利用液体核磁共振技术解析核酸四链体结构

富含G 碱基的DNA 和RNA 序列能够形成四股的G-四链体．基于液体核磁共振波谱在G-四链体结构、动力学、相互作用研究中的核心地位,该综述详细回顾阐述
了G-四链体结构和相互作用研究中的核磁共振方法、技术和进展．     

Effect of interaction between loop bases and ions on stability of G-quadruplex DNA

G-quadruplexes(GQs) are guanine-rich, non-canonical nucleic acid structures that play fundamental roles in biological processes. The topology of GQs is associated with the sequences and lengths of DNA, the types of linking loops, and the associated metal cations. However, our understanding on the basic physical properties of the formation process and the stability of GQs is rather limited. In this work, we employed ab initio, molecular dynamics(MD), and steered MD(SMD)simulations to study the interaction between loop bases and ions, and the effect on the stability of G-quadruplex DNA, the Drude oscillator model was used in MD and SMD simulations as a computationally efficient manner method for modeling electronic polarization in DNA ion solutions. We observed that the binding energy between DNA bases and ions(K⁺/Na⁺)is about the base stacking free energies indicates that there will be a competition among the binding of M⁺-base, H-bonds between bases, and the base-stacking while ions were bound in loop of GQs. Our SMD simulations indicated that the side loop inclined to form the base stacking while the loop sequence was Thy or Ade, and the cross-link loop upon the G-tetrads was not easy to form the base stacking. The base stacking side loop complex K+was found to have a good stabilization synergy. Although a stronger interaction was observed to exist between Cyt and K+, such an interaction was unable to promote the stability of the loop with the sequence Cyt.     

Mono and Trimethine Cyanines Cyan 40 and Cyan 2 as Probes for Highly Selective Fluorescent Detection of Non-canonical DNA Structures

Two of earlier reported dsDNA sensitive cyanine dyes??monomethine Cyan 40 and meso-substituted trimethine Cyan 2 were studied for their ability to interact with non-canonical DNA conformations. These dyes were characterized by spectral-luminescent methods in the presence of G-quadruplex, triplex and dsDNA motifs. We have demonstrated that Cyan 2 binds strongly and preferentially to triple- and quadruple-stranded DNA forms that results in a strong enhancement of the dye fluorescence, as compared to dsDNA, while Cyan 40 form fluorescent complexes preferentially only with the triplex form. Highly fluorescent complexes of Cyan 2 with DNA triplexes and G-quadruplexes and Cyan 40 with DNA triplexes are very stable and do not dissociate during gel electrophoresis, leading to preferential staining of the above DNA forms in gels. The data presented point to the intercalation mechanism of the Cyan 2 binding to G4-DNA, while the complexes of Cyan 40 and Cyan 2 with triplex DNA are believed to be formed via groove binding mode. The Cyan dyes can provide a highly sensitive method for detection and quantification of non-canonical structures in genome.     

Analysis of Cation-Dependent DNA (G<Subscript>3</Subscript>T<Subscript>1</Subscript>)<Subscript>4</Subscript> Shape Change Using Fluorescence Correlation Spectroscopy

In G-rich DNA, it is well known that the form changes from single-strand DNA to G-quadruplex due to cations. In this study, we analyze the diffusion coefficient and fluorescence intensity obtained by fluorescence correlation spectroscopy for short G-rich DNA of the (G₃T₁)₄ sequence labeled as 5-Carboxytetramethylrhodamine (TAMRA) with variation of the K⁺ ion concentration. At a K⁺ ion concentration of more than 200 mM, the single-strand DNA was changed to the G-quadruplex. The size of the G-quadruplex decreased to 86% than the size of the single strand DNA at K⁺ ion concentration of 0 M. The size of the G-quadruplex and the fluorescence intensity of TAMRA attached to the DNA were constant with an increase in the K⁺ ion concentration between 200 and 800 mM. This means that the size of the DNA and the fluorescence intensity of the TAMRA are not affected by the K⁺ ion concentration at the G-quadruplex structure because the binding structure of DNA and TAMRA dye leads to stability at a concentration of less than 100 mM K⁺. Based on our short G-rich DNA results, longer G-rich DNA is analyzed for the diffusion coefficient of the DNA and the fluorescence intensity variation of fluorescence dye attached to the DNA.     

Evaluation of alkaloids binding to the parallel quadruplex structure [d(TGGGGT)]4 by electrospray ionization mass spectrometry

In this study, electrospray ionization mass spectrometry (ESI-MS) was used to investigate the binding interaction of six alkaloids with parallel intermolecular G-quadruplex [d(TGGGGT)](4), and five alkaloids including berberine, jatrorrhizine, palmatine, tetrandrine, and fangchinoline showed complexation with the target DNA. Relative binding affinities were estimated on the basis of mass spectrometric data. The slight differences in chemical structures of berberine, jatrorrhizine, and palmatine had little influence on their binding affinities to [d(TGGGGT)](4). Tetrandrine and fangchinoline selectively bound to [d(TGGGGT)](4) versus duplex DNA. Collision-induced dissociation (CID) experiments showed that the complexes with berberine, jatrorrhizine, and palmatine dissociated via strand separation and ligand retaining in the strand while the complexes with tetrandrine and fangchinoline were dissociated via ligand elimination. A comparison of dissociation patterns in CID experiments of complexes with the alkaloids to those with the traditional G-quadruplex DNA binders suggested an end-stacking binding mode for tetrandrine and fangchinoline and an intercalation binding mode for berberine, jatrorrhizine, and palmatine to the target DNA. The current work not only provides deep insight into alkaloid/[d(TGGGGT)](4) complexes and useful guidelines for design of efficient anticancer agents but also demonstrates the utility of ESI-MS as a powerful tool for evaluating interaction between ligand and quadruplex DNA.     

dsDNA与TiO2 (110)在溶液中相互作用的动力学行为和机制

金红石型TiO2 (110)在DNA传感领域具有广阔的应用前景,然而其与DNA在溶液中相互作用的动力学行为和机制尚不清楚。利用分子动力学模拟,深入研究了双链DNA (dsDNA)在初始时沿轴向平行或垂直于金红石型TiO2 (110)表面时二者在溶液中的相互作用。通过分析dsDNA在吸附后的稳定构型、吸附动力学过程和结构稳定性发现,与一些典型二维纳米材料不同,dsDNA倾向于水平吸附到TiO2 (110)表面。水平吸附不仅使得dsDNA的四种碱基均吸附到TiO2 (110)表面,增加了吸附稳定性,而且不破坏dsDNA的结构稳定性。进而,通过分析dsDNA与TiO2 (110)表面的相互作用能和水分子密度/数量发现,dsDNA的平行吸附可能源于二者之间的短程范德华和长程静电相互作用。此外,纳米级脱湿也增强了dsDNA的吸附。对dsDNA与TiO2 (110)在溶液中的相互作用研究有助于实现TiO2 (110)在DNA传感中的应用。     

Coupling of mixing models with manifold based simplified chemistry in PDF modeling of turbulent reacting flows

For general reacting flows the numerical simulation faces two main challenges. One is the high dimensionality and stiffness of the governing conservation equations due to detailed chemistry, which can be solved by using simplified chemical kinetics. The other one is the difficulty of modeling the coupling of turbulence with thermo-chemical source term. The probability density function (PDF) method allows to calculate turbulent reacting flows by solving the thermal-chemical source term in closed form. Usually, the PDF method for turbulent processes such as mixing processes and the reduction method for chemical kinetics are developed separately. However, coupling of both processes plays an important role for the numerical accuracy. To investigate the importance of coupling between turbulence and simplified chemistry, two different coupling strategies for mixing and reduced chemistry are discussed and tested for the well-known Sandia Flames E and F, in which there is a strong interaction between turbulence and chemical kinetics. The EMST mixing model is chosen for turbulent mixing, while the Reaction-Diffusion Manifolds (REDIMs) is used as simplified chemistry. However, the proposed strategies are also valid for other mixing models and manifold based simplified chemistry.     

Formation of a G-quadruplex structure from human mature miR-5196-5p

Some human mature microRNAs are featured of G_≥2N_xG_≥2N_yG_≥2N_zG_≥2 sequences. In this study, a human mature microRNA, miR-5196-5p, was selected as an example to probe the secondary structure of G-rich microRNA. Our results have confirmed that miR-5196-5p could form a stable G-quadruplex structure with three G-quartets and three double-chain-reversal loops by electrospray ionization mass spectrometry, nuclear magnetic resonance, circular dichroism spectroscopy, and molecular dynamics simulation. Our study showed the prevalence of G-rich microRNAs in Homo sapiens, rat, mouse, and Arabidopsis thaliana, and they have great potential to fold into intramolecular G-quadruplexes which may serve as new targets for the regulatory function of G-rich mature microRNAs.     

Generation of Laser Light via Ultrasonic Four-wave Mixing

On the basis of the interaction between phonons in ionic crystals with anharmonic lattice vibration, we present a laser model on acoustic nondegenerate four-wave mixing. Two beams of highfrequency ultrasound, incident on the acoustic cavity fulfilled with the medium of ionic crystal, play the role of pumping and one of the two side-band modes of the pumping frequency as an acoustic signal mode has a strong interaction with the optical cavity mode, the coupling-out of which wiIl be the light (far-infrared) output of a laser. The problem is treated with quantum-mechanics. The theory shows that there is the threshold phenomenon as usual lasers and a so called "phase-matching" condition is derived, which should be satisfied for stability of the system.     

Generation of Laser Light via Ultrasonic Four-wave Mixing

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用全内反射瞬逝场照明磁镊研究Bloom解旋G-四联体

G-四联体(G-quadruplex,G4)是广泛存在于细胞基因组中的一种DNA结构,在DNA的代谢如复制、转录、同源重组等过程中起重要作用.G4解旋酶近年来受到广泛研究,其中Bloom(BLM)解旋酶的研究已经相当丰富,但仍有一些基本问题不清楚.我们应用全内反射瞬逝场照明磁镊对BLM解旋G4的动力学过程进行了深入研究,观察到了BLM解旋G4的分步过程.相对于单分子荧光共振能量转移技术而言,借助磁镊的长时间观测性能,我们在近饱和三磷酸腺苷(ATP)浓度的实验体系中观察到BLM长时间反复解开G4或者长时间维持G4于打开状态的两种作用方式.最后,使用相同的实验条件做了单分子荧光共振能量转移实验,确定了加载2-3 pN的外力对BLM解旋G4没有显著影响.     

Effect of different electronic properties on 9-aryl-substituted BMVC derivatives for new fluorescence probes

We have previously illustrated that the electron donor of carbazole moiety and the electron acceptor of methyl pyridinium cation in 3,6-bis(1-methyl-4-vinylpyridinium) carbazole diiodide (BMVC) molecule could form an intramolecular charge-transfer state. The intramolecular twist of the vinyl group in bridging the donor and acceptor plays an important role in the BMVC fluorescence. Here, we have synthesized three 9-aryl-substituted BMVC derivatives with different electronic properties for the design of the second generation of fluorescence probes. The steady-state solvatochromic studies show no appreciable change to the charge transfer of BMVC by substituting an anisole electron-donating group at 9-position of BMVC. However, substituting a 9-nitrobenzyl electron-withdrawing group in BMVC could restrict the charge transfer in the excited state. Moreover, the increase of the fluorescence yields of 9-anisole BMVC and 9-phenyl BMVC upon interaction with DNA is even higher than that in glycerol, while the fluorescence yield of 9-nitrobenzyl BMVC upon interaction with DNA is much lower than that in glycerol. Although 9-nitrobenzyl BMVC is a good G-quadruplex stabilizer, substituting an electron-withdrawing group at 9-position of BMVC is not recommended for the design of fluorescence probes. On the other hand, co-localization between 9-phenyl BMVC and MitoTracker Red in the merged image of cells indicates that the 9-phenyl BMVC is a potential fluorescent mitochondrial probe.     

Nonlinear Effect and Atomic Entanglement in a Coupled-Cavity Array

By introducing the nonlinear effects that arise from Kerr medium, we theoretically study the nonlinear effect and the entanglement between two atoms in two coupled cavities. We give out the process of dynamic stability and solve the eigen problem of the system under high-intensive fields. The dynamics of the two coupled cavity with high-intensity fields inside is also studied numerically, the effects of atom-field coupling on the self-trapping as well as on the entanglement are also analyzed and discussed. In vacuum and high-intensity fields we calculate the concurrence of the two atoms in both theoretical and realistic situation, and discuss the nonlinear effect on the atomic entanglement. The result shows that the nonlinear interaction can play a controlling role in entangling two atoms.     

Low-Dimensional Forest-Like and Desert-Like Fractal Patterns Formed in a DDAN Molecular System

Two kinds of forest-like and desert-like patterns are formed by thermal evaporation of 4-dicyanovinyl-N, Ndimethylamino-1-naphthalene （DDAN） onto SiO2 substrates. Based on thermal kinetics of the molecules on the substrate the transformation between the forest and desert patterns is due to two factors. The first one is the diffusion length, which is related to the deposition rate, the diffusion potential energy barrier and the substrate temperature. The second one is the strong interaction between the two polarity chemical groups of the molecules, which is beneficial to the formation of branches. Totally different patterns are also found on mica substrates, and are attributed to the anisotropic diffusion and the stronger interaction between DDAN molecules and the mica surface.     

Formation of stable structures from damage elements

Failure is described as the evolution of a kinetic system, and the conditions are considered for the formation of a stable structure arising from damage elements. A parabolic-type equation system describes the kinetics and is constructed on the basis of interaction between damage elements of two types, which are identified as local excited states interacting in accordance with the rules of formal chemical kinetics. The solutions staisfy the general laws of solid-state failure.Translated from Izvestiya Vyssikh Uchebnykh Zavedenii, Fizika, No. 7, pp. 46–49, July, 1987.     

Structure-based simulations complemented by conventional all-atom simulations to provide new insights into the folding dynamics of human telomeric G-quadruplex

The hybrid atomistic structure-based model has been validated to be effective in investigation of G-quadruplex folding. In this study, we performed large-scale conventional all-atom simulations to complement the folding mechanism of human telomeric sequence Htel24 revealed by a multi-basin hybrid atomistic structure-based model. Firstly, the real time-scale of folding rate, which cannot be obtained from the structure-based simulations, was estimated directly by constructing a Markov state model. The results show that Htel24 may fold as fast as on the order of milliseconds when only considering the competition between the hybrid-1 and hybrid-2 G-quadruplex conformations. Secondly, in comparison with the results of structure-based simulations, more metastable states were identified to participate in the formation of hybrid-1 and hybrid-2 conformations. These findings suggest that coupling the hybrid atomistic structure-based model and the conventional all-atom model can provide more insights into the folding dynamics of DNA G-quadruplex. As a result, the multiscale computational framework adopted in this study may be useful to study complex processes of biomolecules involving large conformational changes.     

Polariton condensation in photonic molecules

We report on polariton condensation in photonic molecules formed by two coupled micropillars. We show that the condensation process is strongly affected by the interaction with the cloud of uncondensed excitons and thus strongly depends on the exact localization of these excitons within the molecule. Under symmetric excitation conditions, condensation is triggered on both binding and antibinding polariton states of the molecule. On the opposite, when the excitonic cloud is injected in one of the two pillars, condensation on a metastable state is observed and a total transfer of the condensate into one of the micropillars can be achieved. Our results highlight the crucial role played by relaxation kinetics in the condensation process.     

Morphology of ternary immiscible polymer blends

Ternary blends consisting of thermoplastic and thermotropic immiscible polymers were studied. Both thermodynamic and kinetic considerations were found to affect their multiphase structure. Thermodynamics is expressed by means of spreading coefficients, whereas the kinetic effect is driven by the dispersed phase viscosity ratio. Some morphologies could be predicted, when both effects acted cooperatively. However, in cases where the effects were opposing, kinetics hindered the development of the expected structure; interpenetration between the two minor phases, rather than engulfing or separately dispersed morphology, took place. In cases where two relatively polar phases were dispersed in a nonpolar matrix (e.g., nylon and polycarbonate in polypropylene), the interaction between the two dispersed minor phases always existed due to their low interfacial tension. Spreading of one minor phase over another, rather than penetration, is the dominating mechanism of encapsulation in polymer blends, contrary to low molecular weight liquids where both spreading and penetration play an important role in the structurization.     

A detonation stability formulation for arbitrary equations of state and multi-step reaction mechanisms

A general normal-mode linear stability formulation of steady planar detonation waves is presented that is valid both for an arbitrary equation of state and for multi-step, multi-species chemical kinetics. The general formulation can be used for many purposes, including an examination of gaseous detonation stability with complex reaction kinetics in which the individual reacting species have variable thermochemical properties. In the present paper, we consider two cases that could not be obtained by previous one-step chemistry, polytropic gas formulations: the first concerns the effect of a difference in heat capacities between product and fuel species, as well as a possible mole change, in a single-step irreversible reaction. The second examines the effects of exothermic or endothermic heat release/absorption in the chain-initiation stage of a model three-step reaction.     

Rijke管热声振荡的稳定性切换行为研究

采用数值方法模拟了强弱两种阻尼条件下传热迟滞时间对一维Rijke管热声系统稳定性的影响,发现Rijke管系统存在稳定性切换现象.在推导了无量纲形式的管内声波动量方程和能量方程之后,利用Galerkin方法对控制方程进行展开并在时间域内数值求解.分析了强阻尼和弱阻尼条件下,给定热源的Rijke管热声振荡的稳定性与传热迟滞时间的关系.结果显示:在两类阻尼条件下,持续增大传热与速度的迟滞时间,系统均呈现出稳定性切换现象,即系统在稳定和不稳定两个状态间持续转变;但弱阻尼系统的不稳定区域宽于强阻尼系统的不稳定区域,系统最大振幅相对增大,且系统热声振荡的主模态在不同模态之间发生转换.最后,通过求解系统各阶模态极限环幅值随传热迟滞时间的变化,发现Rijke管热声振荡稳定性切换现象与迟滞时间存在近似周期性关系.