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991.
Bach S Tribouillard D Talarek N Desban N Gug F Galons H Blondel M 《Methods (San Diego, Calif.)》2006,39(1):72-77
Recently, we have developed a yeast-based (Saccharomyces cerevisiae) assay to isolate drugs active against mammalian prions. The initial assumption was that mechanisms controlling prion appearance and/or propagation could be conserved from yeast to human, as it is the case for most of the major cell biology regulatory mechanisms. Indeed, the vast majority of drugs we isolated as active against both [PSI(+)] and [URE3] budding yeast prions turned out to be also active against mammalian prion in three different mammalian cell-based assays. These results strongly argue in favor of common prion controlling mechanisms conserved in eukaryotes, thus validating our yeast-based assay and also the use of budding yeast to identify antiprion compounds and to study the prion world. 相似文献
992.
993.
Le Goffic R Balloy V Lagranderie M Alexopoulou L Escriou N Flavell R Chignard M Si-Tahar M 《PLoS pathogens》2006,2(6):e53
Influenza A virus (IAV) is the etiological agent of a highly contagious acute respiratory disease that causes epidemics and considerable mortality annually. Recently, we demonstrated, using an in vitro approach, that the pattern recognition Toll-like receptor (TLR)3 plays a key role in the immune response of lung epithelial cells to IAV. In view of these data and the fact that the functional role of TLR3 in vivo is still debated, we designed an investigation to better understand the role of TLR3 in the mechanisms of IAV pathogenesis and host immune response using an experimental murine model. The time-course of several dynamic parameters, including animal survival, respiratory suffering, viral clearance, leukocyte recruitment into the airspaces and secretion of critical inflammatory mediators, was compared in infected wild-type and TLR3(-/-) mice. First, we found that the pulmonary expression of TLR3 is constitutive and markedly upregulated following influenza infection in control mice. Notably, when compared to wild-type mice, infected TLR3-/- animals displayed significantly reduced inflammatory mediators, including RANTES (regulated upon activation, normal T cell expressed and secreted), interleukin-6, and interleukin-12p40/p70 as well as a lower number of CD8+ T lymphocytes in the bronchoalveolar airspace. More important, despite a higher viral production in the lungs, mice deficient in TLR3 had an unexpected survival advantage. Hence, to our knowledge, our findings show for the first time that TLR3-IAV interaction critically contributes to the debilitating effects of a detrimental host inflammatory response. 相似文献
994.
The concept of metabolite profiling has been around for decades, but technical innovations are now enabling it to be carried out on a large scale with respect to the number of both metabolites measured and experiments carried out. Here we provide a detailed protocol for gas chromatography mass spectrometry (GC-MS)-based metabolite profiling that offers a good balance of sensitivity and reliability, being considerably more sensitive than NMR and more robust than liquid chromatography-linked mass spectrometry. We summarize all steps from collecting plant material and sample handling to derivatization procedures, instrumentation settings and evaluating the resultant chromatograms. We also define the contribution of GC-MS-based metabolite profiling to the fields of diagnostics, gene annotation and systems biology. Using the protocol described here facilitates routine determination of the relative levels of 300-500 analytes of polar and nonpolar extracts in approximately 400 experimental samples per week per machine. 相似文献
995.
996.
Chevalier F Centeno D Rofidal V Tauzin M Martin O Sommerer N Rossignol M 《Journal of proteome research》2006,5(3):512-520
Replicate 2-D gels were stained with four visible or fluorescent dyes using published procedures, and 48 co-detected spots were selected for contrasting values in abundance, M(r) and pI. Success rate of identification and sequence coverage were affected in a dye-dependent manner by the three parameters. Frequency of missed cleavages and recovery of sulfur-containing peptides also depended on the dye. Finally, the dataset was used to predict the number of proteins identifiable when integrating the differential contribution of each parameter. Sypro Ruby appeared to combine several favorable features: no dependence of the identification rate upon the physicochemical properties of proteins, no impact on frequency of missed cleavages, and a higher predicted identification rate. 相似文献
997.
Berry V Nicolas F 《IEEE/ACM transactions on computational biology and bioinformatics / IEEE, ACM》2006,3(3):289-302
Given a set of evolutionary trees on a same set of taxa, the maximum agreement subtree problem (MAST), respectively, maximum compatible tree problem (MCT), consists of finding a largest subset of taxa such that all input trees restricted to these taxa are isomorphic, respectively compatible. These problems have several applications in phylogenetics such as the computation of a consensus of phylogenies obtained from different data sets, the identification of species subjected to horizontal gene transfers and, more recently, the inference of supertrees, e.g., Trees Of Life. We provide two linear time algorithms to check the isomorphism, respectively, compatibility, of a set of trees or otherwise identify a conflict between the trees with respect to the relative location of a small subset of taxa. Then, we use these algorithms as subroutines to solve MAST and MCT on rooted or unrooted trees of unbounded degree. More precisely, we give exact fixed-parameter tractable algorithms, whose running time is uniformly polynomial when the number of taxa on which the trees disagree is bounded. The improves on a known result for MAST and proves fixed-parameter tractability for MCT. 相似文献
998.
999.
Previous microdialysis studies performed in rats have revealed a decrease of striatal dopamine and glutamate induced by nitrogen
narcosis. We sought to establish the hypothetical role of the glutamatergic corticostriatal pathway because of the glutamate
deficiency which occurs in the basal ganglia in this hyperbaric syndrome. Retrodialysis with 1 mM of Saclofen and 100 mM of
KCl in the prefrontal cortex under normobaric conditions led to an increase in striatal levels of glutamate by 95.2% and no
changes in dopamine levels. Under 3 MPa of nitrogen and with the infusion, the rate of striatal glutamate decreased by 51.3%,
to a greater extent than under pressurised nitrogen alone (−23.8%). The rate of dopamine decreased, which also occurred under
pressurised nitrogen (−36.9 and −31.4%, respectively). In conclusion, the function of the corticostriatal pathway is affected
by nitrogen under pressure. This suggests that the nitrogen-induced break point seems to be located at the glutamatergic striatopetal
neurons. 相似文献
1000.
Arindam Talukdar Ekaterina Morgunova Jianxin Duan Winfried Meining Nicolas Foloppe Lennart Nilsson Adelbert Bacher Boris Illarionov Markus Fischer Rudolf Ladenstein Mark Cushman 《Bioorganic & medicinal chemistry》2010,18(10):3518-3534
Virtual screening of a library of commercially available compounds versus the structure of Mycobacterium tuberculosis lumazine synthase identified 2-(2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)acetic acid (9) as a possible lead compound. Compound 9 proved to be an effective inhibitor of M. tuberculosis lumazine synthase with a Ki of 70 μM. Lead optimization through replacement of the carboxymethylsulfonamide sidechain with sulfonamides substituted with alkyl phosphates led to a four-carbon phosphate 38 that displayed a moderate increase in enzyme inhibitory activity (Ki 38 μM). Molecular modeling based on known lumazine synthase/inhibitor crystal structures suggests that the main forces stabilizing the present benzindolone/enzyme complexes involve π–π stacking interactions with Trp27 and hydrogen bonding of the phosphates with Arg128, the backbone nitrogens of Gly85 and Gln86, and the side chain hydroxyl of Thr87. 相似文献