Atomic structure and chemistry of human serum albumin.

The three-dimensional structure of human serum albumin has been determined crystallographically to a resolution of 2.8 A. It comprises three homologous domains that assemble to form a heart-shaped molecule. Each domain is a product of two subdomains that possess common structural motifs. The principal regions of ligand binding to human serum albumin are located in hydrophobic cavities in subdomains IIA and IIIA, which exhibit similar chemistry. The structure explains numerous physical phenomena and should provide insight into future pharmacokinetic and genetically engineered therapeutic applications of serum albumin.     

Purification, cloning, expression and biological characterization of an interleukin-1 receptor antagonist protein

A human myelomonocytic cell line, U937, produced an interleukin-1 (IL-1) receptor antagonist protein (IRAP) which was purified and partially sequenced. A complementary DNA coding for IRAP was cloned and sequenced. The mature translation product of the cDNA has been expressed in Escherichia coli and was an active competitive inhibitor of the binding of IL-1 to the T-cell/fibroblast form of the IL-1 receptor. Recombinant IRAP specifically inhibited IL-1 bioactivity on T cells and endothelial cells in vitro and was a potent inhibitor of IL-1 induced corticosterone production in vivo.     

污泥龄对活性污泥处理微量磺胺类药物的影响

为了研究污泥龄对活性污泥系统处理微量磺胺类药物（5 μg/L）的影响,共运行了4个试验室规模（3L）的序批式活性污泥反应器（SBR）,其污泥龄分别为2、8、14、20 d。批次摇瓶试验通过设置3个工况（正常运行,加入生物抑制剂,无微生物）来讨论在1个运行周期（8 h）中对浓度惟5 μg/L磺胺甲恶唑的吸附作用、生物降解作用和挥发损失。试验结果显示对磺胺甲恶唑的总去除量为2.14 ± 0.60 μg/g SS,吸附作用占总去除量的63%;磺胺嘧啶为1.14 ± 0.63 μg/g SS,83%;磺胺间二甲氧为2.33± 0.67 μg/g SS, 35%;磺胺甲基嘧啶为2.45 ± 0.85 μg/g SS,55%;磺胺类药物的去除效果与污泥的污泥龄有着非常显著的关系（p<0.02）。通过运行加入磺胺甲恶唑（进水5 μg/L)的反应器60 d,4个反应器对磺胺甲恶唑的平均去除率分别为10%、41%、51%、58%,处理效果随着污泥龄的增加而变好,同时单位污泥去除率随着污泥龄的增加而降低,SRT=2 d的反应器由于存在大量的丝状菌,使得单位污泥对磺胺甲恶唑去除率大大高于其他3个反应器。通过分子生物学分析,发现微生物群落结构的变化不大,从而说明了影响磺胺类药物处理效果的主要因素在于更强的吸附能力,更高的污泥浓度。     

Melanoma genome sequencing reveals frequent PREX2 mutations

Melanoma is notable for its metastatic propensity, lethality in the advanced setting and association with ultraviolet exposure early in life. To obtain a comprehensive genomic view of melanoma in humans, we sequenced the genomes of 25 metastatic melanomas and matched germline DNA. A wide range of point mutation rates was observed: lowest in melanomas whose primaries arose on non-ultraviolet-exposed hairless skin of the extremities (3 and 14 per megabase (Mb) of genome), intermediate in those originating from hair-bearing skin of the trunk (5-55 per Mb), and highest in a patient with a documented history of chronic sun exposure (111 per Mb). Analysis of whole-genome sequence data identified PREX2 (phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 2)--a PTEN-interacting protein and negative regulator of PTEN in breast cancer--as a significantly mutated gene with a mutation frequency of approximately 14% in an independent extension cohort of 107 human melanomas. PREX2 mutations are biologically relevant, as ectopic expression of mutant PREX2 accelerated tumour formation of immortalized human melanocytes in vivo. Thus, whole-genome sequencing of human melanoma tumours revealed genomic evidence of ultraviolet pathogenesis and discovered a new recurrently mutated gene in melanoma.     

Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn's disease

We report results of a nonsynonymous SNP scan for ulcerative colitis and identify a previously unknown susceptibility locus at ECM1. We also show that several risk loci are common to ulcerative colitis and Crohn's disease (IL23R, IL12B, HLA, NKX2-3 and MST1), whereas autophagy genes ATG16L1 and IRGM, along with NOD2 (also known as CARD15), are specific for Crohn's disease. These data provide the first detailed illustration of the genetic relationship between these common inflammatory bowel diseases.