人类和黑猩猩的回文序列的对称性分析

首次通过分析人类和黑猩猩的X染色体上的一条回文序列,来寻找这种对称性破缺的规律．分析结果表明,与红毛猩猩相比,尽管在人类回文序列上发生的突变总数比在黑猩猩上的少,但是在各自的序列上,它们的左臂的突变总数与右臂的突变总数都基本上是相同的,这意味着它们的回文序列的进化都是同步的．然而,在每个臂上,A／T→G／C的突变数目却大于G／C→A／T的,这表明回文序列的成分并没有达到平衡,并且GC含量有上升的趋势．此外,通过两臂之间的序列比较发现,发生在人类回文序列上的突变数目多于发生在黑猩猩上的突变数目,并且这种突变更容易发生在具有相似化学结构的碱基之间．因此,黑猩狠回文序列上的对称性看起来要比人类回文序列上的对称性高．     

光控CRISPR技术的研究进展

成簇规则间隔短回文重复序列和成簇规则间隔短回文重复序列相关(CRISPR-Cas)系统提供了用于可编程基因组编辑的多功能工具. CRISPR与光遗传学及光化学生物学技术的结合产生了很多新的成果. 光激活的CRISPR-Cas系统能够在空间和时间上更好地调控RNA引导的核酸酶的活性. 近年来, 科学家结合CRISPR和多种光学技术, 开发出了一系列光激活的CRISPR工具. 这些工具让研究人员能够在空间、 时间和基因组坐标上进行高分辨率的生命活动研究. 本文概述了CRISPR系统、 基因编辑技术、 光遗传学和光化学生物学的研究进展, 并对光诱导的CRISPR技术的发展进行了展望.     

DNA序列特征的统计分析

介绍了近年来在多种学科领域对DNA碱基序列的研究中发展起来的定量分析符号序列的方法,归纳了将碱基与数字对应起来的规则和进行统计分析的方法．并给予一定的评价。DNA分子包涵了丰富的化学信息和生物信息,对于DNA序列的统计分析显得非常重要。将DNA序列表达成数字信号通常有从一维到四维4种不同维数空间的映射方式,其相应的统计方法有均方根涨落、熵近似方法、傅立叶变换和小波变换等,各种方法从多个角度多个层次来分析揭示了DNA序列的结构规律。     

He-LiH体系转动非弹性碰撞的理论研究

在单双迭代耦合簇CCSD(T)势能面的基础上,运用密耦方法讨论了He-LiH体系的转动非弹性碰撞.计算结果表明,对LiH分子j=0→j′跃迁,跃迁截面主要由各向异性的短程相互作用和长程的“软”排斥共同作用的结果,未见明显的长程吸引势贡献.态－态跃迁总截面表现出振荡结构,长程“软”排斥分波只对j=0向j′=1、2、3的跃迁总截面有较大贡献,而j′≥ 4跃迁的积分截面则几乎由各向异性的短程部分贡献.     

基于CRISPR/Cas的生物传感平台在分子诊断中的应用

簇状规则间隔短回文重复序列(CRISPR)和CRISPR相关蛋白(Cas)不仅在基因工程领域炙手可热,而且正发展成为核酸精准检测领域的新利器.得益于Cas蛋白对核酸序列的特异性识别以及部分Cas蛋白的附属切割活性,Ⅱ类CRISPR/Cas系统在体外诊断及现场即时检测领域独具优势.该综述简要介绍了CRISPR/Cas系统...     

蛋白质结构的“限域下最低能量结构片段”假说与蛋白质进化的“石器时代”

蛋白质折叠问题被称为第二遗传密码,至今未破译;蛋白质序列的天书仍然是"句读之不知,惑之不解"。在最近工作的基础上,我们提出了蛋白质结构的"限域下最低能量结构片段"假说。这一假说指出,蛋白质中存在一些关键的长程强相互作用位点,这些位点相当于标点符号,将蛋白质序列的天书变成可读的句子(多肽片段)。这些片段的天然结构是在这些强长程相互作用位点限域下的能量最低状态。完整的蛋白质结构由这些"限域下最低能量结构片段"拼合而成,而蛋白质整体结构并不一定是全局性的能量最低状态。在蛋白质折叠过程中,局部片段的天然结构倾向性为强长程相互作用的形成提供主要基于焓效应的驱动力,而天然强长程相互作用的形成为局部片段的天然结构提供主要基于熵效应的稳定性。在蛋白质进化早期,可能存在一个"石器时代",即依附不同界面(比如岩石)的限域作用而稳定的多肽片段先进化出来,后由这些片段逐步进化(包括拼合)而成蛋白质。     

Ni-B非晶态合金超细微粒的表面性质

非晶态合金具有短程有序和长程无序的结构特点,其优良的催化性能引人注目.但通常熔体急冷法制备的非晶样品表面积甚小.近年来采用化学还原方法制备使非晶态合金兼具超细微粒的性质,从而为非晶态合金在多相催化过程中的应用展示了诱人的前景.因此,研究非晶态合金超细微粒的表面性质就具有重要意义.Okamoto 等发现在用NaBH_4还原水溶液中Ni~(2+)离子制得的Ni-B 超细微粒表面除存在以合金方式结合的Ni、B 物类外还存在由B 水解产生的硼氧化物类,但未能将微粒表面性质与合金结构进行关联.本文报导不同结构状态下Ni-B 超细微粒表面性质的研究结果.     

XH-NH3(X=F,Cl,Br)质子传递的溶剂效应:簇模型,连续介质模型和离散-连续组合模型的比较

分别采用分子簇模型、连续介质模型和离散-连续组合模型研究了XH-NH3(X=F,Cl,Br)分子内质子传递的溶剂效应．结果表明,对于弱酸性化合物FH-NH3,其溶剂效应主要为短程作用,3个H2O分子即可使其发生质子传递,而简单的连续介质模型得到的仍为分子化合物形式,需进一步包含溶剂效应短程作用．对于强酸性化合物ClH-NH3和BrH-NH3,较弱的溶剂效应即可促使其发生质子传递,分子簇模型和连续介质模型均可合理描述,且与离散-连续组合模型的结果相近．离散-连续组合模型既在从头算水平考虑了溶质分子和第一溶剂化层中溶剂分子间的短程作用,又包含了溶剂效应的长程静电作用,能更准确地描述溶剂化作用,且对弱酸性化合物和强酸性化合物体系均适用．     

调控CRISPR-Cas9系统用于基因编辑的研究进展

基于操作简便、成本低、快捷高效的优势,规律间隔成簇短回文重复序列及其相关核酸酶（CRISPR-Cas9）系统在基因编辑的基础研究和临床医学方面起到了极为重要的推动作用.在时空维度上调控CRISPR-Cas9发挥功能,对于减少CRISPR-Cas9系统的脱靶效应,提高基因编辑的特异性具有重要意义.本综述介绍了近年来利用化学分子以及光调控CRISPR-Cas9系统发挥功能,进而调控基因编辑的研究进展,并探讨了CRISPR-Cas9调控的前景和面临的挑战.     

流体力学关联对胶体簇团大小的影响

用计算机模拟的方法研究了流体力学关联对胶体簇团大小的影响．研究表明,流体力学关联可使簇团尺寸大大增加,约为无流体力学关联时簇团大小的２～２０倍（在研究情况下）．把该结果与前人的研究作了对照,并解释了其中可能的原因     

Scaling relations,virial theorem,and energy densities for long‐range and short‐range density functionals

Decomposition of the Coulomb electron–electron interaction into a long‐range and a short‐range part is described within the framework of density functional theory, deriving some scaling relations and the corresponding virial theorem. We study the behavior of the local density approximation in the high‐density limit for the long‐range and the short‐range functionals by carrying out a detailed analysis of the correlation energy of a uniform electron gas interacting via a long‐range‐only electron–electron repulsion. Possible definitions of exchange and correlation energy densities are discussed and clarified with some examples. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2006     

Genomic clustering of the Trypanosoma cruzi nonlong terminal L1Tc retrotransposon with defined interspersed repeated DNA elements

We have analyzed the genomic distribution and organization of the long interspersed nucleotide element (LINE) L1Tc, a nonlong terminal repeat (LTR) retrotransposon of Trypanosoma cruzi. The results indicate that the L1Tc element is dispersed along the parasite genome and that in some regions it is organized in tandem repeats. The data allowed us to define the existence of short direct-repeated sequences flanking the genomic L1Tc elements. Relevant is the finding that the LINE L1Tc is located in genomic regions rich in short interspersed nucleotide elements (SINE)-like sequences. In particular, the L1Tc element is found associated to E13-related sequences, redefined in this work and renamed RS13Tc, and to a newly described RS1Tc sequence. The RS1Tc sequence is present, per haploid genome, in about 3,200 copies. Northern blot analysis showed that the RS1Tc is being transcribed into RNAs of different sizes. The analysis of the chromosomal distribution of these elements in various strains of T. cruzi suggested that this type of clustering might be a common feature of the genome of these parasites.     

Two problematic human polymorphic Alu insertions

Analysis of two previously described polymorphic Alu insertions (Sb19.3 and NBC3) in world-wide human populations generated genotypic frequencies grossly in violation of Hardy-Weinberg equilibrium expectations. GenBank searches at the National Center for Biotechnology Information (NCBI) and sequencing analyses revealed that samples homozygous for the Sb19.3 Alu insertion amplify a band indistinguishable in size to the lack of insertion amplicon, corresponding to a paralogous locus on chromosome 4. This locus displays a very similar sequence (84%) to that flanking the Sb19.3 Alu insertion located at chromosome 19. Moreover, we have determined that NBC3, a different Alu insertion, is not located in the pseudoautosomal region of the Y-chromosome, as previously reported, but in position Yq11.2. Also, the band that mimics the lack of insertion amplicon corresponds to a paralogous locus located at chromosome X with a similarity of 92% to the sequence flanking the NBC3 Alu insertion. Finally, the utilization of newly designed primers avoided amplification from the paralogous loci and allowed a reliable assignation of genotypes for both loci. Unlike previously reported, using our new primers the Y-specific locus NBC3 was found not to be polymorphic in the populations analyzed.     

Detection of single and multiple polymorphic loci by synthetic tandem repeats of short oligonucleotides

Loci containing tandem repeats of short sequences are sometimes associated with a high level of polymorphism due to variations in the number of repeats. The different variants can be easily characterized by Southern blotting when the repeats span a range from a few hundred bases to a few kilobases, and probes derived from such tandem repeats constitute convenient genetic markers. These structures, usually called minisatellites, are best documented in the human genome, where their number has been estimated to be at least 1500. However, their role and mode of evolution are poorly understood. We are developing tools to evaluate the number of such redundant sequences in a genome and to gain access to new polymorphic loci. Our strategy is based on the use of polymers of oligonucleotides as DNA probes for hybridization on Southern blots. In a previous report, we made polymers with random units of 14 bp and showed that they detect multiple polymorphic loci on human genomic DNA. At present, we are testing the effect of an increase in the complexity of the polymer, as obtained by the use of a longer random unit, and the effect of slight sequence modifications to a particular tandem repeat sequence. In addition, some of these synthetic probes can detect a single polymorphic locus and directly provide new genetic markers.     

Toward the complete range separation of non‐hybrid exchange–correlation functional

In this study, we use a very simple scheme to achieve range separation of a total exchange–correlation functional. We have utilized this methodology to combine a short‐range pure density functional theory (DFT) functional with a corresponding long‐range pure DFT, leading to a “Range‐separated eXchange–Correlation” (RXC) scheme. By examining the performance of a range of standard exchange–correlation functionals for prototypical short‐ and long‐range properties, we have chosen B‐LYP as the short‐range functional and PBE‐B95 as the long‐range counterpart. The results of our testing using a more diverse range of data sets show that, for properties that we deem to be short‐range in nature, the performance of this prescribed RXC‐DFT protocol does resemble that of B‐LYP in most cases, and vice versa. Thus, this RXC‐DFT protocol already provides meaningful numerical results. Furthermore, we envisage that the general RXC scheme can be easily implemented in computational chemistry software packages. This study paves a way for further refinement of such a range‐separation technique for the development of better performing DFT procedures. © 2015 Wiley Periodicals, Inc.     

A relationship between atomic correlation energy and Tsallis entropy

A new relationship between electron correlation energy and Tsallis entropy is presented. This relationship is a generalization of previous equations which correlate the atomic correlation energy and the Shannon entropy. The results, relatively to the atoms with atomic number 2 < Z < 29, put in evidence the crucial role of the p‐parameter in terms of representation of the long‐range interaction contribution in the correlation energy. Moreover, the p‐values, which reproduce the experimental values of the correlation energy, indicate that the atomic wave functions are more localized with respect to those calculated in the limit of p → 1. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2008     

A relationship between atomic correlation energy of neutral atoms and generalized entropy

In a previous article, hereafter named as Paper I, we have showed a relationship between atomic correlation energy of neutral atoms with 2 < Z < 29 and Tsallis entropy. In this article, we generalize this relation showing the link between the atomic correlation energy and a general form of entropy obtained from deformed algebra. The results evidence the role of both q and Δ parameters of the general entropy, in terms of contribution of the long‐range interactions in the correlation energy. The q and Δ values, obtained as best fit of the atomic correlation energies 2 < Z < 29, indicate that this general form of entropy reduces to the Tsallis one, reproducing well the trend of the correlation energy for low Z. Moreover, as a consequence of these values of the parameters, the state atomic wave function is more localized with respect to the wave function calculated in the limit of Shannon entropy. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

The frequency of poly(G) tracts in the human genome and their use as a sensor of DNA damage

Tandem repeats of short DNA sequences are commonly found in human DNA. These simple sequence repeats or microsatellites are highly polymorphic in the human genome. Since the anti-tumour agent cisplatin preferentially forms DNA adducts at runs of consecutive guanine nucleotides (poly(G)), the position and frequency of occurrence of poly(G) sequences in the updated human genome was investigated. There are more runs of consecutive guanines than would be expected by random chance. This especially true for poly(G) sequences longer than approximately n = 9. A plot of poly(G) length against log(observed/expected) frequency produced a straight line for n > 9. A similar observation was also found for poly(A) DNA sequence repeats. This data implied that the increase in observed/expected frequency is directly related to length of DNA repeat. It was proposed that long runs of consecutive guanine nucleotides could be a sensitive sensor of cellular DNA damage since a number of DNA damaging agents cause lesions at poly(G) sequences.     

Information theoretical measures from cumulative and survival densities in quantum systems

Entropic uncertainty and statistical correlation measures, based on survival and cumulative densities, are explored in some representative quantum systems. We illustrate how the cumulative residual entropy in the quantum well system recovers the correct classical behavior for larger quantum numbers while the Shannon entropy does not. Two interacting and noninteracting oscillators are used to examine two‐particle entropies and their related correlation measures. The joint cumulative residual entropy does distinguish between symmetric and antisymmetric wave functions in interacting systems as the interaction is turned on. The joint Shannon entropy does not distinguish between the symmetries even in the presence of interaction. Conversely, the joint Shannon entropy and joint cumulative residual entropy are both unable to distinguish between the symmetries for certain states of the noninteracting oscillators. As measures of statistical correlation, the mutual information and the cross cumulative residual entropy yield similar behaviors as a function of the strength of the interparticle interaction.     

Characterization of structure and stability of long telomeric DNA G-quadruplexes

In the current study, we used a combination of gel electrophoresis, circular dichroism, and UV melting analysis to investigate the structure and stability of G-quadruplexes formed by long telomeric DNAs from Oxytricha and human, where the length of the repeat (n)=4 to 12. We found that the Oxytricha telomeric DNAs, which have the sequence (TTTTGGGG)n, folded into intramolecular and intermolecular G-quadruplexes depending on the ionic conditions, whereas human telomeric DNAs, which have the sequence (TTAGGG)n, formed only intramolecular G-quadruplexes in all the tested conditions. We further estimated the thermodynamic parameters of the intramolecular G-quadruplex. We found that thermodynamic stabilities of G-quadruplex structures of long telomeric DNAs (n=5 to 12) are mostly independent of sequence length, although telomeric DNAs are more stable when n=4 than when n>or=5. Most importantly, when n is a multiple of four, the change in enthalpy and entropy for G-quadruplex formation increased gradually, demonstrating that the individual G-quadruplex units are composed of four repeats and that the individual units do not interact. Therefore, we propose that the G-quadruplexes formed by long telomeric DNAs (n>or=8) are bead-on-a-string structures in which the G-quadruplex units are connected by one TTTT (Oxytricha) or TTA (human) linker. These results should be useful for understanding the structure and function of telomeres and for developing improved therapeutic agents targeting telomeric DNAs.