Recognition and cleavage of 5-methylcytosine DNA by bacterial SRA-HNH proteins

SET and RING-finger-associated (SRA) domain is involved in establishment and maintenance of DNA methylation in eukaryotes. Proteins containing SRA domains exist in mammals, plants, even microorganisms. It has been established that mammalian SRA domain recognizes 5-methylcytosine (5mC) through a base-flipping mechanism. Here, we identified and characterized two SRA domain-containing proteins with the common domain architecture of N-terminal SRA domain and C-terminal HNH nuclease domain, Sco5333 from Streptomyces coelicolor and Tbis1 from Thermobispora bispora. Both sco5333 and tbis1 cannot establish in methylated Escherichia coli hosts (dcm⁺), and this in vivo toxicity requires both SRA and HNH domain. Purified Sco5333 and Tbis1 displayed weak DNA cleavage activity in the presence of Mg²⁺, Mn²⁺ and Co²⁺ and the cleavage activity was suppressed by Zn²⁺. Both Sco5333 and Tbis1 bind to 5mC-containing DNA in all sequence contexts and have at least a preference of 100 folds in binding affinity for methylated DNA over non-methylated one. We suggest that linkage of methyl-specific SRA domain and weakly active HNH domain may represent a universal mechanism in competing alien methylated DNA but to maximum extent minimizing damage to its own chromosome.     

中国红菇属种类及其分布

通过系统的文献收集,汇总了中国红菇属(Russula Pers.)真菌的179个名称记录,并对其生境、用途及分布或分类进行了简述。文献调查表明,红菇属种类广泛分布于中国30个省区。在已报道的红菇属名称记录中,有效名称有159个,包括148种、9变种和2变型,其中新名称1个、新拟汉名8个,无效或不合格名称10个,错拼名称8个,存疑种3个,中国特有种13种,一些种类具有显著的经济价值。     

Synthesis and HMG-CoA reductase inhibition of 2-cyclopropyl-4-thiophenyl-quinoline mevalonolactones

A novel series of 2-cyclopropyl-4-thiophenyl quinoline-based mevalonolactones were synthesized from the substituted anilines by several reactions. Among them, (4R,6S)-6-[(E)-2-(2-cyclopropyl-6-fluoro-4-(4-fluoro-thiophenyl)-quinoline-3-yl)-ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one (1d), (4R,6S)-6-[(E)-2-(2-cyclopropyl-6-fluoro-4-(3-methoxy-thiophenyl)-quinoline-3-yl)-ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one (1f) and (4R,6S)-6-[(E)-2-(2-cyclopropyl-6-fluoro-4,7-di(3-methoxy-thiophenyl)-quinoline-3-yl)-ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one (1q) showed potent HMG-CoA reductase inhibitory activity comparable with pitavastatin.     

Runx2参与调控Osterix 启动子活性及其基因表达

尽管Runx2和Osterix都是成骨细胞分化途径中关键的转录因子,但是Runx2是否能够调控Osterix,还不为所知.研究发现,在非成骨细胞系,无论是间充质干细胞还是已分化的细胞,以及成骨细胞系中,Runx2都能诱导Osterix的表达.同时Runx2能够上调3.2kb人的Osterix基因启动子活性.进一步实验证明,在这一段启动子中存在Runx2功能性的结合位点.因而,实验结果有力地支持了这样一个假设,即Runx2参与了Osterix基因的表达调控.瞬时转染和荧光素酶双报告分析结果显示,在非成骨细胞中,Osterix明显上调2.3kb的Ⅰ型胶原蛋白启动子活性,但Runx2却不能.这样的差别暗示,在成骨细胞分化过程中位于Runx2下游的转录因子Osterix是刺激Ⅰ型胶原蛋白基因表达所必需的.     

Targeted Inhibition of LPL/FABP4/CPT1 fatty acid metabolic axis can effectively prevent the progression of nonalcoholic steatohepatitis to liver cancer

Rationale: Nonalcoholic steatohepatitis (NASH), as one of the key stages in the development of nonalcoholic fatty liver disease (NAFLD), can directly progress to HCC, but the underlying mechanism is not fully understood.Methods: Differentially expressed genes (DEGs) in each stage of disease development were studied through a GEO dataset deriving from a Stelic Animal Model (STAM), which can simulate the evolution of NAFLD/NASH to HCC in humans. GSVA analysis was performed to analyze the differentially expressed oncogenic signatures in each stage. A human NAFLD-related dataset from GEO database was utilized for gene expression verification and further validated in the protein level in STAM mice. Small molecule inhibitors were applied to STAM mice for investigating whether inhibition of the LPL/FABP4/CPT1 axis could prevent the occurrence of NASH-related HCC in vivo. Microsphere formation and clonal formation assays in vitro were applied to study if inhibition of the LPL/FABP4/CPT1 axis can reduce the viability of liver cancer stem cells (LCSCs).Results: We found that upregulation of the LPL/FABP4/CPT1 molecular axis, as a fatty acid metabolic reprogramming process, occurred specifically during the NASH phase. GSVA analysis showed widespread activation of a large number of oncogenic signals, which may contribute to malignant transformation during NASH. Furthermore, inhibition of the LPL/FABP4/CPT1 axis could effectively delay the tumor growth in STAM mice. Cell assays revealed inhibitors targeting this axis can significantly reduce the sphere-forming, proliferation, and clonality of LCSCs.Conclusion: These results suggest that activation of the LPL/FABP4/CPT1 axis is essential for LCSCs maintenance, which acts synergistically with a variety of up-regulated oncogenic signals that drive the hepatocyte-LCSCs transdifferentiation during NASH to HCC progression. Thus, targeting the LPL/FABP4/CPT1 axis may provide a potential direction for NASH-related HCC prevention.     

Association of α-Dystrobrevin with Reorganizing Tight Junctions

Alpha-dystrobrevin (-DB) has been described primarily as a cytoplasmic component of the dystrophin-glycoprotein complex in skeletal muscle cells. Isoforms of -DB show different localization in cells and tissues; at basolateral membranes in epithelial cells, dystrobrevins mediate contact with the extracellular matrix, peripheral and transmembrane proteins and the filamentous actin cytoskeleton. Beside their structural role, -DBs are assumed to be important in cell signalling and cell differentiation. We have primarily assessed the role of -DB in two epithelial cell lines (MDCK I, HT 29), which represent different developmental stages and exhibit distinct permeability characteristics. Using a polyclonal anti--DB antibody, we have investigated its expression, localization and association with tight junction (TJ)- associated proteins (ZO-1, occludin) before and after protein kinase C (PKC) activation with phorbol myristate acetate. Distinct subsets of -DB isoforms were detected in the two cell lines by immunoblotting. In both cell lines there was submembranous localization of -DB both apically and basolaterally, shown with confocal imaging. PKC activation caused a reorganization of TJ, which was parallel to increased localization of -DB to TJ areas, most pronounced in MDCK I cells. Moreover, actin and ZO-1 co-immunoprecipitated with a-DB, as displayed with immunoblotting. Our findings suggest that a-dystrobrevin specifically is associated with the tight junctions during their reorganization.     

Spatial Imprint of Food Consumption: A Historical Analysis for Sweden, 1870–2000

Depending on quantity and composition of food as well as on production conditions and techniques, the space needed to sustain an individual’s nourishment varies. The amount of space needed also depends on the use of resources such as energy, water, and fertilizers, as well as potential land degradation and water pollution. Our study focuses on the changing spatial imprint of an average inhabitant of an expanding Swedish city, Linköping, from 1870 to 2000 taking into account both shifts in consumption as well as agricultural productivity and practices. Despite the distinctly larger amount of animal food products, such as meat and fish, consumed in 2000, we calculate the area needed to sustain an individual’s annual food consumption could be less than one fourth of that needed in 1870. However, if the import of various globally produced foods is included in our calculations, the land needed to sustain the consumption of an inhabitant of Linköping in 2000 doubles. We also argue that an examination of this regional imprint can be used to explore and evaluate possibilities for regional development.     

Bioprocess control from a multivariate process trajectory

A multivariate bioprocess control approach, capable of tracking a pre-set process trajectory correlated to the biomass or product concentration in the bioprocess is described. The trajectory was either a latent variable derived from multivariate statistical process monitoring (MSPC) based on partial least squares (PLS) modeling, or the absolute value of the process variable. In the control algorithm the substrate feed pump rate was calculated from on-line analyzer data. The only parameters needed were the substrate feed concentration and the substrate yield of the growth-limiting substrate. On-line near-infrared spectroscopy data were used to demonstrate the performance of the control algorithm on an Escherichia coli fed-batch cultivation for tryptophan production. The controller showed good ability to track a defined biomass trajectory during varying process dynamics. The robustness of the control was high, despite significant external disturbances on the cultivation and control parameters.     

川西亚高山不同暗针叶林群落类型的冠层降水截留特征

在林分和小流域尺度上,应用模型研究了四川卧龙亚高山暗针叶林冠层的降水截留特征.结果表明:生长季节(5—10月),箭竹-岷江冷杉原始林冠层截留系数在33%～72%之间,平均48%;冠层截留量与降水量之间呈显著的线性关系,截留系数与降水量之间呈负指数函数关系;试验小流域内,植被冠层最大截留量的平均值为1.74mm,不同林分间的差异显著,其顺序为藓类-箭竹-岷江冷杉林>草类-箭竹-岷江冷杉林>藓类-杜鹃-岷江冷杉林>草类-杜鹃-岷江冷杉林>杜鹃灌丛;冠层最大截留量与叶面积指数(LAI)之间呈极显著的线性关系;冠层截留量、冠层最大截留量、附加截留量分别占同期降水量的39%、25%和14%.所选模型对整个生长季平均截留量的模拟效果较好,相对误差为9%～14%.     

广东沿海与粤北山区中小型水库浮游生物群落比较分析

于丰水期和枯水期对广东山区水库(赤石迳水库)、沿海水库(大水桥、赤沙水库)三个水库的湖泊区和河流区进行研究,分析水质和浮游生物群落结构。三个水库之间的浮游生物群落均有所区别,地理位置和地形不同而引起的温度差异以及外源性营养盐输入是造成浮游生物种类和数量差异的主要原因。沿海水库不分层,而山区水库丰水期温跃层明显。各水库的氮磷比均较高,chl.a水平主要受磷限制,沿海水库则多喜暖性的种类,如裸藻、隐藻、沙居剑水蚤等,山区水库发现较多喜冷性浮游生物,如金藻、透明溞等,丰水期的甲藻丰度也相对高于枯水期。