众说纷纭的大牌明星基尔默

前些时候,美国公映了电影《圣徒》,片中的主人公西蒙·坦普拉在欧美家喻户晓。圣徒西蒙的故事起源于30年代的通俗小说家莱斯利·查特里斯,他的这部作品多次被搬上银幕,60年代由罗杰·摩尔主演的电视剧集《圣徒》也曾风靡一时。最新版本的《圣徒》推出后,旋即打进北美卖座片排行榜,受到观众欢迎。

名人争当快乐四眼

曾经一度,电影明星们戴上墨镜以躲避热情过头的追星族、擅自闯入的指影师,以及——偶尔有时候是——太阳光。但如今。

RELATIONSHIP OF HOMOCYSTEINE AND GENE POLYMORPHISMS OF ITS RELATED METABOLIC ENZYMES WITH ALZHEIMER'S DISEASE

Objective To investigate the relationship of plasma homocysteine (Hcy) levels and the gene polymorphisms of N5, N10-methylenetetrahydrofolate reductase (MTHFR), cystathionine β-synthase (CBS) with Alzheimer’s disease (AD). Methods Plasma Hcy levels were measured by means of high voltage capillary electrophoresis with ultra-violet detection, the polymorphisms of C677T in exon 4 of MTHFR gene and 844ins68 in exon 8 of CBS gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 105 AD patients and 102 non-AD controls. All controls were excluded from cardiocerebrovascular disorders and other diseases. Results The plasma Hcy level in AD patients (16.04 ± 3.84 μmol/L) was significantly higher than that in the controls(11.94 ± 3.87 μmol/L, P < 0.001). There were no significant differences of the genotype and allele frequencies of MTHFR C677T mutation and CBS 844ins68 mutation between the patients and controls. However, the T allele of MTHFR gene was found to relate with the plasma Hcy level increase in all subjects. Conclusion The elevated plasma Hcy level in AD patients is probably involved in the pathogenesis of AD, which may be due to the environmental factor rather than genetic factors of the mutations of MTHFR and CBS.

ANALYSIS OF INTERLEUKIN-1 RECEPTOR ANTAGONIST GENE POLYMORPHISM IN CHINESE PATIENTS WITH ALZHEIMER'S DISEASE

Objective To identify an interaction between the interleukin-1 receptor antagonist gene polymorphism and risk of Al-zheimer’s disease. Methods The study included 117 healthy controls, 85 patients with Alzheimer’s disease in a Northeastern Chinese popu-lation of Han nationality. Genotypes were determined by a polymerase chain reaction amplification of the intron 2 fragment, harbouring a variable number of short tandem nucleotide sequences. Amplification products were separated on a 2% agarose gel. Results The allele 2 frequency was 27% in healthy controls, and 21% in patients with Alzheimer’s disease. Thus for all-ele 2 as well as for all other alleles, genotypes, or carriage rates, no significant differences compared with controls. Conclusions No association of interleukin-1 receptor antagonist gene polymorphism with Alzheimer’s disease was iden-tified in this population. It is also possible that the increased risk and disease modifying effects are caused by linkage disequ-ilibrium with other genomic variants in other nearby genes.

Expression of the apoptosis-related proteins caspase-3 and NF-κB in the hippocampus of Tg2576 mice

Objective To investigate the relations between neuroapoptosis and the onset and development of Alzheimer’s disease （AD）, especially the role of NF-κB in the regulation of neuroapoptosis. Methods Caspase-3 and NF-κB （p50） expressions in the CA3 region of the hippocampus in APPswe Tg2576 transgenic mice were studied from postnatal day 0-180, using Nissl staining, immunohistochemistry and RT-PCR methods. Results Both neuronal apoptosis and NF-κB activity decreased gradually with the increase of age in wild type and Tg2576 mice. However, the number of caspase-3-positive or NF- κB-positive pyramidal cells in Tg2576 mice was greater than that in age-matched wild type mice, with significant differences after postnatal day 14 （P 0.01 or P 0.05）. Linear regression analyses of caspase-3 and NF-κB expression demonstrated a correlation between neuroapoptosis and activity of NF-κB. Conclusion The process of neuroapoptosis is consistent with the onset and development of AD. Furthermore, the observed correlation between neuroapoptosis and NF-κB activity suggests a role of NF-κB in hippocampal neuroapoptosis.

Oxidative damage increased in presenilin1/presenilin2 conditional double knockout mice

Objective This report aims to describe the oxidative damage profile in brain ofpresenilinl andpresenilin2 conditional double knockout mice （dKO） at both early and late age stages, and to discuss the correlation between oxidative stress and the Alzheimer-like phenotypes of dKO mice. Methods The protein level of Aβ42 in dKO cortex and free 8-OHdG level in urine were measured by ELISA. Thiobarbituric acid method and spectrophotometric DNPH assay were used to determine the lipid peroxidation and protein oxidation in cortex, respectively. SOD and GSH-PX activities were assessed by SOD Assay Kit-WST and GSH-PX assay kit, separately. Results Significant decrease of Aβ42 was verified in dKO cortex at 6 months as compared to control mice. Although lipid peroxidation （assessed by MDA） was increased only in dKO cortex at 3 months and protein oxidation （assessed by carbonyl groups） was basically unchanged in dKO cortex, ELISA analysis revealed that free 8-OHdG, which was an indicator of DNA lesion, was significantly decreased in urine of dKO mice from 3 months to 1 2 months. Activities of SOD and GSH-PX in dKO and control cortices showed no statistical difference except a significant increase of GSH-PX activity in dKO mice at 9 months. Conclusion Oxidative damage, especially DNA lesion, was correlated with the neurodegenerative symptoms that appeared in dKO mice without the deposition of Aβ42. Triggers of oxidative damage could be the inflammatory mediators released by activated microglia and astrocytes.

《狂热》

《狂热》编导：迈克尔·曼主要演员：罗伯特·德尼罗、艾尔·帕西诺等美国影片１９９５故事梗概四个蒙面大盗在路口截住一辆运送贵重物品的邮车，炸开保险箱，取走１６０万元债券。其中一个开枪把三个警卫全部打死，然后四匪逃得无影无踪。此案由洛杉矶抢劫和凶杀案组负责...

借问:君能造树否?——关于《树》之思

借问：君能造树否？——关于《树》之思冯世则……“民胞物与”实难做到，但至少让树们比较地“地得其所”，虽有憾焉而略减报载上海市民“告别小手帕、流行餐巾纸”，见之慨然，想起了自己悖于此风的做法。人家已然时兴用纸巾揩鼻涕擦油嘴，连小手帕（即男士叠出三尖、洁...

喜剧才子亚当·桑德勒

亨利·罗斯是一个海洋生物兽医,他在夏威夷奥湖岛上工作。一天亨利在咖啡店遇到了美丽、聪明、可爱的露西·怀特摩尔。愉快的交谈之后,亨利约露西第二天再见面,可他并不知道,露西因为一年前一次交通意外事故而损伤了大脑,使她每天早晨醒来都会把前一天的事情忘得一干二净。由此,亨利为赢得露西的芳心,他只有把每次见面当作初次约会一样……

The Gab2 in signal transduction and its potential role in the pathogenesis of Alzheimer’s disease

The growth factor receptor-bound protein 2 （Grb2） -associated binder （Gab） proteins are intracellular scaffolding/ docking molecules,and participate in multiple signaling pathways,usually acting as the downstream effector of protein-tyrosine kinases （PTKs） -triggered signal transduction pathway.When phosphorylated by PTKs,Gab proteins can recruit several signaling molecules （p85,SHP2,and Crk） ,and subsequently activate multiple transmitting signals that are critical for cell growth,survival,differentiation and apoptosis.Recently,it has been reported that Gab2 polymorphism is associated with the increase in the risk of Alzheimer’s disease （AD） and is involved in the pathogenesis of AD.This review mainly focuses on the structure and function of Gab2 protein and its role in the pathogenesis of AD.

Association between NMDA receptor subunit 2b gene polymorphism and Alzheimer’s disease in Chinese Han population in Shanghai

Objective N-methyl-D-aspartate（NMDA）receptor has been indicated to be involved in the pathogenesis of Alzheimer’s disease（AD）.The NMDA receptor subunit 2b（NR2B）has attracted more attention due to its characteristic distribution and selective reduction in AD brain.The present study aimed to explore the association between NMDA gene polymorphism and AD.Methods A total of 63 AD patients and 68 normal controls in Shanghai city were employed in this study.Genotype of C2664T variant（rs1806201）in the exon13 of GRIN2B gene was determined by gene sequencing. Results Among AD patients,15（23.6%）subjects were identified as C/C genotype,and 35（55.6%）were identified as C/T genotype.The left 13（20.6%）subjects were identified as T/T genotype.In normal controls,15（22.1%）subjects were identified as C/C genotype,39（57.4%）as C/T genotype and 14（20.6%）as T/T genotype.The distribution frequency of neither GRIN2B C2664T genotype（P=0.895）nor allele（P=0.790）was significantly different between AD patients and normal controls,even when the subjects were stratified by gender and age of disease onset in AD patients.Conclusion The results suggest that there is no relation between GRIN2B C2664T polymorphism and AD in Chinese Han population of Shanghai City.

Alzheimer's disease treated with combined therapy based on nourishing marrow and reinforcing Qi

OBJECTIVE:To study the efficacy and safety of combined Traditional Chinese Medicine(TCM) therapy based on nourishing marrow to improve intellect and reinforcing Qi to activate bloodon mild to moderate Alzheimer's disease(AD).METHODS:Sixty-six patients with AD,whoseMini-Mental State Examination(MMSE) score were from 10-24,were randomized equally into an intervention group and a control group.The control group was given Aricept(5 mg,once daily).The intervention group was further divided into Yang-Qi deficiency(n = 18) and of Yin-Qi deficiency(n = 15)subgroups.Patients in the Yang-Qi deficiency group were intravenously administered Shenfu injection,60 mL,and deproteinized calf blood injection(DCBl),1.2 g,once daily.The Yin-Qi deficiency group was given Shenmai injection,60 mL,and DCBl,1.2 g,once daily.Each course lasted 21 days.RESULTS:Compared with the control group and with pre-treatment in the same group,MMSE,clinical dementia rating,and activities of daily living scale scores in the intervention group were significantly improved(all P<0.05).These metrics mildly improved in the control group compared with before treatment(P>0.05).No adverse effects were observed in any group during treatment.CONCLUSION:We found that combined TCM therapy is effective and safe for managing mild to moderate AD.

Effect of Xixin decoction on O-linked N-acetylglucosamine Glycosylation of tau proteins in rat brain with sporadic Alzheimer disease

OBJECTIVE： To study the effects of Xixin decoction （XXD） on O-linked N-acetylglucosamine （O-GIcNAc） glycosylation of tau proteins in rat brain with spo- radic Alzheimer disease （SAD）, and discuss its possi- ble mechanism on prevention and treatment of SAD. METHODS： The rat model of SAD was established by intracerebroventricular injection of streptozoto- cin. The specific pathogen free male Sprague-Daw- ley rats were randomly divided into sham-opera- tion group （S）, model group （M）, donepezil group （D）, XXD at a low dose group （XL）, XXD at a medium dose group （XM） and XXD at a high dose group （XH）. After treatment and praxiology test, immuno- histochemistry and western blotting were used to detect O-GIcNAc glycosylation level of tau proteins in rat brain with SAD. O-GIcNAc glycosylation and expression of tau proteins were detected by O-GIcNAc-specific antibodies RL2 and CTD110.6. RESULTS： O-GIcNAc glycosylated proteins enriched by succinylated wheat germ agglutinin significant- ly improved in the hippocampus of SAD rats. Thedifferences were statistically significant among XXD groups （P〈0.05, P〈0.01）, while no obvious dif- ferences were observed between D group and M group （P〉0.05）. CONCLUSION： XXD can significantly improve O-GIcNAc glycosylation level of tau proteins in the hippocampus of SAD rats, which maybe inhibit hy- perphosphorylation of tau proteins on key sites and its toxicity, and prevent the pathological pro- cess of SAD.

A genome-wide association study of Alzheimer's disease using random forests and enrichment analysis

Alzheimer's disease(AD) is a serious neurodegenerative disorder and its cause remains largely elusive.In past years,genome-wide association(GWA) studies have provided an effective means for AD research.However,the univariate method that is commonly used in GWA studies cannot effectively detect the biological mechanisms associated with this disease.In this study,we propose a new strategy for the GWA analysis of AD that combines random forests with enrichment analysis.First,backward feature selection using random forests was performed on a GWA dataset of AD patients carrying the apolipoprotein gene(APOEε4) and 1058 susceptible single nucleotide polymorphisms(SNPs) were detected,including several known AD-associated SNPs.Next,the susceptible SNPs were investigated by enrichment analysis and significantly-associated gene functional annotations,such as 'alternative splicing','glycoprotein',and 'neuron development',were successfully discovered,indicating that these biological mechanisms play important roles in the development of AD in APOEε4 carriers.These findings may provide insights into the pathogenesis of AD and helpful guidance for further studies.Furthermore,this strategy can easily be modified and applied to GWA studies of other complex diseases.

Design and synthesis of 2-aminobenzimidazoles as potential BACE1 inhibitors

Fragment-based drug discovery （FBDD） has been widely applied in the research of aspartyl protease inhibitors. In the present study, we reported our work on 2-aminobenzimidazole as the original fragment, which was predicted to bind with the catalytic aspartyl dyad （Asp228 and Asp32） of D-site amyloid precursor protein cleaving enzyme 1 （BACE1）. A series of novel 2-aminobenzimidazole derivatives were designed and synthesized. The results from FRET assay revealed that three out of the 12 designed 2-aminobenzimidazoles could inhibit more than 50% of the enzymatic potency of BACE1 at 10 pM. Docking study showed that 2-aminobenzimidazole could form multiple hydrogen bonds and occupy S1/$2＇ pockets well.