拓扑异构酶的结构、功能与进化的结构生物信息学研究

拓扑异构酶（topoisomerase）是一类控制和修改双螺旋DNA复制和转录过程中的拓扑结构的酶，是生命活动中最重要的酶。以IA类和II类拓扑异构酶中共存的toprim以及CAP-like结构域为研究对象，对拓扑异构酶中的三大类酶的分子进化情况进行了分析。结果显示在IA类和II类酶之间序列保守性很低，但是具有两个保守的结构域，在IIB类拓扑异构酶中toprim结构域中存在着和其他toprim结构域相同的四个保守位点，而在CAP-like结构域中IA类和II类中存在较大差异，没有明显的序列保守性，IIB类和IIA类的CAP-like结构域在二级结构上非常相似。从toprim结构域系统进化研究中我们发现IIA类和皿类中toprim结构域的进化关系很近，两类酶的toprim结构域在亲缘关系上和primase较远，而以上三者和IA类的进化关系最远。CAP-like结构域的系统进化研究发现IIA类以及IA类的domain4的CAP-like结构域进化关系比较近，IIB类和他们之间关系稍微远一些，IA类的domain3和以上几个结构域的关系较远，这也与他们的二级结构上的一致性是相同的。通过分析，IIA、IIB类起源于类似IA类的古老的拓扑异构酶，'在IA类进化中经过基因复制产生了两个不同的CAP-like结构域。然后祖先拓扑异构酶发生了变化，N'端加入了ATPase结构域和DNAgyrase/Mutlsecond结构域，形成了严格依赖ATP供能的真核生物IIA类，在细菌中断开成为两个亚基的细菌中IIA类。IIB类是祖先细胞的IIA类的一个或者是两个亚单位在古细菌以及真核生物中通过复制、重组和缺失造成的，IIB类中的toprim结构域很接近IIA类，可以认为，llB类中的toPrim结构域直接由IIA类转移而来，而IIB类中的cAP一1汰e结构域较IIA类中产生更早一些，应该是由拓扑异构酶祖先中产生的二级结构为aβaaββ的CAP-like结构域直接进化而来。然而，两个结构域的基因在连接到一起时候发生了不同于一般顺序的拼接，于是nB类中两个结构域形成了不同于现在的IA类和IIA类的顺序。

Syntheses and reactions of heterometallic complexes of nickel and copper with tetrathiotungstates. The molecular structures of [Ph(4)P](2)[S2W(mu-S)(2)Ni(S-2)] and W(mu-S)(4)Cu-2(PPh(3))(4)center dot py

Reaction of [Ph(4)P]2WS4 With NiCl2 in methanol solution in the presence of NaOCH3 leads to the formation of [Ph(4)P](2) [S2W(mu-S)(2)Ni(S-2)] (I) A Similar reaction between (NH4)(2)WS4 and NiCl2 under O-2 atmosphere in the presence of Ph(4)PCl or (n)Bu(4)NCl affords [Ph(4)P](2)([(S-2)W(O)(mu-S)(2)]Ni-2] (IIa) and [(n)Bu(4)N](2)([(S-2)W(O)(mu-S)(2)]Ni-2} (IIb) Under argon the same reaction gives [Ph(4)P](2)[Ni(WS4)(2)] (IIIa) and [(n)Bu(4)N](2)[Ni(WS4)(2)] (IIIb). [Ph(4)P](2)[Ni(WOS3)(2)] (IV) and [Ph(4)P](2)[Ni(WO2S2)(2)] (V) can be prepared from the reaction of [Ph(4)P]2WOS3 and [Ph(4)P]2WO2S2 with NiCl2. Treatment of (NH4)(2)WS4 with CuCl in the presence of PPh(3) in boiling pyridine produces W(mu-S)(4)Cu-2(PPh(3))(3) (VI), which can further react with excess PPh(3) to give W(mu-S)(4)Cu-2(PPh(3))(4) . py (VII). Complex I crystallizes in the space group P2(1)/n with the cell parameters: a = 20.049(4), b = 17.010(4), c = 14.311(7) Angstrom; beta = 110.24(3)degrees and Z = 4; R = 0.058 for 4267 independent reflections. The structural study confirms that complex I contains two terminal sulfide ligands, two bridging sulfide ligands, a side-on disulfide ligand, and a planar central W(mu-S)(2)Ni four membered ring. Complex VII crystallizes in the space group C2/c with the cell parameters: a = 26.436(8), b = 20.542(6), c = 19.095(8) Angstrom; beta = 125.00(3)degrees and Z = 4; R = 0.080 for 3802 independent reflections. The structural study reveals a perfect linear arrangement of the three metal atoms Cu-W-Cu.

CeO_2纳米晶的制备及其在电化学上的应用

纳米材料的合成、结构功能特性及其应用的研究成为人们共同关注的前沿课题.CeO_2是一种廉价而用途极广的材料,如用于发光材料、催化剂、电子陶瓷等.细胞色素c是一种含血红素的金属蛋白质分子,通过对其电化学行为的研究,为认识生物体内的电子传递反应机理和能量转换提供有用信息,对于揭示生命现象的本质具有重大意义.细胞色素c在裸金电极上是极不可逆的,现已发现了加速其可逆反应的多种促进剂,对其电化学反应机理也进行了深入的讨论.本文用溶胶-凝胶法合成了CeO_2纳米晶;将CeO_2纳米晶修饰在金电极上研究了细胞色素c的电子传递反应,发现CeO_2纳米晶是一种良好的促进剂.1 样品的制备与测试称取一定量草酸铈(GR),用蒸馏水调成浆状,滴加浓HNO_3(GR)和H_2O_2(AR),完全溶解后加入柠檬酸(GR),于50～70℃时缓慢蒸发形成溶胶,继续加热有大量气泡产生,并有白色凝胶形成,体积膨胀,有大量棕色烟放出.将凝胶于120℃干燥12h,得到淡黄色干凝胶,将其在不同温度下进行热处理,即得到CeO_2纳米晶.用日本理学D/MAX-IIB型X射线衍射仪进行结构分析;用H-600型透射电子显微镜进行粒子形貌分析和大小测定;...

辽河油田大民屯凹陷下第三系生油岩生烃及排烃的实验研究

本文以生烃性能、排烃量、排烃效率以及运移过程中石油的变化作为研究方向，以辽河油田大民屯凹陷下第三系生油岩为研究对象，探讨有关石油（天然气）生成和初次运移的一些重要理论问题，同时解决油田生产中遇到的一些实际问题。本文分为两个部分，第一部分着重研究生油岩的特征及生烃性能，第二部分重点研究了生油岩的非烃性能，所获得的主要成果概括如下。1.提出了大民屯凹陷下第三系III型生油岩无阶段连续生烃演化模式，根据此模式对大民屯凹陷“小而肥”的问题可以作出较一些合理的解释。2.建立了大民屯凹陷下第三系生油岩的排烃模式，此模式表明大民屯凹陷下第三系生油岩中液态烃的排出不是间歇式而是连续进行的。3.大民屯凹陷下第三系生油岩中IIb型生油岩的全油排烃效率为13.8-92.3%，III型生油岩的全油排烃效率为18.9-86.8%。研究表明生油岩的有机质丰度制约其排烃量，但并不制约其排烃效率，排烃量大的其排烃效率不一定大。对大民屯凹陷下第三系生油岩而言，多数情况下III型生油岩的排烃效率大于IIb型生油岩的排烃效率。4.在国内首次对烷烃单个化合物的热模拟排烃效率、围岩粒度及受热时间等因素对排出烃和残留烃组成的影响的进行了研究。根据烷烃单个化合物的排烃效率推断，原油可能是以富油流体的形式从油岩中运移出来的，即使如此排出油仍将发生组分分馏。围岩粒度对排出烃的组成有一定的影响。受热时间对于不同类型生油岩残留烃和排出烃烷烃组成的影响也有差异。由于影响残留烃和排出烃组成的因素较多，因此很难用一个模式来概括其变化规律，对具体的盆地和生油岩要做具体分析才能得出正确的认识。6.对比了残留烃和排出烃的五环三萜烷参数和甾烷参数，发现排烃作用对生物标志物的组成有相当大的影响，使目前所用的一些指示有机质来源和成熟度的甾、萜参数的适用范围受到了限制。这些分子有机地球化学参数在用作生油岩中有机质来源和成熟度指标时必须以生油岩未发生过排烃前提，而在用作运移研究指标时则必须以所研究的原油和生油岩处在相同的成熟度水平为前提，否则其地质意义就可能解释不清。

Os solos do Vale dos Vinhedos.

INTRODUÇÃO. CARACTERIZAÇÃO DA ÁREA. MATERIAL E MÉTODOS. RESULTADOS. CONSIDERAÇÕES FINAIS. REFERÊNCIAS. ANEXOS: Anexo I - Mapa impresso; Mapa de solos do Vale dos Vinhedos, RS. Anexo II - CD-ROM. Anexo IIA - Arquivos digitais para reprodução de cópias impressas - formato pdf (portable document file). Anexo IIB - Arquivos digitais estruturados para uso em SIG - formato shape file. Anexo IIC - Descrição dos perfis do levantamento detalhado de solos do Vale dos Vinhedos, RS

Anti-AIDS agents 81. Design, synthesis, and structure-activity relationship study of betulinic acid and moronic acid derivatives as potent HIV maturation inhibitors.

In our continuing study of triterpene derivatives as potent anti-HIV agents, different C-3 conformationally restricted betulinic acid (BA, 1) derivatives were designed and synthesized in order to explore the conformational space of the C-3 pharmacophore. 3-O-Monomethylsuccinyl-betulinic acid (MSB) analogues were also designed to better understand the contribution of the C-3' dimethyl group of bevirimat (2), the first-in-class HIV maturation inhibitor, which is currently in phase IIb clinical trials. In addition, another triterpene skeleton, moronic acid (MA, 3), was also employed to study the influence of the backbone and the C-3 modification toward the anti-HIV activity of this compound class. This study enabled us to better understand the structure-activity relationships (SAR) of triterpene-derived anti-HIV agents and led to the design and synthesis of compound 12 (EC(50): 0.0006 microM), which displayed slightly better activity than 2 as a HIV-1 maturation inhibitor.

The massive binary companion star to the progenitor of supernova 1993J

The massive star that underwent a collapse of its core to produce supernova (SN)1993J was subsequently identified as a non-variable red supergiant star in images of the galaxy M81 taken before explosion(1, 2). It showed an excess in ultraviolet and B-band colours, suggesting either the presence of a hot, massive companion star or that it was embedded in an unresolved young stellar association1. The spectra of SN1993J underwent a remarkable transformation from the signature of a hydrogen-rich type II supernova to one of a helium-rich (hydrogen-deficient) type Ib(3, 4). The spectral and photometric peculiarities were best explained by models in which the 13�20 solar mass supergiant had lost almost its entire hydrogen envelope to a close binary companion(5, 6, 7), producing a 'type IIb' supernova, but the hypothetical massive companion stars for this class of supernovae have so far eluded discovery. Here we report photometric and spectroscopic observations of SN1993J ten years after the explosion. At the position of the fading supernova we detect the unambiguous signature of a massive star: the binary companion to the progenitor.

The death of massive stars - I. Observational constraints on the progenitors of Type II-P supernovae

We present the results of a 10.5-yr, volume-limited (28-Mpc) search for supernova (SN) progenitor stars. In doing so we compile all SNe discovered within this volume (132, of which 27 per cent are Type Ia) and determine the relative rates of each subtype from literature studies. The core-collapse SNe break down into 59 per cent II-P and 29 per cent Ib/c, with the remainder being IIb (5 per cent), IIn (4 per cent) and II-L (3 per cent). There have been 20 II-P SNe with high-quality optical or near-infrared pre-explosion images that allow a meaningful search for the progenitor stars. In five cases they are clearly red supergiants, one case is unconstrained, two fall on compact coeval star clusters and the other twelve have no progenitor detected. We review and update all the available data for the host galaxies and SN environments (distance, metallicity and extinction) and determine masses and upper mass estimates for these 20 progenitor stars using the STARS stellar evolutionary code and a single consistent homogeneous method. A maximum likelihood calculation suggests that the minimum stellar mass for a Type II-P to form is m(min) = 8.5(-1.5)(+1) M-circle dot and the maximum mass for II-P progenitors is m(max) = 16.5 +/- 1.5 M-circle dot, assuming a Salpeter initial mass function holds for the progenitor population (in the range Gamma = -1.35(-0.7)(+0.3)). The minimum mass is consistent with current estimates for the upper limit to white dwarf progenitor masses, but the maximum mass does not appear consistent with massive star populations in Local Group galaxies. Red supergiants in the Local Group have masses up to 25 M-circle dot and the minimum mass to produce a Wolf-Rayet star in single star evolution (between solar and LMC metallicity) is similarly 25-30 M-circle dot. The reason we have not detected any high-mass red supergiant progenitors above 17 M-circle dot is unclear, but we estimate that it is statistically significant at 2.4 sigma confidence. Two simple reasons for this could be that we have systematically underestimated the progenitor masses due to dust extinction or that stars between 17-25 M-circle dot produce other kinds of SNe which are not II-P. We discuss these possibilities and find that neither provides a satisfactory solution. We term this discrepancy the 'red supergiant problem' and speculate that these stars could have core masses high enough to form black holes and SNe which are too faint to have been detected. We compare the Ni-56 masses ejected in the SNe to the progenitor mass estimates and find that low-luminosity SNe with low Ni-56 production are most likely to arise from explosions of low-mass progenitors near the mass threshold that can produce a core-collapse.

Activation of GPVI by collagen is regulated by alpha(2)beta(1) and secondary mediators

We have compared the roles of adenosine diphosphate (ADP), thromboxanes and the integrin alpha(2)beta(1) in the activation of washed platelets by collagen in the presence of the alpha(IIb)beta3 antagonist lotrafiban. The stimulation of protein tyrosine phosphorylation by a collagen suspension is markedly delayed in the presence of the above inhibitors but shows substantial recovery with time. In comparison, activation of phospholipase C (PLC), Ca2+ elevation and dense granule secretion are more severely suppressed by the above inhibitors. blockade has a slightly greater inhibitory effect on all of the above responses than a combination of ADP receptor antagonists and cyclooxygenase inhibitor. Platelets exposed to a collagen monolayer show robust elevation of Ca2+ that is delayed in the presence of the above inhibitors and which is accompanied by of-granule secretion. These results demonstrate that secondary mediators and alpha(2)beta(1) modulate collagen-induced intracellular signaling but have negligible effect on GPVI signaling induced by the specific agonist convulxin. This work supports the postulate that the major role of of alpha(2)beta(1) is to increase the avidity of collagen for the platelet surface and by doing so enhance activation of GPVI. Therefore we propose an important role of secondary mediators in collagen-induced signaling is the indirect regulation of GPVI signaling via activation of alpha(2)beta(1).

Thrombin-induced conversion of fibrinogen to fibrin results in rapid platelet trapping which is not dependent on platelet activation or GPIb

1 Activation of human platelets by thrombin is mediated by the proteolytic cleavage of two G-protein coupled protease-activated receptors, PAR-1 and PAR-4. However, thrombin also binds specifically to the platelet surface glycoprotein GPIb. It has been claimed that thrombin can induce aggregation of platelets via a novel GPIb-mediated pathway, which is independent of PAR activation and fibrinogen binding to alpha(IIb)beta(3) integrin, but dependent upon polymerizing fibrin and the generation of intracellular signals.

The Yellow Supergiant Progenitor of the Type II Supernova 2011dh in M51

We present the detection of the putative progenitor of the Type IIb SN 2011dh in archival pre-explosion Hubble Space Telescope images. Using post-explosion Adaptive Optics imaging with Gemini NIRI+ALTAIR, the position of the supernova (SN) in the pre-explosion images was determined to within 23 mas. The progenitor candidate is consistent with an F8 supergiant star (logL/L sun = 4.92 ± 0.20 and T eff = 6000 ± 280 K). Through comparison with stellar evolution tracks, this corresponds to a single star at the end of core C-burning with an initial mass of M ZAMS = 13 ± 3 M sun. The possibility of the progenitor source being a cluster is rejected, on the basis of: (1) the source not being spatially extended, (2) the absence of excess Ha emission, and (3) the poor fit to synthetic cluster spectral energy distributions (SEDs). It is unclear if a binary companion is contributing to the observed SED, although given the excellent correspondence of the observed photometry to a single star SED we suggest that the companion does not contribute significantly. Early photometric and spectroscopic observations show fast evolution similar to the transitional Type IIb SN 2008ax and suggest that a large amount of the progenitor's hydrogen envelope was removed before explosion. Late-time observations will reveal if the yellow supergiant or the putative companion star were responsible for this SN explosion.

Observational Constraints on the Progenitors of Core-Collapse Supernovae: The Case for Missing High-Mass Stars

Over the last 15 years, the supernova community has endeavoured to directly identify progenitor stars for core-collapse supernovae discovered in nearby galaxies. These precursors are often visible as resolved stars in high-resolution images from space-and ground-based telescopes. The discovery rate of progenitor stars is limited by the local supernova rate and the availability and depth of archive images of galaxies, with 18 detections of precursor objects and 27 upper limits. This review compiles these results (from 1999 to 2013) in a distance-limited sample and discusses the implications of the findings. The vast majority of the detections of progenitor stars are of type II-P, II-L, or IIb with one type Ib progenitor system detected and many more upper limits for progenitors of Ibc supernovae (14 in all). The data for these 45 supernovae progenitors illustrate a remarkable deficit of high-luminosity stars above an apparent limit of log L/L-circle dot similar or equal to 5.1 dex. For a typical Salpeter initial mass function, one would expect to have found 13 high-luminosity and high-mass progenitors by now. There is, possibly, only one object in this time-and volume-limited sample that is unambiguously high-mass (the progenitor of SN2009ip) although the nature of that supernovae is still debated. The possible biases due to the influence of circumstellar dust, the luminosity analysis, and sample selection methods are reviewed. It does not appear likely that these can explain the missing high-mass progenitor stars. This review concludes that the community's work to date shows that the observed populations of supernovae in the local Universe are not, on the whole, produced by high-mass (M greater than or similar to 18 M-circle dot) stars. Theoretical explosions of model stars also predict that black hole formation and failed supernovae tend to occur above an initial mass of M similar or equal to 18 M-circle dot. The models also suggest there is no simple single mass division for neutron star or black-hole formation and that there are islands of explodability for stars in the 8-120 M-circle dot range. The observational constraints are quite consistent with the bulk of stars above M similar or equal to 18 M-circle dot collapsing to form black holes with no visible supernovae.

Optical and near-infrared observations of SN 2011dh - The first 100 days

We present optical and near-infrared (NIR) photometry and spectroscopy of the Type IIb supernova (SN) 2011dh for the first 100 days. We complement our extensive dataset with Swift ultra-violet (UV) and Spitzer mid-infrared (MIR) data to build a UV to MIR bolometric lightcurve using both photometric and spectroscopic data. Hydrodynamical modelling of the SN based on this bolometric lightcurve have been presented in Bersten et al. (2012, ApJ, 757, 31). We find that the absorption minimum for the hydrogen lines is never seen below ~11 000 km s-1 but approaches this value as the lines get weaker. This suggests that the interface between the helium core and hydrogen rich envelope is located near this velocity in agreement with the Bersten et al. (2012) He4R270 ejecta model. Spectral modelling of the hydrogen lines using this ejecta model supports the conclusion and we find a hydrogen mass of 0.01-0.04 M⊙ to be consistent with the observed spectral evolution. We estimate that the photosphere reaches the helium core at 5-7 days whereas the helium lines appear between ~10 and ~15 days, close to the photosphere and then move outward in velocity until ~40 days. This suggests that increasing non-thermal excitation due to decreasing optical depth for the γ-rays is driving the early evolution of these lines. The Spitzer 4.5 μm band shows a significant flux excess, which we attribute to CO fundamental band emission or a thermal dust echo although further work using late time data is needed. Thedistance and in particular the extinction, where we use spectral modelling to put further constraints, is discussed in some detail as well as the sensitivity of the hydrodynamical modelling to errors in these quantities. We also provide and discuss pre- and post-explosion observations of the SN site which shows a reduction by ~75 percent in flux at the position of the yellow supergiant coincident with SN 2011dh. The B, V and r band decline rates of 0.0073, 0.0090 and 0.0053 mag day-1 respectively are consistent with the remaining flux being emitted by the SN. Hence we find that the star was indeed the progenitor of SN 2011dh as previously suggested by Maund et al. (2011, ApJ, 739, L37) and which is also consistent with the results from the hydrodynamical modelling. Figures 2, 3, Tables 3-10, and Appendices are available in electronic form at http://www.aanda.orgThe photometric tables are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/562/A17

Force potentiation in the MDX mouse

Large forces are the primary mechanism of injury in muscular dystrophy, and muscular dystrophy is especially damaging to type IIB muscle fibers. It was hypothesized that post-tetanic potentiation (PTP) would be down-regulated to prevent damage in Xlinked muscular dystrophy (mdx) mice since PTP increases force and PTP effects are greatest in IIB fibers. PTP experiments were performed on the extensor digitorum longus (EDL) of 50 day old mdx (YM) and C57BL/10 (YC) mice and 10 month old mdx (OM) and C57B1710 (OC) mice. Twitch and tetanic forces were lower in mdx than controls and lower in younger than older mice. Contrary to the hypothesis, PTP was higher in both mdx groups compared to controls. OM potentiated more than any other condition (OM: 29.8%, OC: 23.2%, YM: 21.9%, YC: 17.2%). In accordance with literature PTP increased in the older groups. To explain PTP changes, fiber typing and Western blots for myosin light chain kinase (MLCK) were performed. YM and YC had similar fiber type profiles (2% I, 58% IIX/D and 40% IIB). In accordance with literature but contrary to expected conditions for elevated PTP, OM had a slower fiber type profile (1.7% I, 69% IIX/D and 29% IIB) than OC (0.4% I, 61% IIX/D and 38% IIB). No differences were found in MLCK expression. It seems that PTP is up-regulated to maintain muscle function rather than being down-regulated to prevent muscle damage. Ca""^ transient and myosin phosphorylation measurements would be beneficial in explaining increased PTP seen in this study.