Alzheimer’s Disease Animal Models: Elucidation of Biomarkers and Therapeutic Approaches for Cognitive Impairment

Alzheimer’s disease (AD) is an age-related and progressive neurodegenerative disorder. It is widely accepted that AD is mainly caused by the accumulation of extracellular amyloid β (Aβ) and intracellular neurofibrillary tau tangles. Aβ begins to accumulate years before the onset of cognitive impairment, suggesting that the benefit of currently available interventions would be greater if they were initiated in the early phases of AD. To understand the mechanisms of AD pathogenesis, various transgenic mouse models with an accelerated accumulation of Aβ and tau tangles have been developed. However, none of these models exhibit all pathologies present in human AD. To overcome these undesirable phenotypes, APP knock-in mice, which were presented with touchscreen-based tasks, were developed to better evaluate the efficacy of candidate therapeutics in mouse models of early-stage AD. This review assesses several AD mouse models from the aspect of biomarkers and cognitive impairment and discusses their potential as tools to provide novel AD therapeutic approaches.     

EFFECT OF UNCOUPLING OXIDATIVE PHOSPHORYLATION ON THE ECONOMICS OF THE ACTIVATED SLUDGE PROCESS

Conventionally, activated sludge units are aerated continuously for the biological oxidation of organic carbon and ammonium. The respiration of the microflora which develops is tightly coupled to adenosine triphosphate (ATP) formation. (ATP is the energy currency of the cell, growth is proportional to the ATP formed). A management strategy is reported here which uses alternating periods of aeration and non-aeration (AAA process), then respiration is uncoupled from ATP formation and hence from cell growth. Less sludge is formed but the removal of Biochemical Oxygen Demand (BOD) is no less efficient.

In addition, ammonium is oxidized to nitrate during aeration and is then denitrified in the non-aerated period. Savings of 25% to 40% in aeration charges have been demonstrated. This entails no change in the physical design of the plant, no reductant is needed for denitrification, foam is reduced and the sludge settles well. The final effluent demands less chlorine and has a low nitrogen content. The control of the periods of air on/air off can be automated in response to the rate of uptake of dissolved oxygen (DO).     

Copula选择方法

介绍了当前常用的Copula函数的参数估计方法及最优Copula函数的选择方法,着重研究了一种基于贝叶斯理论的Copula函数的择优选择方法.最后对上海证券综合指数和深圳证券成分指数进行Copula函数择优选择,结果表明,得到的Copula较好地描述了其相依结构.     

Monophosphorylation of cornstarch to improve its sizing properties for heat‐sensitive wool yarns at reduced temperature

Commercial cornstarch was mono‐phosphorylated to different levels of substitution in order to investigate the effect of phosphorylation on the properties of cornstarch for sizing heat‐sensitive wool yarns at reduced temperature. The influences of starch phosphorylation and sizing temperature upon apparent viscosity and viscosity stability of cooked starch paste, starch retrogradation, adhesion to wool fibers, performance of starch film, aerobic biodegradation, mechanical properties, and hairiness of sized wool yarns were evaluated. The phosphorylation level was varied from 0.021 to 0.082 in degree of substitution (DS), while the temperature considered was from 60 to 95°C. It was found that mono‐phosphorylation of starch resulted in enhanced paste stability, reduced retrogradation, strong adhesion to wool fibers, increased performances of starch film, improved mechanical properties of sized wool yarns, and decreased hairiness on surface of sized yarns even if paste temperature was lowered to 60°C. Initially increasing phosphorylation level enhanced positive effects, but excessively increasing the level was not applicable due to marked reduction in tensile strength of starch film. The phosphorylation with a DS value of 0.061 could improve the performances of cornstarch for sizing wool yarns at 60–80°C. Moreover, measurement on BOD₅/COD ratios demonstrated that the phosphorylation did not impede aerobic biodegradation of starch. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

携带socs3基因的溶瘤腺病毒的构建及体外抗肿瘤活性的研究

SOCS3（suppressor of cytokine signaling 3）是JAK/STAT信号通路的负调控因子,SOCS3间接调控的STAT3磷酸化与肿瘤的发生密切相关。本试验构建携带socs3的溶瘤腺病毒AdCN305-SOCS3,在细胞水平研究socs3对肿瘤的抑制作用,并评估AdCN305-SOCS3的抗肿瘤效果。该病毒感染多种肿瘤细胞,均能特异性扩增,同时表达功能正常的SOCS3蛋白,从而抑制STAT3磷酸化,引起肿瘤细胞的明显凋亡。对AdCN305-SOCS3的研究,证实SOCS3蛋白和AdCN305-SOCS3病毒都具有抗肿瘤的功能,在肿瘤的靶向基因治疗研究中具有广阔的应用前景。     

植物的线粒体基因组研究

线粒体作为最重要的细胞器之一,是细胞氧化磷酸化进行的场所。它有其自身的基因组,也有其独立的转录、翻译体系,甚至其使用的遗传密码也与核基因组的有所不同。本文介绍了高等植物线粒体基因组的特点及研究现状。由于高等植物的细胞质雄性不育性与线粒体ＤＮＡ有密切关系,本文对此也作了阐述。     

小麦面筋蛋白的磷酸化改性研究

用正交试验法对小麦面筋蛋白进行磷酸化改性的工艺条件优选。结果表明 ,在三聚磷酸钠与小麦面筋蛋白之比为 3∶1 0、反应时间为 0 5h、反应温度为 2 0℃及反应pH值为 1 0 0的最佳条件下制备的磷酸化小麦面筋蛋白功能特性有大幅度提高     

增强型LMS自适应电网畸变电流检测算法研究

为解决常规LMS自适应算法在电网畸变电流检测中存在收敛速度和稳态误差之间的矛盾,本文提出了一种增强型LMS自适应算法。该算法通过对输入信号环节进行预置带通滤波处理,改善信号的自相关数值,实现了基波处的幅值无衰减且相位无延时,同时通过对LMS算法权值和误差环节嵌入低通滤波拓扑结构,达到了降低畸变电流波动的目的。最后在对常规算法与增强型LMS算法分析比较的基础上,通过仿真和实验证明了本文理论分析的可行性,验证了此算法在畸变电流检测中的有效性和准确性。     

Tau Exon 10 Inclusion by PrPC through Downregulating GSK3β Activity

Tau protein is largely responsible for tauopathies, including Alzheimer’s disease (AD), where it accumulates in the brain as insoluble aggregates. Tau mRNA is regulated by alternative splicing, and inclusion or exclusion of exon 10 gives rise to the 3R and 4R isoforms respectively, whose balance is physiologically regulated. In this sense, one of the several factors that regulate alternative splicing of tau is GSK3β, whose activity is inhibited by the cellular prion protein (PrP^C), which has different physiological functions in neuroprotection and neuronal differentiation. Moreover, a relationship between PrP^C and tau expression levels has been reported during AD evolution. For this reason, in this study we aimed to analyze the role of PrP^C and the implication of GSK3β in the regulation of tau exon 10 alternative splicing. We used AD human samples and mouse models of PrP^C ablation and tau overexpression. In addition, we used primary neuronal cultures to develop functional studies. Our results revealed a paralleled association between PrP^C expression and tau 4R isoforms in all models analyzed. In this sense, reduction or ablation of PrP^C levels induces an increase in tau 3R/4R balance. More relevantly, our data points to GSK3β activity downstream from PrP^C in this phenomenon. Our results indicate that PrP^C plays a role in tau exon 10 inclusion through the inhibitory capacity of GSK3β.