Human cytomegalovirus UL97 open reading frame encodes a protein that phosphorylates the antiviral nucleoside analogue ganciclovir.

Human cytomegalovirus (HCMV, a betaherpes virus) is the cause of serious disease in immunologically compromised individuals, including those with acquired immunodeficiency syndrome. One of the compounds used in the chemotherapy of HCMV infections is the nucleoside analogue 9-(1,3-dihydroxy-2-propoxymethyl)-guanine (ganciclovir). The mechanism of action of this drug is dependent on the formation of the nucleoside triphosphate, which is a strong inhibitor of the viral DNA polymerase. Thymidine kinase, which is encoded by many of the herpesviruses, catalyses the initial phosphorylation of ganciclovir. But there is no evidence for the coding of this enzyme by HCMV, and DNA sequence analysis of the HCMV genome has shown that there is no open reading frame characteristic of a herpesvirus thymidine kinase. Here we present biochemical and immunological evidence that the HCMV UL97 open reading frame codes for a protein capable of phosphorylating ganciclovir. This protein seems to be responsible for the selectivity of ganciclovir and will be useful tool in the understanding and refinement of the antiviral activity of new selective anti-HCMV compounds.     

A genome-wide association study in Han Chinese identifies new susceptibility loci for ankylosing spondylitis

To identify susceptibility loci for ankylosing spondylitis, we performed a two-stage genome-wide association study in Han Chinese. In the discovery stage, we analyzed 1,356,350 autosomal SNPs in 1,837 individuals with ankylosing spondylitis and 4,231 controls; in the validation stage, we analyzed 30 suggestive SNPs in an additional 2,100 affected individuals and 3,496 controls. We identified two new susceptibility loci between EDIL3 and HAPLN1 at 5q14.3 (rs4552569; P = 8.77 × 10(-10)) and within ANO6 at 12q12 (rs17095830; P = 1.63 × 10(-8)). We also confirmed previously reported associations in Europeans within the major histocompatibility complex (MHC) region (top SNP, rs13202464; P < 5 × 10(-324)) and at 2p15 (rs10865331; P = 1.98 × 10(-8)). We show that rs13202464 within the MHC region mainly represents the risk effect of HLA-B*27 variants (including HLA-B*2704, HLA-B*2705 and HLA-B*2715) in Chinese. The two newly discovered loci implicate genes related to bone formation and cartilage development, suggesting their potential involvement in the etiology of ankylosing spondylitis.     

Reversible inactivation of the nitrate reductase of rice plants

Summary Studies of the inactivation of the rice nitrate reductase showed that the nitrate-reducing moiety and not the diaphorase moiety was reversibly inactivated by NADH and cyanide. Ferricyanide could reverse the inactivation, and nitrate could protect the enzyme against inactivation. Although the general characteristics of the reversible inactivation of rice nitrate reductase appeared similar to those of the algal nitrate reductase, it was found that the rice enzyme was automatically reactivated when NADH and cyanide were removed. Attempts to isolate inactivated nitrate reductase from ammonium-treated tissue were unsuccessful.     

Compensatory caspase activation in MPP+-induced cell death in dopaminergic neurons

Many have hypothesized that cell death in Parkinsons disease is via apoptosis and, specifically, by the mitochondrial-mediated apoptotic pathway. We tested this hypothesis using a mouse dopaminergic cell line of mesencephalic origin, MN9D, challenged with the Parkinsonism-causing neurotoxin MPP⁺ (1-methyl-4-phenylpyridinium ion). Apoptosis was the main mode of cell death when the cells were subjected to MPP⁺ treatment under serum-free conditions for 24 h. Caspase-3 and caspase-9, however, were not activated, thus indicating the existence of alternate or compensatory cell death pathway(s) in dopaminergic neuronal cells. Using caspase inhibitors, we demonstrated that these pathways involve caspase-2, –8, –6 and –7. A time-course study indicated that activation of caspase-2 and –8 occurred upstream of caspase-6 and caspase-7. Upon MPP⁺ challenge, the apoptosis-inducing factor was translocated from the mitochondria into the MN9D cytosol and nucleus. These results suggest the existence of alternative apoptotic pathways in dopaminergic neurons.Received 20 September 2004; received after revision 5 November 2004; accepted 22 November 2004     

圈的推广Mycielski图的圆色数

Mycielski图是1955年由Mycielski提出来的．任给一个图G和一个非负整数m,G的推广Mycielski图μm(G)是G的Mycielski图的一个自然的推广．推广Mycielski图的性质以及它们的点色数、圆色数和分数色数等已有许多研究．本文研究圈的推广Mycielski图的圆色数．定义Cn为n个顶点的圈．对任意非负整数m和大于2的整数n,本文确定了图μm(Cn)的圆色数,同时还得到了图μm(Cn)-v的圆色数的一些结果．     

族群认同与国家认同:以马来西亚为例(下)

运用马来西亚的事例强调了族群性与国家权力之间的关系并强调了涉及不同族群的政治程序的重要意义。族群的形成涉及一系列的过程 ,这些过程使人们在一国家内意识到一个共同想象的社群。创制族群和国家认同的过程实际上构成了同一历史过程的重要部分。在一国家范畴内 ,不同的族群对国家认同有不同的憧憬 ,因此有必要将国家认同与族群性相关联思考。论述了马来人和华人的族群划分问题以及沙捞越土著人复杂的族群认同意识和族群形成问题。     

The effect of photodynamic therapy on tumor angiogenesis

Photodynamic therapy (PDT), the activation of a photosensitive drug in tumor tissue with light of specific wavelength, has been used effectively to treat certain solid tumors. Though therapeutic responses are encouraging, PDT-mediated oxidative stress can act as an angiogenic switch that ultimately leads to neovascularization and tumor recurrence. This article explores the effect of PDT on angiogenesis in different tumor models. Overexpression of proangiogenic vascular endothelial growth factor, cyclooxygenase-2 and matrix metalloproteases has often been reported post-illumination. Recent clinical studies have demonstrated that inhibiting angiogenesis after chemotherapy and radiotherapy is an attractive and valuable approach to cancer treatment. In this review, we report the effective therapeutic strategy of combining angiogenesis inhibitors with PDT to control and treat tumors.