Cloning and characterization of a gene that regulates cell adhesion.

Molecules of the cadherin and integrin families involved in cell-cell and cell-matrix adhesion have been implicated in epithelial differentiation, carcinogenesis and metastasis. Having observed that a colon cancer cell line bound avidly to collagen type I, inducing integrin-triggered glandular differentiation, we investigated the regulation of integrin function in these cells. We modified a mammalian expression cloning system that used monoclonal antibody selection to clone cell surface molecules. Using attachment to collagen type I to select for adhesive phenotype, we isolated a complementary DNA clone that increases cell adhesion to components of the extracellular matrix. The corresponding gene (cell adhesion regulator, CAR) is located on the long arm of chromosome 16 (16q) and encodes a protein of 142 amino acids, which has an N-terminal myristoylation motif and a consensus tyrosine-kinase phosphorylation site at the C terminus. Removal of this tyrosine residue abolishes enhancement of cell-matrix adhesion. This gene may encode an adhesion signal transduction molecule that functions in the suppression of tumour invasion.     

brinker is a target of Dpp in Drosophila that negatively regulates Dpp-dependent genes

Growth and patterning of the Drosophila wing is controlled in part by the long-range organizing activities of the Decapentaplegic protein (Dpp). Dpp is synthesized by cells that line the anterior side of the anterior/posterior compartment border of the wing imaginal disc. From this source, Dpp is thought to generate a concentration gradient that patterns both anterior and posterior compartments. Among the gene targets that it regulates are optomotor blind (omb), spalt (sal), and daughters against dpp (dad). We report here the molecular cloning of brinker (brk), and show that brk expression is repressed by dpp. brk encodes, a protein that negatively regulates Dpp-dependent genes. Expression of brk in Xenopus embryos indicates that brk can also repress the targets of a vertebrate homologue of Dpp, bone morphogenetic protein 4 (BMP-4). The evolutionary conservation of Brk function underscores the importance of its negative role in proportioning Dpp activity.     

A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery

One of the earliest marks of a double-strand break (DSB) in eukaryotes is serine phosphorylation of the histone variant H2AX at the carboxy-terminal SQE motif to create gammaH2AX-containing nucleosomes. Budding-yeast histone H2A is phosphorylated in a similar manner by the checkpoint kinases Tel1 and Mec1 (ref. 2; orthologous to mammalian ATM and ATR, respectively) over a 50-kilobase region surrounding the DSB. This modification is important for recruiting numerous DSB-recognition and repair factors to the break site, including DNA damage checkpoint proteins, chromatin remodellers and cohesins. Multiple mechanisms for eliminating gammaH2AX as DNA repair completes are possible, including removal by histone exchange followed potentially by degradation, or, alternatively, dephosphorylation. Here we describe a three-protein complex (HTP-C, for histone H2A phosphatase complex) containing the phosphatase Pph3 that regulates the phosphorylation status of gammaH2AX in vivo and efficiently dephosphorylates gammaH2AX in vitro. gammaH2AX is lost from chromatin surrounding a DSB independently of the HTP-C, indicating that the phosphatase targets gammaH2AX after its displacement from DNA. The dephosphorylation of gammaH2AX by the HTP-C is necessary for efficient recovery from the DNA damage checkpoint.     

Molecular identification of a renal urate anion exchanger that regulates blood urate levels

Urate, a naturally occurring product of purine metabolism, is a scavenger of biological oxidants implicated in numerous disease processes, as demonstrated by its capacity of neuroprotection. It is present at higher levels in human blood (200 500 microM) than in other mammals, because humans have an effective renal urate reabsorption system, despite their evolutionary loss of hepatic uricase by mutational silencing. The molecular basis for urate handling in the human kidney remains unclear because of difficulties in understanding diverse urate transport systems and species differences. Here we identify the long-hypothesized urate transporter in the human kidney (URAT1, encoded by SLC22A12), a urate anion exchanger regulating blood urate levels and targeted by uricosuric and antiuricosuric agents (which affect excretion of uric acid). Moreover, we provide evidence that patients with idiopathic renal hypouricaemia (lack of blood uric acid) have defects in SLC22A12. Identification of URAT1 should provide insights into the nature of urate homeostasis, as well as lead to the development of better agents against hyperuricaemia, a disadvantage concomitant with human evolution.     

辉发河干流中下游河道自净需水量研究

松花湖是吉林省的重要水源地,随着经济的发展,松花湖的水质正逐年下降.辉发河是松花湖的一个主要污染源,探讨其自净需水量,可有效保护松花湖水资源.以点污染源为例计算了辉发河干流中下游河道自净需水量,结果表明:辉发河河道自净需水量严重缺乏,自净缺水量主要集中在非汛期,但同一河段相同年份各月的自净需水量差别不大,且自净需水量随年径流量变化不大.     

ESBLs病原菌医院下呼吸道感染临床及耐药性38例分析

目的 :了解产ESBLs病原菌医院下呼吸道感染的临床特点、菌群分布、耐药状况、治疗效果 ,为临床诊治提供依据。方法 :对产ESBLs病原菌医院下呼吸道感染的临床特点、治疗有效率、细菌清除率等资料进行分析 ,用常规痰培养方法检测病原菌 ,Kirby -Bauer方法测定药敏 ,Etest确定ESBLs阳性菌株。结果 :38株ESBLs阳性菌中 ,肺炎克雷伯菌占 39 5 %、大肠埃希氏菌占 36 8%、阴沟肠杆菌占 13 2 %、铜绿假单胞菌占 7 9%、产气肠杆菌占 2 6 %;对ESBLs阳性菌的耐药率亚胺培南为 5 3%、阿米卡星为 5 7 9%、庆大霉素为 6 0 5 %、头孢他啶为 6 8 4 %;肺炎克雷伯菌对亚胺培南耐药率为 6 7%、对环丙沙星耐药率为 73 3%,对其余抗生素耐药率高达 80 %～ 10 0 %,大肠埃希氏菌耐药率亚胺培南为 0、阿米卡星为 35 7%、妥布霉素为 5 0 %、头孢他啶为 4 2 9%、庆大霉素为 6 4 3%,其余抗生素达 78 6 %～ 10 0 %,阴沟肠杆菌耐药率亚胺培南为 2 0 %、环丙沙星 6 0 %,其余抗生素80 %～ 10 0 %,铜绿假单胞菌、产气肠杆菌均对亚胺培南敏感 ;临床有效率、细菌清除率亚胺培南分别为 71 4 %、6 4 3%,明显高于其他抗生素。结论 :产ESBLs病原菌菌种有增加趋势 ,产ESBLs病原菌对亚胺培南敏感性高 ,对常用抗生素耐药     

内蒙古额吉淖尔盐碱湖嗜盐古菌的抗生素抗性及分泌的嗜盐菌素的抑菌性

本实验室从内蒙古额吉淖尔湖盐碱土样分离得到一株属于Natrinema属的嗜盐古菌。本文对其进行了抗生素抗性实验以及对其产生的嗜盐菌素进行了抑菌性研究。结果表明诺氟沙星对该菌具有较强的抑菌作用,头孢氨苄对该菌具有微弱的抑菌作用。通过测定抑菌圈的大小表明该菌株对抗生素具有一定的抗性。该菌株所生产的嗜盐菌素对蛋白酶K 较敏感,对大肠杆菌和金黄色葡萄球菌具有抑菌作用。