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171.
Daniel A. Bachovchin Monique R. Wolfe Kim Masuda Steven J. Brown Timothy P. Spicer Virneliz Fernandez-Vega Peter Chase Peter S. Hodder Hugh Rosen Benjamin F. Cravatt 《Bioorganic & medicinal chemistry letters》2010,20(7):2254-2258
We recently described a fluorescence polarization platform for competitive activity-based protein profiling (fluopol-ABPP) that enables high-throughput inhibitor screening for enzymes with poorly characterized biochemical activity. Here, we report the discovery of a class of oxime ester inhibitors for the unannotated serine hydrolase RBBP9 from a full-deck (200,000+ compound) fluopol-ABPP screen conducted in collaboration with the Molecular Libraries Screening Center Network (MLSCN). We show that these compounds covalently inhibit RBBP9 by modifying enzyme’s active site serine nucleophile and, based on competitive ABPP in cell and tissue proteomes, are selective for RBBP9 relative to other mammalian serine hydrolases. 相似文献
172.
A review on the molecular diagnostics of Lynch syndrome: a central role for the pathology laboratory
173.
Marie Gérard-Champod Stéphanie Blanquet-Diot Jean-Michel Cardot David Bravo Monique Alric 《Applied and environmental microbiology》2010,76(16):5592-5600
Following the January 2006 European ban of antibiotics used as growth promoters in the veal calf industry, new feed additives are needed in order to maintain animal health and growth performance. As an alternative to in vivo experiments in the testing of such additives, an in vitro system modeling the intestinal ecosystem of the veal calf was developed. Stabilization of the main cultured microbial groups and their metabolic activity were tracked in an in vitro continuous fermentor operated under anaerobiosis, at pH 6.5, and at a temperature of 38.5°C and supplied with one of three different nutritive media (M1, M2, or M3). These media mainly differed in their concentrations of simple and complex carbohydrates and in their lipid sources. In vitro microbial levels and fermentative metabolite concentrations were compared to in vivo data, and the biochemical composition of the nutritive media was compared to that of the veal calf intestinal content. All three nutritive media were able to stabilize anaerobic and facultative anaerobic microflora, lactate-utilizing bacteria, bifidobacteria, lactobacilli, enterococci, and Bacteroides fragilis group bacteria at levels close to in vivo values. The microbiota was metabolically active, with high concentrations of lactate, ammonia, and short-chain fatty acids found in the fermentative medium. Comparison with in vivo data indicated that M3 outperformed M1 and M2 in simulating the conditions encountered in the veal calf intestine. This in vitro system would be useful in the prescreening of new feed additives by studying their effect on the intestinal microbiota levels and fermentative metabolite production.European regulations introduced in January 2006 banned the use of antibiotics as growth promoters (AGP) at subtherapeutic levels in animal feed (regulation EC 1831/2003), particularly for veal calves. AGP generated significantly enhanced growth performance via complex processes. The mechanism of growth promotion is still speculative, but many studies suggest the involvement of the intestinal microbiota (7, 9). First of all, AGP did not promote the growth of germfree animals (6). Moreover, they strongly inhibited the bacterial catabolism of urea and amino acids and the fermentation of carbohydrates both in vitro and in vivo (10, 28, 35). AGP treatment thus provided the animal with higher nutrient availability and led to a decrease in the toxic metabolites produced by bacteria, like ammonia or amines, limiting the energy needed by the animal to detoxify the organism. Some authors also argue that another beneficial effect of AGP results from improved control of intestinal pathologies, such as necrotic enteritis in poultry (12). The January 2006 ban is thus expected to have an impact on veal calf health by leading to more frequent digestive disorders, as previously observed in pigs and poultry in the Nordic countries (36), where AGP have been totally prohibited since the 1990s. Even though no scientific study has yet been done on calves, there have already been reports of higher death rates on experimental commercial farms subsequent to the withdrawal of AGP. The main digestive diseases leading to veal calf deaths are enteritis and enterotoxemia, which are mainly triggered by pathogenic strains of Escherichia coli and Clostridium perfringens (22, 30).Veal calf producers are looking for new feed additives to allay the consequences of the AGP ban. Alternative approaches include the use of prebiotics, probiotics, or plant extracts. Several studies have reported both consistent improvements in weight gain and feed conversion and a reduction of the incidence of diarrhea with the addition of such additives to the veal calf diet (1, 11, 14). One of the hypotheses used to explain these beneficial effects involves the modulation of the intestinal microbiota. In particular, oligosaccharides containing mannose or fructose are known to selectively increase the growth of beneficial intestinal bacteria, including lactobacilli and bifidobacteria (21). Timmerman et al. (33) showed that a calf-specific probiotic containing six Lactobacillus species reduced the fecal counts of E. coli. Green tea extracts also improved the intestinal microbial balance by maintaining high fecal levels of Bifidobacterium and Lactobacillus spp. and decreasing those of C. perfringens (16).As indicated above, it is important to assess the action of newly developed feed additives on the veal calf intestinal microbiota. High interindividual variability makes it difficult and expensive to carry out in vivo studies. Alternatively, experiments can be conducted via in vitro systems modeling the intestinal environment of the animals, provided the model has been checked as pertinent. This approach should allow an economical and ethical way to prescreen feed additives by studying their effects on the intestinal microbiota cultured in the in vitro system and its metabolic activity. With this objective in mind, a necessary requirement is knowledge of the veal calf intestinal ecosystem. Thus, the bacterial and biochemical composition of the jejunoileal chyme of calves was previously characterized (13).The aims of the present study were (i) to set up an in vitro system where the main cultured microbial groups identified in the veal calf intestinal chyme are reproducibly stabilized and metabolically active and (ii) to validate our model by comparing the in vitro and in vivo levels of selected biotic and abiotic variables. 相似文献
174.
Frank A. de Latour Lilian S. Amer Emilios A. Papanstasiou Monique L. van Hoek 《Biochemical and biophysical research communications》2010,396(4):825-830
We have identified an 11-residue pattern (KR(F/A)KKFFKK(L/P)K), which we have named the ATRA motif, within the sequence of the Chinese cobra (Naja atra) cathelicidin. A series of 11-residue peptides (ATRA-1, -2, -1A and -1P) were designed to probe the significance of the conserved residues within the ATRA motif, and their contributions to antimicrobial performance. The antimicrobial activities of the peptides were assessed against Escherichia coli K12 strain and Aggregatibacter actinomycetemcomitans Y4. ATRA-1 and -1A, demonstrated potencies comparable to that of N. atra cathelicidin. Structural examination by circular dichroism of the four short peptides suggested the significance of specific amino acid positions within the motif by their contribution to helicity. The results of these studies indicate that short peptides derived from the repeated ATRA motif from the N. atra cathelicidin can demonstrate both low toxicity against host cells and high antimicrobial activity against the gram-negative bacteria used in this study. They constitute novel, effective antimicrobial peptides that are much shorter (and thus less expensive to produce) than the natural cathelicidins, and they may represent new templates for therapeutic drug development. 相似文献
175.
We have measured the pH-dependent (1)H, (13)C, and (15)N NMR spectra of pyridoxal 5'-phosphate ((13)C(2)-PLP) mixed with equal amounts of either doubly (15)N-labeled diaminopropane, (15)N(α)-labeled l-lysine, or (15)N(ε)-labeled l-lysine as model systems for various intermediates of the transimination reaction in PLP-dependent enzymes. At low pH, only the hydrate and aldehyde forms of PLP and the free protonated diamines are present. Above pH 4, the formation of single- and double-headed aldimines (Schiff bases) with the added diamines is observed, and their (13)C and (15)N NMR parameters have been characterized. For 1:1 mixtures the single-headed aldimines dominate. In a similar way, the NMR parameters of the geminal diamine formed with diaminopropane at high pH are measured. However, no geminal diamine is formed with l-lysine. In contrast to the aldimine formed with the ε-amino group of lysine, the aldimine formed with the α-amino group is unstable at moderately high pH but dominates slightly below pH 10. By analyzing the NMR data, both the mole fractions of the different PLP species and up to 6 different protonation states including their pK(a) values were obtained. Furthermore, the data show that all Schiff bases are subject to a proton tautomerism along the intramolecular OHN hydrogen bond, where the zwitterionic form is favored before deprotonation occurs at high pH. This observation, as well as the observation that around pH 7 the different PLP species are present in comparable amounts, sheds new light on the mechanism of the transimination reaction. 相似文献
176.
177.
Monique Deu F. Sagnard J. Chantereau C. Calatayud Y. Vigouroux J. L. Pham C. Mariac I. Kapran A. Mamadou B. Gérard J. Ndjeunga G. Bezançon 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2010,120(7):1301-1313
The dynamics of crop genetic diversity need to be assessed to draw up monitoring and conservation priorities. However, few surveys have been conducted in centres of diversity. Sub-Saharan Africa is the centre of origin of sorghum. Most Sahel countries have been faced with major human, environmental and social changes in recent decades, which are suspected to cause genetic erosion. Sorghum is the second staple cereal in Niger, a centre of diversity for this crop. Niger was submitted to recurrent drought period and to major social changes during these last decades. We report here on a spatio-temporal analysis of sorghum genetic diversity, conducted in 71 villages covering the rainfall gradient and range of agro-ecological conditions in Niger’s agricultural areas. We used 28 microsatellite markers and applied spatial and genetic clustering methods to investigate change in genetic diversity over a 26-year period (1976–2003). Global genetic differentiation between the two collections was very low (F st = 0.0025). Most of the spatial clusters presented no major differentiation, as measured by F st, and showed stability or an increase in allelic richness, except for two of them located in eastern Niger. The genetic clusters identified by Bayesian analysis did not show a major change between the two collections in the distribution of accessions between them or in their spatial location. These results suggest that farmers’ management has globally preserved sorghum genetic diversity in Niger. 相似文献
178.
Clarisse Barro-Kondombo Fabrice Sagnard Jacques Chantereau Monique Deu Kirsten vom Brocke Patrick Durand Eric Gozé Jean Didier Zongo 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2010,120(8):1511-1523
Diversity among 124 sorghum landraces from 10 villages surveyed in 3 regions of Burkina Faso covering different agroecological zones was assessed by 28 agromorphological traits and 29 microsatellite markers. 94.4% of the landraces collected belonged to the botanical race guinea (consisting of 96.6% guinea gambicum and 3.4% guinea margaritiferum), 74.2% had white kernels, 13.7% had orange and 12.1% had red kernels. Compared to the “village nested within zone” factor, the “variety nested within village within zone” factor predominately contributed to the diversity pattern for all nine statistically analysed quantitative traits. The multivariate analyses performed on ten morphological traits identified five landrace groups, and of these, the red kernel sorghum types appeared the most homogenous. 2 to 17 alleles were detected per locus with a mean 4.9 alleles per locus and a gene diversity (He) of 0.37. Landraces from the sub-Sahelian zone had the highest gene diversity (He = 0.38). Cluster analysis revealed that the diversity was weakly stratified and could not be explained by any biophysical criteria. One homogenous guinea margaritiferum group was distinguished from other guinea landraces. The red kernel type appeared to be genetically distinct from all other guinea landraces. The kernel colour was the principal structuring factor. This is an example of a homogeneous group of varieties selected for a specific use (for local beer preparation), mainly grown around the households in compound fields, and presenting particular agromorphological and genetic traits. This is the most original feature of sorghum diversity in Burkina Faso and should be the focus of special conservation efforts. 相似文献
179.
Julio Aires Patricia Anglade Fabienne Baraige Monique Zagorec Marie-Christine Champomier-Vergès Marie-José Butel 《BMC microbiology》2010,10(1):29
Background
Bifidobacteria are natural inhabitants of the human gastrointestinal tract. In full-term newborns, these bacteria are acquired from the mother during delivery and rapidly become the predominant organisms in the intestinal microbiota. Bifidobacteria contribute to the establishment of healthy intestinal ecology and can confer health benefits to their host. Consequently, there is growing interest in bifidobacteria, and various strains are currently used as probiotic components in functional food products. However, the probiotic effects have been reported to be strain-specific. There is thus a need to better understand the determinants of the observed benefits provided by these probiotics. Our objective was to compare three human B. longum isolates with the sequenced model strain B. longum NCC2705 at the chromosome and proteome levels. 相似文献180.
Jean-Luc Boutry Monique Bordes Alain Février Michel Barbier 《Journal of experimental marine biology and ecology》1978,33(2):113-118
An 8-day culture was made of the marine diatom Chaetoceros simplex calcitrans Paulsen in the presence of cholesterol-4 14C. The collected cells were then introduced into a replacement medium for a new period of 8 days. The capture and metabolism of the sterol were followed and information was obtained concerning the exchanges between the cells and the medium; for this purpose, hydrocarbons and fatty acids have been analysed. Evidence for the degradation of cholesterol into acetate is established. The observed phenomena are rapid, complex, and apparently modulated at all levels of the exchanges. 相似文献