Amelioration of sepsis by inhibiting sialidase-mediated disruption of the CD24-SiglecG interaction

Suppression of inflammation is critical for effective therapy of many infectious diseases. However, the high rates of mortality caused by sepsis attest to the need to better understand the basis of the inflammatory sequelae of sepsis and to develop new options for its treatment. In mice, inflammatory responses to host danger-associated molecular patterns (DAMPs), but not to microbial pathogen-associated molecular patterns (PAMPs), are repressed by the interaction [corrected] of CD24 and SiglecG (SIGLEC10 in human). Here we use an intestinal perforation model of sepsis to show that microbial sialidases target the sialic acid-based recognition of CD24 by SiglecG/10 to exacerbate inflammation. Sialidase inhibitors protect mice against sepsis by a mechanism involving both CD24 and Siglecg, whereas mutation of either gene exacerbates sepsis. Analysis of sialidase-deficient bacterial mutants confirms the key contribution of disrupting sialic acid-based pattern recognition to microbial virulence and supports the clinical potential of sialidase inhibition for dampening inflammation caused by infection.     

MicroRNA-30a functions as tumor suppressor and inhibits the proliferation and invasion of prostate cancer cells by down-regulation of SIX1

Increasing reports have demonstrated that aberrant expression of microRNAs (miRNAs) is found in multiple human cancers. Many studies have shown that down-regulated level of miR-30a is in a variety of cancers including prostate cancer (PCa). However, the precise mechanisms of miR-30a in PCa have not been well explored. In this study, we investigated the biological functions and molecular mechanism of miR-30a in PCa cell lines, discussing whether it could be a therapeutic biomarker of PCa in the future. We found that miR-30a is down-regulated in PCa tissues and cell lines. Moreover, the low level of miR-30a was associated with increased expression of SIX1 in PCa tissues and cell lines. Up-regulation of miR-30a significantly inhibited proliferation of PCa cells. In addition, invasion of PCa cells was suppressed by overexpression of miR-30a. However, down-regulation of miR-30a promoted cell growth and invasion of PCa cells. Bioinformatics analysis predicted that the SIX1 was a potential target gene of miR-30a. Next, luciferase reporter assay confirmed that miR-30a could directly target SIX1. Consistent with the effect of miR-30a, down-regulation of SIX1 by siRNA inhibited proliferation and invasion of PCa cells. Overexpression of SIX1 in PCa cells partially reversed the effect of miR-30a mimic. In conclusion, introduction of miR-30a dramatically inhibited proliferation and invasion of PCa cells by down-regulating SIX1 expression, and that down-regulation of SIX1 was essential for inhibition of cell growth and invasion of PCa cells by overexpression of miR-30a.     

Nucleoplasmin facilitates reprogramming and in vivo development of bovine nuclear transfer embryos

Successful cloning by somatic cell nuclear transfer (NT) involves an oocyte-driven transition in gene expression from an inherited somatic pattern, to an embryonic form, during early development. This reprogramming of gene expression is thought to require the remodeling of somatic chromatin and as such, faulty and/or incomplete chromatin remodeling may contribute to the aberrant gene expression and abnormal development observed in NT embryos. We used a novel approach to supplement the oocyte with chromatin remodeling factors and determined the impact of these molecules on gene expression and development of bovine NT embryos. Nucleoplasmin (NPL) or polyglutamic acid (PGA) was injected into bovine oocytes at different concentrations, either before (pre-NT) or after (post-NT) NT. Pre-implantation embryos were then transferred to bovine recipients to assess in vivo development. Microinjection of remodeling factors resulted in apparent differences in the rate of blastocyst development and in pregnancy initiation rates in both NPL- and PGA-injected embryos, and these differences were dependent on factor concentration and/or the time of injection. Post-NT NPL-injected embryos that produced the highest rate of pregnancy also demonstrated differentially expressed genes relative to pre-NT NPL embryos and control NT embryos, both of which had lower pregnancy rates. Over 200 genes were upregulated following post-NT NPL injection. Several of these genes were previously shown to be downregulated in NT embryos when compared to bovine IVF embryos. These data suggest that addition of chromatin remodeling factors to the oocyte may improve development of NT embryos by facilitating reprogramming of the somatic nucleus.     

央地两级政府生态治理行动的演化博弈分析——基于财政分权视角

生态环境是人类社会经济发展过程中的重要组成部分,然而由于粗放的经济发展模式,生态系统退化严重,影响人类幸福感和可持续发展。中央政府和地方政府是生态环境的主要治理主体,因此研究两类群体在生态治理过程中的行为互动机制具有较强的现实意义。基于财政分权的背景,从微观主体的收益函数出发,构建央地两级政府生态治理行动的演化博弈模型,探究两类主体的行为特征及其影响因素。根据复制动态方程分析参与主体的演化规律,采用MATLAB仿真工具分析不同情形下演化均衡状态及收敛趋势。研究结果表明,中央政府与地方政府在一定程度上都是"理性经济人",系统稳定均衡策略取决于地方政府"严格执行"生态治理的净收益和中央政府"严格监管"的净收益,其中关键指标包括:地方政府生态治理执行力度和成本、政绩考核体系中生态指标和经济指标的权重系数、中央政府的监管成本、监管力度和惩罚金额。据此提出"财政分权同时创新地方政绩考核机制、发展比较优势、拓宽监管渠道"等对策建议,引导央地两级政府共同促进生态治理工作有效实施。     

环境筛选和扩散限制对长江流域湖北段湿地植物群落构建的共同影响

湿地植物群落构建机制的研究可为湿地生态系统管理和受损湿地生态恢复与重建提供重要理论依据。地处长江流域的湖北省是我国湿地资源最为丰富的地区之一,通过野外调查研究了长江流域湖北段内不同类型湿地中的主要湿地植物群落类型,分析了研究区内湿地植物群落物种β多样性格局;利用相关性检验(Mantel test)方法和基于相似或相异度矩阵的多元回归模型(MRM)分析了环境差异和地理距离与湿地植物群落的物种相异性的相关性,及其对该区域湿地植物群落构建的相对贡献率。结果表明长江流域湖北段8个不同类型湿地内的湿地植物群落物种相异性指数差异显著,群落间物种相异性指数与地理距离和环境距离均呈显著正相关关系;MRM分析表明环境筛选和扩散限制共同解释了研究区内群落物种变异指数的54.72%;其中,环境距离独立解释率为22.03%,地理距离独立解释率为9.98%,二者联合解释率为22.71%。结果表明环境筛选和扩散限制共同影响了长江流域湖北段湿地植物群落构建过程,且环境筛选贡献更大。建议除了考虑空间尺度、环境因子、植被类型外,未来需进一步研究时间尺度及人类干扰等因子对该区域湿地植物群落构建的影响。     

A novel EB-1/AIDA-1 isoform,AIDA-1c,interacts with the Cajal body protein coilin

Background  

Cajal bodies (CBs) are nuclear suborganelles that play a role in the biogenesis of small nuclear ribonucleoproteins (snRNPs), which are crucial for pre-mRNA splicing. Upon nuclear reentry, Sm-class snRNPs localize first to the CB, where the snRNA moiety of the snRNP is modified. It is not clear how snRNPs target to the CB and are released from this structure after their modification. Coilin, the CB marker protein, may participate in snRNP biogenesis given that it can interact with snRNPs and SMN. SMN is crucial for snRNP assembly and is the protein mutated in the neurodegenerative disease Spinal Muscular Atrophy. Coilin knockout mice display significant viability problems and altered CB formation. Thus characterization of the CB and its associated proteins will give insight into snRNP biogenesis and clarify the dynamic organization of the nucleus.