Tissue-specific and reversible RNA interference in transgenic mice

Genetically engineered mice provide powerful tools for understanding mammalian gene function. These models traditionally rely on gene overexpression from transgenes or targeted, irreversible gene mutation. By adapting the tetracycline (tet)-responsive system previously used for gene overexpression, we have developed a simple transgenic system to reversibly control endogenous gene expression using RNA interference (RNAi) in mice. Transgenic mice harboring a tet-responsive RNA polymerase II promoter driving a microRNA-based short hairpin RNA targeting the tumor suppressor Trp53 reversibly express short hairpin RNA when crossed with existing mouse strains expressing general or tissue-specific 'tet-on' or 'tet-off' transactivators. Reversible Trp53 knockdown can be achieved in several tissues, and restoring Trp53 expression in lymphomas whose development is promoted by Trp53 knockdown leads to tumor regression. By leaving the target gene unaltered, this approach permits tissue-specific, reversible regulation of endogenous gene expression in vivo, with potential broad application in basic biology and drug target validation.     

BRD7 regulates the insulin-signaling pathway by increasing phosphorylation of GSK3β

Reduced hepatic expression levels of bromodomain-containing protein 7 (BRD7) have been suggested to play a role in the development of glucose intolerance in obesity. However, the molecular mechanism by which BRD7 regulates glucose metabolism has remained unclear. Here, we show that BRD7 increases phosphorylation of glycogen synthase kinase 3β (GSK3β) in response to activation of the insulin receptor-signaling pathway shortly after insulin stimulation and the nutrient-sensing pathway after feeding. BRD7 mediates phosphorylation of GSK3β at the Serine 9 residue and this effect on GSK3β occurs even in the absence of AKT activity. Using both in vitro and in vivo models, we further demonstrate that BRD7 mediates phosphorylation of ribosomal protein S6 kinase (S6K) and leads to increased phosphorylation of the eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and, therefore, relieves its inhibition of the eukaryotic translation initiation factor 4E (eIF4E). However, the increase in phosphorylation of 4E-BP1 with BRD7 overexpression is blunted in the absence of AKT activity. In addition, using liver-specific BRD7 knockout (LBKO) mice, we show that BRD7 is required for mTORC1 activity on its downstream molecules. These findings show a novel basis for understanding the molecular dynamics of glucose metabolism and suggest the unique function of BRD7 in the regulation of glucose homeostasis.     

Genome-wide association studies of 14 agronomic traits in rice landraces

Uncovering the genetic basis of agronomic traits in crop landraces that have adapted to various agro-climatic conditions is important to world food security. Here we have identified ～ 3.6 million SNPs by sequencing 517 rice landraces and constructed a high-density haplotype map of the rice genome using a novel data-imputation method. We performed genome-wide association studies (GWAS) for 14 agronomic traits in the population of Oryza sativa indica subspecies. The loci identified through GWAS explained ～ 36% of the phenotypic variance, on average. The peak signals at six loci were tied closely to previously identified genes. This study provides a fundamental resource for rice genetics research and breeding, and demonstrates that an approach integrating second-generation genome sequencing and GWAS can be used as a powerful complementary strategy to classical biparental cross-mapping for dissecting complex traits in rice.     

视觉感知结合学习的自然图像轮廓检测

本文结合非经典感受野的视觉特性与机器学习的方法,提出了一种自然图像轮廓检测模型.当非经典感受野中的刺激与感受野中心刺激形成一种精确的空间结构时,将对中心产生一种增强效应;另一方面非经典感受野中抑制作用会降低同质成分的响应,我们将这两个机制分别用于增强光滑的轮廓和减少背景中与结构无关的干扰成分.利用逻辑回归概率模型将感受野中的信息与来自非经典感受野中的信息进行有效融合,并根据图像的手工标注数据库,通过学习方法获得一组最优的模型参数.自然图像的实验结果表明该轮廓检测方法能极大地抑制来自纹理的局部边缘,减少虚假轮廓,同时能增强具有一致空间结构的成分,避免轮廓缺失.最后利用Berkeley图像数据库定量地评价了我们方法的性能,并与相关方法进行了比较.该模型不仅为复杂场景中的轮廓检测提供了一个可行的策略,并有助于对生理视觉机制的理解.     

Tl-Ba-Ca-Cu-O系超导体相结构和掺Mn影响的电镜研究

Tl-Ba-Ca-Cu-O系超导体多相同时存在,多至6相,均属四方晶系钙钛矿结构,其中(2223)(2212)相共生,其衍射谱给出c≈33A的假象.加Mn可以部分取代Tl,但增加Mn的含量将失去高温超导性.     

上游无情报的水文预报技术初探

以珠江水系上游左江的龙州水文站为例，对水文站网或是通讯设施跟不上的上游无情报提供的流域，进行水文预报方法的探讨，寻求增长中下游洪水预报预见期。     

一种自适应PID控制系统

本文根据Ｗｉｄｒｏｗ－ＨｏｆｆＬＭＳ算法，对数字ＰＩＤ增量型控制算法进行分析，导出一种具有自学功能的自适应ＰＩＤ控制系统，使其能自动调整最佳控制参数．     

Effect of matrix metallo-proteinase-26 (MMP-26) during embryo implantation in the mouse

Matrix metalloproteinase-26 (MMP-26, endometase and matrilysin-2), a novel member of the MMPs family, is detected not only in the placenta and uterus, but is widely expressed in malignant tumors from different sources as well as in diverse tumor cell lines. However, the function of MMP-26 in the reproductive system has never been reported. Expression of MMP-26 in mouse embryos and the function of the MMP-26 antibody during mouse embryo implantation was examined for the first time by injecting the uterine horn, immunohistochemistry,in situ hybridization, co-culture of mouse blastocysts and uterine monolayer epithelial cells, Western blot, RT-PCR, Northern blot and zymography. Our results show that there is strong expression of MMP-26 mRNA and protein in the mouse embryo. Furthermore, the MMP-26 antibody dramatically inhibited mouse embryo implantation and significantly inhibited adhesion and outgrowth of mouse blastocysts onin vitro uterine monolayer epithelial cells. At the same time, the MMP-26 antibody inhibited the expression of integrin αV mRNA and protein in a dose-dependent manner. These data suggest that MMP-26 may play a role in some of the tissue-remodeling events associated with the invasion of the endometrium by trophoblast cells and facilitate successfully embryo implantation.     

基质金属蛋白酶-26(MMP-26)在小鼠胚胎植入过程中的作用

基质金属蛋白酶-26（MMP-26，又称Endometase或基质水解素-2）是MMPs家族的一个新成员，它可在胎盘，子宫以及不同肿瘤细胞系中表达，采用子宫角注射，免疫组化，原位杂交，胚泡与子宫上皮单层培养，免疫印迹，RT-PCR和RNA印迹等多种体内外实验方法研究并报道了MMP-26在小鼠胚胎中的表达以及MMP-26抗体在胚胎植入中的作用，研究表明，MMP-26的mRNA与蛋白在小鼠胚泡中均有强烈的表达，此外，体内研究显示，MMP-26抗体能显著抑制小鼠胚胎的着床；在体外培养体系中，MMP-26抗体可显著抑制小鼠胚泡在子宫上皮单层上的黏附与扩展；同时，MMP-26抗体以剂量依赖关系抑制整合素αV亚基mRNA和蛋白的表达，研究提示，MMP-26可能直接或间接参与滋养层细胞侵入子宫内膜的过程，促使小鼠胚泡成功植入。     

采绒革盖菌锰过氧化物酶的诱导及部分特性研究

研究了不同碳源、氮源对采绒革盖菌锰过氧化物酶分泌的影响及锰过氧化物酶的部分特性 ;结果表明 ,淀粉为碳源 ,玉米粉为氮源有利于锰过氧化物酶的分泌 ;在 30℃、110r/min恒温振荡培养条件下 ,第 9天达产酶高峰 ,峰值酶活 345 2u/ml;酶作用的最适pH为 4 0 ,最适温度 30℃ ,Mg2 、Mn2 等离子对锰过氧化物酶有激活作用 ,Ag 、Cl- 等离子对酶活有明显的抑制作用 .