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91.
Ayumu Niida Yoko Kanematsu-Yamaki Tomoko Asakawa Yoshimasa Ishimura Hisashi Fujita Kouta Matsumiya Naoki Nishizawa Yusuke Adachi Taisuke Mochida Kazue Tsuchimori Mariko Yoneyama-Hirozane Junichi Sakamoto Hideki Hirabayashi Hideo Fukui Shiro Takekawa Taiji Asami 《Bioorganic & medicinal chemistry》2018,26(3):566-572
Neuropeptide Y2 receptor (Y2R) agonism is an important anorectic signal and a target of antiobesity drug discovery. Recently, we synthesized a short-length Y2R agonist, PYY-1119 (4-imidazolecarbonyl-[d-Hyp24,Iva25,Pya(4)26,Cha27,36,γMeLeu28,Lys30,Aib31]PYY(23–36), 1) as an antiobesity drug candidate. Compound 1 induced marked body weight loss in diet-induced obese (DIO) mice; however, 1 also induced severe vomiting in dogs at a lower dose than the minimum effective dose administered to DIO mice. The rapid absorption of 1 after subcutaneous administration caused the severe vomiting. Polyethylene glycol (PEG)- and alkyl-modified derivatives of 1 were synthesized to develop Y2R agonists with improved pharmacokinetic profiles, i.e., lower maximum plasma concentration (Cmax) and longer time at maximum concentration (Tmax). Compounds 5 and 10, modified with 20?kDa PEG at the N-terminus and eicosanedioic acid at the Lys30 side chain of 1, respectively, showed high Y2R binding affinity and induced significant body weight reduction upon once-daily administration to DIO mice. Compounds 5 and 10, with their relatively low Cmax and long Tmax, partially attenuated emesis in dogs compared with 1. These results indicate that optimization of pharmacokinetic properties of Y2R agonists is an effective strategy to alleviate emesis induced by Y2R agonism. 相似文献
92.
Wataru Kojima Wataru Kitamura Sachie Kitajima Yoko Ito† Keisuke Ueda† Go Fujita & Hiroyoshi Higuchi 《Ethology : formerly Zeitschrift fur Tierpsychologie》2009,115(10):939-947
Female mate choice is responsible for the evolution of male secondary sexual ornaments. If male ornamental traits reflect indirect, genetic benefits and/or direct, material benefits to females, choosy females may benefit from their choice, indirectly and/or directly. We examined a breeding population of Japanese barn swallows Hirundo rustica gutturalis to determine whether male tail streamer length reflected indirect and/or direct benefits to females. There was no significant positive relationship between male streamer length and the number of extra-pair young (EPY) sired, suggesting that male tail streamers are not a signal of indirect benefits (i.e. good genes theory). In addition, we found no evidence that males with longer streamers fed their offspring more frequently or sired more within-pair young (WPY). The result indicates that male streamer length probably does not act as a signal of direct benefits. Our finding that the length of tail streamers in Japanese barn swallows plays no role in sexual selection is not consistent with studies on European subspecies, but is consistent with studies on North American subspecies where sexual selection on tail streamer is weak. The present study supports the recent suggestion that the pattern of sexual selection on tail streamer length in barn swallows varies geographically. Instead of tail length, males in better condition sired more EPY and WPY. Males in better condition, however, did not feed their nestling more frequently. These results indicate that females gain indirect benefits but not direct benefits, in terms of feeding of young, on choosing social mates. 相似文献
93.
Kentaro Nagamine Yoko Kuzuhara Tsugunori Notomi 《Biochemical and biophysical research communications》2002,290(4):1195-1198
Loop-mediated isothermal amplification (LAMP), in which a specific DNA sequence can be directly amplified under isothermal conditions, yields DNA in large quantities of more than 500 microg/ml. We have developed a method to isolate single-stranded DNA fragments from LAMP products that are stem-loop DNAs with several inverted repeats of the target DNA. This method requires the TspRI restriction enzyme, a primer hybridized to the 3' overhanging sequence at its cleavage site, and a DNA polymerase with strand displacement activity. The LAMP products are digested with TspRI and are then extended using the primer, producing the strand-specific DNA fragments. All processes, from LAMP reaction to primer extension, can be carried out at the same temperature. The use of strand-specific DNA would be conducive for detection by hybridization technique such as DNA microarrays. 相似文献
94.
Dr. Yoko Kameda 《Cell and tissue research》1982,225(3):693-697
Summary Small follicles composed solely of C cells were occasionally observed in large C cell groups of dog thyroid glands. The lumina of C-cell follicles were filled with, or contained peripheral depositions of PAS-positive amorphous material, which was similar in ultrastructural features to thyroglobulin-containing colloid in typical thyroid follicles. This indicates that C cells, in addition to secreting calcitonin, produce a glycoprotein that can be stored in the lumina of the follicles. 相似文献
95.
Mizuha Y Yamamoto H Sato T Tsuji M Masuda M Uchida M Sakai K Taketani Y Yasutomo K Sasaki H Takeda E 《BioFactors (Oxford, England)》2007,30(2):105-116
It has been reported that Cordyceps sinensis, a traditional Chinese medicine, has various pharmacological effects. The aim of this study was to clarify the effect of water extract of Cordyceps sinensis (WECS) on osteoclast differentiation in vitro. In mouse bone marrow cells and monocyte/macrophage cell line RAW264.7, WECS dose-dependently inhibited the receptor activator of nuclear factor kappa B (NF-kappaB) ligand (RANKL)-induced osteoclast differentiation by tartrate-resistant acid phosphatase (TRAP) staining. In fact, cytotoxic effect was not observed in the RAW264.7 cells treated with WECS. Moreover, the mRNA expression of osteoclast related genes (calcitonin receptor, cathepsin K, matrix metalloprotease 9 and nuclear factor of activated T cells c1) was also inhibited by WECS. Investigation of inhibitory mechanism by using electrophoretic mobility shift assay (EMSA) and Western blot analysis revealed that WECS inhibited the activation of NF-kappaB through the prevention of IkappaBalpha phosphorylation. In conclusion, the present results demonstrate for the first time that WECS is a potent inhibitor of the RANKL-induced osteoclast differentiation through a mechanism involving the NF-kappaB pathway. 相似文献
96.
Saino H Ukita Y Ago H Irikura D Nisawa A Ueno G Yamamoto M Kanaoka Y Lam BK Austen KF Miyano M 《The Journal of biological chemistry》2011,286(18):16392-16401
Leukotriene (LT) C(4) and its metabolites, LTD(4) and LTE(4), are involved in the pathobiology of bronchial asthma. LTC(4) synthase is the nuclear membrane-embedded enzyme responsible for LTC(4) biosynthesis, catalyzing the conjugation of two substrates that have considerably different water solubility; that amphipathic LTA(4) as a derivative of arachidonic acid and a water-soluble glutathione (GSH). A previous crystal structure revealed important details of GSH binding and implied a GSH activating function for Arg-104. In addition, Arg-31 was also proposed to participate in the catalysis based on the putative LTA(4) binding model. In this study enzymatic assay with mutant enzymes demonstrates that Arg-104 is required for the binding and activation of GSH and that Arg-31 is needed for catalysis probably by activating the epoxide group of LTA(4). 相似文献
97.
98.
Yoko Yamauchi Hikari Kimoto Xianyu Yang Sergey Filkin Yuri Utkin Tai Kubo 《Bioscience, biotechnology, and biochemistry》2016,80(1):158-161
Three-finger toxins (3FTxs) are one of the major components in snake venoms. In this study, we isolated a cDNA encoding a short-chain 3FTx, Pr-SNTX, from Pseudechis rossignolii. The amino acid sequence of Pr-SNTX is nearly identical to that of its ortholog in Pseudechis australis. Pr-SNTX protein inhibited muscle-type (α2βδε), but not neuronal α7 nicotinic acetylcholine receptor (nAChR) activity. 相似文献
99.
Takayoshi Wakagi Eriko Fukuda Yoko Ogawa Hiroyasu Kino Hiroshi Matsuzawa 《FEBS letters》2002,510(3):196-200
An enzyme, which catalyzes both decarboxylation of indolepyruvate and subsequent oxidation of indoleacetaldehyde into indoleacetate, was purified from a thermoacidophilic archaeon, Sulfolobus sp. strain 7. The enzyme showed a Mr of 280 kDa on gel filtration and was composed of three subunits (a, 89; b, 30; and c, 19 kDa), possibly in a stoichiometry of 2:2:2. Mo and Fe were detected. Thiamine pyrophosphate was absent. Biotin was suggested to bind to the b-subunit. The first step, the decarboxylation reaction, was specific for 2-oxoacids with an aromatic group, while in the second reaction, various aldehydes including glyceraldehyde, which is a glycolytic intermediate in the organism, were oxidized. 相似文献
100.
Yoko Takematsu Kohei Kambara Takashi Yamaguchi Kazuaki Mitsumaki 《Entomological Science》2013,16(3):355-359
In Lambir Hills National Park, Sarawak, Malaysia, there are four species of processional termites that coexist: Hospitalitermes hospitalis, H. lividiceps, H. rufus and Longipeditermes longipes. This paper presents the results of our investigation on the spatial distribution of nests and the foraging activities of the four species in coexistence. The results show that there are fairly marked differences in nesting sites, as well as in foraging activities, among the four species. It is noteworthy that H. rufus inhabits only the canopy area over 20 m above ground, apparently segregated from the other three species, and that their foraging activities are limited also to tree canopies over 10 m above ground. In contrast, L. longipes nests underground and forages exclusively on the forest floor. Hospitalitermes hospitalis and H. lividiceps inhabit and forage over wide areas, from the forest floor to tree canopies. The upper parts of the tree canopy (over 10 m) are also foraging territories of the secluded H. rufus, but there were no observations of simultaneous foraging of the three Hospitalitermes species in the same canopy areas. 相似文献