Huntington’s disease: from huntingtin function and dysfunction to therapeutic strategies

Huntington’s disease (HD) is a neurodegenerative disorder that usually starts in middle age and is characterized by involuntary movements (chorea), personality changes and dementia, leading to death within 10–20 years. The defective gene in HD contains a trinucleotide CAG repeat expansion within its coding region that expresses a polyglutamine repeat in the protein huntingtin. Together with the characteristic formation of aggregates in HD, aberrant protein interactions and several post-translational modifications affect huntingtin during disease progression and lead to the dysfunction and death of selective neurons in the brains of patients. The exact molecular mechanisms by which mutant huntingtin induces cell death are not completely understood but may involve the gain of new toxic functions and the loss of the beneficial properties of huntingtin. This review focuses on the cellular functions in which huntingtin is involved and how a better understanding of pathogenic pathways can lead to new therapeutic approaches. Received 24 May 2006; received after revision 5 July 2006; accepted 23 August 2006     

Effect of Ab_(1-40) on membrane permeability and intracellular free Ca~(2+) of nerve cells

Alzheimers disease (AD) is a kind of progressive neurodegenerative disease, characterized by intracellularfibrillar tangles and extracellular senile plaques, the main component of the plaques are b-amyloid (Ab), composed of 3943 amino acids[1]. Glenner and Wong first isolated Ab peptide and determined the sequence in 1984, after-wards, a series of researches were done on its production, structure determination, aggregation, hydrophobicity, re-ceptor and cell toxicity. Ab is the abnormal fiss…     

基于视频特征聚合的细胞形变动态建模

提出了一种基于图像处理架构对活细胞视频中细胞动态进行建模的方法.在这个架构下,视频中两帧间的细胞动态被表示为细胞轮廓形变和细胞内部运动的动态特征.其中,前者细胞轮廓形变利用形状上下文进行度量,而后者细胞内部运动则通过尺度不变特征变换（SIFT）流进行建模.为了更好的刻画细胞质流动,基于SIFT流的细胞运动场进一步构建细胞外观变化场.在获得上述帧级细胞动态特征之后,引入时间序列建模的方法来生成视频级的细胞动态特征.具体地,基于紧凑编码的时序特征聚合方法可以捕获整个视频中的细胞动态演变过程.活细胞视频数据库被建立以用于验证提出方法的有效性,实验结果表明提出方法对于细胞形变动态度量和分类的性能优于其它主流方法.     

铜基纳米材料在增强化学动力学治疗上的应用研究

和传统治疗相比,化学动力学治疗(CDT)被认为是一种低副作用且无创的治疗方法,在众多的治疗方法中脱颖而出.CDT通过金属离子介导的芬顿反应或类芬顿反应,将肿瘤中过表达的过氧化氢(H2O2)分解为剧毒的羟基自由基(·OH),从而杀死肿瘤细胞.近年来,铜基纳米材料在CDT中蓬勃发展,极大地提高了CDT的效率.因此,基于铜基纳米材料,归纳了通过调节肿瘤微环境来增强CDT以及其他疗法的协同治疗,为开发新型的类芬顿试剂提供了思路借鉴.     

Effects of pCai and pHi on cell-to-cell coupling

Summary Internal longitudinal resistance (r_i), a determinant of cardiac conduction, is affected by changes in intracellular calcium and protons. However, the role and mechanism by which H⁺ and Ca²⁺ may modulate r_i is uncertain. Cable analysis was performed in cardiac Purkinje fibers to measure r_i during various interventions. In some experiments, intracellular pH (pH_i) was recorded simultaneously to study the pH_i-r_i relation. Both intracellular Ca²⁺ and H⁺ independently modified r_i. However, internal resistance of cardiac fibers was insensitive to pH_i changes compared to other tissues. A latent period preceded the pH_i-related changes in r_i and the amount of change depended upon methodology. The results suggest that direct action of protons on r_i may be subordinate to other regulatory processes. Ionic regulation of internal longitudinal resistance may occur by more than one mechanism: i) direct cationic binding to sites on junctional membrane proteins; and ii) H⁺- or Ca²⁺-dependent phosphorylation of junctional proteins.     

骨桥蛋白在免疫中的作用

骨桥蛋白（OPN）是一种多功能的磷酸化糖蛋白,其涉及多种病理生理学过程.近来研究发现骨桥蛋白通过不同的翻译起始位点产生两种形式的蛋白,即分泌型骨桥蛋白（ sOPN,secreted OPN）和胞内型骨桥蛋白（iOPN,intracellular OPN）.本文主要介绍了sOPN及iOPN在免疫应答中的作用.     

Preparation and cellular uptake of PLGA particles loaded with lamivudine

Poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles loaded with lamivudine and coated with bovine serum albumin (BSA) were prepared via a double emulsion method. The influences of experiments parameters such as volume of inner aqueous phase, concentration of organic phase and ultrasonication time on the particle size and drug entrapment efficiency were investigated, obtaining PLGA particles with a diameter of ~260 nm and drug entrapment efficiency of ~35%. The particles were observed by scanning electron microscopy and transmittance electron microscopy, showing a core-shell structure. BCA assay found that 58 mg BSA was present on/in 1 g LPB particles. The loaded lamivudine showed a burst release at beginning and sustained release until 24 h in physiological conditions. Low pH could accelerate the release of lamivudine from PLGA particles, making the PLGA particles potential intelligent intracellular drug carriers. The PLGA particles were readily internalized into the human liver cells within a short time and increased gradually with the prolongation of incubation time regardless of the loading of lamivudine. The particles either resided within lysosomes or transferred to cytoplasm, but could not enter into the cell nucleus. The cell viability was not significantly influenced in the presence of the particles regardless of lamivudine encapsulation, suggesting that this kind of particles may be a good candidate for the intracellular anti-hepatitis B drug delivery.     

不同木质底物诱导下桦剥管菌细胞内差异蛋白质分析

【目的】研究桦剥管菌在不同木质底物诱导下细胞内蛋白的差异表达情况,探讨桦剥管菌降解木材机理。【方法】以白桦、云杉木屑为诱导底物,利用蛋白质组双向电泳技术(2-DE)结合质谱技术(MALDI-TOF/TOF MS),检测桦剥管菌在不同树种木屑诱导下与对照组(未加木屑)相比菌体胞内蛋白质变化情况,对差异蛋白进行生物信息学分析。【结果】在白桦和云杉木屑诱导下,桦剥管菌细胞内蛋白表达发生了明显变化,处理组(添加木屑)共检测到32个细胞内差异表达蛋白点,经质谱检测及数据库检索,成功鉴定17个差异蛋白点,这些蛋白具有转移酶、水解酶、蛋白结合、细胞信号转导等分子功能,涉及分解代谢、有机物质代谢、氮化合物代谢、初级代谢、细胞生物合成和刺激响应过程。【结论】桦剥管菌降解木材是多种蛋白质共同作用的结果,通过调节多种代谢过程中的相关蛋白表达来发挥作用。     

一类具有时滞及非线性感染率的病毒感染模型的稳定性及分支分析

将时滞及饱和发生率引入到一类具有初级细胞毒性T淋巴细胞(CTLp)和效应细胞毒性T淋巴细胞(CTLe)免疫反应的病毒感染模型,证明了改进后模型无病毒感染平衡点及无免疫平衡点的全局渐近稳定性.同时,给出了免役应答平衡点(正平衡点)产生Hopf分支的充分条件.最后,数值模拟验证了理论结果.     

水库藻类细胞内微囊藻毒素变化规律

摘要:应用高效液相色谱,对北方某水库5个采样点藻类细胞内3种微囊藻毒素(MC-LR,RR和YR)进行了为期一年的监测.研究了细胞内微囊藻毒素随时间的变化规律,并探讨了环境因子对细胞内微囊藻毒素产生的影响.结果表明,藻类细胞内3种微囊藻毒素被检出的时间不一致,LR异构体在4月份下旬即可检测到,而RR和YR异构体则要到5月份中旬才能检测到.LR和YR异构体在9月份出现高峰值,而RR异构体在10月份达到全年的最大值.4—9月份,LR异构体含量最大,RR异构体次之,YR异构体含量最小;10—12月份,RR异构体含量最大,10月和11月LR含量大于YR,但是12月份LR未检出,而YR含量比11月份还高.环境因子对细胞内微囊藻毒素的影响也不一致:溶解氧和硝酸盐氮都与3种异构体呈显著负相关;总磷、溶解性总磷和磷酸盐都与RR异构体呈显著正相关,氨氮和LR异构体之间存在显著负相关.