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991.
A C 26 -sterol in the clam, Tapes philippinarum 总被引:1,自引:0,他引:1
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Nobuaki Takahashi Kyohei Hayashi Yusuke Nakagawa Yutaka Furutani Mariko Toguchi Yumi Shiozaki-Sato Masayuki Sudoh Soichi Kojima Hideaki Kakeya 《Bioorganic & medicinal chemistry》2019,27(3):470-478
Hepatitis B, a viral infectious disease caused by hepatitis B virus (HBV), is a life-threatening disease that leads liver cirrhosis and liver cancer. Because the current treatments for HBV, such as an interferon (IFN) formulation or nucleoside/nucleotide analogues, are not sufficient, the development of a more effective agent for HBV is urgent required.CDM-3008 (1, 2-(2,4-bis(trifluoromethyl)imidazo[1,2-a][1,8]naphthyridin-8-yl)-1,3,4-oxadiazole) (RO8191)) is a small molecule with an imidazo[1,2-a][1,8]naphthyridine scaffold that shows anti-HCV activity with an IFN-like effect. Here, we report that 1 was also effective for HBV, although the solubility and metabolic stability were insufficient for clinical use. Through the structure-activity relationship (SAR), we discovered that CDM-3032 (11, N-(piperidine-4-yl)-2,4-bis(trifluoromethyl)imidazo[1,2-a][1,8]naphthyridine-8-carboxamide hydrochloride) was more soluble than 1 (>30?mg/mL for 11 versus 0.92?mg/mL for 1). In addition, the half-life period of 11 was dramatically improved in both mouse and human hepatic microsomes (T1/2, >120?min versus 58.2?min in mouse, and >120?min versus 34.1?min in human, for 11 and 1, respectively). 相似文献
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Storz JF Sabatino SJ Hoffmann FG Gering EJ Moriyama H Ferrand N Monteiro B Nachman MW 《PLoS genetics》2007,3(3):e45
Elucidating genetic mechanisms of adaptation is a goal of central importance in evolutionary biology, yet few empirical studies have succeeded in documenting causal links between molecular variation and organismal fitness in natural populations. Here we report a population genetic analysis of a two-locus α-globin polymorphism that underlies physiological adaptation to high-altitude hypoxia in natural populations of deer mice, Peromyscus maniculatus. This system provides a rare opportunity to examine the molecular underpinnings of fitness-related variation in protein function that can be related to a well-defined selection pressure. We surveyed DNA sequence variation in the duplicated α-globin genes of P. maniculatus from high- and low-altitude localities (i) to identify the specific mutations that may be responsible for the divergent fine-tuning of hemoglobin function and (ii) to test whether the genes exhibit the expected signature of diversifying selection between populations that inhabit different elevational zones. Results demonstrate that functionally distinct protein alleles are maintained as a long-term balanced polymorphism and that adaptive modifications of hemoglobin function are produced by the independent or joint effects of five amino acid mutations that modulate oxygen-binding affinity. 相似文献
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Yuichi Yamaoka Hayato Masuya Wen-Hsin Chung Hideaki Goto Chaiwat To-Anun Seiji Tokumasu 《Mycoscience》2007,48(2):100-103
Two species of Leptographium were isolated from blue-stained sapwood of Pinus khasya and bark beetle galleries in pine trees near Chiang Mai, Thailand. Based on morphological observations, these two species
were identified as L. pini-densiflorae and L. yunnanense. This is the first record of these fungi in Thailand. Leptographium yunnanense appeared to be associated with Polygraphus major.
This is contribution No. 206, Laboratory of Plant Parasitic Mycology, Graduate School of Life & Environmental Sciences, University
of Tsukuba 相似文献