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31.
Masako Nomaguchi Masaru Yokoyama Ken Kono Emi E. Nakayama Tatsuo Shioda Naoya Doi Sachi Fujiwara Akatsuki Saito Hirofumi Akari Kei Miyakawa Akihide Ryo Hirotaka Ode Yasumasa Iwatani Tomoyuki Miura Tatsuhiko Igarashi Hironori Sato Akio Adachi 《Journal of virology》2013,87(21):11447-11461
Human immunodeficiency virus type 1 (HIV-1) replication in macaque cells is restricted mainly by antiviral cellular APOBEC3, TRIM5α/TRIM5CypA, and tetherin proteins. For basic and clinical HIV-1/AIDS studies, efforts to construct macaque-tropic HIV-1 (HIV-1mt) have been made by us and others. Although rhesus macaques are commonly and successfully used as infection models, no HIV-1 derivatives suitable for in vivo rhesus research are available to date. In this study, to obtain novel HIV-1mt clones that are resistant to major restriction factors, we altered Gag and Vpu of our best HIV-1mt clone described previously. First, by sequence- and structure-guided mutagenesis, three amino acid residues in Gag-capsid (CA) (M94L/R98S/G114Q) were found to be responsible for viral growth enhancement in a macaque cell line. Results of in vitro TRIM5α susceptibility testing of HIV-1mt carrying these substitutions correlated well with the increased viral replication potential in macaque peripheral blood mononuclear cells (PBMCs) with different TRIM5 alleles, suggesting that the three amino acids in HIV-1mt CA are involved in the interaction with TRIM5α. Second, we replaced the transmembrane domain of Vpu of this clone with the corresponding region of simian immunodeficiency virus SIVgsn166 Vpu. The resultant clone, MN4/LSDQgtu, was able to antagonize macaque but not human tetherin, and its Vpu effectively functioned during viral replication in a macaque cell line. Notably, MN4/LSDQgtu grew comparably to SIVmac239 and much better than any of our other HIV-1mt clones in rhesus macaque PBMCs. In sum, MN4/LSDQgtu is the first HIV-1 derivative that exhibits resistance to the major restriction factors in rhesus macaque cells. 相似文献
32.
Tracy M. Crotty Tomoyuki Nakano Diana M. Stafforini Matthew K. Topham 《The Journal of biological chemistry》2013,288(3):1439-1447
Discovering proteins that modulate Akt signaling has become a critical task, given the oncogenic role of Akt in a wide variety of cancers. We have discovered a novel diacylglycerol signaling pathway that promotes dephosphorylation of Akt. This pathway is regulated by diacylglycerol kinase δ (DGKδ). In DGKδ-deficient cells, we found reduced Akt phosphorylation downstream of three receptor tyrosine kinases. Phosphorylation upstream of Akt was not affected. Our data indicate that PKCα, which is excessively active in DGKδ-deficient cells, promotes dephosphorylation of Akt through pleckstrin homology domain leucine-rich repeats protein phosphatase (PHLPP) 2. Depletion of either PKCα or PHLPP2 rescued Akt phosphorylation in DGKδ-deficient cells. In contrast, depletion of PHLPP1, another Akt phosphatase, failed to rescue Akt phosphorylation. Other PHLPP substrates were not affected by DGKδ deficiency, suggesting mechanisms allowing specific modulation of Akt dephosphorylation. We found that β-arrestin 1 acted as a scaffold for PHLPP2 and Akt1, providing a mechanism for specificity. Because of its ability to reduce Akt phosphorylation, we tested whether depletion of DGKδ could attenuate tumorigenic properties of cultured cells and found that DGKδ deficiency reduced cell proliferation and migration and enhanced apoptosis. We have, thus, discovered a novel pathway in which diacylglycerol signaling negatively regulates Akt activity. Our collective data indicate that DGKδ is a pertinent cancer target, and our studies could lay the groundwork for development of novel cancer therapeutics. 相似文献
33.
Katsumi Kadekawa Kimio Sugaya Saori Nishijima Katsuhiro Ashitomi Minoru Miyazato Tomoyuki Ueda Hideyuki Yamamoto 《Life sciences》2013,92(20-21):1024-1028
AimsAlpha1D-adrenoceptors (α1D-ARs) located in the spinal cord are involved in the control of lower urinary tract function. In order to clarify the effect of α1D-ARs on storage function in the spinal cord, we examined the effect of oral administration and intrathecal injection of the α1D/A-AR antagonist, naftopidil, on bladder activity, as well as the effect of naftopidil on bladder wall histology, in female rats with spinal cord injury (SCI).Main methodsAdult female Sprague–Dawley rats with Th9–10 spinal cord transection were used. In SCI rats with or without 5 mg/day of naftopidil for 4 weeks, bladder activity was examined via continuous cystometry. In other SCI rats, bladder activity was examined before and after intrathecal injection of naftopidil. In addition, bladder wall histology was compared between SCI rats with or without oral administration of naftopidil for 4 weeks.Key findingsOral administration of naftopidil decreased the number of non-voiding contractions (NVCs). Intrathecal injection of naftopidil prolonged the interval between voiding contractions, decreased the maximum voiding contraction pressure and the number of NVCs, and increased bladder capacity without affecting the residual urine volume. Oral administration of naftopidil also decreased bladder wall fibrosis.SignificanceThe α1D/A-AR antagonist naftopidil might act on the bladder and spinal cord to improve detrusor hyperreflexia in the storage state in SCI female rats. Naftopidil also suppressed bladder wall fibrosis, suggesting that it may be effective for the treatment of neurogenic lower urinary tract dysfunction after SCI. 相似文献
34.
Lisa R. W. Plano Tomoyuki Shibata Anna C. Garza Jonathan Kish Jay M. Fleisher Christopher D. Sinigalliano Maribeth L. Gidley Kelly Withum Samir M. Elmir Suzanne Hower Charlene R. Jackson John B. Barrett Timothy Cleary Maureen Davidson Johnnie Davis Sampa Mukherjee Lora E. Fleming Helena M. Solo-Gabriele 《Microbial ecology》2013,65(4):1039-1051
Reports of Staphylococcus aureus including methicillin-resistant S. aureus (MRSA) detected in marine environments have occurred since the early 1990s. This investigation sought to isolate and characterize S. aureus from marine waters and sand at a subtropical recreational beach, with and without bathers present, in order to investigate possible sources and to identify the risks to bathers of exposure to these organisms. During 40 days over 17 months, 1,001 water and 36 intertidal sand samples were collected by either bathers or investigators at a subtropical recreational beach. Methicillin-sensitive S. aureus (MSSA) and MRSA were isolated and identified using selective growth media and an organism-specific molecular marker. Antimicrobial susceptibility, staphylococcal cassette chromosome mec (SCCmec) type, pulsed-field gel electrophoresis (PFGE) pattern, multi-locus sequence type (MLST), and staphylococcal protein A (spa) type were characterized for all MRSA. S. aureus was isolated from 248 (37 %) bather nearby water samples at a concentration range of <2–780 colony forming units per ml, 102 (31 %) ambient water samples at a concentration range of <2–260 colony forming units per ml, and 9 (25 %) sand samples. Within the sand environment, S. aureus was isolated more often from above the intertidal zone than from intermittently wet or inundated sand. A total of 1334 MSSA were isolated from 37 sampling days and 22 MRSA were isolated from ten sampling days. Seventeen of the 22 MRSA were identified by PFGE as the community-associated MRSA USA300. MRSA isolates were all SCCmec type IVa, encompassed five spa types (t008, t064, t622, t688, and t723), two MLST types (ST8 and ST5), and 21 of 22 isolates carried the genes for Panton–Valentine leukocidin. There was a correlation (r?=?0.45; p?=?0.05) between the daily average number of bathers and S. aureus in the water; however, no association between exposure to S. aureus in these waters and reported illness was found. This report supports the concept that humans are a potential direct source for S. aureus in marine waters. 相似文献
35.
Climate changes on various time scales often shape genetic novelty and adaptive variation in many biotas. We explored molecular signatures of directional selection in populations of the ice goby Leucopsarion petersii inhabiting a unique sea basin, the Sea of Japan, where a wide variety of environments existed in the Pleistocene in relation to shifts in sea level by repeated glaciations. This species consisted of two historically allopatric lineages, the Japan Sea (JS) and Pacific Ocean (PO) lineages, and these have lived under contrasting marine environments that are expected to have imposed different selection regimes caused by past climatic and current oceanographic factors. We applied a limited genome‐scan approach using seven candidate genes for phenotypic differences between two lineages in combination with 100 anonymous microsatellite loci. Neuropeptide Y (NPY) gene, which is an important regulator of food intake and potent orexigenic agent, and three anonymous microsatellites were identified as robust outliers, that is, candidate loci potentially under directional selection, by multiple divergence‐ and diversity‐based outlier tests in comparisons focused on multiple populations of the JS vs. PO lineages. For these outlier loci, populations of the JS lineage had putative signals of selective sweeps. Additionally, real‐time quantitative PCR analysis using fish reared in a common environment showed a higher expression level for NPY gene in the JS lineage. Thus, this study succeeded in identifying candidate genomic regions under selection across populations of the JS lineage and provided evidence for lineage‐specific adaptive evolution in this unique sea basin. 相似文献
36.
Chie Hashimoto Tetsuo Narumi Hiroyuki Otsuki Yuki Hirota Hiroshi Arai Kazuhisa Yoshimura Shigeyoshi Harada Nami Ohashi Wataru Nomura Tomoyuki Miura Tatsuhiko Igarashi Shuzo Matsushita Hirokazu Tamamura 《Bioorganic & medicinal chemistry》2013,21(24):7884-7889
To date, several small molecules of CD4 mimics, which can suppress competitively the interaction between an HIV-1 envelope glycoprotein gp120 and a cellular surface protein CD4, have been reported as viral entry inhibitors. A lead compound 2 (YYA-021) with relatively high potency and low cytotoxicity has been identified previously by SAR studies. In the present study, the pharmacokinetics of the intravenous administration of compound 2 in rats and rhesus macaques is reported. The half-lives of compound 2 in blood in rats and rhesus macaques suggest that compound 2 shows wide tissue distribution and relatively high distribution volumes. A few hours after the injection, both plasma concentrations of compound 2 maintained micromolar levels, indicating it might have promise for intravenous administration when used combinatorially with anti-gp120 monoclonal antibodies. 相似文献
37.
Kenji Seiwa Yoshiko Miwa Shigetoshi Akasaka Hiroshi Kanno Mizuki Tomita Tomoyuki Saitoh Naoto Ueno Megumi Kimura Yoichi Hasegawa Miki Konno Kazuhiko Masaka 《Ecological Research》2013,28(1):29-41
To evaluate the extent to which landslides affect community dynamics and consequent species diversity in a beech-dominated forest, differences in the composition and size structure of tree species were compared between landslide and adjacent stable (control) stands. Demography and changes in size were compared between the two stands over a 5-year period about 60 years after a landslide. In the control stand, replacement occurred even amongst late-successional species, with beech (Fagus crenata)—the most dominant species—increasing in relative abundance. In the landslide stand, very few large individuals of late-successional species occurred, whereas large individuals of early-successional species occurred only in the landslide stand. The traits indicate that the landslide strongly facilitated species diversity, not only by reducing the dominance of late-successional species, but also by promoting recruitment of early-successional species. However, new recruitment of early-successional species was inhibited in the landslide stand, although we observed succeeding regeneration and subsequent population growth of late-successional species there. As a result, the relative dominance of late-successional species increased with succession after the landslide, thus decreasing future species diversity. In beech-dominant forest landscapes in Japan that include communities with different developmental stages, the mosaic of serial stages may facilitate species diversity after a landslide. 相似文献
38.
Tomoyuki Tsuneya Masakazu Ishihara Haruyasu Shiota Minoru Shiga 《Bioscience, biotechnology, and biochemistry》2013,77(11):2495-2502
Steam distilled oil of quince fruit (Cydonia oblonga Mill.=C. vulgaris Pers., marmelo in Japanese) was analyzed by gas chromatography and gas chromatography-mass spectrometry. Sixty-two compounds, 2 hydrocarbons, 13 esters, 11 alcohols, 11 aldehydes, 11 ketones, 5 lactones and 9 miscellaneous compounds, were identified. Of them, the chemical structures of two new oxide compounds, trans- and cis-3-methyl-5-[(E)-3′-methyl-13′-butadien-1′-yl]tetrahydrofuran, were elucidated by instrumental analyses. 相似文献
39.
Tomoyuki Numata 《Bioscience, biotechnology, and biochemistry》2013,77(3):347-353
Bacteria and archaea have 2-lysylcytidine (L or lysidine) and 2-agmatinylcytidine (agm2C or agmatidine), respectively, at the first (wobble) position of the anticodon of the AUA codon-specific tRNAIle. These lysine- or agmatine-conjugated cytidine derivatives are crucial for the precise decoding of the genetic code. L is synthesized by tRNAIle-lysidine synthetase (TilS), which uses l-lysine and ATP as substrates. Agm2C formation is catalyzed by tRNAIle-agm2C synthetase (TiaS), which uses agmatine and ATP for the reaction. Despite the fact that TilS and TiaS synthesize structurally similar cytidine derivatives, these enzymes belong to non-related protein families. Therefore, these enzymes modify the wobble cytidine by distinct catalytic mechanisms, in which TilS activates the C2 carbon of the wobble cytidine by adenylation, while TiaS activates it by phosphorylation. In contrast, TilS and TiaS share similar tRNA recognition mechanisms, in which the enzymes recognize the tRNA acceptor stem to discriminate tRNAIle and tRNAMet. 相似文献
40.
Tôru Nagasawa Kazuyasu Umemoto Tomoyuki Tsuneya Minoru Shiga 《Bioscience, biotechnology, and biochemistry》2013,77(10):2083-2084
The most effective electro-energizing fermentation (E-E F) conditions for l-glutamate (l-Glu) production by Brevibacterium flavum No. 2247 were determined. The adding of 0.01 mm neutral red at the beginning of cultivation was found most effective. A 1.5 V direct current was applied to the culture broth at 6~8 hr after inoculation in the cathode compartment, l-Glu was produced at 51.0 mg per ml, and this is about a 15 % increase in yield compared to the yield of the not electro-energizing (E-E) control (44.3 mg/ml). 相似文献