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301.
Hiroshi Kadokura Michiko Saito Akio Tsuru Akira Hosoda Takao Iwawaki Kenji Inaba Kenji Kohno 《Biochemical and biophysical research communications》2013
ERdj5 (also known as JPDI) is a member of PDI family conserved in higher eukaryotes. This protein possesses an N-terminal J domain and C-terminal four thioredoxin domains each having a redox active site motif. Despite the insights obtained at the cellular level on ERdj5, the role of this protein in vivo is still unclear. Here, we present a simple method to purify and identify the disulfide-linked complexes of this protein efficiently from a mouse tissue. By combining acid quenching and thiol-alkylation, we identified a number of potential redox partners of ERdj5 from the mouse epididymis. Further, we show that ERdj5 indeed interacted with two of the identified proteins via formation of intermolecular disulfide bond. Thus, this approach enabled us to detect and identify redox partners of a PDI family member from an animal tissue. 相似文献
302.
Akiharu Kubo Aiko Shiohama Takashi Sasaki Kazuhiko Nakabayashi Hiroshi Kawasaki Toru Atsugi Showbu Sato Atsushi Shimizu Shuji Mikami Hideaki Tanizaki Masaki Uchiyama Tatsuo Maeda Taisuke Ito Jun-ichi Sakabe Toshio Heike Torayuki Okuyama Rika Kosaki Kenjiro Kosaki Jun Kudoh Kenichiro Hata Akihiro Umezawa Yoshiki Tokura Akira Ishiko Hironori Niizeki Kenji Kabashima Yoshihiko Mitsuhashi Masayuki Amagai 《American journal of human genetics》2013,93(5):945-956
“Nagashima-type” palmoplantar keratosis (NPPK) is an autosomal recessive nonsyndromic diffuse palmoplantar keratosis characterized by well-demarcated diffuse hyperkeratosis with redness, expanding on to the dorsal surfaces of the palms and feet and the Achilles tendon area. Hyperkeratosis in NPPK is mild and nonprogressive, differentiating NPPK clinically from Mal de Meleda. We performed whole-exome and/or Sanger sequencing analyses of 13 unrelated NPPK individuals and identified biallelic putative loss-of-function mutations in SERPINB7, which encodes a cytoplasmic member of the serine protease inhibitor superfamily. We identified a major causative mutation of c.796C>T (p.Arg266∗) as a founder mutation in Japanese and Chinese populations. SERPINB7 was specifically present in the cytoplasm of the stratum granulosum and the stratum corneum (SC) of the epidermis. All of the identified mutants are predicted to cause premature termination upstream of the reactive site, which inhibits the proteases, suggesting a complete loss of the protease inhibitory activity of SERPINB7 in NPPK skin. On exposure of NPPK lesional skin to water, we observed a whitish spongy change in the SC, suggesting enhanced water permeation into the SC due to overactivation of proteases and a resultant loss of integrity of the SC structure. These findings provide an important framework for developing pathogenesis-based therapies for NPPK. 相似文献
303.
304.
Mitsutaka Ogawa Naosuke Nakamura Yoshiaki Nakayama Akira Kurosaka Hiroshi Manya Motoi Kanagawa Tamao Endo Koichi Furukawa Tetsuya Okajima 《Biochemical and biophysical research communications》2013
Hypoglycosylation is a common characteristic of dystroglycanopathy, which is a group of congenital muscular dystrophies. More than ten genes have been implicated in α-dystroglycanopathies that are associated with the defect in the O-mannosylation pathway. One such gene is GTDC2, which was recently reported to encode O-mannose β-1,4-N-acetylglucosaminyltransferase. Here we show that GTDC2 generates CTD110.6 antibody-reactive N-acetylglucosamine (GlcNAc) epitopes on the O-mannosylated α-dystroglycan (α-DG). Using the antibody, we show that mutations of GTDC2 identified in Walker–Warburg syndrome and alanine-substitution of conserved residues between GTDC2 and EGF domain O-GlcNAc transferase resulted in decreased glycosylation. Moreover, GTDC2-modified GlcNAc epitopes are localized in the endoplasmic reticulum (ER). These data suggested that GTDC2 is a novel glycosyltransferase catalyzing GlcNAcylation of O-mannosylated α-DG in the ER. CTD110.6 antibody may be useful to detect a specific form of GlcNAcylated O-mannose and to analyze defective O-glycosylation in α-dystroglycanopathies. 相似文献
305.
Minoru Nakao Antti Lavikainen Tetsuya Yanagida Akira Ito 《International journal for parasitology》2013,43(12-13):1017-1029
Echinococcosis is a serious helminthic zoonosis in humans, livestock and wildlife. The pathogenic organisms are members of the genus Echinococcus (Cestoda: Taeniidae). Life cycles of Echinococcus spp. are consistently dependent on predator–prey association between two obligate mammalian hosts. Carnivores (canids and felids) serve as definitive hosts for adult tapeworms and their herbivore prey (ungulates, rodents and lagomorphs) as intermediate hosts for metacestode larvae. Humans are involved as an accidental host for metacestode infections. The metacestodes develop in various internal organs, particularly in liver and lungs. Each metacestode of Echinococcus spp. has an organotropism and a characteristic form known as an unilocular (cystic), alveolar or polycystic hydatid. Recent molecular phylogenetic studies have demonstrated that the type species, Echinococcus granulosus, causing cystic echinococcosis is a cryptic species complex. Therefore, the orthodox taxonomy of Echinococcus established from morphological criteria has been revised from the standpoint of phylogenetic systematics. Nine valid species including newly resurrected taxa are recognised as a result of the revision. This review summarises the recent advances in the phylogenetic systematics of Echinococcus, together with the historical backgrounds and molecular epidemiological aspects of each species. A new phylogenetic tree inferred from the mitochondrial genomes of all valid Echinococcus spp. is also presented. The taxonomic nomenclature for Echinococcus oligarthrus is shown to be incorrect and this name should be replaced with Echinococcus oligarthra. 相似文献
306.
Hiroki Takagi Akira Abe Kentaro Yoshida Shunichi Kosugi Satoshi Natsume Chikako Mitsuoka Aiko Uemura Hiroe Utsushi Muluneh Tamiru Shohei Takuno Hideki Innan Liliana M. Cano Sophien Kamoun Ryohei Terauchi 《The Plant journal : for cell and molecular biology》2013,74(1):174-183
The majority of agronomically important crop traits are quantitative, meaning that they are controlled by multiple genes each with a small effect (quantitative trait loci, QTLs). Mapping and isolation of QTLs is important for efficient crop breeding by marker‐assisted selection (MAS) and for a better understanding of the molecular mechanisms underlying the traits. However, since it requires the development and selection of DNA markers for linkage analysis, QTL analysis has been time‐consuming and labor‐intensive. Here we report the rapid identification of plant QTLs by whole‐genome resequencing of DNAs from two populations each composed of 20–50 individuals showing extreme opposite trait values for a given phenotype in a segregating progeny. We propose to name this approach QTL‐seq as applied to plant species. We applied QTL‐seq to rice recombinant inbred lines and F2 populations and successfully identified QTLs for important agronomic traits, such as partial resistance to the fungal rice blast disease and seedling vigor. Simulation study showed that QTL‐seq is able to detect QTLs over wide ranges of experimental variables, and the method can be generally applied in population genomics studies to rapidly identify genomic regions that underwent artificial or natural selective sweeps. 相似文献
307.
Koji Ochiai Satoshi Takita Akihiko Kojima Tomohiko Eiraku Kazuhiko Iwase Tetsuya Kishi Akira Ohinata Yuichi Yageta Tokutaro Yasue David R. Adams Yasushi Kohno 《Bioorganic & medicinal chemistry letters》2013,23(1):375-381
(?)-6-(7-Methoxy-2-(trifluoromethyl)pyrazolo[1,5-a]pyridin-4-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one (KCA-1490) exhibits moderate dual PDE3/4-inhibitory activity and promises as a combined bronchodilatory/anti-inflammatory agent. N-alkylation of the pyridazinone ring markedly enhances potency against PDE4 but suppresses PDE3 inhibition. Addition of a 6-aryl-4,5-dihydropyridazin-3(2H)-one extension to the N-alkyl group facilitates both enhancement of PDE4-inhibitory activity and restoration of potent PDE3 inhibition. Both dihydropyridazinone rings, in the core and extension, can be replaced by achiral 4,4-dimethylpyrazolone subunits and the core pyrazolopyridine by isosteric bicyclic heteroaromatics. In combination, these modifications afford potent dual PDE3/4 inhibitors that suppress histamine-induced bronchoconstriction in vivo and exhibit promising anti-inflammatory activity via intratracheal administration. 相似文献
308.
Akira Muto Masamichi Ohkura Gembu Abe Junichi Nakai Koichi Kawakami 《Current biology : CB》2013,23(4):307-311
Download : Download video (74MB) 相似文献
309.
Akihiko Kojima Satoshi Takita Tatsunobu Sumiya Koji Ochiai Kazuhiko Iwase Tetsuya Kishi Akira Ohinata Yuichi Yageta Tokutaro Yasue Yasushi Kohno 《Bioorganic & medicinal chemistry letters》2013,23(19):5311-5316
We previously identified KCA-1490 [(?)-6-(7-methoxy-2-trifluoromethyl-pyrazolo[1,5-a]pyridin-4-yl)-5-methyl-4,5-dihydro-3-(2H)-pyridazinone], a dual PDE3/4 inhibitor. In the present study, we found highly potent selective PDE4 inhibitors derived from the structure of KCA-1490. Among them, N-(3,5-dichloropyridin-4-yl)-7-methoxy-2-(trifluoromethyl)pyrazolo[1,5-a]pyridine-4-carboxamide (2a) had good anti-inflammatory effects in an animal model. 相似文献
310.
Yuusuke Tamura Kyouhei Hayashi Naoki Omori Yuji Nishiura Kana Watanabe Nobuyuki Tanaka Masahiko Fujioka Naoki Kouyama Akira Yukimasa Yukari Tanaka Takeshi Chiba Hideki Tanioka Hirohide Nambu Hideo Yukioka Hiroki Sato Takayuki Okuno 《Bioorganic & medicinal chemistry letters》2013,23(1):90-95
Optimization of HTS hit 1 for NPY Y5 receptor binding affinity, CYP450 inhibition, solubility and metabolic stability led to the identification of some orally available oxygen-linker derivatives for in vivo study. Among them, derivative 4i inhibited food intake induced by the NPY Y5 selective agonist, and chronic oral administration of 4i in DIO mice caused a dose-dependent reduction of body weight gain. 相似文献