微核技术研究进展

微核试验作为检测染色体损伤最常用而有效的细胞遗传学检测方法之一,经济、简便、快速,在敏感性、特异性和准确性方面,与经典的染色体畸变分析方法基本相当。主要综述国内外微核检测技术的最新研究进展,尤其是微核的自动化检测技术。其中流式细胞仪自动化检测和激光扫描细胞仪自动化检测,以及微核试验高内涵筛选方法由于其特有的优势,应用和发展前景广阔。     

滞育和非滞育棉铃虫前胸腺的形态解剖学比较研究

该文用解剖镜和电子显微镜对滞育和非滞育棉铃虫Helicoverpa armigera前胸腺的形态解剖结构进行了比较研究。结果发现滞育棉铃虫的前胸腺细胞及其细胞间隙相对较小,不易着色,细胞核规则,较小,细胞质中几乎见不到光滑内质网和粗面内质网,线粒体极少,这些观察到的现象充分说明滞育棉铃虫的前胸腺活性较低。     

皖南尖吻蝮蛇毒出血毒素Ⅳ的纯化与初步鉴定

从皖南尖吻蝮蛇（Ａｇｋｉｓｔｒｏｄｏｎａｃｕｔｕｓ）毒液中经ＤＥＡＥ－Ｓｅｐｈａｒｏｓｅ和ＳｅｐｈａｃｒｙｌＳ－２００两步凝胶柱层析首次纯化出一种中分子量出血毒素（简称ＡａＨⅣ）．经ＳＤＳ－ＰＡＧＥ和等电聚焦凝胶电泳测定其分子量为４４ｋＤ,等电点为ｐＨ５．０．从５００ｍｇ粗毒中可获得２０ｍｇＡａＨⅣ纯品．ＡａＨⅣ有较强的出血活性,最小出血剂量（ＭＨＤ）为０．４μｇ．     

绢丝丽蚌胚胎发育的研究

绢丝丽蚌卵为均黄卵,爱精卵在雌蚌外鳃中进行胚胎发育,其卵裂为不等完全卵裂。在秋季自然常湿（水温变幅为２４－８℃）时,胚胎发育历时５１ｄ,经过卵裂期、原肠期,发育为具有透明原壳、过钩、闭壳肌丝、内足丝、刚毛和外足丝的成熟钩介幼虫。胚胎发育的不同时期与外鳃特征具相关性。     

Optimization of novel monobactams with activity against carbapenem-resistant Enterobacteriaceae – Identification of LYS228

Metallo-β-lactamases (MBLs), such as New Delhi metallo-β-lactamase (NDM-1) have spread world-wide and present a serious threat. Expression of MBLs confers resistance in Gram-negative bacteria to all classes of β-lactam antibiotics, with the exception of monobactams, which are intrinsically stable to MBLs. However, existing first generation monobactam drugs like aztreonam have limited clinical utility against MBL-expressing strains because they are impacted by serine β-lactamases (SBLs), which are often co-expressed in clinical isolates. Here, we optimized novel monobactams for stability against SBLs, which led to the identification of LYS228 (compound 31). LYS228 is potent in the presence of all classes of β-lactamases and shows potent activity against carbapenem-resistant isolates of Enterobacteriaceae (CRE).     

Disease-driven detection of differential inherited SNP modules from SNP network

Detection of the synergetic effects between variants, such as single-nucleotide polymorphisms (SNPs), is crucial for understanding the genetic characters of complex diseases. Here, we proposed a two-step approach to detect differentially inherited SNP modules (synergetic SNP units) from a SNP network. First, SNP-SNP interactions are identified based on prior biological knowledge, such as their adjacency on the chromosome or degree of relatedness between the functional relationships of their genes. These interactions form SNP networks. Second, disease-risk SNP modules (or sub-networks) are prioritised by their differentially inherited properties in IBD (Identity by Descent) profiles of affected and unaffected sibpairs. The search process is driven by the disease information and follows the structure of a SNP network. Simulation studies have indicated that this approach achieves high accuracy and a low false-positive rate in the identification of known disease-susceptible SNPs. Applying this method to an alcoholism dataset, we found that flexible patterns of susceptible SNP combinations do play a role in complex diseases, and some known genes were detected through these risk SNP modules. One example is GRM7, a known alcoholism gene successfully detected by a SNP module comprised of two SNPs, but neither of the two SNPs was significantly associated with the disease in single-locus analysis. These identified genes are also enriched in some pathways associated with alcoholism, including the calcium signalling pathway, axon guidance and neuroactive ligand-receptor interaction. The integration of network biology and genetic analysis provides putative functional bridges between genetic variants and candidate genes or pathways, thereby providing new insight into the aetiology of complex diseases.     

Screening of binding proteins that interact with human Salvador 1 in a human fetal liver cDNA library by the yeast two-hybrid system

Salvador promotes both cell cycle exit and apoptosis through the modulation of both cyclin E and Drosophila inhibitor of apoptosis protein in Drosophila. However, the cellular function of human Salvador (hSav1) is rarely reported. To screen for novel binding proteins that interact with hSav1, the cDNA of hSav1 was cloned into a bait protein plasmid, and positive clones were screened from a human fetal liver cDNA library by the yeast two-hybrid system. hSav1 mRNA was expressed in yeast and there was no self-activation and toxicity in the yeast strain AH109. Twenty proteins were found to interact with hSav1, including HS1 (haematopoietic cell specific protein1)-associated protein X-1 (HAX-1); neural precursor cell expressed, developmentally down-regulated 9, pyruvate kinase, liver and RBC, cytochrome c oxidase subunit Vb, enoyl coenzyme A hydratase short chain 1, and NADH dehydrogenase (ubiquinone) 1 beta subcomplex, demonstrating that the yeast two-hybrid system is an efficient method for investigating protein interactions. Among the identified proteins, there were many mitochondrial proteins, indicating that hSav1 may play a role in mitochondrial function. We also confirmed the interaction of HAX-1 and hSav1 in mammalian cells. This investigation provides functional clues for further exploration of potential apoptosis-related proteins in disease biotherapy.     

土族生物资源利用相关的传统知识多样性

生物资源利用相关的传统知识是对生物资源进行识别和利用的传统知识系统。随着现代生物技术的发展, 这类传统知识显示出其在科学、经济、文化乃至粮食安全战略方面的价值。本研究根据《生物多样性相关传统知识分类、调查与编目技术规定(试行)》, 对我国青海省土族聚集区的土族生物资源利用相关的传统知识进行了系统调查与编目, 并借鉴生物多样性测度方法, 创建了传统知识多样性指数计算方法, 对土族生物资源利用相关传统知识多样性进行分析。结果如下: (1)编目现存的土族生物资源利用相关的传统知识词条共424条; (2)土族传统知识的α多样性指数D_TK = 0.67, 表明其传统知识多样性较高; 土族传统知识的β_wtk多样性指数在不同的县域差异较大, 表明其在县域之间存在差异, 在空间上分布不连续、不均匀。本研究利用生物多样性指数验证了传统知识的定量研究方法, 说明传统知识多样性指数不仅可用于定量研究表征区域传统知识的多样性, 揭示不同空间区域内的分布特征, 还可为未来构建传统知识的定量研究体系提供重要的参考依据。     

Response of osteoblasts to low fluid shear stress is time dependent

The process of mechanotransduction of bone, the conversion of a mechanical stimulus into a biochemical response, is known to occur in osteoblasts in response to fluid shear stress. In order to understand the reaction of osteoblasts to various times of flow perfusion, osteoblasts were seeded on three-dimensional scaffolds, and cultured in the following conditions: continuous flow perfusion, intermittent flow perfusion, and static condition. We collected samples on day 4, 8 and 12 for analysis. Osteoblast proliferation was demonstrated by cell proliferation and scanning electron microscopy assay. Additionally, the expression of known markers of differentiation, including alkaline phosphatase and osteocalcin, were tested by qRT-PCR and alkaline phosphatase activity assay, and the deposition of calcium was used as an indicator of mineralization demonstrated by calcium content assay. The results supported that low fluid shear stress plays an important role in the activation of osteoblasts: enhance cell proliferation, increase calcium deposition, and promote the expression of osteoblastic markers. Furthermore, the continuous flow perfusion is a more favorable environment for the initiation of osteoblast activity compared with intermittent flow perfusion. Therefore, the force and time of fluid shear stress are important parameters for osteoblast activation.