13 research outputs found

    Solvent-induced Intramolecular Charge Transfer in D-σ-A Dyads and Triads with Narrow HOMO-LUMO Gaps: A Theoretical Investigation

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    由强电子给体与强电子受体基团通过饱和s桥键连而成的D-s-A型二对物及A-s-D-s-A型三对物分子化合物,极易受环境因素的诱导发生分子内的电荷/电子转移(ICT),而表现出双稳态。该特性为分子水平上设计和制作多功能的有机分子材料提供了极大可能性,已成为新型分子器件的研究热点。针对这类可能具有双稳态特性的桥连二对物与三对物分子,本文基于现有的理论溶剂模型,采用量子化学计算,系统地研究了一系列基于TTF(TTF=trathiafulvalene)为电子给体的D-s-A型二对物及A-s-D-s-A型三对物分子的电子结构性质,以及溶剂对这类化合物电子态及相关性质的影响。具体结果总结如下:一、对于强电...The molecular D-s-A dyads and A-s-D-s-A triads, containing a strong electron-donor (D) and an electron-acceptor (A) linked by a saturated covalent , have narrow HOMO-LUMO gaps and readily undergo intramolecular charge/ transfer (ICT) upon various external stimulations and exhibit bistability as well as fascinating phenomena, e.g., solvatochromism. Accordingly, they are promising building blocks o...学位:理学博士院系专业:化学化工学院化学系_物理化学学号:1912005140307

    Hippo Signaling Suppresses Cell Ploidy and Tumorigenesis through Skp2

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    大多数真核生物的体细胞是二倍体,即仅含有两组染色体,分别遗传自父本和母本。而一些特定组织如心脏、肝脏等就含有多倍体细胞,特别是肝脏组织含有较高比例的四、八倍体等多倍体细胞。肝脏是人体的重要解毒器官,同时酒精、肝炎病毒等毒性物质或毒性代谢物容易诱发肝细胞的基因突变,多倍体被认为有利于提供代偿性的正常基因来维持肝脏稳态。然而肝脏受损后,多倍体细胞将会受胁迫进行增殖,再生修复受损的肝组织。因此研究机体调控多倍体细胞产生及多倍体细胞进行细胞分裂的调控机理对于理解肝癌的发病机理和肝癌的治疗至关重要。Hippo信号通路在调节组织成体干细胞的分化和增殖,调控器官再生与尺寸大小中具有重要作用。深入研究发现, Hippo信号通路下游效应分子YAP通过AKT-SKP2信号促进二倍体细胞向多倍体转化及多倍体细胞的生长增殖。本项研究阐明了Hippo缺失及YAP激活促进多倍体细胞产生及增殖作为肝癌发生发展中的一个重要机制,为肝癌诊疗提供了新的策略。 周大旺,博士,厦门大学生命科学学院教授、副院长、国家杰出青年基金获得者。【Abstract】Polyploidy can lead to aneuploidy and tumorigenesis. Here, we report that the Hippo pathway effector Yap promotes the diploid-polyploid conversion and polyploid cell growth through the Akt-Skp2 axis. Yap strongly induces the acetyltransferase p300-mediated acetylation of the E3 ligase Skp2 via Akt signaling. Acetylated Skp2 is exclusively localized to the cytosol, which causes hyper-accumulation of the cyclin-dependent kinase inhibitor p27, leading to mitotic arrest and subsequently cell polyploidy. In addition, the pro-apoptotic factors FoxO1/3 are overly degraded by acetylated Skp2, resulting in polyploid cell division, genomic instability, and oncogenesis. importantly, the depletion or inactivation of Akt or Skp2 abrogated Hippo signal deficiency-induced liver tumorigenesis, indicating their epistatic interaction. Thus, we conclude that Hippo-Yap signaling suppresses cell polyploidy and oncogenesis through Skp2.该研究工作获得了国家自然科学基金委、国家重点基础研究发展计划(973)项目、青年千人计划和中央高校基本科研基金的资助。 The Yap (S127A) transgenic mice were kindly provided by Dr. Fernando Camargo from Harvard Medical School, Boston, MA. D.Z. and L.C. were supported by the National Natural Science Foundation of China (31625010,U1505224, and J1310027 to D.Z.; 81422018, U1405225, and 81372617 to L.C.; 81472229 to L.H.), the National Basic Research Program (973) of China (2015CB910502 to L.C.), the Fundamental Research Funds for the Central Universities of China-Xiamen University (20720140551 to L.C. and 2013121034 and 20720140537 to D.Z.)

    废轮胎热解特性研究

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    利用TG/DTG对不同来源的三种废轮胎样品的热解特性进行了研究,并得到了热解动力学参数.结果表明,新旧废外轮胎样品热解趋势基本一致,均经历了一个不明显的失重过程和两个明显的失重过程,其原因是由于废外轮胎中的橡胶组分比较复杂;内轮胎样品中的组分比较单一,其热解过程比较简单,仅经历了一个不明显的失重过程和一个明显的失重过程;三种样品的主要失重温度为600 K~800 K,转化率为0.2~0.8;使用一级动力学反应模型很好的拟和了三种样品的主要失重过程,并求出了热解动力学参数

    基于领域数据库的科技期刊知识服务模式的探索与实践

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    【目的】探讨科技期刊与相关领域数据库相结合的模式,为读者提供多资源、多层次的知识服务内容,为科技期刊探索知识服务的范围及方法提供参考和借鉴。【方法】以整合生物学期刊网的3种中文学术期刊——《植物生态学报》《植物学报》《生物多样性》为研究对象,分析科技期刊基于学科领域专业数据库提供知识服务的可能性及意义,提出设计思路及整体架构,探索科技期刊与不同类型数据库的合作方式。【结果】经过实践,所提出的知识服务模式已在3种中文期刊中全面应用,促进了知识传播,提升了期刊影响力。【结论】基于领域数据库的科技期刊知识服务模式实现了多资源、多层次的"网络化""立体化"出版,可为读者提供广泛而精准的专业知识服务。此模式可供其他学科领域科技期刊、期刊群、期刊全文数据库参考应用

    甲壳素类液晶高分子的研究Ⅷ. N-邻苯二甲酰化壳聚糖/DMSO液晶溶液的热致相转变

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    合成了氮上完全取代的邻苯二甲酰化壳聚糖 (PhthCS) .用DSC研究了PhthCS DMSO液晶溶液的热致相转变 .偏光显微镜和DSC测定都表明临界浓度为 43wt% .在浓度高于 43wt%的溶液的DSC曲线中观察到了除了液晶 各向同性液体转变 (清亮点 )外还有一个明显的凝胶 溶胶转变 .凝胶 溶胶转变温度和转变焓均比文献报道的不规则取代的N 邻苯二甲酰化 O 乙酰化壳聚糖大得多 ,可见取代的规整性对凝胶 溶较转变有很大的影响 .根据DSC研究结果绘制了PhthCS DMSO体系的相

    AFF1 is a ubiquitous P-TEFb partner to enable Tat extraction of P-TEFb from 7SK snRNP and formation of SECs for HIV transactivation

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    Public Health Service from the National Institutes of Health (NIH) [R01AI095057, R01AI041757]; NIH [P50 GM082250, P01 AI090935, P50 GM081879]; National Natural Science Foundation of China [81201276]; Natural Science Foundation of Fujian [2012J05067]The positive transcription elongation factor b (P-TEFb) stimulates RNA polymerase elongation by inducing the transition of promoter proximally paused polymerase II into a productively elongating state. P-TEFb itself is regulated by reversible association with various transcription factors/cofactors to form several multi-subunit complexes [e. g., the 7SK small nuclear ribonucleoprotein particle (7SK snRNP), the super elongation complexes (SECs), and the bromodomain protein 4 (Brd4)-P-TEFb complex] that constitute a P-TEFb network controlling cellular and HIV transcription. These complexes have been thought to share no components other than the core P-TEFb subunits cyclin-dependent kinase 9 (CDK9) and cyclin T (CycT, T1, T2a, and T2b). Here we show that the AF4/FMR2 family member 1 (AFF1) is bound to CDK9-CycT and is present in all major P-TEFb complexes and that the tripartite CDK9-CycT-AFF1 complex is transferred as a single unit within the P-TEFb network. By increasing the affinity of the HIV-encoded transactivating (Tat) protein for CycT1, AFF1 facilitates Tat's extraction of P-TEFb from 7SK snRNP and the formation of Tat-SECs for HIV transcription. Our data identify AFF1 as a ubiquitous P-TEFb partner and demonstrate that full Tat transactivation requires the complete SEC

    Mutual information analysis reveals coevolving residues in Tat that compensate for two distinct functions in HIV-1 gene expression

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    Viral genomes are continually subjected to mutations, and functionally deleterious ones can be rescued by reversion or additional mutations that restore fitness. The error prone nature of HIV-1 replication has resulted in highly diverse viral sequences, and it is not clear how viral proteins such as Tat, which plays a critical role in viral gene expression and replication, retain their complex functions. Although several important amino acid positions in Tat are conserved, we hypothesized that it may also harbor functionally important residues that may not be individually conserved yet appear as correlated pairs, whose analysis could yield new mechanistic insights into Tat function and evolution. To identify such sites, we combined mutual information analysis and experimentation to identify coevolving positions and found that residues 35 and 39 are strongly correlated. Mutation of either residue of this pair into amino acids that appear in numerous viral isolates yields a defective virus; however, simultaneous introduction of both mutations into the heterologous Tat sequence restores gene expression close to wild-type Tat. Furthermore, in contrast to most coevolving protein residues that contribute to the same function, structural modeling and biochemical studies showed that these two residues contribute to two mechanistically distinct steps in gene expression: binding P-TEFb and promoting P-TEFb phosphorylation of the C-terminal domain in RNAPII. Moreover, Tat variants that mimic HIV-1 subtypes B or C at sites 35 and 39 have evolved orthogonal strengths of P-TEFb binding versus RNAPII phosphorylation, suggesting that subtypes have evolved alternate transcriptional strategies to achieve similar gene expression levels
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