胰腺癌发展中的关键信号通路及其作用

胰腺癌是常见的消化道恶性肿瘤之一,起病隐匿、恶性程度高、预后差。胰腺癌发生受多种因素调节,发病机制不清,具有复杂分子发病机。而且,胰腺癌细胞内在的基因异常表达、表观遗传基因突变等因素对胰腺癌发生发展起重要作用。目前研究显示,胰腺癌发生过程与多种信号通路的交互作用密切相关,这些信号通路的研发都体现了临床分子靶向治疗的潜在前景。本文对近年研究的一些与胰腺癌发生相关的信号通路做了总结,这些通路主要包括Wnt信号通路、MAPK信号通路、PI3K/AKT/m TOR信号通路、Hedgehog信号通路等。主要瞄准这些通路在胰腺癌发生、发展过程中的作用,它们的变化特征以及异常变化所导致的结果等方面的最新研究进展,以期为胰腺癌的早诊早治、个体化诊疗等的基础、临床研究提供前言资料。     

Wnt通路中β-catenin在恶性肿瘤中的异常表达

在肿瘤生物学的研究中,Wnt信号通路具有举足轻重的作用.Wnt家族基因编码一组糖蛋白信号分子,这些糖蛋白分子激活的信号通路在人类不同肿瘤中的作用是相互交织的.Wnt信号通路有三种模式,而经典的信号通路与癌症的发生有着十分密切的联系,β-catenin是Wnt经典信号通路正向调节重要效应物,其在胞质内降解及在核内积累可激活一系列靶基因的转录导致肿瘤的发生.了解这条通路在肿瘤发生过程中具体的分子机制有助于为临床诊断提供依据,为早期干预治疗提供方法.     

靶向Wnt/β-catenin信号通路抑制剂研究进展

Wnt/β-catenin信号通路高度复杂,与Notch通路、Hedgehog通路等都有密切联系,参与机体胚胎发育、调控生物体细胞增殖、代谢等多个方面.研究发现,该信号通路的异常激活与肿瘤密切相关.据汤森路透数据库统计发现,截至2014-04-24,共报道Wnt信号通路抑制剂228个,主要分为受体抑制剂和胞内小分子抑制剂等.本文综述了Wnt/β-catenin信号通路抑制剂及其调控机制,旨在为肿瘤预防与治疗提供新素材.     

环二鸟苷酸对细菌运动调控的研究进展

细菌中的第二信使环二鸟苷酸(c-di-GMP)对细菌的运动性有调节作用.c-di-GMP调控鞭毛的生物合成、菌毛形成和菌毛蛋白的组成,以及其他一些与运动相关的蛋白的合成.细菌的运动性与其毒力、致病性、粘附性、趋化性、生物膜组成等密切相关.在革兰氏阴性细菌中,关于c-di-GMP的信号通路的研究较为清晰,而在革兰氏阳性细菌中,关于该信号转导通路的研究较少.此外,有关c-di-GMP的信号通路的研究主要集中在病原菌.该文主要综述了一些常见病原菌中c-di-GMP对其运动性的调控机制,为研究其他细菌c-di-GMP信号通路提供思路.     

Wnt/β-catenin信号通路对舌味觉乳头发育及舌癌的调控作用

Wnt经典信号通路(Wnt/β-catenin信号通路)在小鼠舌味觉乳头的早期发育以及味蕾再生过程中具有重要的调控作用,该信号通路的关键因子的缺失或者过表达可导致舌味觉乳头发育缺陷以及味蕾功能异常.此外,Wnt/β-catenin信号通路在成体舌的异常还与舌癌的发生有关.     

肌营养不良蛋白dys参与调控Hippo信号通路

Hippo信号通路最早在黑腹果蝇中发现,现已被证明在哺乳动物中也是保守的.Hippo通路在器官发 育和组织稳态中起着重要作用,Hippo信号通路异常与许多癌症的发生相关.Hippo信号通路依赖于核心激酶级 联反应,磷酸化转录共激活因子Yorkie(Yki)进而调控下游靶基因的转录.尽管Wts是Hippo通路的关键激酶组 分,但其蛋白质活性调节机制仍有待深入研究.通过质谱分析,发现并验证了Hippo信号通路核心激酶Wts与杜 氏肌营养不良症相关蛋白dys之间存在相互作用,并发现dys能够通过促进Wts的细胞膜定位激活Wts进而调控 果蝇器官大小.     

绿茶提取物EGCG治疗乳腺癌分子机制的生物信息学分析

在PubChem数据库中查找绿茶提取物茶多酚(EGCG)活性靶蛋白,从Gene数据库中查找乳腺癌相关基因,运用Ingenuity Pathway Analysis(IPA)软件,构建二者信号通路和分子网络并进行分析.结果显示:二者共同作用的通路有235条,排在前面的主要是癌症分子机制通路、炎症反应通路、糖皮质激素受体信号通路、NF-κB信号通路;共同的分子网络有5个,也主要体现在"转录后修饰与调控,细胞生长、发育,DNA的复制、重组、修复,细胞死亡与生存"等生物学功能上.     

胃癌芯片数据中异常转录因子推断与信号通路分析

用一种新的转录因子介导的信号通路分析方法分析肿瘤芯片数据,从中推断异常的转录因子和信号通路.先通过统计目标基因的表达推断转录因子的活性,然后将那些活性异常的转录因子映射到KEGG信号通路上.此方法整合了基因表达调控的实验数据和信号通路信息.利用此方法,对斯坦福芯片数据库中的162个人类胃癌数据进行分析,结果发现,大部分芯片中的TGF-beta,JAK-STAT,NF-kappaB和Notch信号通路被异常激活.进一步对这些通路进行研究,将有助于探究胃癌的发生、发展机理和进行合理的药物设计.     

ROCK1 与CD40相互作用的质谱分析及在CD40信号通路中功能的初探

为鉴定和验证ROCK1和CD40的相互作用,探索ROCK1在CD40通路中可能发挥的作用,应用HD质谱分析ROCK1和CD40的相互作用,用免疫共沉淀实验验证其相互作用, 用ROCK1抑制剂研究ROCK1对CD40通路的影响. 结果ROCK1与CD40存在相互作用;并参与CD40介导的信号通路.说明ROCK1能与CD40发生相互作用,为CD40信号通路的研究提供了新的线索.     

多泛素链延伸酶E4B对TLR信号通路的调节作用

研究多泛素链延伸酶E4B对TLR信号通路的影响.在HEK293T细胞中,通过双荧光报告系统检测E4B对TLR信号通路的影响,并且用免疫共沉淀的方法鉴定E4B的相互作用蛋白质.发现多泛素链延伸酶E4B能够抑制TLR通路的下游转录因子NF-κB和IRFs的转录活性,并且能与TRAF6发生相互作用.提示多泛素链延伸酶E4B可能参与TLR信号通路的调控,为TLR信号通路的研究提供新的线索.     

Markedness and its Interpretation in Language Use

Language markedness is a common phenomenon in languages, and is reflected from hearing, vision and sense, i.e. the variation in the three aspects such as phonology, morphology and semantics. This paper focuses on the interpretation of markedness in language use following the three perspectives, i.e. pragmatic interpretation, psychological interpretation and cognitive interpretation, with an aim to define the function of markedness.     

Characterization of Ordovician carbonate reservoirs, southeastern Saskatchewan, Canada

The discovery of the prolific Ordovician Red River reservoirs in 1995 in southeastern Saskatchewan was the catalyst for extensive exploration activity which resulted in the discovery of more than 15 new Red River pools. The best yields of Red River production to date have been from dolomite reservoirs. Understanding the processes of dolomitization is, therefore, crucial for the prediction of the connectivity, spatial distribution and heterogeneity of dolomite reservoirs.The Red River reservoirs in the Midale area consist of 3～4 thin dolomitized zones, with a total thickness of about 20 m, which occur at the top of the Yeoman Formation. Two types of replacement dolomite were recognized in the Red River reservoir: dolomitized burrow infills and dolomitized host matrix. The spatial distribution of dolomite suggests that burrowing organisms played an important role in facilitating the fluid flow in the backfilled sediments. This resulted in penecontemporaneous dolomitization of burrow infills by normal seawater. The dolomite in the host matrix is interpreted as having occurred at shallow burial by evaporitic seawater during precipitation of Lake Almar anhydrite that immediately overlies the Yeoman Formation. However, the low δ18O values of dolomited burrow infills (-5.9‰～ -7.8‰, PDB) and matrix dolomites (-6.6‰～ -8.1‰, avg. -7.4‰ PDB) compared to the estimated values for the late Ordovician marine dolomite could be attributed to modification and alteration of dolomite at higher temperatures during deeper burial, which could also be responsible for its 87Sr/86Sr ratios (0.7084～0.7088) that are higher than suggested for the late Ordovician seawaters (0.7078～0.7080). The trace amounts of saddle dolomite cement in the Red River carbonates are probably related to "cannibalization" of earlier replacement dolomite during the chemical compaction.     

低渗透非均质砂岩油藏启动压力梯度研究

理论推导与室内实验相结合,建立了低渗透非均质砂岩油藏启动压力梯度确定方法。首先借助油藏流场与电场相似的原理,推导了非均质砂岩油藏启动压力梯度计算公式。其次基于稳定流实验方法,建立了非均质砂岩油藏启动压力梯度测试方法。结果表明:低渗透非均质砂岩油藏的启动压力梯度确定遵循两个等效原则。平面非均质油藏的启动压力梯度等于各级渗透率段的启动压力梯度关于长度的加权平均;纵向非均质油藏的启动压力梯度等于各渗透率层的启动压力梯度关于渗透率与渗流面积乘积的加权平均。研究成果可用于有效指导低渗透非均质砂岩油藏的合理井距确定,促进该类油藏的高效开发。     

A computer generator for randomly layered structures

AcomputergeneratorforrandomlylayeredstructuresYUJia shun1,2,HEZhen hua2(1.TheInstituteofGeologicalandNuclearSciences,NewZealand;2.StateKeyLaboratoryofOilandGasReservoirGeologyandExploitation,ChengduUniversityofTechnology,China)Abstract:Analgorithmisintrod…     

On Tragic Consciousness In The Works By Ernest Hemingway

As an American modern novelist who were famous in the literary world, Hemingway was not a person who always followed the trend but a sharp observer. At the same time, he was a tragedy maestro, he paid great attention on existence, fate and end-result. The dramatis personae's tragedy of his works was an extreme limit by all means tragedy on the meaning of fearless challenge that failed. The beauty of tragedy was not produced on the destruction of life, but now this kind of value was in the impact activity. They performed for the reader about the tragedy on challenging for the limit and the death.     

An Index mechanism for multi-scale view in spatial databases

There are numerous geometric objects stored in the spatial databases. An importance function in a spatial database is that users can browse the geometric objects as a map efficiently. Thus the spatial database should display the geometric objects users concern about swiftly onto the display window. This process includes two operations:retrieve data from database and then draw them onto screen. Accordingly, to improve the efficiency, we should try to reduce time of both retrieving object and displaying them. The former can be achieved with the aid of spatial index such as R-tree, the latter require to simplify the objects. Simplification means that objects are shown with sufficient but not with unnecessary detail which depend on the scale of browse. So the major problem is how to retrieve data at different detail level efficiently. This paper introduces the implementation of a multi-scale index in the spatial database SISP (Spatial Information Shared Platform) which is generalized from R-tree. The difference between the generalization and the R-tree lies on two facets: One is that every node and geometric object in the generalization is assigned with a importance value which denote the importance of them, and every vertex in the objects are assigned with a importance value,too. The importance value can be use to decide which data should be retrieve from disk in a query. The other difference is that geometric objects in the generalization are divided into one or more sub-blocks, and vertexes are total ordered by their importance value. With the help of the generalized R-tree, one can easily retrieve data at different detail levels.Some experiments are performed on real-life data to evaluate the performance of solutions that separately use normal spatial index and multi-scale spatial index. The results show that the solution using multi-scale index in SISP is satisfying.     

海南岛地体及其毗邻陆缘晚中生代—新生代古地磁研究和构造演化

本文叙述了对海南岛及其毗邻大陆边缘白垩纪到第四纪地层岩石进行古地磁研究的全部工作过程。通过分析岩石中剩余磁矢量的磁偏角及磁倾角的变化,提出海南岛白垩纪以来经历的构造演化模式如下:早期伴随顺时针旋转而向南迁移,后期伴随逆时针转动并向北运移。联系该地区及邻区的地质、地球物理资料,对海南岛上述的构造地体运动提出以下认识:北部湾内早期有一拉张作用,主要是该作用使湾内地壳显著伸长减薄,形成北部湾盆地。从而导致了海南岛的早期构造运动,而海南岛后期的构造运动则主要是受南海海底扩张的影响。海南地体运动规律的阐明对于了解北部湾油气盆地的形成演化有重要的理论和实际意义。     

《Chinese Science Bulletin》SUBJECT INDEX TO VOLUME 59(2014)

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Achieving Unusual States of Matter Under High Pressure

The elongation method,originally proposed by Imamura was further developed for many years in our group.As a method towards O(N)with high efficiency and high accuracy for any dimensional systems.This treatment designed for one-dimensional(ID)polymers is now available for three-dimensional(3D)systems,but geometry optimization is now possible only for 1D-systems.As an approach toward post-Hartree-Fock,it was also extended to     

Exciton Seebeck in Molecular Systems

Various applications relevant to the exciton dynamics,such as the organic solar cell,the large-area organic light-emitting diodes and the thermoelectricity,are operating under temperature gradient.The potential abnormal behavior of the exicton dynamics driven by the temperature difference may affect the efficiency and performance of the corresponding devices.In the above situations,the exciton dynamics under temperature difference is mixed with