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991.
Kakizawa S Yamazawa T Chen Y Ito A Murayama T Oyamada H Kurebayashi N Sato O Watanabe M Mori N Oguchi K Sakurai T Takeshima H Saito N Iino M 《The EMBO journal》2012,31(2):417-428
Mobilization of intracellular Ca(2+) stores regulates a multitude of cellular functions, but the role of intracellular Ca(2+) release via the ryanodine receptor (RyR) in the brain remains incompletely understood. We found that nitric oxide (NO) directly activates RyRs, which induce Ca(2+) release from intracellular stores of central neurons, and thereby promote prolonged Ca(2+) signalling in the brain. Reversible S-nitrosylation of type 1 RyR (RyR1) triggers this Ca(2+) release. NO-induced Ca(2+) release (NICR) is evoked by type 1 NO synthase-dependent NO production during neural firing, and is essential for cerebellar synaptic plasticity. NO production has also been implicated in pathological conditions including ischaemic brain injury, and our results suggest that NICR is involved in NO-induced neuronal cell death. These findings suggest that NICR via RyR1 plays a regulatory role in the physiological and pathophysiological functions of the brain. 相似文献
992.
Symplocarpus renifolius and Arum maculatum are known to produce significant heat during the course of their floral development, but they use different regulatory mechanisms, i.e. homoeothermic compared with transient thermogenesis. To further clarify the molecular basis of species-specific thermogenesis in plants, in the present study we have analysed the native structures and expression patterns of the mitochondrial respiratory components in S. renifolius and A. maculatum. Our comparative analysis using Blue native PAGE combined with nano LC (liquid chromatography)-MS/MS (tandem MS) has revealed that the constituents of the respiratory complexes in both plants were basically similar, but that several mitochondrial components appeared to be differently expressed in their thermogenic organs. Namely, complex II in S. renifolius was detected as a 340?kDa product, suggesting an oligomeric or supramolecular structure in vivo. Moreover, the expression of an external NAD(P)H dehydrogenase was found to be higher in A. maculatum than in S. renifolius, whereas an internal NAD(P)H dehydrogenase was expressed at a similar level in both species. Alternative oxidase was detected as smear-like signals that were elongated on the first dimension with a peak at around 200?kDa in both species. The significance and implication of these data are discussed in terms of thermoregulation in plants. 相似文献
993.
Glutaminase is an enzyme that catalyzes the hydrolysis of l-glutamine to l-glutamate, and it plays an important role in the production of fermented foods by enhancing the umami taste. By using the genome sequence and expressed sequence tag data available for Aspergillus oryzae RIB40, we cloned a novel glutaminase gene (AsgahA) from Aspergillus sojae, which was similar to a previously described gene encoding a salt-tolerant, thermostable glutaminase of Cryptococcus nodaensis (CnGahA). The structural gene was 1,929 bp in length without introns and encoded a glutaminase, AsGahA, which shared 36% identity with CnGahA. The introduction of multiple copies of AsgahA into A. oryzae RIB40 resulted in the overexpression of glutaminase activity. AsGahA was subsequently purified from the overexpressing transformant and characterized. While AsGahA was located at the cell surface in submerged culture, it was secreted extracellularly in solid-state culture. The molecular mass of AsGahA was estimated to be 67 kDa and 135 kDa by SDS-PAGE and gel filtration chromatography, respectively, indicating that the native form of AsGahA was a dimer. The optimal pH of the enzyme was 9.5, and its optimal temperature was 50°C in sodium phosphate buffer (pH 7.0). Analysis of substrate specificity revealed that AsGahA deamidated not only free l-glutamine and l-asparagine but also C-terminal glutaminyl or asparaginyl residues in peptides. Collectively, our results indicate that AsGahA is a novel peptidoglutaminase-asparaginase. Moreover, this is the first report to describe the gene cloning and purification of a peptidoglutaminase-asparaginase. 相似文献
994.
Sakaguchi K Matsuda T Kobayashi T Ohara J Hamaguchi R Abe E Nagano N Hayashi M Ueda M Honda D Okita Y Taoka Y Sugimoto S Okino N Ito M 《Applied and environmental microbiology》2012,78(9):3193-3202
A versatile transformation system for thraustochytrids, a promising producer for polyunsaturated fatty acids and fatty acid-derived fuels, was established. G418, hygromycin B, blasticidin, and zeocin inhibited the growth of thraustochytrids, indicating that multiple selectable marker genes could be used in the transformation system. A neomycin resistance gene (neo(r)), driven with an ubiquitin or an EF-1α promoter-terminator from Thraustochytrium aureum ATCC 34304, was introduced into representatives of two thraustochytrid genera, Aurantiochytrium and Thraustochytrium. The neo(r) marker was integrated into the chromosomal DNA by random recombination and then functionally translated into neo(r) mRNA. Additionally, we confirmed that another two genera, Parietichytrium and Schizochytrium, could be transformed by the same method. By this method, the enhanced green fluorescent protein was functionally expressed in thraustochytrids. Meanwhile, T. aureum ATCC 34304 could be transformed by two 18S ribosomal DNA-targeting vectors, designed to cause single- or double-crossover homologous recombination. Finally, the fatty acid Δ5 desaturase gene was disrupted by double-crossover homologous recombination in T. aureum ATCC 34304, resulting in an increase of dihomo-γ-linolenic acid (C(20:3n-6)) and eicosatetraenoic acid (C(20:4n-3)), substrates for Δ5 desaturase, and a decrease of arachidonic acid (C(20:4n-6)) and eicosapentaenoic acid (C(20:5n-3)), products for the enzyme. These results clearly indicate that a versatile transformation system which could be applicable to both multiple transgene expression and gene targeting was established for thraustochytrids. 相似文献
995.
AG Bick J Flannick K Ito S Cheng RS Vasan MG Parfenov DS Herman SR Depalma N Gupta SB Gabriel BH Funke HL Rehm EJ Benjamin J Aragam HA Taylor ER Fox C Newton-Cheh S Kathiresan CJ O'Donnell JG Wilson DM Altshuler JN Hirschhorn JG Seidman C Seidman 《American journal of human genetics》2012,91(3):513-519
Rare sarcomere protein variants cause dominant hypertrophic and dilated cardiomyopathies. To evaluate whether allelic variants in eight sarcomere genes are associated with cardiac morphology and function in the community, we sequenced 3,600 individuals from the Framingham Heart Study (FHS) and Jackson Heart Study (JHS) cohorts. Out of the total, 11.2% of individuals had one or more rare nonsynonymous sarcomere variants. The prevalence of likely pathogenic sarcomere variants was 0.6%, twice the previous estimates; however, only four of the 22 individuals had clinical manifestations of hypertrophic cardiomyopathy. Rare sarcomere variants were associated with an increased risk for adverse cardiovascular events (hazard ratio: 2.3) in the FHS cohort, suggesting that cardiovascular risk assessment in the general population can benefit from rare variant analysis. 相似文献
996.
Fujii S Fukamachi K Tsuda H Ito K Ito Y Ochiai A 《Biochemical and biophysical research communications》2012,417(3):1074-1079
The neoplastic transformation by mutant RAS is thought to require remodeling of expression of an entire set of genes. However, the underlying mechanism for initiation of gene expression remodeling in tumorigenesis remains elusive. This study was aimed to define the oncogenic role of EZH2, a histone modifier protein that is induced by oncogenic mutant RAS, using pancreatic cancers of transgenic rats exogenously expressing human mutant RAS. Immunohistochemical observation of preneoplastic or cancerous lesions in the animal model suggested that upregulation of Ezh2 protein is an initiating event in pancreatic carcinogenesis. MEK-inhibition or Elk-1-knockdown downregulated EZH2, and MEK-inhibition or EZH2-knockdown restored expression of a tumor suppressor, RUNX3 in human and rat pancreatic cancer cells activated by the oncogenic RAS. Furthermore, Elk-1- or EZH2-knockdown inhibited growth of the cancer cells. These results strongly suggested that the oncogenic RAS upregulates EZH2 through MEK-ERK signaling, resulted in downregulation of tumor suppressors including RUNX3 in pancreatic carcinogenesis. 相似文献
997.
998.
Kuwahara T Tonegawa R Ito G Mitani S Iwatsubo T 《The Journal of biological chemistry》2012,287(10):7098-7109
α-Synuclein is causative for autosomal dominant familial Parkinson disease and dementia with Lewy bodies, and the phosphorylation of α-synuclein at residue Ser-129 is a key posttranslational modification detected in Parkinson disease/dementia with Lewy bodies lesions. However, the role of Ser-129 phosphorylation on the pathogenesis of Parkinson disease/dementia with Lewy bodies remains unclear. Here we investigated the neurotoxicity of Ser-129-substituted α-synuclein in the transgenic Caenorhabditis elegans (Tg worm) model of synucleinopathy. Tg worms pan-neuronally overexpressing nonphosphorylatable (S129A) α-synuclein showed severe defects including motor dysfunction, growth retardation, and synaptic abnormalities. In contrast, Tg worms expressing phosphorylation mimic (S129D) α-synuclein exhibited nearly normal phenotypes. Biochemical fractionation revealed that the level of membrane-bound α-synuclein was significantly increased in S129A-α-synuclein Tg worms, whereas S129D- as well as A30P-α-synuclein displayed lower membrane binding properties. Furthermore, A30P/S129A double mutant α-synuclein did not cause neuronal dysfunction and displayed low membrane binding property. In human neuroblastoma SH-SY5Y cells, localization of S129A-α-synuclein to membranes was significantly increased. Finally, gene expression profiling of S129A-Tg worms revealed a dramatic up-regulation of Daf-16/FOXO pathway genes, which likely act against the dysfunction caused by S129A-α-synuclein. These results imply a role of Ser-129 phosphorylation of α-synuclein in the attenuation of α-synuclein-induced neuronal dysfunction and downstream stress response by lowering the membrane binding property. 相似文献
999.
Hikaru Nakagawa Hideyuki Yamane Masaki Yasugi Tomohiko Fujita Kenichi Yokoi Hiroshi Ashiwa Naoki Kitada Hiroki Takano Noriyasu Suzuki Junpei Kishimoto Hajime Maeda Hitomi Yamano Takehiko Ito Hiroaki Maruyama Koji Tominaga Emi Hatakeyama Motoyasu Goto Daisuke Takahashi 《Ecological Research》2012,27(2):417-426
Interspecific variation in diel-scale temporal niches is common in natural communities. Such variation changes population dynamics via effects on the growth and reproduction of individuals. Also at the community level, theory predicts that animals can reduce competition for shared resources by changing diel activity in certain situations. However, the role of diel activity at the community-level has not been examined sufficiently. In this study, to examine whether the diel-scale temporal niche act as a competition-mitigating mechanism for stream fishes at the community level, we surveyed diel changes in microhabitat use and foraging, and the pattern of interspecific diet overlap in the middle reaches of a temperate stream where various fish species that seemed to be either nocturnal or diurnal coexisted. Our results suggest that the fishes forage during both daytime and night, but change their foraging mode at different times of the day, so that the foraging habits of these fish species cannot be divided simply into nocturnal and diurnal. Furthermore, fishes appeared to aggregate in the vicinity of common food resources during time zones with high availability of the resources, and therefore, inter-guild diet overlap was high during certain time zones. On the other hand, when inter-guild diet overlap was low, each fish species used foods or microhabitats that did not any have the potential to be used by species of another guild. Therefore, we conclude that variation in diel niche use is influenced by variation in the fundamental niche and food supply or availability rather than by competitive interaction between fishes in the stream fish community. 相似文献
1000.
Ito D Yoshimura K Ishikawa K Ogawa T Maruta T Shigeoka S 《Bioscience, biotechnology, and biochemistry》2012,76(1):139-147
Coenzyme A (CoA) is an essential, ubiquitous cofactor in all biological systems, where it acts as the major acyl group carrier in various central metabolic reactions. Although much is known about CoA biosynthesis, it is unclear how the CoA pool is regulated the various cellular compartments. It has been found that the nucleoside diphosphates linked to some moiety X (Nudix) hydrolases, AtNUDX11 and 15, have pyrophosphohydrolase activity toward CoA and its derivatives. In this study we identified two alternatively spliced variants, AtNUDX15 and 15a, produced from the AtNUDX15 gene, and carried out comparative studies of the gene regulation, the kinetic parameters, and the intracellular localization of AtNUDX11, 15, and 15a. The present findings indicate that AtNUDX11 and AtNUDX15(a) function in the hydrolysis of malonyl-CoA in cytosol and succinyl-CoA in the mitochondria, respectively, suggesting their impact not only on CoA biosynthesis but also on various CoA-related pathways such as the TCA cycle. 相似文献