大分子拥挤对DNA结构的影响

大分子拥挤(macromolecular crowding effect)代表了细胞内高度拥挤状态,其源于非特异性容积排斥效应,是细胞内与pH、离子强度等同等重要的生理因素。生物大分子介导的拥挤环境对于DNA-DNA、DNA-蛋白质的相互作用以及DNA高级结构、细胞核或核区结构的稳定具有重要作用。在拥挤环境中,大分子总浓度的增加将增强溶质的浓缩倾向,从而降低溶液的自由能。拥挤效应是胞内大分子环境的总体反映,具有高度的缓冲性,保证了胞内反应的稳定进行及细胞功能的正常行使。     

分子拥挤条件下生物大分子性质研究

细胞中成千上万种生物分子以不同的浓度发挥着各自的生理作用,但是体外研究中常常忽略细胞内的拥挤环境,随着分子拥挤理论的提出,体外添加大分子拥挤试剂被越来越多的生物学家和化学家所重视,众多的研究结果显示分子拥挤试剂的加入对细胞内的生物大分子的性质造成了一定的影响。从分子拥挤试剂对蛋白质折叠与聚集以及核酸分子结构与性质的影响等方面探讨了拥挤环境下生物大分子的性质和功能,为以后大分子拥挤条件下生物分子的研究提供一定的参考依据。     

细胞内蛋白质运输及神经递质释放的分子机理

细胞内蛋白质及神经递质等生物活性物质的运输,分泌和释放都是以运输囊泡作为载体,经过运转囊泡的出芽,形成,移位,入坞等步骤,最终与靶膜融合将内容物排出,这些过程都是以动转囊泡膜,胞浆和靶膜的多种不同功能的蛋白质相互作用的结果。     

分子印迹技术用于生物大分子的识别

分子印迹技术是一种人工合成具有分子识别功能的介质的一种新技术,近年来在许多领域都得到很大的发展。本文介绍了分子印迹技术的发展现状,尤其对生物大分子的分子印迹技术进行了详细论述,对生物大分子印迹采用的功能单体,印迹分子的种类,印迹的方法,印迹的机理,存在的问题和应用的前景等分别进行了讨论。     

分子印迹技术用于生物大分子的识别

分子印迹技术是一种人工合成具有分子识别功能的介质的一种新技术,近年来在许多领域都得到很大的发展。本文介绍了分子印迹技术的发展现状,尤其对生物大分子的分子印迹技术进行了详细论述,对生物大分子印迹采用的功能单体、印迹分子的种类、印迹的方法、印迹的机理、存在的问题和应用的前景等分别进行了讨论。     

视觉拥挤效应的神经机制

当出现在边缘视野的一个物体被周围其他物体包围时,视觉系统对它的识别会很困难,这种现象叫做视觉拥挤效应.研究拥挤效应既有利于理解人类进行客体识别的过程,也对治疗黄斑变性、弱视和阅读障碍等视觉病变有显著的临床意义.自拥挤效应被提出以来,对拥挤效应的特性、神经机制和影响因素等都做了深入地研究.本文将系统地综述拥挤效应的研究进展,包括其特性、现有的理论假设、计算模型、可能涉及的大脑区域以及近年来利用知觉学习消除拥挤效应的一些工作,最后对该领域的未来发展给出建议.尽管在这个领域已经获得了丰富的成果,但在许多问题上仍有争议,未来还需要更为巧妙的设计和精确的技术进一步解决这些问题.     

目标和干扰子之间的拓扑性质差异可以削弱拥挤效应

\"拥挤效应\"被认为是外周视觉物体辨认过程中的一个重要瓶颈.它是指当目标被干扰子包围,在外周视野呈现时,观察者辨认目标的能力被大大削弱,尤其是当目标和干扰子之间存在某种相似性时.许多研究分别试图在不同层次上提出解释这一现象的机制.本文通过三个实验,使用了不同的视觉刺激图形的辨认任务(例如,三角形和箭头的朝向判断、数字和字母的辨认以及S形图形的朝向辨认),测量了目标和干扰子之间中心距离的阈值,结果一致地发现,当目标和干扰子之间存在拓扑性质差异(洞的个数差异)时,拥挤效应会显著降低,并且排除了目标和干扰子之间的主观相似性、形状和面积差异等可能的因素.从知觉组织的角度验证了当目标和干扰子之间存在拓扑性质差异时,拥挤效应会显著降低,这是首次发现的一个影响拥挤效应的新的维度.本文结果不仅为拥挤效应的机制提供了一个新的解释,也为大范围首先拓扑知觉在知觉物体形成中的作用提供了支持性证据.     

集合种群空间混沌的模拟研究以及Allee效应、拥挤效应与捕食效应对空间模式的影响

集合种群的空间模式研究是当今生态学的核心问题之一。本研究利用常微分动力系统以及基于网格模型的元胞自动机模型对Allee效应、拥挤效应以及捕食作用集合种群的空间分布模式做了全面的模拟研究。Allee效应描述当种群水平低于某一阈值时会发生由生殖成功几率下降造成的种群负增长率,而拥挤效应是指当种群密度过高时引起的个体性为异常从而达到调节种群增长率的作用。文章组建了3个空间确定性模型：局部作用模型(CIM)、距离敏感模型(DSM)和集合种群捕食模型(MMP)。局部作用模型显示在一维生境中空斑块形成金字塔状,二维模型显示出明显的动态拟周期性以及由空间混沌所形成的异质性。距离敏感模型可导致由迁移个体中密度制约强度决定的集合种群大小复杂动态与种群密度的双峰分布。这些结果说明动态行为的复杂性,不仅可用于表征研究物种的特性,而且可以表明该物种的续存能力与灭绝风险。集合种群捕食模型是概率转换空间模型,利用该模型得出了依赖于模型参数和生境尺度的白组织种群概率空间分布模式。模拟的结果表明,系统的内在机制和这种白组织模式导致捕食者形成集团型不明显的“捕食小组”或“杀手小组”,并具有较高扩散力．但却包括侵占率低、灭绝率高的特点。而使猎物种群形成高集团性、高侵占率、低灭绝率、低扩散力的种群集团。这种特点又使捕食者种群在生境中处于中心地带,而使猎物种群形成在捕食者和生境边缘间的环状分布。这些结果还说明了尺度对于生态学的研究是至关重要的,不同的尺度将产生不同的系统模式。     

生物大分子的类型

生物大分子是细胞的基本结构和功能单位,也是研究生命现象中的物质基础。生物体内的分子组成如何?哪些分子才算生物大分子?这些大分子有没有分子量的下限?     

植物细胞内的钙通道

就高等植物细胞质膜和细胞内膜系统上钙通道的类型、对不同离子的选择性和活性调控因素及其对抑制剂的反应的研究进展进行了评述     

Protein unfolding in crowded milieu: what crowding can do to a protein undergoing unfolding?

The natural environment of a protein inside a cell is characterized by the almost complete lack of unoccupied space, limited amount of free water, and the tightly packed crowd of various biological macromolecules, such as proteins, nucleic acids, polysaccharides, and complexes thereof. This extremely crowded natural milieu is poorly mimicked by slightly salted aqueous solutions containing low concentrations of a protein of interest. The accepted practice is to model crowded environments by adding high concentrations of various polymers that serve as model “crowding agents” to the solution of a protein of interest. Although studies performed under these model conditions revealed that macromolecular crowding might have noticeable influence on various aspects related to the protein structure, function, folding, conformational stability, and aggregation propensity, the complete picture describing conformational behavior of a protein under these conditions is missing as of yet. Furthermore, there is an accepted belief that the conformational stability of globular proteins increases in the presence crowding agents due to the excluded volume effects. The goal of this study was to conduct a systematic analysis of the effect of high concentrations of PEG-8000 and Dextran-70 on the unfolding behavior of eleven globular proteins belonging to different structural classes.     

Biochemical effects of molecular crowding

Cell cytoplasm contains high concentrations of high-molecular-weight components that occupy a substantial part of the volume of the medium (crowding conditions). The effect of crowding on biochemical processes proceeding in the cell (conformational transitions of biomacromolecules, assembling of macromolecular structures, protein folding, protein aggregation, etc.) is discussed in this review. The excluded volume concept, which allows the effects of crowding on biochemical reactions to be quantitatively described, is considered. Experimental data demonstrating the biochemical effects of crowding imitated by both low-molecular-weight and high-molecular-weight crowding agents are summarized.Translated from Biokhimiya, Vol. 69, No. 11, 2004, pp. 1522–1536.Original Russian Text Copyright © 2004 by Chebotareva, Kurganov, Livanova.     

Effect of dextran on protein stability and conformation attributed to macromolecular crowding

Thermally induced transition curves of hen egg-white lysozyme were measured in the presence of several concentrations of dextran at pH 2.0 by near-UV and far-UV CD. The transition curves were fitted to a two-state model by a non-linear, least-squares method to obtain the transition temperature (T(m)), enthalpy change (deltaH(u)(T(m))), and free energy change (deltaG(u)(T)) of the unfolding transition. An increase in T(m) and almost constant deltaH(u)(T(m)) values were observed in the presence of added dextran at concentrations exceeding ca 100 g l(-1). In addition, dextran-induced conformational changes of fully unfolded protein were investigated by CD spectroscopy. Addition of high concentrations of dextran to solutions of acid-unfolded cytochrome c at pH 2.0 results in a shift of the CD spectrum from that characteristic of the fully unfolded polypeptide to that characteristic of the more compact, salt-induced molten globule state, a result suggesting that the molten globule-like state is stabilized relative to the fully unfolded form in crowded environments. Both observations are in qualitative accord with predictions of a previously proposed model for the effect of intermolecular excluded volume (macromolecular crowding) on protein stability and conformation.     

Effects of pH, salt, and macromolecular crowding on the stability of FK506-binding protein: an integrated experimental and theoretical study

Environmental variables can exert significant influences on the folding stability of a protein, and elucidating these influences provides insight on the determinants of protein stability. Here, experimental data on the stability of FKBP12 are reported for the effects of three environmental variables: pH, salt, and macromolecular crowding. In the pH range of 5-9, contribution to the pH dependence of the unfolding free energy from residual charge-charge interactions in the unfolded state was found to be negligible. The negligible contribution was attributed to the lack of sequentially nearest neighboring charged residues around groups that titrate in the pH range. KCl lowered the stability of FKBP12 and the E31Q/D32N double mutant at small salt concentrations but raised stability after approximately 0.5 M salt. Such a turnover behavior was accounted for by the balance of two opposing types of protein-salt interactions: the Debye-Hückel type, modeling the response of the ions to protein charges, favors the unfolded state while the Kirkwood type, accounting for the disadvantage of the ions moving toward the low-dielectric protein cavity from the bulk solvent, disfavors the unfolded state. Ficoll 70 as a crowding agent was found to have a modest effect on protein stability, in qualitative agreement with a simple model suggesting that the folded and unfolded states are nearly equally adversely affected by macromolecular crowding. For any environmental variable, it is the balance of its effects on the folded and unfolded states that determines the outcome on the folding stability.