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71.
Richter HG Adams DR Benardeau A Bickerdike MJ Bentley JM Blench TJ Cliffe IA Dourish C Hebeisen P Kennett GA Knight AR Malcolm CS Mattei P Misra A Mizrahi J Monck NJ Plancher JM Roever S Roffey JR Taylor S Vickers SP 《Bioorganic & medicinal chemistry letters》2006,16(5):1207-1211
Further lead optimization efforts on previously described 1,2,3,4,10,10a-hexahydro-1H-pyrazino[1,2-a]indoles led to the new class of 5,5a,6,7,8,9-hexahydro-pyrido[3',2':4,5]pyrrolo[1,2-a]pyrazines culminating in the discovery of (5aR,9R)-2-[(cyclopropylmethoxy)methyl]-5,5a,6,7,8,9-hexahydro-9-methyl-pyrido[3', 2':4,5]pyrrolo[1,2-a]pyrazine 18 as a potent, full 5-HT(2C) receptor agonist with an outstanding selectivity profile and excellent hERG and phospholipidosis properties. 相似文献
72.
Coulon A Cosson JF Morellet N Angibault JM Cargnelutti B Galan M Aulagnier S Hewison AJ 《Proceedings. Biological sciences / The Royal Society》2006,273(1584):341-348
Dispersal is frequently more prevalent in one sex compared to the other. Greenwood proposed that patterns of sex-biased dispersal among birds and mammals are linked to their mating strategies. For species where males defend resources rather than females, he predicted female-biased dispersal, because males should remain at their birth site where they are familiar with the distribution of the resources that they must defend. Greenwood's hypothesis has been extensively supported among birds, where most species exhibit a resource-defence mating strategy. However, almost no equivalent information is available for mammals as males generally defend mates in this group. An exception is the European roe deer, a resource-defence mating ungulate. We thus tested Greenwood's hypothesis on this atypical mammalian model, looking for female-biased dispersal using sex-specific inter-individual genetic distances. We conclusively show that gene flow is not higher among females compared to males in the studied roe deer population, and hence that dispersal is not female-biased, suggesting that male mating strategy is not the primary selective force driving the evolution of dispersal in roe deer. We discuss the role of female mate choice and intra-sexual competition as possible alternative selective pressures involved. 相似文献
73.
Virginie Rimbert Hubert Vidal Cyrille Debard Yves Boirie Jean-Michel Chardigny Béatrice Morio 《FEBS letters》2009,583(17):2927-32800
The association between impairment in mitochondrial muscle fat oxidative capacity (OXFA) and occurrence of insulin resistance was examined in 14 healthy trained men (age, 24 ± 4 yr) submitted to 4 weeks of training cessation. Training stop induced a significant decrease in mRNA levels of proteins involved in muscle fat metabolism, particularly PPARα (−58%, P < 0.01) and PGC-1α (−30%, P < 0.05), a 21% reduction in OXFA (P < 0.01), and reduced fat oxidation during moderately intense exercise (P < 0.05). In contrast, there was no significant alteration in insulin sensitivity. In conclusion, decline in OXFA is a rapid metabolic event following training cessation. It is involved in the regulation of whole body fat balance but not in the deterioration of insulin sensitivity. 相似文献
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Photocatalytic degradation of pesticide methomyl: determination of the reaction pathway and identification of intermediate products. 总被引:1,自引:0,他引:1
M Tamimi S Qourzal A Assabbane J-M Chovelon C Ferronato Y Ait-Ichou 《Photochemical & photobiological sciences》2006,5(5):477-482
The degradation of pesticide methomyl in aqueous solution by UV-irradiation in the presence of TiO2 "Degussa P-25" has been studied. It was found that mineralisation to carbon dioxide, water, sulfate and ammonia took place during the process. The rate of photodecomposition of methomyl was measured using high performance liquid chromatography (HPLC), while its mineralization was followed using ion chromatography (IC), and total organic carbon (TOC) analysis. The identification of reaction intermediate products was carried out using coupled techniques HPLC-MS (electrospray ionization in positive mode) and a degradation pathway was proposed. Under our conditions, complete disappearance of 1.23 x 10(-4) mol l(-1) of pure pesticide occurred within 45 min of illumination and 80% TOC removal occurred in less than 4 h. Three main intermediates were identified resulting from (i) the rupture of the ester bond (or the N-O bond), (ii) the hydroxylation of methyl group borne by the nitrogen atom and (iii) the product resulting from the decarboxylation of the oxidized hydroxylated methyl group (photo-Kolbe reaction). In order to be sure that the photocatalytic results were consistent, hydrolysis and photolysis tests were performed. Photocatalysis proved to be an excellent new advanced oxidation technology (AOT) to eliminate methomyl present in water. 相似文献
76.
A critical role for the glial-derived neuromodulator D-serine in the age-related deficits of cellular mechanisms of learning and memory 总被引:5,自引:0,他引:5
Mothet JP Rouaud E Sinet PM Potier B Jouvenceau A Dutar P Videau C Epelbaum J Billard JM 《Aging cell》2006,5(3):267-274
Age-associated deficits in learning and memory are closely correlated with impairments of synaptic plasticity. Analysis of N-methyl-D-aspartate receptor (NMDAr)-dependent long-term potentiation (LTP) in CA1 hippocampal slices indicates that the glial-derived neuromodulator D-serine is required for the induction of synaptic plasticity. During aging, the content of D-serine and the expression of its synthesizing enzyme serine racemase are significantly decreased in the hippocampus. Impaired LTP and NMDAr-mediated synaptic potentials in old rats are rescued by exogenous D-serine. These results highlight the critical role of glial cells and presumably astrocytes, through the availability of D-serine, in the deficits of synaptic mechanisms of learning and memory that occur in the course of aging. 相似文献
77.
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79.
Ngondi-Ekome J Thiebault F Strub JM Van Dorsselaer A Bonaly R Contino-Pepin C Wathier M Pucci B Coulon J 《Biochimie》2003,85(1-2):133-143
The lectin-like theory suggest that yeast flocculation is mediated by an aggregating lectinic factor. In this study we isolated an agglutinating factor, which corresponds to lectin, from whole cells by treating the flocculent wild-type Saccharomyces cerevisiae NCYC 625 strain and its weakly flocculent mutant [rho degrees ] with EDTA and two non-ionic surfactants (Hecameg and HTAC). The dialysed crude extracts obtained in this way agglutinated erythrocytes and this hemagglutination was specifically inhibited by mannose and mannose derivatives. However, SDS-PAGE profiles showed that the three reagents had different effects on the yeast cells. The non-ionic surfactants appeared to be the most efficient, as their extracts possessed the highest specific agglutinating activity. The products released by the wild-type strain presented a higher specific agglutinating activity than those released by the [rho degrees ] mutant. Purification of the agglutinating factor from extracts of both strains by affinity chromatography revealed two active bands of relative mass of 26 and 47 kDa on SDS-PAGE. Mass spectrometry analysis by MALDI-TOF, identified a 26 kDa band as the triose phosphate isomerase (TPI) whereas a 47 kDa band was identical to enolase. Edman degradation showed that the N-terminal sequences of these proteins were similar to TPI and enolase, respectively. The difference in the flocculation behaviour of the two strains is due to changes in the protein composition of the cell wall and in the protein structure involved in cell-cell recognition. 相似文献
80.
Catabolism of hydroxyacids and biotechnological production of lactones by Yarrowia lipolytica 总被引:6,自引:0,他引:6
The gamma- and delta-lactones of less than 12 carbons constitute a group of compounds of great interest to the flavour industry. It is possible to produce some of these lactones through biotechnology. For instance, gamma-decalactone can be obtained by biotransformation of methyl ricinoleate. Among the organisms used for this bioproduction, Yarrowia lipolytica is a yeast of choice. It is well adapted to growth on hydrophobic substrates, thanks to its efficient and numerous lipases, cytochrome P450, acyl-CoA oxidases and its ability to produce biosurfactants. Furthermore, genetic tools have been developed for its study. This review deals with the production of lactones by Y. lipolytica with special emphasis on the biotransformation of methyl ricinoleate to gamma-decalactone. When appropriate, information from the lipid metabolism of other yeast species is presented. 相似文献