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101.
Ryuta Uraki Maki Kiso Kiyoko Iwatsuki-Horimoto Satoshi Fukuyama Emi Takashita Makoto Ozawa Yoshihiro Kawaoka 《Journal of virology》2013,87(14):7874-7881
Vaccination is an effective means to protect against influenza virus. Although inactivated and live-attenuated vaccines are currently available, each vaccine has disadvantages (e.g., immunogenicity and safety issues). To overcome these problems, we previously developed a replication-incompetent PB2-knockout (PB2-KO) influenza virus that replicates only in PB2 protein-expressing cells. Here, we generated two PB2-KO viruses whose PB2-coding regions were replaced with the HA genes of either A/California/04/2009 (H1N1pdm09) or A/Vietnam/1203/2004 (H5N1). The resultant viruses comparably, or in some cases more efficiently, induced virus-specific antibodies in the serum, nasal wash, and bronchoalveolar lavage fluid of mice relative to a conventional formalin-inactivated vaccine. Furthermore, mice immunized with these PB2-KO viruses were protected from lethal challenges with not only the backbone virus strain but also strains from which their foreign HAs originated, indicating that PB2-KO viruses with antigenically different HAs could serve as bivalent influenza vaccines. 相似文献
102.
Takanori Awata Mamoru Oshiki Tomonori Kindaichi Noriatsu Ozaki Akiyoshi Ohashi Satoshi Okabe 《Applied and environmental microbiology》2013,79(13):4145-4148
The phylogenetic affiliation and physiological characteristics (e.g., Ks and maximum specific growth rate [μmax]) of an anaerobic ammonium oxidation (anammox) bacterium, “Candidatus Scalindua sp.,” enriched from the marine sediment of Hiroshima Bay, Japan, were investigated. “Candidatus Scalindua sp.” exhibits higher affinity for nitrite and a lower growth rate and yield than the known anammox species. 相似文献
103.
104.
Ryoko Okajima Satoshi Chiba 《Evolution; international journal of organic evolution》2013,67(2):429-437
The adaptations that occur for support and protection can be studied with regard to the optimal structure that balances these objectives with any imposed constraints. The shell inclination of terrestrial gastropods is an appropriate model to address this problem. In this study, we examined how gastropods improve shell angles to well‐balanced ones from geometrically constrained shapes. Our geometric analysis and physical analysis showed that constantly coiled shells are constrained from adopting a well‐balanced angle; the shell angle of such basic shells tends to increase as the spire index (shell height/width) increases, although the optimum angle for stability is 90° for flat shells and 0° for tall shells. Furthermore, we estimated the influences of the geometric rule and the functional demands on actual shells by measuring the shell angles of both resting and active snails. We found that terrestrial gastropods have shell angles that are suited for balance. The growth lines of the shells indicated that this adaptation depends on the deflection of the last whorl: the apertures of flat shells are deflected downward, whereas those of tall shells are deflected upward. Our observations of active snails demonstrated that the animals hold their shells at better balanced angles than inactive snails. 相似文献
105.
Chisato Kusunoki Liu Yang Takeshi Yoshizaki Fumiyuki Nakagawa Atsushi Ishikado Motoyuki Kondo Katsutaro Morino Osamu Sekine Satoshi Ugi Yoshihiko Nishio Atsunori Kashiwagi Hiroshi Maegawa 《Biochemical and biophysical research communications》2013,430(1):225-230
Oxidative stress is produced in adipose tissue of obese subjects and has been associated with obesity-related disorders. Recent studies have shown that omega-3 polyunsaturated fatty acid (ω3-PUFA) has beneficial effects in preventing atherosclerotic diseases and insulin resistance in adipose tissue. However, the role of ω3-PUFA on adipocytes has not been elucidated. In this study, 3T3-L1 adipocytes were treated with ω3-PUFA and its metabolites, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or 4-hydroxy hexenal (4-HHE). ω3-PUFA and its metabolites dose-dependently increased mRNA and protein levels of the anti-oxidative enzyme, heme oxygenase-1 (HO-1); whereas no changes in the well-known anti-oxidant molecules, superoxide dismutase, catalase, and glutathione peroxidase, were observed. Knockdown of nuclear factor erythroid 2-related factor 2 (Nrf-2) significantly reduced EPA, DHA or 4-HHE-induced HO-1 mRNA and protein expression. Also, pretreatment with ω3-PUFA prevented H2O2-induced cytotoxicity in a HO-1 dependent manner. In conclusion, treatment with EPA and DHA induced HO-1 through the activation of Nrf-2 and prevented oxidative stress in 3T3-L1 adipocytes. This anti-oxidant defense may be of high therapeutic value for clinical conditions associated with systemic oxidative stress. 相似文献
106.
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
107.
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
108.
Yoshiya Ikawa Satoshi Touden Sho Katsumata Hiroyuki Furuta 《Bioorganic & medicinal chemistry》2013,21(21):6501-6505
A water-soluble derivative of N-fused porphyrin (NFP) possessing four cationic side-arms (pPyNFP) serves as a unique class of colorimetric/fluorogenic reporters that selectively react with biothiols in aquaous media to afford N-confused porphyrin (NCP) derivatives, while other nucleophilic amino acids were inert under a wide range of pH conditions. Owing to the large difference of the optical properties between NCP and NFP, the transformation enabled selective detection of biothiols in colorimetric/fluorogenic manner, especially in the near-infrared region. To the best our knowledge, this is the first example of porphyrin-based thiol detection systems that use the direct attack of thiol group on the optical reporter. 相似文献
109.
Hirotaka Kashiwagi Yoshiyuki Ono Masateru Ohta Susumu Itoh Fumihiko Ichikawa Suguru Harada Satoshi Takeda Nobuo Sekiguchi Masaki Ishigai Tadakatsu Takahashi 《Bioorganic & medicinal chemistry》2013,21(7):1823-1833
In an extension of our study on gamma hydroxy carboxylic acid analogs, we explored a series of nonsecosteroidal vitamin D receptor (VDR) agonists in which 1,3-diol of 1,25(OH)2D3 had been replaced by aryl acetic acid. These analogs showed very potent activity in vitro compared with 1,25(OH)2D3. An X-ray analysis of 8d showed that the inserted phenyl ring well mimicked the folded methylene linker of the gamma hydroxy carboxylic acid moiety but the carboxylic acid of 8d interacted with VDR in a different manner from gamma hydroxy carboxylic acids. Through our in vivo screening in an osteoporosis rat model using immature rats, we identified a potent active vitamin D3 analog, compound 7e. In mature rats of the same model, compound 7e also showed good PK profiling and excellent ability to prevent bone mineral density loss without severe hypercalcemia. Our nonsecosteroidal VDR agonist 7e (CH5036249) could be a possible new drug candidate for treating osteoporosis in human. 相似文献
110.
Keiji Saito Akira Nakao Tsuyoshi Shinozuka Kousei Shimada Satoshi Matsui Kiyoshi Oizumi Kazuki Yano Keiko Ohata Daisuke Nakai Yoko Nagai Satoru Naito 《Bioorganic & medicinal chemistry》2013,21(7):1628-1642
A cell-based assay was performed for the discovery of novel bone anabolic agents. Alkaline phosphatase (ALPase) activity of ST2 cells was utilized as an indicator of osteoblastic differentiation, and thienopyridine derivative 1 was identified as a hit compound. 3-Aminothieno[2,3-b]pyridine-2-carboxamide was confirmed to be a necessary core structure for the enhancement of ALPase activity, and then optimization of the C4-substituent on the thienopyridine ring was carried out. Introduction of cyclic amino groups to the C4-position of the thienopyridine ring improved the activity. Especially, N-phenyl-homopiperazine derivatives were found to be strong enhancers of ALPase among this new series. Furthermore, 3-amino-4-(4-phenyl-1,4-diazepan-1-yl)thieno[2,3-b]pyridine-2-carboxamide (15k) was orally administered to ovariectomized (OVX) rats over 6 weeks for evaluating the effects on areal bone mineral density (aBMD), and statistically significant improvements in aBMD were observed from the dosage of 10 mg/kg/day. 相似文献