Nek2 targets the mitotic checkpoint proteins Mad2 and Cdc20: A mechanism for aneuploidy in cancer

In mitosis, the duplicated chromosomes are separated and equally distributed to progeny cells under the guidance of the spindle, a dynamic microtubule network. Previous studies revealed a mitotic checkpoint that prevents segregation of the chromosomes until all of the chromosomes are properly attached to microtubules through the kinetochores. A variety of kinetochore-localized proteins, including Mad2 and Cdc20, have been implicated in controlling the mitotic checkpoint. Here we report that both Mad2 and Cdc20 can physically associate with Nek2, a serine/threonine kinase implicated in centrosome functions. We show that, similar to Nek2, the endogenous Cdc20 protein can be detected in the centrosome and the spindle poles. Both Cdc20 and Mad2 can be phosphorylated by Nek2. Moreover, our studies demonstrate that overexpression of Nek2 enhances the ability of Mad2 to induce a delay in mitosis. These observations indicate that Nek2 may act upon the Mad2-Cdc20 protein complex and play a critical role in regulating the mitotic checkpoint protein complex. We propose that overexpression of Nek2 may promote aneuploidy by disrupting the control of the mitotic checkpoint.     

Genetic diversity of the S10 RNA segment of field and vaccine strains of bluetongue virus from the P. R. China

Bluetongue virus (BTV) infection of ruminants is endemic throughout tropical and subtropical regions of the world. However, the molecular epidemiology of BTV infection in China has not yet been reported. In this study, the S10 gene segments from 30 BTV isolates, one attenuated BTV strain, one vaccine BTV strain, and one South Africa BTV prototype strain, were sequenced. Phylogenetic analysis of the S10 genes showed that Chinese BTV isolates could be classified into two phyletic subgroups, and the clustering of Chinese BTV viruses was dependent on their geographical origin and the number of generations for which they had been propagated, rather than their host species or year of isolation.     

河北省精神分裂症患者应用抗精神病药物治疗现状

目的调查河北省精神分裂症患者抗精神病药的使用现状及三级(省级、市级、县级)医院的处方差异。方法使用自制调查问卷,按一定的抽样比例,选择河北省37家专科医院或综合医院精神科进行调查,共调查603例精神分裂症患者。结果 1接受单一药物治疗421例(69.8%),联合治疗182例(30.2%);2使用频率前7位的药物分别是:氯氮平、利培酮、氯丙嗪、奋乃静、奎硫平、氟哌啶醇和奥氮平;3氯氮平、氯丙嗪的使用频率市级、县级医院高于省级医院(P0.05,P0.01),奎硫平的使用频率省级医院高于市级、县级医院(P0.01);氯氮平的使用剂量县级医院高于省级、市级医院(P0.01);4合并使用安坦者30.4%,合并苯二氮卓类药物者22.2%,合并使用β-受体阻滞剂者17.1%,合并心境稳定剂者11.8%,合并抗抑郁剂者5.8%;合并心境稳定剂及安坦者市级、县级医院高于省级医院(P0.05,P0.01)。结论河北省精神分裂症精神药物的使用方式合理,多数患者接受单一药物治疗,药物剂量在临床推荐的治疗剂量范围内。第二代抗精神病药的使用逐渐增多。氯氮平的广泛应用仍是我省精神药物使用的一个特点。3个级别的医院在药物选择上有些差异,受医生的用药习惯影响。     

Polymorphisms in the promoter regions of the matrix metalloproteinases-7, -9 and the risk of endometriosis and adenomyosis in China

Matrix metalloproteinases (MMPs) may contribute to the development of endometriosis. The aim of this study was to assess the effects of the polymorphisms in the promoters of MMP-7 (181A/G) and MMP-9 (1562C/T) on the risk of occurrence of endometriosis and adenomyosis. We genotyped 219 patients (143 women with endometriosis, 76 women with adenomyosis) and 160 control women in North China. There was a significant difference in frequency of the MMP-7 genotype between endometriosis and controls (P = 0.01) and also between adenomyosis and controls (P = 0.01). The frequency of the G allele in two groups of patients (7.3 and 7.9%) was significantly higher than in the controls (2.8%) (P = 0.01 and 0.01, respectively). Compared to the A/A genotype, the genotype with the -181G allele showed a significantly increased susceptibility to both diseases, with adjusted odds ratio of 2.62 [95% confidence interval (CI) = 1.17-5.87] for endometriosis and 3.14 (95% CI = 1.26-7.81) for adenomyosis. However, the overall genotype and allelotype distribution of the MMP-9 in the two case groups were not different from that of controls. We conclude that MMP-7-181A/G polymorphism has a potential to be a susceptibility factor for endometriosis and adenomyosis while MMP-9-1562C/T polymorphism may not provide a useful marker to predict susceptibility to endometriosis and adenomyosis, at least in women from North China.     

Age effects on atrophy rates of entorhinal cortex and hippocampus

The effects of age, subcortical vascular disease, apolipoprotein E (APOE) epsilon4 allele and hypertension on entorhinal cortex (ERC) and hippocampal atrophy rates were explored in a longitudinal MRI study with 42 cognitively normal (CN) elderly subjects from 58 to 87 years old. The volumes of the ERC, hippocampus, and white matter hyperintensities (WMH) and the presence of lacunes were assessed on MR images. Age was significantly associated with increased atrophy rates of 0.04+/-0.02% per year for ERC and 0.05+/-0.02% per year for hippocampus. Atrophy rates of hippocampus, but not that of ERC increased with presence of lacunes, in addition to age. WMH, APOE epsilon4 and hypertension had no significant effect on atrophy rates. In conclusion, age and presence of lacunes should be taken into consideration in imaging studies of CN subjects and AD patients to predict AD progression and assess the response to treatment trials.     

Functional signatures of protective antiviral T-cell immunity in human virus infections

Summary: The most common human viruses have different abilities to establish persistent chronic infection. Virus‐specific T‐cell responses are critical in the control of virus replication and in the prevention of disease in chronic infection. A large number of phenotypic markers and a series of functions have been used to characterize virus‐specific CD4⁺ and CD8⁺ T‐cell responses, and these studies have shown great phenotypic and functional heterogeneity of the T‐cell responses against different viruses. The heterogeneity of the T‐cell response has been proposed to be specific to each virus. However, over the past 2 years, several studies have provided evidence that the phenotypic and functional heterogeneity of CD4⁺ and CD8⁺ T‐cell responses is predominantly regulated by the levels of antigen load. The levels of antigen load modulate the phenotypic and functional patterns of the T‐cell response within the same virus infection. Furthermore, the functional characterization of virus‐specific CD4⁺ and CD8⁺ T‐cell responses has identified signatures of protective antiviral immunity. Polyfunctional, i.e. interleukin‐2 and interferon‐γ (IFN‐γ) secretion and proliferation, and not monofunctional, i.e. IFN‐γ secretion, CD4⁺ and CD8⁺ T‐cell responses represent correlates of protective antiviral immunity in chronic virus infections.     

城市生活垃圾低碳管理及碳减排潜力估算

以山东省章丘市生活垃圾收运及处理管理系统为例,分析了目前生活垃圾收运及处理系统的碳排放量,提出了低碳管理的改进措施,并据此预测了生活垃圾收运及处理系统碳减排的潜力。     

外科手术中大血管意外损伤的救治(附34例报告)

目的探讨外科手术中大血管意外损伤的救治经验。方法回顾分析34例术中大血管意外损伤的经验,研究其原因、特点、救治方法。结果34例中血管吻合5例(14.7%),自体静脉移植7例(20.6%), 人造血管移植1例(2.9%),血管修补9例(26.5%),血管结扎6例(17.7%),压迫等保守治疗4例(11.8%), 无法处理或未来得及处理术中死亡2例(5.9%)。输血800～15200ml,平均2862ml。结果本组死亡 6例(17.7%),截肢1例(2.9%),手术成功修复27例(79.4%)。结论 (1)手术中大血管意外损伤,可引起严重并发症和造成严重后果。(2)人为因素是主要原因,提高医生的警觉性及手术技巧,规范操作可有效地降低发生率。(31)损伤以单纯的动脉损伤为最多见,单纯静脉损伤次之,因此治疗以修补为主,静脉移植次之。(4)患者常常并发较严重的原发病,为避免顾此失彼,多脏器的兼顾与多科室问的协调在救治中较为重要。     

Fusion of CpG-ODN-stimulating dendritic cells with Lewis lung cancer cells can enhance anti-tumor immune responses

Immunogenicity of tumor cells is generally weak. Therefore, dendritic cells (DCs) have been used to boost anti-tumor responses of DC-based vaccines. DC function is highly dependent on its subsets and the level of its maturation. Nowadays, DC/tumor cell fusion vaccines are already used in clinical trials, and there are numerous studies discussing the effects of cytidine-phosphate-guanosine-containing oligonucleotides (CpG-ODN) on various cell types including DC. CpG-ODN a powerful immuno-stimulant can drive DCs fully mature, thus improve the efficacy of vaccine therapy. There are two simple ways to help load tumor antigens onto DCs by direct contact with cells themselves: fusion or co-culture of DCs with whole tumor cells. In this study, we combined these two approaches to improve the efficacy of DC/tumor cell-based vaccine. Mature DCs are adept at presenting processed Ag to T cells with loss of its capacity to capture Ag, while immature DCs are on the contrary. Our results emphasize the necessity of considering the stage of DC maturation and corresponding choice of tumor antigen delivery when designing approaches for prophylaxis or therapy of tumors using DC-based immunization protocols. We used CpG-ODN-1826-stimulated mature DCs and non-CpG-ODN-stimulating DCs as sources of tumor antigen carriers to investigate the appropriate Ag-loading ways between fusion and co-culture. Our results displayed that DC/tumor vaccine using CpG-ODN-stimulating mature DCs fused, not co-cultured, with tumor cells can generate a consistent and highly effective anti-tumor immune responses in vivo.