Effects of oxaliplatin on DNA condensation

In this paper the interactions between DNA and anti-cancer drug oxaliplatin were investigated by using magnetic tweezers. The dynamics of DNA condensation due to oxaliplatin was traced under various forces. It is found that torsion constraint in DNA enhances the ability of oxaliplatin for shortening DNA. The transplatin helps oxaliplatin combine to DNA and increase the rate of DNA condensation. All these results are consistent to the previously proposed model and are helpful for further investigation of interaction between DNA and oxaliplatin.     

基于变温紫外分光光度法研究温度对DNA凝聚过程影响

荧光单分子实验结果表明温度能够促进DNA凝聚,随着温度升高,精胺(亚精胺)-DNA凝聚体系中DNA凝聚构象趋于更加紧致、有序。为探究温度对不同高价离子-DNA凝聚体系的影响,利用自行搭建的变温紫外分光光度计,通过系统研究荧光单分子实验中采用的精胺(亚精胺)-DNA凝聚体系及去离子水中DNA在260 nm处特征吸收值随温度变化情况,确定了DNA凝聚构象与其260 nm处特征吸收值之间的对应关系为：DNA凝聚构象越紧致、有序,其对应的260 nm处紫外吸收值越低。在此基础上,系统地研究了DNA凝聚实验中常用四种钴胺化合物-DNA凝聚体系随温度变化情况,结果表明三氯六胺合钴与精胺(亚精胺)类似,其对应的DNA凝聚体系在260 nm特征吸收值,随着温度升高而逐渐降低,即DNA凝聚构象趋于更加紧致、有序。而三(乙二胺)氯化钴、反式双(乙二胺)氯化钴、五胺氯化钴的情况却不同,与其对应的DNA凝聚体系在260 nm特征吸收值,随着温度升高,呈现先增加,再降低,然后再增加的规律。     

Processes of DNA condensation induced by multivalent cations： Approximate annealing experiments and molecular dynamics simulations

The condensation of DNA induced by spermine is studied by atomic force microscopy （AFM） and molecular dynamics （MD） simulation in this paper. In our experiments, an equivalent amount of multivalent cations is added to the DNA solutions in different numbers of steps, and we find that the process of DNA condensation strongly depends on the speed of adding cations. That is, the slower the spermine cations are added, the slower the DNA aggregates. The MD and steered molecular dynamics （SMD） simulation results agree well with the experimental results, and the simulation data also show that the more steps of adding multivalent cations there are, the more compact the condensed DNA structure will be. This investigation can help us to control DNA condensation and understand the complicated structures of DNA--cation complexes.     

Twisting DNA: single molecule studies

Over the past 10 years a number of new techniques have emerged that allow the manipulation of single DNA molecules and other biopolymers (RNA, proteins, etc.). These experiments have permitted the measurement of the DNA stretching and twisting elasticity and have consequently revealed the essential role played by the DNA mechanical properties in its interactions with proteins. We shall first describe the different methods used to stretch and twist single DNA molecules. We will then focus on its behaviour under torsion, especially by discussing the different methods used to estimate its torsional modulus.     

Deep metastable eutectic nanometer-scale particles in the MgO–Al<Subscript>2</Subscript>O<Subscript>3</Subscript>–SiO<Subscript>2</Subscript> system

Laboratory vapor phase condensation experiments systematically yield amorphous, homogeneous, nanoparticles with unique deep metastable eutectic compositions. They formed during the nucleation stage in rapidly cooling vapor systems. These nanoparticles evidence the complexity of the nucleation stage. Similar complex behavior may occur during the nucleation stage in quenched-melt laboratory experiments. Because of the bulk size of the quenched system many of such deep metastable eutectic nanodomains will anneal and adjust to local equilibrium but some will persist metastably depending on the time–temperature regime and melt/glass transformation.     

Single Molecule Fluorescence Imaging and Its Application to the Study of DNA Condensation

Single molecule fluorescence imaging incorporated with optical tweezers and a laminar flow cell has been used to monitor the kinetic process of DNA condensation induced by spermidine. It was found that at least two steps were involved in the condensation process of the hydrodynamically-stretched linear DNA; a lag period followed by a rapid collapse of DNA. The lag time increased with the flow speed and the collapse time remained short within the range of the flow speed studied. The effect of salt concentration on the condensation process was examined, and the results suggest that the longer lag time observed in the higher salt buffer probably results from the displacement of bound cations and rearrangement of spermidine on the DNA. The flow-speed dependence of the lag time suggests that a nucleation event at the free end of the DNA, i.e. formation of a loop, may play a vital role in the kinetic process of condensation.     

一类检测DNA凝聚过程中“铰链结构”的氟化物探针

Bloomfield很早指出,在DNA凝聚过程中,急剧弯折会导致DNA分子中出现“铰链(kink)”结构,但未见实验证实。基于紫外可见分光光度法,分别在精胺、亚精胺与DNA凝聚体系中加入氟化物以及氯化物,发现二者虽同为卤族,但对精胺-DNA凝聚体系的效应不同。氟离子使精胺-DNA凝聚体系中出现了“蓝移增色”现象,氯离子仅使该体系出现微弱的增色效应, 而二者对亚精胺-DNA凝聚体系的效应基本相同,均出现微弱增色效应。基于氟离子特殊性质,设计一种能够有效探测DNA凝聚过程中“铰链(kink)”结构氟化物探针,而且证实,第二类“铰链(kink)”结构出现在精胺-DNA凝聚体系中。     

Direct Observation of Histone-Induced DNA Shortening

We construct a system of magnetic tweezers and apply it to study the interaction between histones and DNA. The condensation of DNA by purified histones at low ionic strengths is directly monitored by recording the length of the DNA as a function of elapsed time. It is found that DNA condensates in a dynamic manner. The binding of hist, ones to DNA is energetically favoured, but the ten,sion applied on DNA tends to unravel the DNA-histone complex, The competition between the two processes determiners the rate of the DNA condensation.     

透平级中自发凝结及叶栅中非均质凝结流动的初步研究

湿蒸汽流动问题研究对提高蒸汽透平设计水平具有重要意义。本文对级环境下的自发凝结流动和和叶栅中的非均质凝结流动进行了数值研究。结果表明,透平级环境下的凝结不仅使流动模式发生了变化,也改变了级的反动度;蒸汽中一定量的杂质对叶栅中湿蒸汽凝结流动的流场发生变化,使流动情况得到改善。要使这些影响从工程上具有指导意义,在此基础上还需要进一步的研究。     

Role of tension and twist in single-molecule DNA condensation

Using magnetic tweezers, we study in real time the condensation of single DNA molecules under tension. We find that DNA condensation occurs via discrete nucleated events. By measuring the influence of an imposed twist, we show that condensation is initiated by the formation of a plectonemic supercoil. This demonstrates a strong interplay between the condensation transition and externally imposed mechanical constraints.     

Fermion Interactions,Cosmological Constant and Space-Time Dimensionality in a Unified Approach Based on Affine Geometry

One of the main features of unified models, based on affine geometries, is that all possible interactions and fields naturally arise under the same standard. Here, we consider, from the effective Lagrangian of the theory, the torsion induced 4-fermion interaction. In particular, how this interaction affects the cosmological term, supposing that a condensation occurs for quark fields during the quark-gluon/hadron phase transition in the early universe. We explicitly show that there is no parity-violating pseudo-scalar density, dual to the curvature tensor (Holst term) and the spinor-bilinear scalar density has no mixed couplings of A-V form. On the other hand, the space-time dimensionality cannot be constrained from multidimensional phenomenological models admitting torsion.     

Theory of DNA condensation in the presence of stretching force: Zimm-Bragg model

A theory of DNA condensation by multivalent cations in the presence of an external stretching force is presented. It is shown that in the mean-field approximation the system is described by the Zimm-Bragg model with effective parameters of growth of ordered phase and cooperativity. Within the frames of the proposed model the experimental results on stretching of a double-stranded DNA of λ-phage are interpreted. Possible scenarios of homo- and heteropolymeric behavior of DNA during condensation are analyzed. A possible mechanism restricting the growth of linear size of DNA is proposed.     

Packing of elastic wires in spherical cavities

We investigate the morphologies and maximum packing density of thin wires packed into spherical cavities. Using simulations and experiments, we find that ordered as well as disordered structures emerge, depending on the amount of internal torsion. We find that the highest packing densities are achieved in low torsion packings for large systems, but in high torsion packings for small systems. An analysis of both situations is given in terms of energetics and comparison is made to analytical models of DNA packing in viral capsids.     

Effects of Ionic Dependence of DNA Persistence Length on the DNA Condensation at Room Temperature

DNA persistence length is a key parameter for quantitative interpretation of the conformational properties of DNA and related to the bending rigidity of DNA.A series of experiments pointed out that,in the DNA condensation process by multivalent cations,the condensed DNA takes elongated coil or compact globule states and the population of the compact globule states increases with an increase in ionic concentration.At the same time,single molecule experiments carried out in solution with multivalent cations(such as spermidine,spermine)indicated that DNA persistence length strongly depends on the ionic concentration.In order to revolve the effects of ionic concentration dependence of persistence length on DNA condensation,a model including the ionic concentration dependence of persistence length and strong correlation of multivalent cation on DNA is provided.The autocorrelation function of the tangent vectors is found as an effective way to detect the ionic concentration dependence of toroidal conformations.With an increase in ion concentration,the first periodic oscillation contained in the autocorrelation function shifts,the number of segment contained in the first periodic oscillation decreases gradually.According to the experiments,the average long-axis length is defined to estimate the ionic concentration dependence of condensation process further.The relation between long-axis length and ionic concentration matches the experimental results qualitatively.     

Torsion and entropy driven denaturation of DNA

A unified theory of the denaturation transition having torsion energy as the control parameter has been formulated here in the framework of the mapping of a DNA molecule onto a Heisenberg spin system. The torsion energy incorporates the torque, tension and temperature, the latter being associated with the twist angle. The denaturation transition can be mapped onto the quantum phase transition induced by a quench when the temperature effect is incorporated in the quench time and torsion takes the role of the external field. The denaturation transition occurs when the entanglement entropy of the spin system vanishes.     

Influence of conformation on electron transport properties of oligophenyleneimine molecular wires

We propose molecular wires based on oligophenyleneimine (OPI) sandwiched between two gold electrodes. The electron transport properties of molecular wires attached to side groups are investigated using steady-state theoretical model and density functional theory by using GAUSSIAN 09 software. We investigate the influence of the side group and torsion angle on the electronic properties of molecular wires. We calculate the spatial distribution of the frontier orbitals, energy gap, transmission probability and the current rectifying ratio for OPI, OPI-pyridine, OPI-pyrazine, OPI-thiophene and OPI-thiazole. The transmission spectra change remarkably depending on the type of side group and torsion angle. The current rectifying ratio will increase by increasing the difference between torsion angles depending on the type of side group. That means the OPI-side group can be employed in molecular electronics.     

On the kinematics of the torsion of space-time

On a macroscopic level we take general relativity as the appropriate theory of space-time and gravity. We will argue that, on a more microscopic level, in the Compton wavelength regime of elementary particles, there are good reasons for suspecting the presence of a torsion of space-time. A corresponding gaugetheoretical formalism related to the Poincaré group is reviewed, and the kinematical consequences of the presence of a torsion are worked out. In particular we discuss the operational meaning and the measurability of torsion. The dynamics of torsion is left for a forthcoming article.     

Chromatin condensation and sensitivity of DNA in situ to denaturation during cell cycle and apoptosis--a confocal microscopy study

The goal of this study was to construct high resolution 3D confocal images of regions of condensed and extended chromatin in cell nuclei and individual chromosomes. It has been shown previously that sensitivity of DNA in situ to denaturation correlates with chromatin condensation and varies during cell cycle and apoptosis. Thus, detection of DNA which was partially denatured in situ provided a means to image areas of condensed chromatin. DNA denaturation was detected using a metachromatic dye acridine orange (AO) which differentially stains single stranded (ss) and double-stranded (ds) DNA sections. Early studies of denaturability of cellular DNA utilized flow cytometry and standard fluorescence microscopy. These techniques could not reveal small local differences in DNA denaturability within cell nucleus or in individual chromosomes. For instance, it was not possible to detect the initial points of chromosome condensation in G2-phase of the division cycle or in apoptosis. In order to achieve this goal we have recently extended these studies by applying confocal microscopy. We investigated DNA denaturability in normal human fibroblasts and HL-60 leukemic cells, at different stages of cell cycle and apoptosis. Following removal of RNA and partial denaturation of DNA with acid cells were stained with AO. Green (530 nm) and red (640 nm) fluorescence (exc. 457 nm) of non-denatured and denatured DNA was imaged by confocal microscopy. Blind deconvolution was used to further improve the quality of 3D images. Photobleaching of AO fluorescence was minimized and a correction for chromatic aberration and register shift was implemented. Nuclei of interphase cells exhibited predominantly green fluorescence representing AO binding to ds DNA. Punctuate areas of red fluorescence representing AO binding to denatured DNA and most likely associated with local regions of condensed chromatin were also present in all interphase nuclei. The proportion of denatured DNA increased in cells entering mitosis. In prophase individual condensing chromosomes exhibited varied proportions of green and red fluorescence indicating different content of denatured chromatin. In some chromosomes bands of denatured and denaturation-resistant chromatin were clearly resolved. In metaphase and anaphase chromosomes exhibited red fluorescence along all length of their arms indicating the highest and uniform susceptibility to denaturation. In telophase chromosomes contained predominantly denaturation-resistant DNA again and denaturated regions were significantly less abundant. At cytokinesis some decondensing chromosomes were still resolved. At this stage almost all regions of denatured DNA were located close to nuclear envelope. These regions may correspond to pockets of heterochromatin reforming at nuclear periphery. In early apoptosis condensation of chromatin appeared to commence in several distinct regions within nucleus. Some apoptotic bodies contained condensed chromatin surrounding central regions of extended chromatin. At late stages of apoptosis the whole volume of apoptotic bodies was occupied by condensed chromatin.     

Double-stranded RNA resists condensation

Much attention has been focused on DNA condensation because of its fundamental biological importance. The recent discovery of new roles for RNA duplexes demands efficient packaging of double-stranded RNA for therapeutics. Here we report measurements of short DNA and RNA duplexes in the presence of trivalent ions. Under conditions where UV spectroscopy indicates condensation of DNA duplexes into (insoluble) precipitates, RNA duplexes remain soluble. Small angle x-ray scattering results suggest that the differing surface topologies of RNA and DNA may be crucial in generating the attractive forces that result in precipitation.