Glycogen synthase kinase 3β and Alzheimer’s disease: pathophysiological and therapeutic significance

Alzheimer’s disease (AD) is a neurodegenerative disorder associated with cognitive and behavioral dysfunction and is the leading cause of dementia in the elderly. Several studies have implicated molecular and cellular signaling cascades involving the serine-threonine kinase, glycogen synthase kinase β(GSK-3β) in the pathogenesis of AD. GSK-3β may play an important role in the formation of neurofibrillary tangles and senile plaques, the two classical pathological hallmarks of AD. In this review, we discuss the interaction between GSK-3β and several key molecules involved in AD, including the presenilins, amyloid precursor protein, tau, and β-amyloid. We identify the signal transduction pathways involved in the pathogenesis of AD, including Wnt, Notch, and the PI3 kinase/Akt pathway. These may be potential therapeutic targets in AD. Received 19 December 2005; received after revision 24 January 2006; accepted 6 February 2006     

用柱层析和TLC分离小麦PGIP和植保素

植物抗病能力大小的测定需要比较准确可靠且相对简便的办法。采用接种病菌于植物上观察染菌情况虽然直观,但受病菌本身的生理状态及外界环境影响很大,且不便于定量的表述。因此,选择合适的生理生化指标作为植物抗性大小的衡量标准,对于植物病理的研究具有重要的意义。选择了小麦体系的两种抗性物质－ 小麦植保素和 Ｐ Ｇ Ｉ Ｐ作为小麦的抗性指标来分离分析     

博格达山南缘芦草沟组的浊积扇

根据岩性、沉积构造、古生物化石和地球化学标志,系统分析了博格达山南缘广泛发育的二叠系芦草沟组的沉积环境。研究表明：博格达山南缘芦草沟组深湖相沉积十分发育,并在此背景上沉积了近岸浊积扇和远岸浊积扇。其中,深湖相暗色泥、页岩和油页岩构成了良好的烃源岩。同时,认为吐哈盆地前侏罗系具有良好的勘探前景。     

中祁连地块东段元古宙基底湟源群沉积构造环境

通过对中祁连地块东段元古宙基底湟源群原岩建造及其地球化学特征的研究,认为：湟源群主要由各种千枚岩、片岩、变粒岩、大理岩、石英岩和斜长角闪岩等组成的中浅变质的表壳岩组合;其原岩为一套由陆源碎屑岩、不纯碳酸盐岩、中基性大山岩等组成的火山岩沉积岩组合;湟源群中变质沉积岩系中沉积韵律、沉积条带构造的广泛发育以及浊积层的存在等,指示了其原岩建造具有复理石或类复理石建造的特征;其中变质杂砂岩的地球化学特征类似于大陆岛弧或安底斯岛弧型杂砂岩的特征;湟源群变质中基性火山岩的地球化学特征类似于岛弧或活动大陆边缘的钙碱性火山岩的特征。经综合分析得出,湟源群沉积构造环境可能为陆缘弧后盆地且靠近大陆一侧。     

DNA-dependent protein kinase is not required for the p53-dependent response to DNA damage.

Damage to DNA in the cell activates the tumour-suppressor protein p53, and failure of this activation leads to genetic instability and a predisposition to cancer. It is therefore crucial to understand the signal transduction mechanisms that connect DNA damage with p53 activation. The enzyme known as DNA-dependent protein kinase (DNA-PK) has been proposed to be an essential activator of p53, but the evidence for its involvement in this pathway is controversial. We now show that the p53 response is fully functional in primary mouse embryonic fibroblasts lacking DNA-PK: irradiation-induced DNA damage in these defective fibroblasts induces a normal response of p53 accumulation, phosphorylation of a p53 serine residue at position 15, nuclear localization and binding to DNA of p53. The upregulation of p53-target genes and cell-cycle arrest also occur normally. The DNA-PK-deficient cell line SCGR11 contains a homozygous mutation in the DNA-binding domain of p53, which may explain the defective response by p53 reported in this line. Our results indicate that DNA-PK activity is not required for cells to mount a p53-dependent response to DNA damage.     

Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse.

Amyloid-beta peptide (Abeta) seems to have a central role in the neuropathology of Alzheimer's disease (AD). Familial forms of the disease have been linked to mutations in the amyloid precursor protein (APP) and the presenilin genes. Disease-linked mutations in these genes result in increased production of the 42-amino-acid form of the peptide (Abeta42), which is the predominant form found in the amyloid plaques of Alzheimer's disease. The PDAPP transgenic mouse, which overexpresses mutant human APP (in which the amino acid at position 717 is phenylalanine instead of the normal valine), progressively develops many of the neuropathological hallmarks of Alzheimer's disease in an age- and brain-region-dependent manner. In the present study, transgenic animals were immunized with Abeta42, either before the onset of AD-type neuropathologies (at 6 weeks of age) or at an older age (11 months), when amyloid-beta deposition and several of the subsequent neuropathological changes were well established. We report that immunization of the young animals essentially prevented the development of beta-amyloid-plaque formation, neuritic dystrophy and astrogliosis. Treatment of the older animals also markedly reduced the extent and progression of these AD-like neuropathologies. Our results raise the possibility that immunization with amyloid-beta may be effective in preventing and treating Alzheimer's disease.     

Sequence and analysis of chromosome 2 of the plant Arabidopsis thaliana

Arabidopsis thaliana (Arabidopsis) is unique among plant model organisms in having a small genome (130-140 Mb), excellent physical and genetic maps, and little repetitive DNA. Here we report the sequence of chromosome 2 from the Columbia ecotype in two gap-free assemblies (contigs) of 3.6 and 16 megabases (Mb). The latter represents the longest published stretch of uninterrupted DNA sequence assembled from any organism to date. Chromosome 2 represents 15% of the genome and encodes 4,037 genes, 49% of which have no predicted function. Roughly 250 tandem gene duplications were found in addition to large-scale duplications of about 0.5 and 4.5 Mb between chromosomes 2 and 1 and between chromosomes 2 and 4, respectively. Sequencing of nearly 2 Mb within the genetically defined centromere revealed a low density of recognizable genes, and a high density and diverse range of vestigial and presumably inactive mobile elements. More unexpected is what appears to be a recent insertion of a continuous stretch of 75% of the mitochondrial genome into chromosome 2.