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91.
Gavaghan CL Nicholson JK Connor SC Wilson ID Wright B Holmes E 《Analytical biochemistry》2001,291(2):245-252
We report here the first combined use of NMR-PR (pattern recognition) analysis and directly coupled HPLC--NMR analysis to identify metabolic subpopulations in normal laboratory animals and their discriminating endogenous urinary biomarkers. Urine samples obtained from control Sprague-Dawley rats (n = 68) were analyzed using (1)H NMR spectroscopy and principal components (PC) analysis to investigate physiological variability. Two distinct subpopulations of animals were classified based on metabolite excretion profiles. Analysis of the PC loadings established the spectral regions that were responsible for classification of the subpopulations and was used to direct the identification of biomarkers using a directly coupled HPLC--NMR analysis. One population had low urinary hippurate levels together with an increased concentration of 3-(3-hydroxyphenyl)propionic acid (3-HPPA)and 3-hydroxycinnamic acid (3-HCA). The other subpopulation excreted high levels of hippurate. Thus, we report the bimodal occurrence of hippuric acid and chlorogenic acid metabolites in a genetically homogeneous population of rats maintained under identical conditions, which may have significance in relation to the understanding of the consequences of biochemical variation in animals used for drug toxicity testing. 相似文献
92.
The ribonuclease III superfamily represents a structurally related group of double-strand (ds) specific endoribonucleases which play key roles in diverse prokaryotic and eukaryotic RNA maturation and degradation pathways. A dsRNA-binding domain (dsRBD) is a conserved feature of the superfamily and is important for substrate recognition. RNase III family members also exhibit a "catalytic" domain, in part defined by a set of highly conserved amino acids, of which at least one (a glutamic acid) is important for cleavage but not for substrate binding. However, it is not known whether the catalytic domain requires the dsRBD for activity. This report shows that a truncated form of Escherichia coli RNase III lacking the dsRBD (RNase III[DeltadsRBD]) can accurately cleave small processing substrates in vitro. Optimal activity of RNase III[DeltadsRBD] is observed at low salt concentrations (<60 mM Na(+)), either in the presence of Mg(2+) (>25 mM) or Mn(2+) ( approximately 5 mM). At 60 mM Na(+) and 5 mM Mn(2+) the catalytic efficiency of RNase III[DeltadsRBD] is similar to that of RNase III at physiological salt concentrations and Mg(2+). In the presence of Mg(2+) RNase III[DeltadsRBD] is less efficient than the wild-type enzyme, due to a higher K(m). Similar to RNase III, RNase III[DeltadsRBD] is inhibited by high concentrations of Mn(2+), which is due to metal ion occupancy of an inhibitory site on the enzyme. RNase III[DeltadsRBD] retains strict specificity for dsRNA, as indicated by its inability to cleave (rA)(25), (rU)(25), or (rC)(25). Moreover, dsDNA, ssDNA, or an RNA-DNA hybrid are not cleaved. Low (micromolar) concentrations of ethidium bromide block RNase III[DeltadsRBD] cleavage of substrate, which is similar to the inhibition seen with RNase III and is indicative of an intercalative mode of inhibition. Finally, RNase III[DeltadsRBD] is sensitive to specific Watson-Crick base-pair substitutions which also inhibit RNase III. These findings support an RNase III mechanism of action in which the catalytic domain (i) can function independently of the dsRBD, (ii) is dsRNA-specific, and (iii) participates in cleavage site selection. 相似文献
93.
For individuals with temporomandibular disorder (TMD) it has been theorized that stressful events trigger oral habits (e.g., teeth grinding), thereby increasing masticatory muscle tension and subsequent pain. Recent research involving adjunctive behaviors found an increase in masseter surface EMG (sEMG) and oral habits when students with TMD symptomatology were placed on a fixed-time reinforcement schedule. The current study used a treatment-seeking community sample with TMD symptomatology in a competitive task designed to be a more naturalistic Fixed Time task. The experiment consisted of Adaptation, Free-Play, Scheduled-Play, and Recovery phases. During the Scheduled-Play phase participants played, and waited to play, an electronic poker game. Results indicated that masseter muscle tension in the Scheduled-Play phase was significantly higher (p<.001) than in any other phase. Moreover, during the Scheduled-Play phase masseter sEMG was higher (p#60;.001) when participants waited to play. Self-reported oral habits and overall affect were significantly higher (p's<.05) in the Free-Play and Scheduled-Play phases relative to Adaptation and Recovery. The observation that masseter sEMG was elevated during the Scheduled-Play phase relative to all other phases, and within the Scheduled-Play phase sEMG was highest while waiting, suggests that adjunctive oral habits may lead to TMD symptomatology. 相似文献
94.
Caspase structure, proteolytic substrates, and function during apoptotic cell death 总被引:29,自引:0,他引:29
Nicholson DW 《Cell death and differentiation》1999,6(11):1028-1042
Caspases play an essential role during apoptotic cell death. These enzymes define a new class of cysteine proteases and comprise a multi-gene family with more than a dozen distinct mammalian family members. The discrete and highly limited subset of cellular polypeptides that are cleaved by these proteases is sufficient to account for the majority of cellular and morphological events that occur during cell death. In some cases, caspases also play a contributory role in escalating the propensity for apoptosis, and in doing so may exacerbate disease pathogenesis. 相似文献
95.
96.
Nicholson IC Zou X Popov AV Cook GP Corps EM Humphries S Ayling C Goyenechea B Xian J Taussig MJ Neuberger MS Brüggemann M 《Journal of immunology (Baltimore, Md. : 1950)》1999,163(12):6898-6906
We have produced mice that carry the human Ig heavy (IgH) and both kappa and lambda light chain transloci in a background in which the endogenous IgH and kappa loci have been inactivated. The B lymphocyte population in these translocus mice is restored to about one-third of normal levels, with preferential (3:1) expression of human lambda over human kappa. Human IgM is found in the serum at levels between 50 and 400 microg/ml and is elevated following immunization. This primary human Ab repertoire is sufficient to yield diverse Ag-specific responses as judged by analysis of mAbs. The use of DH and J segments is similar to that seen in human B cells, with an analogous pattern of N nucleotide insertion. Maturation of the response is accompanied by somatic hypermutation, which is particularly effective in the light chain transloci. These mice therefore allow the production of Ag-specific repertoires of both IgM,kappa and IgM,lambda Abs and should prove useful for the production of human mAbs for clinical use. 相似文献
97.
Endospores of Bacillus spp. were purified from three Sonoran desert soil samples by Chelex extraction and NaBr density gradient centrifugation and their UV resistances compared with that of B. subtilis strain 168. Natural spore populations exhibited tight adherence to soil particles which was not readily overcome by the extraction and purification procedure. It was observed that spores purified from soil exhibited 2-3 fold higher resistance to UV (as measured by the 90% lethal dose, LD90) than did B. subtilis strain 168 grown on NSM, a standard laboratory sporulation medium, and purified by the same extraction procedure. Cultivation of spore-forming bacteria isolated from soil on NSM resulted in production of spores with essentially identical UV resistance as strain 168, suggesting that spore UV resistance is influenced by the environment in which spores are produced. 相似文献
98.
99.
The low-affinity receptor for IgG, FcgammaRIIb, negatively regulates B cell antigen receptor (BCR)-mediated proliferative signalling. FcgammaRIIb has been reported to mediate this inhibition by uncoupling the BCR from the RasMAPkinase pathway. We now show that FcgammaRIIb-mediated negative feedback inhibition also correlates with induction of an Erk-associated phosphatase activity that reflects the rapid association of Erk and the MAPkinase phosphatase, Pac-1, and dephosphorylation and inactivation of ErkMAPkinase. This mechanism of abrogating ongoing ErkMAPkinase signalling therefore provides a rationale for rapid immune-complex-mediated feedback inhibition of active antigen-driven B cell responses. In addition, FcgammaRIIb signalling also induces the recruitment and activation of the 3'-inositol phosphatase, PTEN, which by antagonising PI 3kinase activity and inhibiting BCR-coupling to the anti-apoptotic kinase, Akt, provides an additional mechanism for FcgammaRIIb-mediated negative regulation of BCR-coupling to ErkMAPkinase, cell survival and proliferation. 相似文献
100.
Markha KR Bloor SJ Nicholson R Rivera R Shemluck M Kevan PG Michener C 《Zeitschrift für Naturforschung. C, Journal of biosciences》2004,59(9-10):625-630
The major pigments responsible for the flower color within the black flowered Gentianaceae, Lisianthius nigrescens, were characterized by HPLC and chemical analyses HPLC analysis showed one major and one minor anthocyanin and 3 major and 3 minor flavone glycosides. The anthocyanins [delphinidin-3-O-rhamnol(1-6)galactoside and its 5-O-glucoside] comprised an extraordinary 24% of the dry weight of wild collected L. nigrescens corallas, and were accompanied in a 1:1 ratio by a range of apigenin and luteolin 8-C-glucosides and their 7-O-methyl ethers. The high levels of anthocyanins and flavones (and their co-pigmentation) is thought to account for the almost complete absorption of both UV and visible wavebands observed by reflectance photography. 相似文献