南京医学院的社会调查

Functional Genetic Variations in Cytotoxic T-Lymphocyte Antigen 4 and Susceptibility to Multiple Types of Cancer

 

Tong Sun,1 Yifeng Zhou,1 Ming Yang,1 Zhibin Hu,3 Wen Tan,1 Xiaohong Han,2 Yuankai Shi,2 Jiarui Yao,2 Yongli Guo,1 Dianke Yu,1 Tian Tian,3 Xiaoyi Zhou,3 Hongbing Shen,3 and Dongxin Lin

 

Departments of 1Etiology and Carcinogenesis and 2Medical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; 3Department of Epidemiology and Biostatistics, Cancer Center, Nanjing Medical University, Nanjing, China

 

Antitumor T lymphocytes play a pivotal role in immunosurveillance of malignancy. The CTL antigen 4 (CTLA-4) is a vital negative regulator of T-cell activation and proliferation. This study examined whether genetic polymorphisms in CTLA-4 are associated with cancer susceptibility. A two-stage investigation using haplotype-tagging single nucleotide polymorphism approach and multiple independent case-control analyses was performed to assess the association between CTLA-4 genotypes and cancer risk. Functional relevance of the polymorphisms was examined by biochemical assays. We found that the 49G>A polymorphism in the CTLA-4 leading sequence causing 17Ala to 17Thr amino acid substitution is associated with increased susceptibility to multiple cancers, including lung, breast, esophagus, and gastric cardia cancers. Genotyping in 5,832 individuals with cancer and 5,831 control subjects in northern and southern Chinese populations showed that the CTLA-4 49AA genotype had an odds ratio of 1.72 (95% confidence interval, 1.50_2.10; P = 3.4 _ 10 _7) for developing cancer compared with the 49GG genotype. Biochemical analyses showed that CTLA-4_17Thr had higher capability to bind B7.1 and stronger inhibitory effect on T-cell activation compared with CTLA-4_17Ala. T cells carrying the 49AA genotype had significantly lower activation and proliferation rates compared with T cells carrying the 49GG genotype upon stimulation. These results are consistent with our hypothesis and indicate that genetic polymorphisms influencing T-cell activation modify cancer susceptibility.

 

南京医学院和北京一所学校在”癌症研究”上发表的报告. 与其说是和生物有关, 其实和社会调查学更有关. 白血球有杀死癌细胞的作用, 而有个基因则能让白血球”休眠”. 于是他们就做了一个调查, 发现这个基因的某些异变比另一些异变的休眠能力更强.

清华无聊的生化报告~~~

Crystal structure of the polymerase PAC-PB1N complex from an avian influenza H5N1 virus

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Vol 454|28 August 2008| doi:10.1038/nature07120

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Xiaojing He1, Jie Zhou1, Mark Bartlam2, Rongguang Zhang3, Jianyuan Ma1, Zhiyong Lou4, Xuemei Li1,4, Jingjing Li1, Andrzej Joachimiak3, Zonghao Zeng1, Ruowen Ge5, Zihe Rao1,2,4 & Yingfang Liu1

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The recent emergence of highly pathogenic avian influenza A virus strains with subtype H5N1 pose a global threat to human health1. Elucidation of the underlying mechanisms of viral replication is critical for development of anti-influenza virus drugs2. The influenza RNA-dependent RNA polymerase (RdRp) heterotrimer has crucial roles in viral RNA replication and transcription. It contains three proteins: PA, PB1 and PB2. PB1 harbours polymerase and endonuclease activities and PB2 is responsible for cap binding3,4; PA is implicated in RNA replication5-10 and proteolytic activity11-14, although its function is less clearly defined. Here we report the 2.9 a°ngstro¨mstructure of avian H5N1 influenza A virus PA (PAC, residues 257-716) in complex with the PA-binding region of PB1 (PB1N, residues 1-25). PAC has a fold resembling a dragon’s head with PB1N clamped into its open ‘jaws’. PB1N is a known inhibitor that blocks assembly of the polymerase heterotrimer and abolishes viral replication. Our structure provides details for the binding of PB1N to PAC at the atomic level, demonstrating a potential target for novel anti-influenza therapeutics. We also discuss a potential nucleotide binding site and the roles of some known residues involved in polymerase activity. Furthermore, to explore the role of PA in viral replication and transcription, we propose a model for the influenza RdRp heterotrimer by comparing PAC with the l3 reovirus polymerase structure, and docking the PAC structure into an available low resolution electron microscopy map.

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啊…本来不想发这篇的, 纯生化的实在是太无聊了, 不过毕竟是自然上的, 而且也没看到其它从中国来的报告. 这篇讲了他们解析出了禽流感的DNA复制的结构. 就这么多.

台湾这次在PNAS上发表的一篇奇怪报告…

Wen-Wei Chang, Chien Hsin Lee, Peishan Lee, Juway Lin, Chun-Wei Hsu, Jung-Tung Hung, Jin-Jin Lin, Jyh-Cherng Yu, Li-en Shao, John Yu, Chi-Huey Wong, and Alice L. Yu

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Genomics Research Center and Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan; ‡Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan; and §General Surgery, Department of Surgery, Tri-Service General Hospital, Taipei 114, Taiwan

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We examined the expression in breast cancer stem cells (BCSCs) of Globo H, a potential tumor-associated antigen for immunotherapy of epithelial cancers including breast cancer. Flow cytometry revealed Globo H expression in 25/41 breast cancer specimens (61.0%). Non-BCSCs from 25/25 and BCSCs from 8/40 (20%) expressed Globo H. We showed the expression of stage-specific embryonic antigen 3 (SSEA3), the pentasaccharide precursor of Globo H, in 31/40 (77.5%) tumors. Non-BCSCs from 29/31 and BCSCs from 25/40 (62.5%) expressed SSEA3. Like Globo H, SSEA3 expression in normal tissues was predominately at the secretory borders of epithelium, where access to the immune system is restricted. Immunization of mice with Globo H-KLH and _-GalCer induced antibodies reactive with Globo H and SSEA3, suggesting that a Globo H-based vaccine will target tumor cells expressing Globo H or SSEA3. We next sought to reduce Globo H expression by siRNA targeting fucosyltransferase (FUT) 1 and 2, which mediate alpha-1,2 linkage of fucose to SSEA3 to generate Globo H. We showed both genes to be involved in the biosynthesis of Globo H. Moreover, FUT2 expression in BCSCs was significantly lower than in non-BCSCs harvested from a primary human breast cancer in NOD/SCID mouse, whereas FUT1 was slightly lower in BCSCs. Thus, the lower expression of Globo H in BCSCs may be attributed to less FUT2/FUT1, and to reduced SSEA3 in BCSCs compared with non- BCSCs. Our findings provide insight into further development of a Globo H-based vaccine and FUT1/FUT2-targeted therapy for breast cancer.

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从台湾来的一篇文章, 发表在PNAS上. 可能我对生化不太熟悉吧, 不过我真的不知道为什么这篇文章能发表在PNAS上. 文章实际上就是介绍了GloboH, 一个表面抗体, 在乳腺癌中的表现率. 确实, 他们用的是人身上的肿瘤, 但我没有觉得这篇文章说明了什么. 它是想说GLOBO H在乳腺癌干细胞中的表现很低呢, 还是就介绍一个事实? 我觉得任何一篇文章或多或少的都应该在最后来个推论, 而我看到的只是一个数据报告而已, 还是在PNAS上发表的.

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PS. 我还在等Xam’d第六集的种子, 这星期MS出的有点慢. 估计明天可以看到.

本期自然关于中国环保的负面报道

前几个星期的自然是正面的, 这期转负面了. URL在这里:

 

http://www.sciencemag.org/current.dtl

 

我觉得这期的比上次的那个更有意义, 因为建议性批评总是好的. 里面讲了很多事情, 比如说三xia, 西部水危机, 北京的空气污染等. 因为文章比较多,我就不做一一评论了.

我建议大家去读一下本期的自然

http://www.nature.com/nature/journal/v454/n7203/

这期的<<自然>>将中国作为一个主题, 对中国自改革开放后的科学进展作出了一系列评价, 而且基本上都是给予了正面的肯定. 绝对值得一读. 因为文章太多, 我就不一一做评价了.

中国环保近期取得的进展的前景

Ecological and socioeconomic effects of China‘s policies for ecosystem services

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Jianguo Liu*†, Shuxin Li*, Zhiyun Ouyang‡, Christine Tam§, and Xiaodong Chen*

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PNAS  July 15, 2008  vol. 105  no. 28  9477-9482

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To address devastating environmental crises and to improve human well-being, China has been implementing a number of national policies on payments for ecosystem services. Two of them, the Natural Forest Conservation Program (NFCP) and the Grain to Green Program (GTGP), are among the biggest programs in the world because of their ambitious goals, massive scales, huge payments, and potentially enormous impacts. The NFCP conserves natural forests through logging bans and afforestation with incentives to forest enterprises, whereas the GTGP converts cropland on steep slopes to forest and grassland by providing farmers with grain and cash subsidies. Overall ecological effects are beneficial, and socioeconomic effects are mostly positive. Whereas there are time lags in ecological effects, socioeconomic effects are more immediate. Both the NFCP and the GTGP also have global implications because they increase vegetative cover, enhance carbon sequestration, and reduce dust to other countries by controlling soil erosion. The future impacts of these programs may be even bigger. Extended payments for the GTGP have recently been approved by the central government for up to 8 years. The NFCP is likely to follow suit and receive renewed payments. To make these programs more effective, we recommend systematic planning, diversified funding, effective compensation, integrated research, and comprehensive monitoring. Effective implementation of these programs can also provide important experiences and lessons for other ecosystem service payment programs in China and many other parts of the world.

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中科院这星期在美国科学进展上发表的文章.主要讲了”退耕还林”和”国家森林保护计划”在2005年截止取得的进展.文章对两个计划从背景,目标,资金,经济影响和社会影响上分析了取得的进展.文章总体上对两个计划持肯定态度,但同时也提到了现在距离当时设定的在2010年的目标还相差很远.我唯一觉得有点不同意的地方就是文章最后提出的一点建议.由于文章中三分之二的作者来自美国,我不知道他们是否意识到体制问题和国情.这些建议包括:

1.ZF应该多听当地人民的意见.

2.寻求民间的资金.

3.足够的来自国家的补贴

4.对进展的更全面的研究.