Extracellular Vesicles: Messengers of p53 in Tumor–Stroma Communication and Cancer Metastasis

Tumor progression to a metastatic and ultimately lethal stage relies on a tumor-supporting microenvironment that is generated by reciprocal communication between tumor and stromal host cells. The tumor–stroma crosstalk is instructed by the genetic alterations of the tumor cells—the most frequent being mutations in the gene Tumor protein p53 (TP53) that are clinically correlated with metastasis, drug resistance and poor patient survival. The crucial mediators of tumor–stroma communication are tumor-derived extracellular vesicles (EVs), in particular exosomes, which operate both locally within the primary tumor and in distant organs, at pre-metastatic niches as the future sites of metastasis. Here, we review how wild-type and mutant p53 proteins control the secretion, size, and especially the RNA and protein cargo of tumor-derived EVs. We highlight how EVs extend the cell-autonomous tumor suppressive activity of wild-type p53 into the tumor microenvironment (TME), and how mutant p53 proteins switch EVs into oncogenic messengers that reprogram tumor–host communication within the entire organism so as to promote metastatic tumor cell dissemination.     

Behavioral Phenotype of the Reeler Mutant Mouse: Effects of Reln Gene Dosage and Social Isolation.

Reeler (rl/rl) and reeler/wild-type (+/rl) mice synthesize Reln at subnormal rates, as do patients with schizophrenia, bipolar disorder, and autism, thereby forming the basis for a Reln hypothesis for vulnerability to these psychopathologies and justifying attention to the behavioral phenotypes of Reln-deficient mice. Tests of gait, emotionality, social aggression, spatial working memory, novel-object detection, fear conditioning, and sensorimotor reflex modulation revealed the behavioral phenotype of rl/rl, but not +/rl, mice to be different from that of wild-type (+/+) mice. These results reveal no effect of Reln gene dosage and provide significant challenges to both the Reln and the neurodevelopmental hypotheses of the etiology of major psychopathologies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

一种基于UML状态图的规约变异测试方法

规约变异测试从软件功能的角度,对规约进行分析,从而揭示规约中存在的问题。本文提出一种基于UML状态图的变异测试方法,针对每种变异算子,分析其是否会引入冲突,进而有效避免不合理的变异操作;分析了每种变异算子产生等价变异体的条件,能够在生成变异体的同时检测并移除等价变异体,进而减少其对测试过程的影响;给出了杀掉每种变异体所需满足的条件,可在此基础上产生杀掉特定变异体所需的测试用例,从而提高测试用例集的质量。在此基础上,根据变异算子的实际功能,整合了功能相同的算子,减少了变异算子的数量,从而进一步降低了变异测试的开销。实验结果表明,本方法能够较好地提高测试用例的质量,进而提升测试的效率。     

重组G145R HBsAg亲和纯化方法的建立及其应用

目的建立重组乙型肝炎病毒G145R变异HBsAg抗体亲和纯化方法。方法用抗-HBs单克隆抗体(D12- McAb)制备亲和层析胶,对2A8细胞(分泌G145R变异HBsAg)培养上清盐析物进行亲和纯化。采用SDS-PAGE、Western blot及ELISA,对纯化产物的纯度、特异性、含量和回收率进行鉴定,并与同法纯化的HBsAg阳性血清及r-wHBsAg提取物进行比较。结果D12-McAb对重组真核表达G145R变异HBsAg、HBsAg阳性血清及r-wHBsAS三者具有相似的亲和性,产物纯度分别为90.3%、95.2%和93.1%,回收率分别为43.3%、72.0%和66.4%。结论已成功地建立了重组G145R变异HBsAg抗体亲和纯化方法,为G145R变异以及其他HBV免疫逃逸变异感染的深入研究奠定了重要的技术基础。     

基于统计占优分析的变异测试

为数众多的变异体产生的高昂测试代价严重影响了变异测试技术在实际程序中的应用.为了大幅度减少弱变异测试中变异体的数量,提出基于统计占优分析的变异体约简方法.该方法首先利用变异前后的语句构造变异分支,并将所有变异分支集成到原程序中,形成新的被测程序;然后,通过统计测试用例对各个变异分支的覆盖信息,确定变异分支之间的占优关系;最后得到非被占优分支集,其对应的变异体就是约简后的变异体.将该方法用于8个程序的测试,结果表明:该方法能够约简平均90%的变异体,从而显著提高了变异测试的效率.     

肺癌组织中SOX4突变蛋白三级结构的建模及分析

SOX家族与很多人类肿瘤的发生有关.对人类肺癌组织中的SOX4进行测序,发现该基因HMG-box区有突变发生并导致SOX4蛋白的107密码子发生突变.以三级结构已知的SOX2为模板,采用同源建模方法对突变和正常SOX4蛋白FMG-box进行建模.结果显示突变和正常SOX4蛋白的三级结构很相似,且突变导致107密码子位置的侧链结构不稳定.提示该位置的不稳定可能会影响突变SOX4蛋白侧链的弹性,并有可能影响相应蛋白的功能.表面静电分析显示SOX4蛋白C端有一个可能与其它小分子或蛋白质的相互作用位点的N/C腔.这些结果显示SOX4蛋白的上述空间结构可能与其活性与功能的调控有关,而SOX4突变可能与肺癌的发生和转移有关.     

Rice PIN Auxin Efflux Carriers Modulate the Nitrogen Response in a Changing Nitrogen Growth Environment

Auxins play an essential role in regulating plant growth and adaptation to abiotic stresses, such as nutrient stress. Our current understanding of auxins is based almost entirely on the results of research on the eudicot Arabidopsis thaliana, however, the role of the rice PIN-FORMED (PIN) auxin efflux carriers in the regulation of the ammonium-dependent response remains elusive. Here, we analyzed the expression patterns in various organs/tissues and the ammonium-dependent response of rice PIN-family genes (OsPIN genes) via qRT–PCR, and attempted to elucidate the relationship between nitrogen (N) utilization and auxin transporters. To investigate auxin distribution under ammonium-dependent response after N deficiency in rice roots, we used DR5::VENUS reporter lines that retained a highly active synthetic auxin response. Subsequently, we confirmed that ammonium supplementation reduced the DR5::VENUS signal compared with that observed in the N-deficient condition. These results are consistent with the decreased expression patterns of almost all OsPIN genes in the presence of the ammonium-dependent response to N deficiency. Furthermore, the ospin1b mutant showed an insensitive phenotype in the ammonium-dependent response to N deficiency and disturbances in the regulation of several N-assimilation genes. These molecular and physiological findings suggest that auxin is involved in the ammonium assimilation process of rice, which is a model crop plant.     

深黄被孢霉H3,3410-5γ-亚麻酸发酵的实验研究

γ-亚麻酸是人体必需脂肪酸。深黄被孢霉被认为是潜力较大的γ-亚麻酸的发酵生产菌。对深黄被孢霉突变株H3,3410-5产γ-亚麻酸发酵培养基和发酵实验优化,结果表明,菌丝体平均得率为25.9 g/L,总油脂平均含量为44.0%,油脂中γ-亚麻酸比率为10.97%。三项指标分别比优化前提高了约6.6%、5.8%和16.3%。     

The Conserved and Specific Roles of the LUX ARRHYTHMO in Circadian Clock and Nodulation

LUX ARRHYTHMO (LUX) plays a key role in circadian rhythms and flowering. Here, we identified the MtLUX gene which is the putative ortholog of LUX in Medicago truncatula. The roles of MtLUX, in both the nodulation belowground and leaf movement aboveground, were investigated by characterizing a loss-of-function mtlux mutant. MtLUX was required for the control of flowering time under both long-day and short-day conditions. Further investigations showed that the early flowering in the mtlux mutant was correlated with the elevated expression level of the MtFTa1 gene but in a CO-like independent manner. MtLUX played a conserved role in the regulatory interactions with MtLHY, MtTOC1, and MtPRR genes, which is similar to those in other species. Meanwhile, the unexpected functions of MtLUX were revealed in nodule formation and nyctinastic leaf movement, probably through the indirect regulation in MtLHY. Its participation in nodulation is of interest in the context of functional conservation and the neo-functionalization of the products of LUX orthologs.     

D-核糖高产菌株的选育及其生产性试验

BacillussubtilisJSIM 10 18菌株是 1株产D 核糖的莽草酸营养缺陷型突变株 ,以此菌株为出发菌株 ,通过甲基磺酸乙酯和紫外线连续、间断诱变处理 ,获得了 1株次黄嘌呤、莽草酸双重缺陷型突变株No .2 71菌株。该突变株摇瓶发酵的D 核糖平均产量为 10 8 1g/L ,比亲株提高了 15 8g/L。在 30 0 0 0L发酵罐中 ,连续 5罐批 ,平均产D 核糖 96 4 g/L ,最高为 98g/L ,比亲株提高了 16 2 5 g/L。