Dual Role of α-Secretase Cleavage in the Regulation of γ-Secretase Activity for Amyloid Production

Processing of the amyloid precursor protein (APP) by β- and γ-secretases generates pathogenic β-amyloid (Aβ) peptides associated with Alzheimer disease (AD), whereas cleavage of APP by α-secretases precludes Aβ formation. Little is known about the role of α-secretase cleavage in γ-secretase regulation. Here, we show that α-secretase-cleaved APP C-terminal product (αCTF) functions as an inhibitor of γ-secretase. We demonstrate that the substrate inhibitory domain (ASID) within αCTF, which is bisected by the α-secretase cleavage site, contributes to this negative regulation because deleting or masking this domain turns αCTF into a better substrate for γ-secretase. Moreover, α-secretase cleavage can potentiate the inhibitory effect of ASID. Inhibition of γ-secretase activity by αCTF is observed in both in vitro and cellular systems. This work reveals an unforeseen role for α-secretase in generating an endogenous γ-secretase inhibitor that down-regulates the production of Aβ. Deregulation of this feedback mechanism may contribute to the pathogenesis of AD.     

Localization of myosin on sperm-cell-associated membranes of tobacco (Nicotiana tabacum L.)

Summary Actomyosin interactions are reportedly the principal mechanism for the transport of nonmotile sperm cells of flowering plants inside the pollen tube and inside the embryo sac. Myosin has been demonstrated on the generative cell (the predecessor of sperm cells), although it is unclear from previous studies whether myosin is located directly on the plasma membrane of the male germ cells or on the external plasma membrane of the pollen cell that surrounds them. Immunogold scanning electron microscopy was used to localize myosin on isolated tobacco sperm cells, with and without associated membranes. When present, the pollen tube plasma membrane surrounding the sperm cells was labeled by an antimyosin antibody, as were pollen tube cytoplasmic organelles. Negligible labeling was observed directly on the plasma membrane of the sperm cells.     

基因型和胚龄对小麦未成熟胚离体培养反应的影响

本文对34种基因型的小麦未成熟胚在离体培养中的反应进行了比较。结果表明,94％的供试基因型愈伤组织诱导率都可达到80％以上,若排除供体植株环境条件的不同和接种过程中的人为因素可能造成的影响,不同基因型的愈伤组织诱导率看来没有根本的差异。愈伤组织分化率因基因型的不同变动在0—60％之间,平均为32.7％。虽然同一基因型的盾片愈伤组织分化率在不同年份中有所不同,但是愈伤组织是否具有再生能力?看来是个稳定的遗传性状。因此小麦未成熟胚对愈伤组织诱导的反应和愈伤组织的再生能力可能具有不同的遗传基础。本文的结果还表明,虽然最适于培养的未成熟胚的大小为1毫米左右,伹小至0.3毫米的未成熱胚仍能以几乎100％的频率形成愈伤组织,60％左右的愈伤组织能分化出再生檀株,只是所需的时间比1毫米左右的胚较长。     

Evaluation of the cytoprotective effects of bovine lactoferrin against intestinal toxins using cellular model systems

This study investigated the effects of bovine lactoferrin (BLf) on the growth of different groups of bacteria in vitro. BLf showed a significant inhibitory effect on the growth of selected pathogens but not probiotics. BLf, in combination with probiotics, has the potential to influence the composition of the gut microflora via inhibition of intestinal pathogens with no significant effect on probiotic bacteria.     

Bt rice expressing Cry1Ab does not stimulate an outbreak of its non-target herbivore, Nilaparvata lugens

In this study, the non-target effects of Bt rice “KMD2” expressing a Cry1Ab protein on the performance of the brown planthopper (BPH), Nilaparvata lugens, over multiple generations were evaluated under laboratory and field conditions. In the laboratory, BPH was reared to observe the impact of the Bt rice as compared to its parental non-Bt cultivar Xiushui 11, while the population dynamics and oviposition performance of BPH were investigated in the field. The survival of BPH nymphs fed Bt and non-Bt rice did not differ significantly. The nymph developmental duration of BPH was significantly delayed by the Bt rice by comparison with the non-Bt rice for the 1st and 2nd but not the 4th generation. Most importantly, the fecundity of BPH on the Bt rice was significantly decreased in every generation when compared with the non-Bt rice. In the field investigations, the population density of BPH nymphs was significantly lower in the Bt rice field. However, the temporal pattern of population dynamics of BPH adults was similar between the Bt and non-Bt rice, presumably due to migratory interference of the adults. In the Bt rice field, the percentage of tillers with eggs and the number of eggs per tiller were also significantly lower from tillering to mature stage. Additionally, Cry1Ab protein could not be detected in guts from single BPH adults. In general, our results suggest that the Bt rice “KMD2” could not stimulate an outbreak of BPH.     

几种同域分布姜花属植物的种间杂交亲和性

种间配子不亲和以及种间杂交种子活力低是众多的物种间杂交隔离机制中的两个方面。通过对云南澜沧地区分布的4种（型）姜花属植物——圆瓣姜花（Hedychium forrestii）、草果药(Hspicatum)、两类型滇姜花（Hyunnanense）间进行野外杂交试验,比较杂交结实率、每果种子数以及杂交种子的萌发参数等指标来分析4种（型）姜花之间的杂交亲和性和杂交后代表现,发现4种（型）姜花属植物配子间都具有不同程度的亲和性,但种间杂交种子的萌发适合度比同种授粉获得的种子低。结果表明,这4种（型）姜花属植物间配子亲和性不是有效的种间隔离机制,种间杂交种子活力低是一种不完全的隔离机制,它们在同域分布的地区,仍然有形成杂交后代的可能性。     

逻辑斯谛增长导致的复杂种群动态及其实验验证

教科书通常用“S”型曲线表示逻辑斯谛增长模型导致的种群动态,事实上,这一模型可以产生包括稳定平衡、周期性振荡、混沌等多种多样的种群动态模式。介绍了如何用Kicker图示的方法分析逻辑斯谛增长可能导致的种群动态模式。同时介绍了相关的实验研究案例,这些实验工作大都是以生活史周期较短的昆虫为材料在相对简单的实验室环境中完成的。     

SAR and molecular mechanism study of novel acylhydrazone compounds targeting HIV-1 CA

We synthesized a series of acylhydrazone compounds bearing naturally occurring amino acids’ side chains as HIV assembly inhibitors. Biological evaluation indicated that the compounds had anti-SIV and capsid assembly inhibitory activities. The structure–activity relationship (SAR) study showed that compounds bearing proper aromatic side chains had potential antiviral activities. The molecular modeling experiments revealed the molecular mechanism that they could bind to CA in the same manner as CAP-1 and occupy two more grooves.     

Synthesis and evaluation of nitric oxide-releasing derivatives of farnesylthiosalicylic acid as anti-tumor agents

Novel furoxan-based nitric oxide (NO)-releasing derivatives (11a–p) of farnesylthiosalicylic acid (FTA) were synthesized. Compounds 11d, 11f, 11k, and 11m–o displayed anti-tumor activities superior to FTA and sorafenib in most cancer cells tested. Analysis of six compounds revealed that 11d, 11f, 11n, 11o, and 11p, but not 11a that had low anti-tumor activity, produced high levels of NO, associated with their strong anti-tumor activity. Furthermore, the anti-tumor activity of 11f was partially mimicked by the furoxan moiety, but reduced by pre-treatment with hemoglobin. Importantly, treatment with 11f inhibited Ras-related signaling in cancer cells. Apparently, the high anti-tumor activity of 11f was attributed to the synergic effect of high levels of NO production and inhibition of Ras-related signaling in cancer cells. Our findings suggest that the furoxan/FTA hybrids may hold greater promise as therapeutic agents for the intervention of human cancers.     

环鸟苷酸对卵巢细胞功能的调控

环鸟苷酸（cGMP）是一种具有广泛生物学活性的环核苷酸。尽管cGMP作为第二信使,在调控卵巢细胞功能中发挥着广泛而重要的作用早有报道,但直至近年,cGMP在生殖活动中的重要作用才受到人们的关注,而成为生殖科学研究领域的热点之一。卵巢是雌性动物的重要器官,而cGMP在卵巢细胞中起着多方面的调节作用。现对卵巢内cGMP的来源,cGMP在卵巢内抑制雌激素（E2）的合成、LH受体表达、卵泡闭锁的作用,以及cGMP的作用机制等方面的研究进展进行综述。