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91.
In the two cold-adapted monomeric isocitrate dehydrogenases from psychrophilic bacteria, Colwellia maris and Colwellia psychrerythraea (CmIDH and CpIDH, respectively), the combined substitutions of amino acid residues between the Leu693, Leu724 and Phe735 residues of CmIDH and the corresponding Phe693, Gln724 and Leu735 residues of CpIDH were introduced by site-directed mutagenesis. A double mutant of CmIDH substituted its Leu724 and Phe735 residues by the corresponding ones of CpIDH, CmL724Q/F735L, and the triple mutant of CpIDH, CpF693L/Q724L/L735F, showed the most decrease and increase of activity, respectively, of each wild-type and its all mutated enzymes. In the case of CmIDH, the substitutions of these three amino acid residues resulted in the decrease of catalytic activity and thermostability for activity, but the combined substitutions of amino acid residues did not necessarily exert additive effects on these properties. On the other hand, similar substitutions in CpIDH had quite opposite effects to CmIDH, and the effects of the combined substitutions were additive. All multiple mutants of CmIDH and CpIDH showed lower and higher catalytic efficiency (k cat/K m) values than the respective wild-type enzymes. Single and multiple mutations of the substituted amino acid residues in the CmIDH and CpIDH led to the increase and decrease of sensitivity to tryptic digestion, indicating that the stability of protein structure was decreased and increased by the mutations, respectively. 相似文献
92.
Ya‐Qian Zhang Yaosen Tian Yihan Xiao Lincoln J. Miara Yuichi Aihara Tomoyuki Tsujimura Tan Shi M. C. Scott Gerbrand Ceder 《Liver Transplantation》2020,10(27)
The interfacial instability between a thiophosphate solid electrolyte and oxide cathodes results in rapid capacity fade and has driven the need for cathode coatings. In this work, the stability, evolution, and performance of uncoated, Li2ZrO3‐coated, and Li3B11O18‐coated LiNi0.5Co0.2Mn0.3O2 cathodes are compared using first‐principles computations and electron microscopy characterization. Li3B11O18 is identified as a superior coating that exhibits excellent oxidation/chemical stability, leading to substantially improved performance over cells with Li2ZrO3‐coated or uncoated cathodes. The chemical and structural origin of the different performance is interpreted using different microscopy techniques which enable the direct observation of the phase decomposition of the Li2ZrO3 coating. It is observed that Li is already extracted from the Li2ZrO3 in the first charge, leading to the formation of ZrO2 nanocrystallites with loss of protection of the cathode. After 50 cycles separated (Co, Ni)‐sulfides and Mn‐sulfides can be observed within the Li2ZrO3‐coated material. This work illustrates the severity of the interfacial reactions between a thiophosphate electrolyte and oxide cathode and shows the importance of using coating materials that are absolutely stable at high voltage. 相似文献
93.
Natsuki Osaka Yu kanesaki Megumi Watanabe Satoru Watanabe Taku Chibazakura Hiraku Takada Hirofumi Yoshikawa Kei Asai 《Molecular microbiology》2020,113(6):1155-1169
In bacteria, guanosine (penta)tetra-phosphate ([p]ppGpp) is essential for controlling intracellular metabolism that is needed to adapt to environmental changes, such as amino acid starvation. The (p)ppGpp0 strain of Bacillus subtilis, which lacks (p)ppGpp synthetase, is unable to form colonies on minimal medium. Here, we found suppressor mutations in the (p)ppGpp0 strain, in the purine nucleotide biosynthesis genes, prs, purF and rpoB/C, which encode RNA polymerase core enzymes. In comparing our work with prior studies of ppGpp0 suppressors, we discovered that methionine addition masks the suppression on minimal medium, especially of rpoB/C mutations. Furthermore, methionine addition increases intracellular GTP in rpoB suppressor and this effect is decreased by inhibiting GTP biosynthesis, indicating that methionine addition activated GTP biosynthesis and inhibited growth under amino acid starvation conditions in (p)ppGpp0 backgrounds. Furthermore, we propose that the increase in intracellular GTP levels induced by methionine is due to methionine derivatives that increase the activity of the de novo GTP biosynthesis enzyme, GuaB. Our study sheds light on the potential relationship between GTP homeostasis and methionine metabolism, which may be the key to adapting to environmental changes. 相似文献
94.
Yuichi Takashi Shun Sawatsubashi Itsuro Endo Yukiyo Ohnishi Masahiro Abe Munehide Matsuhisa Daiji Kawanami Toshio Matsumoto Seiji Fukumoto 《Biochemistry and Biophysics Reports》2021
Fibroblast growth factor (FGF) 23 produced by the bone is the principal hormone to regulate serum phosphate level. Serum FGF23 needs to be tightly regulated to maintain serum phosphate in a narrow range. Thus, we hypothesized that the bone has some phosphate-sensing mechanism to regulate the production of FGF23. Previously we showed that extracellular phosphate induces the phosphorylation of FGF receptor 1 (FGFR1) and FGFR1 signaling regulates the expression of Galnt3, whose product works to increase FGF23 production in vitro. In this study, we show the significance of FGFR1 in the regulated FGF23 production and serum phosphate level in vivo. We generated late-osteoblast/osteocyte-specific Fgfr1-knockout mice (Fgfr1fl/fl; OcnCre/+) by crossing the Ocn-Cre and the floxed Fgfr1 mouse lines. We evaluated serum phosphate and FGF23 levels, the expression of Galnt3 in the bone, the body weight and life span. A selective ablation of Fgfr1 aborted the increase of serum active full-length FGF23 and the enhanced expression of Galnt3 in the bone by a high phosphate diet. These mice showed more pronounced hyperphosphatemia compared with control mice. In addition, these mice fed with a control diet showed body weight loss after 23 weeks of age and shorter life span. These results reveal a novel significance of FGFR1 signaling in the phosphate metabolism and normal life span. 相似文献
95.
Hiroaki Ozaki Yuichi Sato Sadaji Azuma Hiroaki Sawai 《Nucleosides, nucleotides & nucleic acids》2013,32(3):593-601
Abstract 2′-Deoxy-2′-S-hexyluridine derivative was synthesized from 2,2′-anhydrouridine and 1-hexanethiol and incorporated into an oligodeoxyribonucleotide. The thermal stability of the duplexes formed by the 2′-S-hexyl modified ODN with either the complementary DNA or RNA strand was decreased compared to the unmodified counterparts. 相似文献
96.
H. Matsuo T. Takada K. Ichida T. Nakamura A. Nakayama Y. Takada 《Nucleosides, nucleotides & nucleic acids》2013,32(12):1098-1104
The ATP-binding cassette, subfamily G, member 2 gene ABCG2/BCRP locates in a gout-susceptibility locus (MIM 138900) on chromosome 4q. Recent genome-wide association studies also showed that the ABCG2 gene relates to serum uric acid levels and gout. Since ABCG2 is also known as a transporter of nucleotide analogs that are structurally similar to urate, and is an exporter that has common polymorphic reduced functionality variants, ABCG2 could be a urate secretion transporter and a gene causing gout. To find candidate mutations in ABCG2, we performed a mutation analysis of the ABCG2 gene in 90 Japanese patients with hyperuricemia and found six non-synonymous mutations. Among the variants, ATP-dependent urate transport was reduced or eliminated in five variants, and two out of the five variants (Q126X and Q141K) were frequently detected in patients. Haplotype frequency analysis revealed that there is no simultaneous presence of Q126X and Q141K in one haplotype. As Q126X and Q141K are a nonfunctional and half-functional haplotype, respectively, their genotype combinations are divided into four estimated functional groups. The association study with 161 male gout patients and 865 male controls showed that all of those who had dysfunctional ABCG2 had an increased risk of gout, and that a remarkable risk was observed in those with ≤1/4 function (OR, 25.8; 95% CI, 10.3–64.6; p = 3.39 × 10?21). In 2,150 Japanese individuals, the frequency of those with dysfunctional ABCG2 was more than 50%. Our function-based clinicogenetic analysis identified the combinations of dysfunctional variants of ABCG2 as a major contributing factor in Japanese patients with gout. 相似文献
97.
Brian A. Otter Shirish A. Patil Marianne R. Spada Linda A. Jelicks Yuichi Yoshimura Akira Matsuda 《Nucleosides, nucleotides & nucleic acids》2013,32(2-4):615-635
Abstract The 5-oxo-6-methylene-pyrimidine-2,4-dione intermediate (6) that is formed when 5-acetoxy-6-acetoxymethyl-1-β-D-(5-O-acetyl-2,3-O-isopropylidene)-ribofuranosyluracil (5) is treated with sodium hydroxide undergoes cyclization at pH 14 to give 2′,3′-O-isopropylidene-5-hydroxy- O 5, 6-methanouridine (8) in good yield. Conversion of 8 into the 5-triflate ester 14 followed by reduction with [(Ph)3P]4Pd/Bu3SnH and deblocking with acetic acid then affords O 5′, 6-methanouridine (4) Conformational studies (NOE difference spectra, vicinal 1H-13C coupling constants, NOESY and CD spectra, molecular modeling) indicate that the C7-methylene group of 4 projects towards the furanose ring oxygen atom, producing a glycosyl rotation angle of about ? 160°. 相似文献
98.
Hirotaka Matsuo Tappei Takada Kimiyoshi Ichida Takahiro Nakamura Akiyoshi Nakayama Hiroshi Suzuki 《Nucleosides, nucleotides & nucleic acids》2013,32(12):1117-1128
Recent genome-wide association studies showed that serum uric acid (SUA) levels relate to ABCG2/BCRP gene, which locates in a gout-susceptibility locus revealed by a genome-wide linkage study. Together with the ABCG2 characteristics, we hypothesized that ABCG2 transports urate and its dysfunction causes hyperuricemia and gout. Transport assays showed ATP-dependent transport of urate via ABCG2. Kinetic analysis revealed that ABCG2 mediates high-capacity transport of urate (Km: 8.24 ± 1.44 mM) even under high-urate conditions. Mutation analysis of ABCG2 in 90 Japanese hyperuricemia patients detected six nonsynonymous mutations, including five dysfunctional variants. Two relatively frequent dysfunctional variants, Q126X and Q141K, were then examined. Quantitative trait locus analysis of 739 Japanese individuals showed that Q141K increased SUA as the number of minor alleles of Q141K increased (p = 6.60 × 10?5). Haplotype frequency analysis revealed that there is no simultaneous presence of Q126X and Q141K in one haplotype. Becuase Q126X and Q141K are assigned to nonfunctional and half-functional haplotypes, respectively, their genotype combinations are divided into four functional groups. The association study with 161 male gout patients and 865 male controls showed that all of those with dysfunctional ABCG2 increased the gout risk, especially those with ≤1/4 function (OR, 25.8; 95% CI, 10.3–64.6; p = 3.39 × 10?21). These genotypes were found in 10.1% of gout patients, but in only 0.9% of control. Our function-based clinicogenetic (FBCG) analysis showed that combinations of the two dysfunctional variants are major causes of gout, thereby providing a new approach for prevention and treatment of the gout high-risk population. 相似文献
99.
Siriporn Pota Sinchai Chatasiri Yoshitaka Ono Yuichi Yamaoka Makoto Kakishima 《Mycoscience》2013,54(1):19-28
Phakopsora meliosmae, a macrocyclic autoecious rust fungus, is reported to occur on several Meliosma species widely distributed in Asia. Despite the apparent broad host range, a recent molecular phylogenetic study indicated that two rust populations on Meliosma myriantha and Meliosma tenuis respectively in Japan were biologically distinct. To clarify the biological and taxonomic relationships of these populations, cross inoculations and comparative morphological examinations were carried out. Cross inoculations using basidiospores and aeciospores confirmed the macrocyclic, autoecious nature of the life cycle in both rust populations and showed that the two populations were distinct in their host specificity. Furthermore, they were found to be distinct in the structure of the aecial peridium surface, the size and wall thickness of uredinial paraphyses, and the urediniospore size and shape. Consequently, the fungal population on M. tenuis is taxonomically separated from P. meliosmae originally proposed for the fungus on M. myriantha. A new name, Phakopsora orientalis, is proposed for the fungus on M. tenuis. 相似文献
100.
Nami Masubuchi Yuichi Shidoh Shunzo Kondo Jun Takatoh Kazunori Hanaoka 《Experimental Animals》2013,62(3):211-217
Duchenne muscular dystrophy (DMD) is an X-linked recessive progressive muscle
degenerative disorder that causes dilated cardiomyopathy in the second decade of life in
affected males. Dystrophin, the gene responsible for DMD, encodes
full-length dystrophin and various short dystrophin isoforms. In the mouse heart,
full-length dystrophin Dp427 and a short dystrophin isoform, Dp71, are expressed. In this
study, we intended to clarify the functions of these dystrophin isoforms in DMD-related
cardiomyopathy. We used two strains of mice: mdx mice, in which Dp427 was
absent but Dp71 was present, and DMD-null mice, in which both were
absent. By immunohistochemical staining and density-gradient centrifugation, we found that
Dp427 was located in the cardiac sarcolemma and also at the T-tubules, whereas Dp71 was
specifically located at the T-tubules. In order to determine whether T tubule-associated
Dp71 was involved in DMD-related cardiac disruption, we compared the cardiac phenotypes
between DMD-null mice and mdx mice. Both
DMD-null mice and mdx mice exhibited severe necrosis,
which was followed by fibrosis in cardiac muscle. However, we could not detect a
significant difference in myocardial fibrosis between mdx mice and
DMD-null mice. Based on the present results, we have shown that cardiac
myopathy is caused predominantly by a deficiency of full-length dystrophin Dp427. 相似文献