The role of presenilin cofactors in the gamma-secretase complex

Mutations in presenilin genes account for the majority of the cases of the familial form of Alzheimer's disease (FAD). Presenilin is essential for gamma-secretase activity, a proteolytic activity involved in intramembrane cleavage of Notch and beta-amyloid precursor protein (betaAPP). Cleavage of betaAPP by FAD mutant presenilin results in the overproduction of highly amyloidogenic amyloid beta42 peptides. gamma-Secretase activity requires the formation of a stable, high-molecular-mass protein complex that, in addition to the endoproteolysed fragmented form of presenilin, contains essential cofactors including nicastrin, APH-1 (refs 15-18) and PEN-2 (refs 16, 19). However, the role of each protein in complex formation and the generation of enzymatic activity is unclear. Here we show that Drosophila APH-1 (Aph-1) increases the stability of Drosophila presenilin (Psn) holoprotein in the complex. Depletion of PEN-2 by RNA interference prevents endoproteolysis of presenilin and promotes stabilization of the holoprotein in both Drosophila and mammalian cells, including primary neurons. Co-expression of Drosophila Pen-2 with Aph-1 and nicastrin increases the formation of Psn fragments as well as gamma-secretase activity. Thus, APH-1 stabilizes the presenilin holoprotein in the complex, whereas PEN-2 is required for endoproteolytic processing of presenilin and conferring gamma-secretase activity to the complex.     

Heterogeneous Asymmetric Dynamic Conditional Correlation Model with Stock Return and Range

The paper considers the return and range model with dynamic conditional correlations (DCC). The paper suggests the new specifications for the asymmetric effects on log‐volatilities and dynamic correlations, combined with long‐run dependences. The new DCC model can be estimated by the quasi‐maximum likelihood method. Empirical analysis on Nikkei 225, Hang Seng and Straits Times indices shows the daily, weekly and monthly pattern of asymmetric effects. For the period including the global financial crisis, the new DCC model provides plausible one‐step‐ahead forecasts of the VaR thresholds, and yields positive economic values of switching from other DCC models. Copyright © 2013 John Wiley & Sons, Ltd.     

Effects of acetaldehyde and/or ethanol on neutral amino acid transport systems in microvillous brush border membrane vesicles prepared from human placenta

Summary At 20 mM of acetaldehyde, the activities of three transport systems of L-alanine distinguished by the difference in their cation dependence, namely 1) Na⁺-specific, 2) Li⁺-dependent, and 3) Na⁺-independent systems, were significantly reduced in a similar manner. Only the Li⁺-dependent system was selectively inhibited at toxic concentrations of acetaldehyde and ethanol.     

Fruitless specifies sexually dimorphic neural circuitry in the Drosophila brain

The Drosophila fruitless (fru) gene product Fru has been postulated to be a neural sex determination factor that directs development of the central nervous system (CNS), thereby producing male-typical courtship behaviour and inducing male-specific muscle. Male-specific Fru protein is expressed in small groups of neurons scattered throughout the CNS of male, but not female, Drosophila. Collectively, these observations suggest that Fru 'masculinizes' certain neurons, thereby establishing neural substrates for male-typical behaviour. However, specific differences between neurons resulting from the presence or absence of Fru are unknown. Previous studies have suggested that Fru might result in sexual differences in the CNS at the functional level, as no overt sexual dimorphism in CNS structure was discernible. Here we identify a subset of fru-expressing interneurons in the brain that show marked sexual dimorphism in their number and projection pattern. We also demonstrate that Fru supports the development of neurons with male-specific dendritic fields, which are programmed to die during female development as a result of the absence of Fru. Thus, Fru expression can produce a male-specific neural circuit, probably used during heterosexual courtship, by preventing cell death in identifiable neurons.     

Genome sequencing and analysis of Aspergillus oryzae

The genome of Aspergillus oryzae, a fungus important for the production of traditional fermented foods and beverages in Japan, has been sequenced. The ability to secrete large amounts of proteins and the development of a transformation system have facilitated the use of A. oryzae in modern biotechnology. Although both A. oryzae and Aspergillus flavus belong to the section Flavi of the subgenus Circumdati of Aspergillus, A. oryzae, unlike A. flavus, does not produce aflatoxin, and its long history of use in the food industry has proved its safety. Here we show that the 37-megabase (Mb) genome of A. oryzae contains 12,074 genes and is expanded by 7-9 Mb in comparison with the genomes of Aspergillus nidulans and Aspergillus fumigatus. Comparison of the three aspergilli species revealed the presence of syntenic blocks and A. oryzae-specific blocks (lacking synteny with A. nidulans and A. fumigatus) in a mosaic manner throughout the genome of A. oryzae. The blocks of A. oryzae-specific sequence are enriched for genes involved in metabolism, particularly those for the synthesis of secondary metabolites. Specific expansion of genes for secretory hydrolytic enzymes, amino acid metabolism and amino acid/sugar uptake transporters supports the idea that A. oryzae is an ideal microorganism for fermentation.     

Recent development of high efficiency arc welding systems in Japan

Automationhasgivenapowerfulmeansto solvemanyissuesinproductionindustries,e.g.up efficiency,costreduction,manpowerproblems,en vironmentproblems,etc.Automatizationofthe weldingprocesseshavebeenremarkablypro gressedduringaboutthelasthalfcenturyandit wasbasedonthetechnologicaldevelopmentsof manyconstituentssuchas,sensorsandtheirappli cationsystemsforseamtrackingandadaptivecon trol,weldingrobot,weldingmaterial,weldingpow ersource,etc.Particularlyinthelastdecade, throughtheprogressofthecompute…     

Primary structure of alpha-subunit precursor of Torpedo californica acetylcholine receptor deduced from cDNA sequence

DNA sequences complementary to the Torpedo californica electroplax mRNA coding for the alpha-subunit precursor of the acetylcholine receptor were cloned. The nucleotide sequence of the cloned cDNA indicates that the precursor consists of 461 amino acids including a prepeptide of 24 amino acids. Possible sites for acetylcholine binding and antigenic determinants on the alpha-subunit molecule are discussed.     

枯草芽孢杆菌生产鸟苷的途径分析

利用途径分析的方法对枯草芽孢杆菌发酵生产鸟苷的途径进行分析,确定了3个基本反应模型,计算出最优途径的理论产量和通量分布．三个基本模型的理论摩尔产量分别为0．625、0．75、0．667．通过调整化学调节因子NH4^ 和Mg^2 ,可以使鸟苷产量由14．4g／L提高到19．2g／L。