Tau Cleavage Contributes to Cognitive Dysfunction in Strepto-Zotocin-Induced Sporadic Alzheimer’s Disease (sAD) Mouse Model

Tau cleavage plays a crucial role in the onset and progression of Alzheimer’s Disease (AD), a widespread neurodegenerative disease whose incidence is expected to increase in the next years. While genetic and familial forms of AD (fAD) occurring early in life represent less than 1%, the sporadic and late-onset ones (sAD) are the most common, with ageing being an important risk factor. Intracerebroventricular (ICV) infusion of streptozotocin (STZ)—a compound used in the systemic induction of diabetes due to its ability to damage the pancreatic β cells and to induce insulin resistance—mimics in rodents several behavioral, molecular and histopathological hallmarks of sAD, including memory/learning disturbance, amyloid-β (Aβ) accumulation, tau hyperphosphorylation, oxidative stress and brain glucose hypometabolism. We have demonstrated that pathological truncation of tau at its N-terminal domain occurs into hippocampi from two well-established transgenic lines of fAD animal models, such as Tg2576 and 3xTg mice, and that it’s in vivo neutralization via intravenous (i.v.) administration of the cleavage-specific anti-tau 12A12 monoclonal antibody (mAb) is strongly neuroprotective. Here, we report the therapeutic efficacy of 12A12mAb in STZ-infused mice after 14 days (short-term immunization, STIR) and 21 days (long-term immunization regimen, LTIR) of i.v. delivery. A virtually complete recovery was detected after three weeks of 12A12mAb immunization in both novel object recognition test (NORT) and object place recognition task (OPRT). Consistently, three weeks of this immunization regimen relieved in hippocampi from ICV-STZ mice the AD-like up-regulation of amyloid precursor protein (APP), the tau hyperphosphorylation and neuroinflammation, likely due to modulation of the PI3K/AKT/GSK3-β axis and the AMP-activated protein kinase (AMPK) activities. Cerebral oxidative stress, mitochondrial impairment, synaptic and histological alterations occurring in STZ-infused mice were also strongly attenuated by 12A12mAb delivery. These results further strengthen the causal role of N-terminal tau cleavage in AD pathogenesis and indicate that its specific neutralization by non-invasive administration of 12A12mAb can be a therapeutic option for both fAD and sAD patients, as well as for those showing type 2 diabetes as a comorbidity.     

Cyanobacteria,Cyanotoxins, and Neurodegenerative Diseases: Dangerous Liaisons

The prevalence of neurodegenerative disease (ND) is increasing, partly owing to extensions in lifespan, with a larger percentage of members living to an older age, but the ND aetiology and pathogenesis are not fully understood, and effective treatments are still lacking. Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis are generally thought to progress as a consequence of genetic susceptibility and environmental influences. Up to now, several environmental triggers have been associated with NDs, and recent studies suggest that some cyanotoxins, produced by cyanobacteria and acting through a variety of molecular mechanisms, are highly neurotoxic, although their roles in neuropathy and particularly in NDs are still controversial. In this review, we summarize the most relevant and recent evidence that points at cyanotoxins as environmental triggers in NDs development.     

Complex Systems Architecture

Neil Spiller reveals the complexity of architectural systems to us, or is it the complexity of the architectural mind? For Spiller, the potential of a single notation as a seed for a truly ecological architecture provides an essential catalyst, triggering a multifaceted musing that takes in diagrams, Paul Preissner's new competition entry for the Taiwan Centre of Disease Control and his future work with Dr Rachel Armstrong on complex biological systems. Copyright © 2009 John Wiley & Sons, Ltd.     

基于高阶最小生成树的脑网络分析及对阿兹海默氏症患者的分类

利用静息态功能磁共振成像技术来研究大脑的功能连接网络是当前脑疾病研究的重要方法之一。这种方法能准确地检测包括阿兹海默氏症在内的多种脑疾病。然而,传统的网络只是研究两个脑区之间相关程度,而且缺乏对大脑区域之间更深层次的交互信息和功能连接之间关联程度的研究。为了解决这些问题,提出了一种构建高阶最小生成树功能连接网络的方法,该方法不仅保证了功能连接网络的生理学意义,而且研究了网络中更复杂的交互信息,提高了分类的准确率。分类结果显示,基于高阶最小生成树功能连接网络的静息态功能磁共振成像分类方法大幅提高了阿兹海默氏症检测的准确率。     

卷积神经网络诊断阿尔兹海默症的方法

针对阿尔兹海默症（AD）通常会导致海马体区域萎缩的现象,提出一种使用卷积神经网络（CNN）对脑部磁共振成像（MRI）的海马体区域进行AD识别的方法。测试数据来自ADNI数据库提供的188位患者和229位正常人的脑部MRI图像。首先,将所有脑图像进行颅骨剥离,并配准到标准模板;其次,使用线性回归进行脑部萎缩的年龄矫正;然后,经过预处理后,从每个对象的3D脑图像的海马体区域提取出多幅2.5D的图像;最后,使用CNN对这些图像进行训练和识别,将同一个对象的图像识别结果用于对该对象的联合诊断。通过多次十折交叉验证方式进行实验,实验结果表明所提方法的平均识别准确率达到88.02%。与堆叠自动编码器（SAE）方法进行比较,比较结果表明,所提方法在仅使用MRI进行诊断的情况下效果比SAE方法有较大提高。     

BN大鼠食物过敏动物模型的实验研究

为了解挪威棕色大鼠(BN)作为食物过敏动物模型的可行性。将24只BN大鼠随机分为灭菌水组(对照组)、卵清蛋白组(Ovalbumin，OVA)、马铃薯酸性磷酸酶组(Potato acid plaosplaatase，PAP)、鸡蛋清粗提蛋白质组(hen’s egg-white protein，HEWP)，每组6只。对各组大鼠灌胃，1ml／只，OVA、PAP组蛋白质浓度为1mg／ml,HEWP组蛋白质浓度为10．0mg／ml，每天1次．共6周。检测血清中特异IgE抗体滴度，同时进行皮肤过敏反应试验(PCA)。在第28、42天，OVA、HEWP组BN大鼠32倍稀释血清中特异IgE抗体均较对照组升高，并有统计学差异，第14、28、42天的：PAP组及第14天的OVA、HEWP组BN大鼠32倍稀释血清中特异IgE抗体较对照组相比无统计学差异。BN大鼠对常见致敏食物蛋白质OVA和HEWP产生过敏反应，对无致敏史食物蛋白质PAP无过敏反应。BN大鼠模型可能是较为理想的食物过敏动物模型。     

The survival of foot-and-mouth disease virus in raw and pasteurized milk and milk products

The Foot-and-Mouth Disease virus (FMDV) is not a public health threat, but it is highly contagious to cloven-footed animals. The virus is shed into milk up to 33 h before there are apparent signs of the disease in dairy cows, and, in extreme cases, signs of disease may not appear for up to 14 d. During this time, raw milk can serve as a vector for spread of the disease both at the farm and during transport to the processing plant by milk tanker. Raw milk and milk products fed to animals have the potential to cause infection, but the potential for pasteurized milk products to cause infection is largely unknown. Current minimum pasteurization standards may not be adequate to eliminate FMDV in milk completely. The purpose of this paper is to assess the literature on the thermal resistance of FMDV in milk and milk products, to identify the risks associated with ingestion of pasteurized products by animals, and to lay a strategy to prevent the spread of FMDV from contaminated milk.     

2002年湖北省学校食源性疾病的发生状况及对策

为了解湖北省学校集体食堂食源性疾病的发生状况,对湖北省2002年学校食源性疾病的发生状况进行了分析.2002年湖北省共有13所学校发生食源性疾病,773人患病,死亡1人.其中食物中毒发生的起数、发病人数及死亡人数分别占当年湖北省集体食堂食物中毒的46.2%、48.9%和100.0%.引起学校食源性疾病的主要原因为学校食堂采取了以赢利为目的的私人承包制,学校领导及食堂承包人的责任心差、卫生知识缺乏,食堂基础设施差,使用的食品原料安全问题严重.针对学校食源性疾病发生的原因提出对策:山区及农村学校食堂不宜搞承包制;政府应对山区及农村学校有所投入;学校应加强学生食堂的卫生管理;学校食堂的采购应采取定点采购的管理体制.     

烟草赤星病流行动态预测

2001~2002年对黑龙江省宾县和肇州县两个烟草赤星病田间观测点进行了系统调查,种植烤烟品种为NC89,共计获得了13组田间病害流行数据资料,利用多种增长模型对所得数据进行拟合检验,通过比较决定系数和剩余均方,认为Logistic模型能较好地拟合赤星病田间动态变化过程。分析赤星病发病因素,证明初始病情、日平均温度、日平均相对湿度、日降雨量及降雨日数是影响赤星病发生流行的重要因素,利用逐步回归分析建立了烟草赤星病田间增长速率的预测模型,并对田间病害流行动态进行了预测。     

Assessing the Potential Public Health Impacts of Next Generation Foods Derived from Recombinant DNA Technology: A Case Study of Omega-3 Fatty Acids Enhanced Vegetable Oils

We assessed the potential public health impacts of foods derived from recombinant DNA technology that have been modified to have improved nutrient profiles using omega-3-enhanced vegetable oils as an example. Other examples of crops in development include canola plants with increased vitamin C and rice with higher levels of beta-carotene. The change in consumption of omega-3 fatty acids if vegetable oils were replaced with stearidonic acid-enhanced versions was estimated. The results showed that stearidonic acid and gamma-linolenic acid consumption would increase by 5.43 g/d for males and 4.14 g/d for females. The increase in stearidonic acid in eicosapentaenoic acid equivalents was 1.63 g/d for males and 1.24 g/d for females.