抑制性寡脱氧核苷酸的生物学效应及研究进展

DNA对于机体免疫系统具有很多复杂的作用。存在于细菌DNA中的刺激性CpG基序能够促进机体免疫细胞分泌多种细胞因子,使机体产生偏向Th1方向的免疫应答,而抑制性寡脱氧核苷酸(oligodeoxynucleotide,ODN)可以选择性阻断刺激性CpG诱导的免疫激活作用。抑制性ODN按其结构不同大致分为三类,它可能通过影响细胞对CpG-S的结合及摄取、降低CpG-S特异性受体TLR9的表达发挥抑制作用。本综述主要介绍抑制性ODN的结构特征、作用机制和它在一些疾病中发挥的作用。     

SNP identification, linkage disequilibrium, and haplotype analysis for a 200-kb genomic region in a Korean population

Understanding patterns of linkage disequilibrium (LD) across genomes may facilitate association mapping studies to localize genetic variants influencing complex diseases, a recognition that led to the International Haplotype Mapping Project (HapMap). Divergent patterns of haplotype frequency and LD across global populations require that the HapMap database be supplemented with haplotype and LD data from additional populations. We conducted a pilot study of the LD and haplotype structure of a genomic region in a Korean population. A total of 165 SNPs were identified in a 200-kb region of 22q13.2 by direct sequencing. Unphased genotype data were generated for 76 SNPs in 90 unrelated Korean individuals. LD, haplotype diversity, and recombination rates were assessed in this region and compared with the HapMap database. The pattern of LD and haplotype frequencies of Korean samples showed a high degree of similarity with Japanese data. There was a strong correlation between high LD and low recombination frequency in this region. We found considerable similarities in local LD patterns between three Asian populations (Han Chinese, Japanese, and Korean) and the CEPH population. Haplotype frequencies were, however, significantly different between them. Our results should further the understanding of distinctive Korean genomic features and assist in designing appropriate association studies.     

Carbon monoxide produced by heme oxygenase-1 suppresses T cell proliferation via inhibition of IL-2 production

Heme oxygenase-1 (HO-1) catabolizes heme into CO, biliverdin, and free iron and serves as a protective enzyme by virtue of its anti-inflammatory, antiapoptotic, and antiproliferative actions. Previously, we have demonstrated that human CD4(+) T cells express HO-1 and that HO-1-overexpressing Jurkat T cells tend to display lower proliferative response. The aim of this study is to elucidate the mechanism(s) by which HO-1 can mediate its antiproliferative effect on CD4(+) T cells. Among the three HO-1 byproducts, only CO showed suppressive effect on T cell proliferation in response to anti-CD3 plus anti-CD28 Abs, mimicking the antiproliferative action of HO-1. CO blocked the cell cycle entry of T cells, which was independent of the guanylate cyclase/cGMP pathway. CO also suppressed the secretion of IL-2, and this suppressive effect of CO on IL-2 secretion mediated the antiproliferative action of CO. CO selectively inhibited the extracellular signal-regulated kinase pathway, which could explain the suppressive effects of CO on T cell proliferation and IL-2 secretion. Based on these findings, we suggest that HO-1/CO suppresses T cell proliferation and IL-2 secretion, possibly via its inhibition of extracellular signal-regulated kinase activation.     

Isolation of the protein tyrosine phosphatase 1B inhibitory metabolite from the marine-derived fungus Cosmospora sp. SF-5060

In the course of bioassay-guided study on the EtOAc extract of a culture broth of the marine-derived fungus Cosmospora sp. SF-5060, aquastatin A (1) was isolated as a protein tyrosine phosphatase 1B (PTP1B) inhibitory component produced by the fungus. The compound was isolated by various chromatographic methods, and the structure was determined mainly by analysis of NMR spectroscopic data. Compound 1 exhibited potent inhibitory activity against PTP1B with IC₅₀ value of 0.19 μM, and the kinetic analyses of PTP1B inhibition by compound 1 suggested that the compound is inhibiting PTP1B activity in a competitive manner. Aquastatin A (1) also showed modest but selective inhibitory activity toward PTP1B over other protein tyrosine phosphatases, such as TCPTP, SHP-2, LAR, and CD45. In addition, the result of hydrolyzing aquastatin A (1) suggested that the dihydroxypentadecyl benzoic acid moiety in the molecule is responsible for the inhibitory activity.     

威海地区547例甲真菌病真菌培养结果分析

目的了解山东省威海地区甲真菌病的临床分类、菌种构成等流行情况。方法对547例镜检阳性的甲真菌病患者进行真菌培养、鉴定和临床分析。结果547例患者中真菌培养阳性423例,阳性率77.3%,远端侧位甲下型甲真菌病(DLSO)295例(53.9%),白色浅表型甲真菌病(SWO)36例(6.5%),近端侧位甲下型甲真菌病(PSO)78例(14.2%),全甲营养不良型甲真菌病(TDO)138例(25.2%)。共分离出429株真菌,其中皮肤癣菌354株(82.5%),酵母菌61株(14.2%),非皮肤癣菌霉菌14株(3.3%)。结论山东省威海地区甲真菌病病原体的分布以皮肤癣菌为主,其次为酵母菌和非皮肤癣菌霉菌,红色毛癣菌是最常见的皮肤癣菌,临床类型以DLSO型居多,其他依次是TDO、PSO、SWO。就诊人群中以20～50岁年龄段为最多见。     

安徽省蜜蜂种群消长及其分布与自然环境的关系

2002～2004年,对淮北平原、江淮丘陵、沿江平原及皖西和皖南山区四大类型生态区域的蜜蜂种群数量动态与环境因子进行了调查.结果表明,复杂的自然环境与蜜蜂种群特性密切相关.皖南山区和皖西大别山区蜜粉源植物分别为46和37种,中华蜜蜂群体数量多,分布密度分别为2.01和1.95群·km^-2;江淮地区和淮北平原蜜粉源植物分别为17和12种,花期短而集中,且面积大,适宜于意大利蜜蜂采集与生产,中华蜜蜂群体数量少,分布密度分别为0.06和0.02群·km^-2.胡蜂捕食影响蜜蜂种群消长与分布.皖南山区、皖西大别山区、江淮地区和淮北平原,中华蜜蜂分别占本地区蜂群的41.5%、36.8%、3.1%和1.1%,意大利蜜蜂分别占本地区蜂群的58.5%、63.2%、96.9%和98.9%.     

太行山南麓坡面土壤碳氮空间变异性及其影响因素

太行山南麓是我国华北平原的重要生态屏障,研究该区域土壤养分的空间变异性对土石山区林业生态建设具有重要意义.本研究以太行山南麓典型坡面(人工林坡地和自然荒坡地)为对象,采用网格法布设采样点,运用经典统计学、地统计学和约束性排序相结合的方法对土壤养分的空间变异性进行分析.结果 表明:1)太行山南麓的土壤全碳(TC)含量为6...     

不同年份油桃园三种主要害虫与其天敌的关系

为了科学施药,合理保护和利用自然天敌进行油桃害虫的综合防治,用灰色系统分析方法、生态位分析方法和空间格局聚集强度指数分析方法,对2008年及2009年春-夏季油桃园桃蚜、小绿叶蝉和山楂叶螨与其主要捕食性天敌在数量、时间和空间格局等方面关系进行分析,两年春-夏季综合排序的结果是,桃蚜主要捕食性天敌依次是黑带食蚜蝇、异色瓢虫、三突花蟹蛛;小绿叶蝉主要捕食性天敌依次为三突花蟹蛛、锥腹肖蛸和草间小黑蛛;山楂叶螨主要捕食性天敌依次为草间小黑蛛、八斑球腹蛛和三突花蟹蛛。2008年秋季桃蚜的主要天敌依次是八斑球腹蛛、中华草蛉和锥腹肖蛸;小绿叶蝉的主要天敌依次是草间小黑蛛、锥腹肖蛸和黑带食蚜蝇;山楂叶螨的主要天敌依次为八斑球腹蛛、异色瓢虫和中华草蛉。两年春-夏季之间3种害虫及天敌数量差异均不显著。     

Immunogenicity of a Trivalent Human Papillomavirus L1 DNA-Encapsidated,Non-Replicable Baculovirus Nanovaccine

Previously, we developed a non-replicating recombinant baculovirus coated with human endogenous retrovirus envelope protein (AcHERV) for enhanced cellular delivery of human papillomavirus (HPV) 16L1 DNA. Here, we report the immunogenicity of an AcHERV-based multivalent HPV nanovaccine in which the L1 segments of HPV 16, 18, and 58 genes were inserted into a single baculovirus genome of AcHERV. To test whether gene expression levels were affected by the order of HPV L1 gene insertion, we compared the efficacy of bivalent AcHERV vaccines with the HPV 16L1 gene inserted ahead of the 18L1 gene (AcHERV-HP16/18L1) with that of AcHERV with the HPV 18L1 gene inserted ahead of the 16L1 gene (AcHERV-HP18/16L1). Regardless of the order, the bivalent AcHERV DNA vaccines retained the immunogenicity of monovalent AcHERV-HP16L1 and AcHERV-HP18L1 DNA vaccines. Moreover, the immunogenicity of bivalent AcHERV-HP16/18L1 was not significantly different from that of AcHERV-HP18/16L1. In challenge tests, both bivalent vaccines provided complete protection against HPV 16 and 18 pseudotype viruses. Extending these results, we found that a trivalent AcHERV nanovaccine encoding HPV 16L1, 18L1, and 58L1 genes (AcHERV-HP16/18/58L1) provided high levels of humoral and cellular immunogenicity against all three subtypes. Moreover, mice immunized with the trivalent AcHERV-based nanovaccine were protected from challenge with HPV 16, 18, and 58 pseudotype viruses. These results suggest that trivalent AcHERV-HPV16/18/58L1 could serve as a potential prophylactic baculoviral nanovaccine against concurrent infection with HPV 16, 18, and 58.