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51.
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Dordal A Lipkin M Macritchie J Mas J Port A Rose S Salgado L Savic V Schmidt W Serafini MT Spearing W Torrens A Yeste S 《Bioorganic & medicinal chemistry letters》2005,15(16):3679-3684
The metabolic stability of benzoxazinone derivatives, a potent series of NPY Y5 antagonists, has been investigated. This study resulted in the identification of the structural moieties prone to metabolic transformations and which strongly influenced the in vitro half-life. This provides opportunities to optimize the structure of this new class of NPY Y5 antagonists. 相似文献
53.
Pauly D Watson R Alder J 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2005,360(1453):5-12
This contribution, which reviews some broad trends in human history and in the history of fishing, argues that sustainability, however defined, rarely if ever occurred as a result of an explicit policy, but as result of our inability to access a major part of exploited stocks. With the development of industrial fishing, and the resulting invasion of the refuges previously provided by distance and depth, our interactions with fisheries resources have come to resemble the wars of extermination that newly arrived hunters conducted 40,000-50,000 years ago in Australia, and 11,000-13,000 years ago against large terrestrial mammals arrived in North America. These broad trends are documented here through a map of change in fish sizes, which displays characteristic declines, first in the nearshore waters of industrialized countries of the Northern Hemisphere, then spread offshore and to the Southern Hemisphere. This geographical extension met its natural limit in the late 1980s, when the catches from newly accessed stocks ceased to compensate for the collapse in areas accessed earlier, hence leading to a gradual decline of global landing. These trends affect developing countries more than the developed world, which have been able to meet the shortfall by increasing imports from developing countries. These trends, however, together with the rapid growth of farming of carnivorous fishes, which consumes other fishes suited for human consumption, have led to serious food security issues. This promotes urgency to the implementation of the remedies traditionally proposed to alleviate overfishing (reduction of overcapacity, enforcement of conservative total allowable catches, etc.), and to the implementation of non-conventional approaches, notably the re-establishment of the refuges (also known as marine reserves), which made possible the apparent sustainability of pre-industrial fisheries. 相似文献
54.
The deacylated phosphatidylinositol manno-oligosaccharides (dPIMs) from the glycosyl phosphatidylinositol (GPI) carbohydrate antigen anchor of Gordonia sputi were the known 2,6-di-O-alpha-mannopyranosyl-myo-inositol glycerophosphate (dPIM-2) and the illustrated novel compound (dPIM-8), which could not be separated from dPIM-7 and dPIM-6, these three compounds being present in the mixture in the molar ratios 1.0:0.65:0.4. dPIM-8 is an analogue of dPIM-2 (and also of dPIM-7 and dPIM-6) in having alpha-mannopyranose and an alpha-mannopyranosyl linked heptasaccharide bonded to O-2 and O-6, respectively, of the inositol. The dPIM-8 species has not been found previously. [structure: see text] 相似文献
55.
An alternative splicing product of the murine trpv1 gene dominant negatively modulates the activity of TRPV1 channels 总被引:3,自引:0,他引:3
Transient receptor potential vanilloid 1 (TRPV1), or vanilloid receptor 1, is the founding member of the vanilloid type of TRP superfamily of nonselective cation channels. TRPV1 is activated by noxious heat, acid, and alkaloid irritants as well as several endogenous ligands and is sensitized by inflammatory factors, thereby serving important functions in detecting noxious stimuli in the sensory system and pathological states in different parts of the body. Whereas numerous studies have been carried out using the rat and human TRPV1 cDNA, the mouse TRPV1 cDNA has not been characterized. Here, we report molecular cloning of two TRPV1 cDNA variants from dorsal root ganglia of C57BL/6 mice. The deduced proteins are designated TRPV1alpha and TRPV1beta and contain 839 and 829 amino acids, respectively. TRPV1beta arises from an alternative intron recognition signal within exon 7 of the trpv1 gene. We found a predominant expression of TRPV1alpha in many tissues and significant expression of TRPV1beta in dorsal root ganglia, skin, stomach, and tongue. When expressed in HEK 293 cells or Xenopus oocytes, TRPV1alpha formed a Ca(2+)-permeable channel activated by ligands known to stimulate TRPV1. TRPV1beta was not functional by itself but its co-expression inhibited the function of TRPV1alpha. Furthermore, although both isoforms were synthesized at a similar rate, less TRPV1beta than TRPV1alpha protein was found in cells and on the cell surface, indicating that the beta isoform is highly unstable. Our data suggest that TRPV1beta is a naturally occurring dominant-negative regulator of the responses of sensory neurons to noxious stimuli. 相似文献
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Control of virulence by the two-component system CiaR/H is mediated via HtrA, a major virulence factor of Streptococcus pneumoniae 下载免费PDF全文
The CiaR/H two-component system is involved in regulating virulence and competence in Streptococcus pneumoniae. The system is known to regulate many genes, including that for high-temperature requirement A (HtrA). This gene has been implicated in the ability of the pneumococcus to colonize the nasopharynx of infant rats. We reported previously that deletion of the gene for HtrA made the pneumococcal strains much less virulent in mouse models, less able to grow at higher temperatures, and more sensitive to oxidative stress. In this report, we show that the growth phenotype as well as sensitivity to oxidative stress of Delta ciaR mutant was very similar to that of a Delta htrA mutant and that the expression of the HtrA protein was reduced in a ciaR-null mutant. Both the in vitro phenotype and the reduced virulence of Delta ciaR mutant could be restored by increasing the expression of HtrA. 相似文献
58.
Hu HZ Gu Q Wang C Colton CK Tang J Kinoshita-Kawada M Lee LY Wood JD Zhu MX 《The Journal of biological chemistry》2004,279(34):35741-35748
The transient receptor potential (TRP) superfamily contains a large number of proteins encoding cation permeable channels that are further divided into TRPC (canonical), TRPM (melastatin), and TRPV (vanilloid) subfamilies. Among the six TRPV members, TRPV1, TRPV2, TRPV3, and TRPV4 form heat-activated cation channels, which serve diverse functions ranging from nociception to osmolality regulation. Although chemical activators for TRPV1 and TRPV4 are well documented, those for TRPV2 and TRPV3 are lacking. Here we show that in the absence of other stimuli, 2-aminoethoxydiphenyl borate (2APB) activates TRPV1, TRPV2, and TRPV3, but not TRPV4, TRPV5, and TRPV6 expressed in HEK293 cells. In contrast, 2APB inhibits the activity of TRPC6 and TRPM8 evoked by 1-oleolyl-2-acetyl-sn-glycerol and menthol, respectively. In addition, low levels of 2APB strongly potentiate the effect of capsaicin, protons, and heat on TRPV1 as well as that of heat on TRPV3 expressed in Xenopus oocytes. In dorsal root ganglia neurons, supra-additive stimulations were evoked by 2APB and capsaicin or 2APB and acid. Our data suggest the existence of a common activation mechanism for TRPV1, TRPV2, and TRPV3 that may serve as a therapeutic target for pain management and treatment for diseases caused by hypersensitivity and temperature misregulation. 相似文献
59.
Hemal H. Patel Lora L. Hamuro Byeong Jo Chun Yoshitaka Kawaraguchi Alexander Quick Brian Rebolledo Juniper Pennypacker Jackie Thurston Natalia Rodriguez-Pinto Christopher Self Gary Olson Paul A. Insel Wayne R. Giles Susan S. Taylor David M. Roth 《The Journal of biological chemistry》2010,285(36):27632-27640
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