CHEK2*1100delC and susceptibility to breast cancer: a collaborative analysis involving 10,860 breast cancer cases and 9,065 controls from 10 studies

Previous studies of families with multiple cases of breast cancer have indicated that a frameshift alteration in the CHEK2 gene, 1100delC, is associated with an elevated frequency of breast cancer in such families, but the risk associated with the variant in other situations is uncertain. To evaluate the breast cancer risk associated with this variant, 10,860 breast cancer cases and 9,065 controls from 10 case-control studies in five countries were genotyped. CHEK2*1100delC was found in 201 cases (1.9%) and 64 controls (0.7%) (estimated odds ratio 2.34; 95% CI 1.72–3.20; P=.0000001). There was some evidence of a higher prevalence of CHEK2*1100delC among cases with a first-degree relative affected with breast cancer (odds ratio 1.44; 95% CI 0.93–2.23; P=.10) and of a trend for a higher breast cancer odds ratio at younger ages at diagnosis (P=.002). These results confirm that CHEK2*1100delC confers an increased risk of breast cancer and that this risk is apparent in women unselected for family history. The results are consistent with the hypothesis that CHEK2*1100delC multiplies the risks associated with susceptibility alleles in other genes to increase the risk of breast cancer.     

生物处理石油污染的研究概况

自20世纪80年代以来,人们对微生物降解石油进行了深入的研究,并逐步将这一技术应用于实际环境的处理中。处理环境中菌群的数量及组成、生物降解的有效性、实际环境中出现的影响因子对降解的影响、石油的毒性和极限环境下的生物降解石油等,许多学者都进行了广泛的研究。此外,一些研究者也尝试着通过构建生物降解模型,可以使微生物降解石油的研究能从经验上升到理论。     

In vitro Anti-viral Activity of the Total Alkaloids from Tripterygium hypoglaucum against Herpes Simplex Virus Type 1

Herpes simplex virus type 1 (HSV-1) is a commonly occurring human pathogen worldwide. There is an urgent need to discover and develop new alternative agents for the management of HSV-1 infection. Tripterygium hypoglaucum (level) Hutch (Celastraceae) is a traditional Chinese medicine plant with many pharmacological activities such as anti-inflammation, anti-tumor and antifertility. The usual medicinal part is the roots which contain about a 1% yield of alkaloids. A crude total alkaloids extract was prepared ...     

球孢白僵菌Pr1蛋白酶基因cDNA克隆与序列分析

从球孢白僵菌菌株Bb202中克隆了昆虫蛋白酶Pr1的基因。使用特异性引物,分别以基因组DNA和mRNA为模板进行PCR反应,得到了球孢白僵菌的Pr1蛋白酶基因cDNA和结构基因序列。测序结果表明球孢白僵菌Pr1蛋白酶结构基因全长大小为1606bp,含有3个内含子,分别为69、61和68bp。其ORF全长1140bp,预测编码379个氨基酸残基。成熟蛋白理论分子量为38.8kD,理论等电点为8.06。为进一步研究球孢白僵菌Pr1基因,并构建高毒力工程菌株提供了理论基础。     

Ezetimibe blocks the internalization of NPC1L1 and cholesterol in mouse small intestine

The multiple transmembrane protein Niemann-Pick C1 like1 (NPC1L1) is essential for intestinal cholesterol absorption. Ezetimibe binds to NPC1L1 and is a clinically used cholesterol absorption inhibitor. Recent studies in cultured cells have shown that NPC1L1 mediates cholesterol uptake through vesicular endocytosis that can be blocked by ezetimibe. However, how NPC1L1 and ezetimibe work in the small intestine is unknown. In this study, we found that NPC1L1 distributed in enterocytes of villi and transit-amplifying cells of crypts. Acyl-CoA cholesterol acyltransferase 2 (ACAT2), another important protein for cholesterol absorption by providing cholesteryl esters to chylomicrons, was mainly presented in the apical cytoplasm of enterocytes. NPC1L1 and ACAT2 were highly expressed in jejunum and ileum. ACAT1 presented in the Paneth cells of crypts and mesenchymal cells of villi. In the absence of cholesterol, NPC1L1 was localized on the brush border of enterocytes. Dietary cholesterol induced the internalization of NPC1L1 to the subapical layer beneath the brush border and became partially colocalized with the endosome marker Rab11. Ezetimibe blocked the internalization of NPC1L1 and cholesterol and caused their retention in the plasma membrane. This study demonstrates that NPC1L1 mediates cholesterol entering enterocytes through vesicular endocytosis and that ezetimibe blocks this step in vivo.     

Association of N-Terminal Pro-Brain Natriuretic Peptide with Cognitive Function and Depression in Elderly People with Type 2 Diabetes

Background

Type 2 diabetes mellitus is associated with risk of congestive heart failure (CHF), cognitive dysfunction and depression. CHF itself is linked both to poor cognition and depression. The ventricular N-terminal pro-brain natriuretic peptide (NT-proBNP) is a marker of CHF, suggesting potential as a marker for cognitive impairment and/or depression. This was tested in the Edinburgh Type 2 Diabetes Study (ET2DS).

Methodology and Principal Findings

Cross-sectional analysis of 1066 men and women aged 60–75 with type 2 diabetes. Results from seven neuropsychological tests were combined in a standardised general cognitive ability factor, ‘g’. A vocabulary-based test estimated pre-morbid cognitive ability. The Hospital Anxiety and Depression Scale (HADS) assessed possible depression. After adjustment for age and sex, raised plasma NT-proBNP was weakly associated with lower ‘g’ and higher depression scores (ß −0.09, 95% CI −0.13 to −0.03, p = 0.004 and ß 0.08, 95% CI 0.04 to 0.12, p<0.001, respectively). Comparing extreme quintiles of NT-proBNP, subjects in the highest quintile were more likely to have reduced cognitive ability (within the lowest tertile of ‘g’) and ‘possible’ depression (HADS depression ≥8) (OR 1.80; 95% CI: 1.20, 2.70; p = 0.005 and OR 2.18; 95% CI: 1.28, 3.71; p = 0.004, respectively). Associations persisted when pre-morbid ability was adjusted for, but as expected were no longer statistically significant following the adjustment for diabetes-related and vascular co-variates (β −0.02, 95% CI −0.07 to 0.03, p>0.05 for ‘g’; β 0.03, 95% CI −0.02 to 0.07, p>0.05 for depression scores).

Conclusion

Raised plasma NT-proBNP was weakly but statistically significantly associated with poorer cognitive function and depression. The prospective phases of the ET2DS will help determine whether or not NT-proBNP can be considered a risk marker for subsequent cognitive impairment and incident depression and whether it provides additional information over and above traditional risk factors for these conditions.     

超声辅助提取凤丹籽总黄酮的工艺研究

本文以经脱脂处理后的凤丹籽为原料,在单因素实验的基础上,选取乙醇浓度、料液比、超声时间和超声功率为自变量,以总黄酮得率为响应值,采用Box-Behnken响应面设计分析方法优化凤丹籽总黄酮的提取工艺。通过此模型得出:超声时间对凤丹籽总黄酮提取的影响最为显著,超声时间和乙醇浓度,超声时间和料液比,超声时间和超声功率之间的交互作用显著。模型预计凤丹籽总黄酮提取的最佳工艺条件为:乙醇浓度75%,料液比1:21 g/mL,超声时间49 min,超声功率240 w,在此条件下,总黄酮得率平均值为9.015 mg/g。     

亚热带典型树种对模拟酸雨胁迫的高光谱响应

对亚热带地区6种典型树种幼苗在不同模拟酸雨梯度下的光谱响应特征进行了研究。结果表明,针叶树种和阔叶树种对酸雨敏感性具有明显差异。针叶树种马尾松、杉木和香榧对酸雨敏感性高于阔叶树种刨花楠、香樟和杨梅。针叶树种内部,马尾松和杉木叶绿素含量随酸雨浓度变化的幅度明显高于香榧;而阔叶树种内部,刨花楠、香樟和杨梅三者之间无显著差别。马尾松、香樟和香榧不能承受长时间高浓度酸雨胁迫,叶绿素含量呈先增加后减少趋势,杉木则先减少后增加,杨梅能承受长时间高浓度酸雨胁迫,pH值2.5处理下叶绿素含量高于pH值5.6处理。刨花楠4期试验中叶绿素含量变化无明显规律。各受试植物光谱反射率红边位置与其叶绿素含量变化规律基本一致。针叶树种马尾松和香榧主要表现为"蓝移",杉木则先"蓝移"后"红移",表现出对高浓度酸雨长时间的抗性;阔叶树种香樟先"红移"后"蓝移",对高浓度模拟酸雨表现出先促进后抑制现象,杨梅光谱反射率一阶导数曲线比较平缓,无明显"红移"和"蓝移"现象,刨花楠则"红移"和"蓝移"交替出现,与其叶绿素含量变化相一致,对酸雨敏感性不明显。     

PNRC1核定位信号序列的鉴定

为鉴定富含脯氨酸核受体辅调节蛋白1(PNRC1)分子的核定位信号序列（nuclear localization signal sequence, NLS）,在生物信息学方法预测的基础上,先构建野生型PNRC1及删除预测NLS的PNRC1突变体的绿色荧光蛋白（GFP）重组表达载体,转染细胞后通过激光共聚焦显微镜观察PNRC1分子在删除预测NLS后细胞内的定位变化.然后,将预测的NLS编码序列直接连到GFP表达载体上,以及将预测的NLS加到胞浆蛋白上构建其GFP重组表达载体,转染细胞,观察预测的NLS能否把构建的重组体都带到细胞核内.结果显示,删除PNRC1中预测的NLS后,其定位从细胞核中变为主要定位在细胞浆中,而预测的NLS能把GFP或胞浆中的蛋白带到细胞核中.研究表明,预测的NLS为PNRC1分子真正的NLS.     

Governmental policies on HIV infection in China

EVOLUTION OF THE GOVERNMENT POLI- CIES Looking back 20 and more years, one could have hardly imagined that such great changes would have happened to the governmental policies on HIV/AIDS in China. In the earlier phase of the epidemic, laws and regulations were drafted based on the practices and experiences of preven- tion and control of other infectious diseases, such as isolation, quarantine and compulsory testing and examina- tions etc. When the HIV/AIDS epidemic was firstl…