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991.
Sattasuk K Nozawa A Tozawa Y Kakinuma Y Akita M 《Bioscience, biotechnology, and biochemistry》2011,75(11):2200-2206
We identified a gene product of At5g19500 (At5g19500p) from Arabidopsis thaliana that is homologous to EcTyrP, a tyrosine-specific transporter from Escherichia coli. Computational analyses of the amino acid sequence of At5g19500p predicted 11 transmembrane domains (TMDs) and a potential plastid targeting signal at its amino terminus. As a first step toward understanding the possible role of At5g19500p in plant cells, we attempted to determine the localization of At5g19500p by an in vitro chloroplastic import assay using At5g19500p translated in a cell-free wheat germ system (Madin et al., Proc. Natl. Acad. Sci. USA, 97, 559-564 (2000)), followed by subfractionation of the chloroplasts. At5g19500p was successfully imported into chloroplasts, and the newly transported mature form of At5g19500p was recovered from the inner envelope membrane. 相似文献
992.
Miyazawa T Nakagawa K Kimura F Satoh A Miyazawa T 《Bioscience, biotechnology, and biochemistry》2011,75(9):1856-1858
A randomized, double-blind human trial was conducted to assess the effect on the plasma carotenoid concentration of 4- or 12-week astaxanthin supplementation (1 or 3 mg/d) of 20 Japanese middle-aged and senior subjects. The plasma carotenoid concentration was significantly higher after the astaxanthin supplementation than that before in both the 1 mg/d (10 subjects) and 3 mg/d (10 subjects) groups. 相似文献
993.
Nakajima K Koizumi A Iizuka K Ito K Morita Y Koizumi T Asakura T Shimizu-Ibuka A Misaka T Abe K 《Bioscience, biotechnology, and biochemistry》2011,75(8):1600-1602
Neoculin, a sweet protein found in the fruit of Curculigo latifolia, has the ability to change sourness into sweetness. Neoculin turns drinking water sweet, indicating that non-acidic compounds may induce the sweetness. We report that ammonium chloride and certain amino acids elicit the intense sweetness of neoculin. Neoculin can thus sweeten amino acid-enriched foods. 相似文献
994.
A previous genome-wide QTL study revealed many QTLs affecting postnatal body weight and growth in an intersubspecific backcross mouse population between the C57BL/6J (B6) strain and wild Mus musculus castaneus mice captured in the Philippines. Subsequently, several closely linked QTLs for body composition traits were revealed in an F2 intercross population between B6 and B6.Cg-Pbwg1, a congenic strain on the B6 genetic background carrying the growth QTL Pbwg1 on proximal chromosome 2. However, no QTL affecting body weight has been duplicated in the F2 population, except for mapping an overdominant QTL that causes heterosis of body weight. In this study, we developed 17 intersubspecific subcongenic strains with overlapping and nonoverlapping castaneus regions from the B6.Cg-Pbwg1 congenic strain in order to search for and genetically dissect QTLs affecting body weight into distinct closely linked loci. Phenotypic comparisons of several developed subcongenic strains with the B6 strain revealed that two closely linked but distinct QTLs that regulate body weight, named Pbwg1.11 and Pbwg1.12, are located on an 8.9-Mb region between D2Mit270 and D2Mit472 and on the next 3.6-Mb region between D2Mit205 and D2Mit182, respectively. Further analyses using F2 segregating populations obtained from intercrosses between B6 and each of the two selected subcongenic strains confirmed the presence of these two body weight QTLs. Pbwg1.11 had an additive effect on body weight at 6, 10, and 13?weeks of age, and its castaneus allele decreased it. In contrast, the castaneus allele at Pbwg1.12 acted in a dominant fashion and surprisingly increased body weight at 6, 10, and 13?weeks of age despite the body weight of wild castaneus mice being 60% of that of B6 mice. These findings illustrate the complex genetic nature of body weight regulation and support the importance of subcongenic mouse analysis to dissect closely linked loci. 相似文献
995.
Andrews DM Chow MT Ma Y Cotterell CL Watt SV Anthony DA Akira S Iwakura Y Trapani JA Zitvogel L Smyth MJ 《Immunology and cell biology》2011,89(6):739-746
Toll-like receptor-4-lipopolysaccharide (LPS)-mediated inflammation is used to delineate signals involved in cross-talk between antigen-presenting cells (APCs) and lymphocytes such as natural killer (NK) cells. Following APC stimulation and cytokine release, NK cells produce interferon (IFN)-γ. High levels of LPS induce endotoxicosis, a systemic inflammatory disease in which IFN-γ causes significant morbidity and mortality. Several studies have highlighted the role of interleukin (IL)-18, IL-1β, IL-17A and IFN-γ in the development of endotoxicosis, but whether these cytokines interact with each other is yet to be determined. Our data demonstrate that IL-18 and IL-17A have important roles in NK cell IFN-γ production during endotoxicosis. Importantly, we provide the first evidence that IL-18 also has a role in IL-17A production by T-cell receptor (TCR)-δ cells. Furthermore, we demonstrate that IL-18-deficient mice have a defect in γδ T-cell homeostasis and IL-1β production, both of which can contribute to the development of disease through induction of IL-17A. These results reveal novel requirements for IL-18 in innate immune cell homeostasis and activation, demonstrating that the role of IL-18 in innate immunity occurs at a level other than activation. 相似文献
996.
El-Kabbani O Dhagat U Soda M Endo S Matsunaga T Hara A 《Bioorganic & medicinal chemistry letters》2011,21(8):2564-2567
Human 20α-hydroxysteroid dehydrogenase (AKR1C1) is an important drug target due to its role in the development of lung and endometrial cancers, premature birth and neuronal disorders. We report the crystal structure of AKR1C1 complexed with the first structure-based designed inhibitor 3-chloro-5-phenylsalicylic acid (Ki = 0.86 nM) bound in the active site. The binding of 3-chloro-5-phenylsalicylic acid to AKR1C1 resulted in a conformational change in the side chain of Phe311 to accommodate the bulky phenyl ring substituent at the 5-position of the inhibitor. The contributions of the nonconserved residues Leu54, Leu306, Leu308 and Phe311 to the binding were further investigated by site-directed mutagenesis, and the effects of the mutations on the Ki value were determined. The Leu54Val and Leu306Ala mutations resulted in 6- and 81-fold increases, respectively, in Ki values compared to the wild-type enzyme, while the remaining mutations had little or no effects. 相似文献
997.
Mizuhara N Kuroda M Ogita A Tanaka T Usuki Y Fujita K 《Bioorganic & medicinal chemistry》2011,19(18):5300-5310
Cyclothiazomycin B1 (CTB1) is an antifungal cyclic thiopeptide isolated from the culture broth of Streptomyces sp. HA 125-40. CTB1 inhibited the growth of several filamentous fungi including plant pathogens along with swelling of hyphae and spores. The antifungal activity of CTB1 was weakened by hyperosmotic conditions, and hyphae treated with CTB1 burst under hypoosmotic conditions, indicating increased cell wall fragility. CTB1-sensitive fungal species contain high levels of cell wall chitin and/or chitosan. Unlike nikkomycin Z, a competitive inhibitor of chitin synthase (CHS), CTB1 did not inhibit CHS activity. Although CTB1 inhibited CHS biosynthesis, the same result was also obtained with a non-specific proteins inhibitor, cycloheximide, which did not reduce cell wall rigidity. These results indicate that the primary target of CTB1 is not CHS, and we concluded that CTB1 antifungal activity was independent of this sole inhibition. We found that CTB1 bound to chitin but did not bind to β-glucan and chitosan. The results of the present study suggest that CTB1 induces cell wall fragility by binding to chitin, which forms the fungal cell wall. The antifungal activity of CTB1 could be explained by this chitin-binding ability. 相似文献
998.
Chonan T Wakasugi D Yamamoto D Yashiro M Oi T Tanaka H Ohoka-Sugita A Io F Koretsune H Hiratate A 《Bioorganic & medicinal chemistry》2011,19(5):1580-1593
Novel (4-piperidinyl)-piperazine derivatives were synthesized and evaluated as ACC1/2 non-selective inhibitors. Optimization of the substituents on the nitrogen of the piperidine ring led to the identification of the fluorine substituted tert-butoxycarbonyl group. Advanced analog, 1,1,1-trifluoro-2-methylpropan-2-yl 4-{4-[(2-amino-6-methyl-1-benzothiophen-3-yl)carbonyl]piperazin-1-yl}piperidine-1-carboxylate (12c) showed potent inhibitory activities in enzyme-assay and cell-based assays. Compound 12c also exhibited reduction of hepatic de novo fatty acid synthesis in rats after oral administration. 相似文献
999.
Yoshida M Mori A Morimoto S Kotani E Oka M Notoya K Makino H Ono M Shirasaki M Tada N Fujita H Ban J Ikeda Y Kawamoto T Goto M Kimura H Baba A Yasuma T 《Bioorganic & medicinal chemistry》2011,19(6):1881-1894
The calcium-sensing receptor antagonist (CaSR) has been recognized as a promising target of anabolic agents for treating osteoporosis. In the course of developing a new drug candidate for osteoporosis, we found tetrahydropyrazolopyrimidine derivative 1 to be an orally active CaSR antagonist that stimulated transient PTH secretion in rats. However, compound 1 showed poor physical and chemical stability. In order to work out this compound's chemical stability and further understand its in vivo efficacy, we focused on modifying the 2-position of the tetrahydropyrazolopyrimidine. As a result of chemical modification, we discovered (5R)-N-[1-ethyl-1-(4-ethylphenyl)propyl]-2,7,7-trimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide monotosylate 10m (TAK-075), which showed improved solubility, chemical stability, and in vivo efficacy. Furthermore, we describe that evaluating the active metabolite is important during repeated treatment with short-acting CaSR antagonists. 相似文献
1000.
Matsuo O Takahashi Y Abe C Tanaka K Nakashima A Morita H 《Advances in physiology education》2011,35(2):237-240
In most laboratory practices for students in medical schools, a laboratory guidebook is given to the students, in which the procedures are precisely described. The students merely follow the guidebook without thinking deeply, which spoils the students and does not entice them to think creatively. Problem-based learning (PBL) could be one means for the students themselves to actively learn, find problems, and resolve them. Such a learning attitude nurtures medical students with lifelong learning as healthcare professionals. We merged PBL and laboratory practices to promote deep thinking habits and developed an integrated laboratory practice. We gave a case sheet to groups of students from several schools. The students raised hypotheses after vivid discussion, designed experimental protocols, and performed the experiments. If the results did not support or disproved the hypothesis, the students set up another hypothesis followed by experiments, lasting for 4 or 5 consecutive days. These procedures are quite similar to those of professional researchers. The main impact achieved was the fact that the students developed the experimental design by themselves, for the first time in their college lives. All students enjoyed the laboratory practice, which they had never experienced before. This is an antidote to the guidebook-navigated traditional laboratory practice, which disappoints many students. As educators in basic medical sciences stand on the edge in terms of educating the next generation, there is a need to provide a strong foundation for medical students to design and perform scientific experiments. The integrated laboratory practice may provide the solution. 相似文献