Metabolites of Cerebellar Neurons and Hippocampal Neurons Play Opposite Roles in Pathogenesis of Alzheimer's Disease

Metabolites of neural cells, is known to have a significant effect on the normal physiology and function of neurons in brain. However, whether they play a role in pathogenesis of neurodegenerative diseases is unknown. Here, we show that metabolites of neurons play essential role in the pathogenesis of Alzheimer''s disease (AD). Firstly, in vivo and in vitro metabolites of cerebellar neurons both significantly induced the expression of Aβ-degrading enzymes in the hippocampus and cerebral cortex and promoted Aβ clearance. Moreover, metabolites of cerebellar neurons significantly reduced brain Aβ levels and reversed cognitive impairments and other AD-like phenotypes of APP/PS1 transgenic mice, in both early and late stages of AD pathology. On the other hand, metabolites of hippocampal neurons reduced the expression of Aβ-degrading enzymes in the cerebellum and caused cerebellar neurodegeneration in APP/PS1 transgenic mice. Thus, we report, for the first time, that metabolites of neurons not only are required for maintaining the normal physiology of neurons but also play essential role in the pathogenesis of AD and may be responsible for the regional-specificity of Aβ deposition and AD pathology.     

人SDCT2基因的两种不同转录产物选择性转录机理分析

为了克隆人高亲和力钠离子依赖性二羧酸转运蛋白 (highaffinitysodium dependentdicarboxylatetransporter,SDCT2 ,或NaDC3)基因并研究其生理功能 ,用大鼠SDCT2基因序列作为电子杂交探针对人EST数据库进行电子筛选 ,得到了一系列与大鼠SDCT2序列具有高度同源性的人EST序列 ,将它们拼接成 2个基因重叠群 ,设计特异性PCR引物通过RT PCR扩增得到 2条杂交探针用于筛选人肾cDNA文库 .从肾组织中同时克隆出了人SDCT2基因 2种mRNA变异体的全长cDNA(SDCT2α和SDCT2 β) ,两者 5′端前 3435bp序列完全一致 ,但 3′端长度不同 ,SDCT2 β在第 3435bp以后比SDCT2α多出了 5 85bp的序列 .Northern杂交和RT PCR显示 ,SDCT2α在人肾中的表达丰度最高 ,在肝、脾、胎盘、脑及结肠中也有低水平的表达 .而SDCT2 β主要在肾脏中表达 ,在脾也有低水平的表达 .基因组结构分析表明 ,虽然两种mRNAs均由 13个外显子组成 ,但是SDCT2α的第 13外显子含有 1个poly(A)加尾信号AATAAA ,而SDCT2 β的第 13外显子含有 2个poly(A)加尾信号 .这表明在肾脏和脾脏组织中 ,人SDCT2基因可能通过选择性使用位于第 13外显子不同位置的 2个poly(A)信号而转录出 2种不同长度的mRNA变异体 .     

Mistletoes Play Different Roles in a Modular Host–Parasite Network

Antagonistic interactions between host plants and mistletoes often form complex networks of interacting species. Adequate characterization of network organization requires a combination of qualitative and quantitative data. Therefore, we assessed the distribution of interactions between mistletoes and hosts in the Brazilian Pantanal and characterized the network structure in relation to nestedness and modularity. Interactions were highly asymmetric, with mistletoes presenting low host specificity (i.e., weak dependence) and with hosts being highly susceptible to mistletoe‐specific infections. We found a non‐nested and modular pattern of interactions, wherein each mistletoe species interacted with a particular set of host species. Psittacanthus spp. infected more species and individuals and also caused a high number of infections per individual, whereas the other mistletoes showed a more specialized pattern of infection. For this reason, Psittacanthus spp. were regarded as module hubs while the other mistletoe species showed a peripheral role. We hypothesize that this pattern is primarily the result of different seed dispersal systems. Although all mistletoe species in our study are bird dispersed, the frugivorous assemblage of Psittacanthus spp. is composed of a larger suite of birds, whereas Phoradendron are mainly dispersed by Euphonia species. The larger assemblage of bird species dispersing Psittacanthus seeds may also increase the number of hosts colonized and, consequently, its dominance in the study area. Nevertheless, other restrictions on the interactions among species, such as the differential capacity of mistletoe infections, defense strategies of hosts and habitat types, can also generate or enhance the observed pattern. Abstract in Portuguese is available at http://www.blackwell‐synergy.com/loi/btp .     

植物抗病基因的研究进展

近年来,已有１０多个植物抗病基因被克隆并定序。植物抗病基因编码的蛋白,大多含有富氨酸重复单位（ＬＲＲ）和核苷酸结合位点（ＮＢＳ）等结构。在植物与病原物的互作中,这些蛋白可作为受体识别由病原物无毒基因编码的激发子,从而激发一系列防卫反应,使植物表现出抗病性。克隆的植物抗病基因可用于培育基因工程植株而大大加快育种速度。本文对目前植物抗病基因研究中存在的问题及发展前景也进行了探讨。     

A Biochemical Phenotype for a Disease Resistance Gene of Maize

In maize, major resistance to the pathogenic fungus Cochliobolus (Helminthosporium) carbonum race 1 is determined by the dominant allele of the nuclear locus hm. The interaction between C. carbonum race 1 and maize is mediated by a pathogen-produced, low molecular weight compound called HC-toxin. We recently described an enzyme from maize, called HC-toxin reductase, that inactivates HC-toxin by pyridine nucleotide-dependent reduction of an essential carbonyl group. We now report that this enzyme activity is detectable only in extracts of maize that are resistant to C. carbonum race 1 (genotype Hm/Hm or Hm/hm). In several genetic analyses, in vitro HC-toxin reductase activity was without exception associated with resistance to C. carbonum race 1. The results indicate that detoxification of HC-toxin is the biochemical basis of Hm-specific resistance of maize to infection by C. carbonum race 1.     

两个推测的染色质重塑腺苷三磷酸酶基因功能冗余地调控拟南芥种子和胚胎发育

种子及胚胎发育是被子植物个体发育的重要起始阶段,相关调控基因的阐明将有助于认识种子及胚胎发育的分子机制。预测同源基因CHR12和CHR23编码拟南芥依赖于ATP的染色质重塑核心组分—-月泉苷三磷酸酶。T-DNA插入缺失突变体鉴定、遗传杂交及转基因实验表明,两个基因同时缺失阻滞种子的正常发育;胚胎发育进程显微观察表明,与野生型及各自单缺失突变体相比,双重缺失突变体的胚胎发育停滞到了心形胚后期或鱼雷胚早期。这表明CHR12和CHR23在拟南芥种子及胚胎发育过程中功能冗余地发挥着重要调控作用。     

植物抗病基因的进化

植物抗病基因在进化中形成了几种共有的进化形式。植物祖先抗病基因的复制创造了新基因座。基因间和基因内重组导致了变异,也导致了新特异性抗病基因的产生。另外,与特异性识别相关的富含亮氨酸重复区顺应于适应性选择。同样,类转座元件在抗病基因座中的插入加速了抗病基因的进化。随着抗病基因的进化,抗病反应也呈现出多样化,代表着植物与病原物动态进化的不同阶段。     

Distinct Roles of a Mitogen-Activated Protein Kinase in Cytokinesis between Different Life Cycle Forms of Trypanosoma brucei

Mitogen-activated protein kinase (MAPK) modules are evolutionarily conserved signaling cascades that function in response to the environment and play crucial roles in intracellular signal transduction in eukaryotes. The involvement of a MAP kinase in regulating cytokinesis in yeast, animals, and plants has been reported, but the requirement for a MAP kinase for cytokinesis in the early-branching protozoa is not documented. Here, we show that a MAP kinase homolog (TbMAPK6) from Trypanosoma brucei plays distinct roles in cytokinesis in two life cycle forms of T. brucei. TbMAPK6 is distributed throughout the cytosol in the procyclic form but is localized in both the cytosol and the nucleus in the bloodstream form. RNA interference (RNAi) of TbMAPK6 results in moderate growth inhibition in the procyclic form but severe growth defects and rapid cell death in the bloodstream form. Moreover, TbMAPK6 appears to be implicated in furrow ingression and cytokinesis completion in the procyclic form but is essential for cytokinesis initiation in the bloodstream form. Despite the distinct defects in cytokinesis in the two forms, RNAi of TbMAPK6 also caused defective basal body duplication/segregation in a small cell population in both life cycle forms. Altogether, our results demonstrate the involvement of the TbMAPK6-mediated pathway in regulating cytokinesis in trypanosomes and suggest distinct roles of TbMAPK6 in cytokinesis between different life cycle stages of T. brucei.     

P16 and P53 Play Distinct Roles in Different Subtypes of Breast Cancer

Breast cancers are heterogeneous and complex diseases, and subtypes of breast cancers may involve unique molecular mechanisms. The p16^INK4a and p53 pathways are two of the major pathways involved in control of the cell cycle. They also play key roles in tumorigenesis. However, whether the roles of these pathways differ in the subtypes of breast cancer is unclear. Therefore, p16 and p53 expression were investigated in different breast cancer subtypes to ascertain their contributions to these cancers. A total of 400 cases of non-invasive ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC), including the major molecular subtypes luminal-A, luminal-B, Her-2, and triple-negative subtypes, and 50 cases of normal controls were compared. Luminal-A cancers expressed the lowest level of p16 among the subtypes in DCIS, and the level of p16 expression was up-regulated in the luminal-A of IDC (P<0.008). Triple-negative breast cancers were characterized by a correlation of p53 overexpression with a high level of p16 expression. Luminal lesion types with high p16 expression in DCIS were found to be more likely to develop into aggressive breast cancers, possibly promoted by p53 dysfunction. Taken together, the present study suggest that p16 expression in luminal-A breast cancers is associated with their progression from DCIS to IDC, and both p53 and p16 expressions are important for the development of triple-negative breast cancers in DCIS and IDC.     

Specific Matrix Metalloproteinases Play Different Roles in Intraplaque Angiogenesis and Plaque Instability in Rabbits

Background

Ectopic angiogenesis within the intima and media is considered to be a hallmark of advanced vulnerable atherosclerotic lesions. Some studies have shown that specific matrix metalloproteinases (MMPs) might play different roles in angiogenesis. Therefore, we investigated the predominant effects of specific MMPs in intraplaque angiogenesis and plaque instability in a rabbit model of atherosclerosis.

Methods and Results

New Zealand rabbits underwent balloon injury of the abdominal artery and ingestion of a high-cholesterol (1%) diet to establish an atherosclerotic animal model. At weeks 4, 6, 8, 10, and 12 after balloon injury, five rabbits were euthanized and the abdominal aorta was harvested. Blood lipid analysis, intravascular ultrasound imaging, pathologic and immunohistochemical expression studies, and western blotting were performed. From weeks 4 to 12, the expression of MMP-1, -2, -3, and -9 and vascular endothelial growth factor A (VEGF-A) increased with atherosclerotic plaque development in the abdominal aorta, while the expression of MMP-14 substantially decreased. The vulnerability index (VI) gradually increased over time. Intraplaque neovessels appeared at week 8. The microvessel density (MVD) was greater at week 12 than at week 8. The VI, MVD, and VEGF-A level were positively correlated with the MMP-1, -2,-3, and -9 levels within plaques. Negative correlations were noted between the MMP-14 level and the VI, MVD, and VEGF-A level.

Conclusion

Upregulation of MMP-1, -2, -3, and -9 and downregulation of MMP-14 may contribute to intraplaque angiogenesis and plaque instability at the advanced stage of atherosclerosis in rabbits.     

水稻中大麦Mlo和玉米Hm1抗病基因同源序列的分析和定位

大麦抗病基因Mlo和玉米抗病基因Hm1编码的产物不具有绝大多数植物抗病基因产物所含有的保守结构域。这两个抗病基因的作用机理也不符合基因对基因学说。从水稻中分离克隆了Mlo基因的同源序列OsMlo-1和玉米Hm1基因的同源序列DFR－1。利用水稻分子标记遗传连锁图,将OsMlo-1定位于水稻第六染色体的两俱RZ667和RG424之间;Osmlo-1距离这两个分子标记分别为20．6和6．0cM(centi-Morgan)。将DFR－1定位于水稻第一染色体两个分子标记R2635和RG462之间;DFR－1距离这两个分子标记分别为11．3和23．9cM。参照已发表的水稻分子标记连锁图,发现OsMlo-1和DFR－1的染色体位点分别与两个报道的水稻抗稻瘟病数量性状位点（QTL）有较好的对应关系。结果提示,水稻中与大麦Mlo 和玉米Hml同源的基因可能也参于抗病反应的调控。     

大豆抗病基因同源序列的克隆与分析

已克隆的植物抗病基因序列存在一些相对保守的结构区域.利用根据核苷酸结合位点(NBS)结构域扩增所获得的大豆抗病基因同源片段为混合探针,进行大豆cDNA文库筛选.通过筛库和5'RACE-PCR扩增后,获得一全长基因KR3.KR3的长度为2353 bp,编码636个氨基酸.KR3蛋白在结构上与烟草抗花叶病毒N基因蛋白有较高的同源性,具有Toll/白细胞介素-1受体(TIR)、NBS等抗病基因的分子特征.Southern杂交显示KR3在基因组中为低拷贝;RT-PCR分析表明,该基因的表达受外源水杨酸的诱导.     

大豆抗病基因同源序列的克隆与分析

已克隆的植物抗病基因序列存在一些相对保守的结构区域。利用根据核苷酸结合位点(NBS)结构域扩增所获得的大豆抗病基因同源片段为混合探针,进行大豆cDNA文库筛选。通过筛库和5′RAcE-PcR扩增后,获得一全长基因KR3。KR3的长度为2353 bp,编码636个氨基酸。KR3蛋白在结构上与烟草抗花叶病毒N基因蛋白有较高的同源性,具有Toll／白细胞介素-1受体(TIR)、NBS等抗病基因的分了特征。Southern 杂交显KR3在基因组中为低拷贝：RT-PCR分析表明,该基因的表达受外源水杨酸的诱导。     

Structures of the Mouse Central Nervous System Contain Different Quantities of Proteasome Gene Transcripts

Molecular Biology - Proteasomes are multisubunit complexes that degrade most intracellular proteins. Three of the 14&nbsp;subunits of the 20S proteasome, specifically β1, β2, and...