aminosalicylic Acid

The aim of this study was to investigate the influence of different processing methods on the profiles of 5-aminosalicylic acid dissolution from controlled-release matrix systems based on Eudragit® RL and Eudragit® RS water-insoluble polymers. The pure polymers and their mixtures were studied as matrix formers using different processing methods, i.e., direct compression, wet granulation of the active ingredient with the addition of polymer(s) to the external phase, wet granulation with water, and wet granulation with aqueous dispersions. In comparison with the directly compressed tablets, tablets made by wet granulation with water demonstrated a 6–19% increase in final drug dissolution, whereas when polymers were applied in the external phase during compression, a 0–13% decrease was observed in the amount of drug released. Wet granulation with aqueous polymer dispersions delayed the release of the drug; this was especially marked (a 54–56% decrease in drug release) in compositions, which contained a high amount of Eudragit RL 30D. The release profiles were mostly described by the Korsmeyer–Peppas model or the Hopfenberg model.KEY WORDS: controlled release, matrix tablet, polymethacrylates, release kinetics