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101.
Cdc13p is a single strand telomere-binding protein of Saccharomyces cerevisiae; its telomere-binding region is within amino acids 451-693, Cdc13(451-693)p. In this study, we used purified Cdc13p and Cdc13(451-693)p to characterize their telomere binding activity. We found that the binding specificity of single-stranded TG(1-3) DNA by these two proteins is similar. However, the affinity of Cdc13(451-693)p to DNA was slightly lower than that of Cdc13p. The binding of telomeric DNA by these two proteins was disrupted at NaCl concentrations higher than 0.3 m, indicating that electrostatic interaction contributed significantly to the binding process. Because both proteins bound to strand TG(1-3) DNA positioned at the 3' end, the 5' end, or in the middle of the oligonucleotide substrates, our results indicated that the location of TG(1-3) in single-stranded DNA does not appear to be important for Cdc13p binding. Moreover, using DNase I footprint analysis, the structure of the telomeric DNA complexes of Cdc13p and Cdc13(451-693)p was analyzed. The DNase I footprints of these two proteins to three different telomeric DNA substrates were virtually identical, indicating that the telomere contact region of Cdc13p is within Cdc13(451-693)p. Together, the binding properties of Cdc13p and its binding domain support the theory that the specific binding of Cdc13p to telomeres is an important feature of telomeres that regulate telomerase access and/or differentiate natural telomeres from broken ends. 相似文献
102.
2-Naphthylamine, a compound found in cigarette smoke, decreases both monoamine oxidase A and B catalytic activity 总被引:2,自引:0,他引:2
Cigarette smokers exhibit a lower monoamine oxidase (MAO; EC 1.4.3.4) activity than nonsmokers. MAO is located in the outer membrane of mitochondria and exists as two isoenzymes, MAO A and B. MAO A prefers 5-hydroxytryptamine (serotonin), and MAO B prefers phenylethylamine (PEA) as substrate. Dopamine is a substrate for both forms. 2-Naphthylamine is a carcinogen found in high concentrations in cigarette smoke. The results of this study show that 2-naphthylamine has the ability to inhibit mouse brain MAO A and B in vitro by mixed type inhibition (competitive and non-competitive). The Ki for MAO A was determined to be 52.0 microM and for MAO B 40.2 microM. The inhibitory effect of 2-naphthylamine on both MAO A and B catalytic activity, supports the hypothesis that smoking decreases MAO activity in vivo, instead that smokers with lower MAO activity are more prone to become a smoker. 相似文献
103.
Signaling events in the hypoxic induction of alcohol dehydrogenase gene in Arabidopsis 总被引:9,自引:0,他引:9
Expression of the alcohol dehydrogenase gene (ADH) of Arabidopsis is induced during hypoxia. Because many plants increase their ethylene production in response to hypoxic stress, we examined in this report whether ethylene is involved in the hypoxic induction of ADH in Arabidopsis. We found that the hypoxic induction of ADH can be partially inhibited by aminooxy acetic acid, an inhibitor of ethylene biosynthesis. This partial inhibition can be reversed by the addition of 1-aminocyclopropane-1-carboxylic acid, a direct precursor of ethylene. In addition, the hypoxic induction of the ADH gene is also reduced in etr1-1 and ein2-1, two ethylene insensitive mutants in ethylene-signaling pathways, whereas the addition of exogenous ethylene or an increase in cellular ethylene alone does not induce ADH under normoxic conditions. Kinetic analyses of ADH mRNA accumulation indicated that an ethylene signal is required for the induction of ADH during later stages of hypoxia. Therefore, we conclude that ethylene is needed, but not sufficient for, the induction of ADH in Arabidopsis during hypoxia. 相似文献
104.
Maragos WF Young KL Altman CS Pocernich CB Drake J Butterfield DA Seif I Holschneider DP Chen K Shih JC 《Neurochemical research》2004,29(4):741-746
Intrastriatal administration of the succinate dehydrogenase (SDH) inhibitor malonate produces neuronal injury by a "secondary excitotoxic" mechanism involving the generation of reactive oxygen species (ROS). Recent evidence indicates dopamine may contribute to malonate-induced striatal neurodegeneration; infusion of malonate causes a pronounced increase in extracellular dopamine and dopamine deafferentation attenuates malonate toxicity. Inhibition of the catabolic enzyme monoamine oxidase (MAO) also attenuates striatal lesions induced by malonate. In addition to forming 3,4-dihydroxyphenylacetic acid, metabolism of dopamine by MAO generates H2O2, suggesting that dopamine metabolism may be a source of ROS in malonate toxicity. There are two isoforms of MAO, MAO-A and MAO-B. In this study, we have investigated the role of each isozyme in malonate-induced striatal injury using both pharmacological and genetic approaches. In rats treated with either of the specific MAO-A or -B inhibitors, clorgyline or deprenyl, respectively, malonate lesion volumes were reduced by 30% compared to controls. In knock-out mice lacking the MAO-A isoform, malonate-induced lesions were reduced by 50% and protein carbonyls, an index ROS formation, were reduced by 11%, compared to wild-type animals. In contrast, mice deficient in MAO-B showed highly variable susceptibility to malonate toxicity precluding us from determining the precise role of MAO-B in this form of brain damage. These findings indicate that normal levels of MAO-A participate in expression of malonate toxicity by a mechanism involving oxidative stress. 相似文献
105.
Xu Z Escamilla-Treviño L Zeng L Lalgondar M Bevan D Winkel B Mohamed A Cheng CL Shih MC Poulton J Esen A 《Plant molecular biology》2004,55(3):343-367
In plants, Glycoside Hydrolase (GH) Family 1 -glycosidases are believed to play important roles in many diverse processes including chemical defense against herbivory, lignification, hydrolysis of cell wall-derived oligosaccharides during germination, and control of active phytohormone levels. Completion of the Arabidopsis thalianagenome sequencing project has enabled us, for the first time, to determine the total number of Family 1 members in a higher plant. Reiterative database searches revealed a multigene family of 48 members that includes eight probable pseudogenes. Manual reannotation and analysis of the entire family were undertaken to rectify existing misannotations and identify phylogenetic relationships among family members. Forty-seven members (designated BGLU1 through BGLU47) share a common evolutionary origin and were subdivided into approximately 10 subfamilies based on phylogenetic analysis and consideration of intron–exon organizations. The forty-eighth member of this family (At3g06510; sfr2) is a -glucosidase-like gene that belongs to a distinct lineage. Information pertaining to expression patterns and potential functions of Arabidopsis GH Family 1 members is presented. To determine the biological function of all family members, we intend to investigate the substrate specificity of each mature hydrolase after its heterologous expression in the Pichia pastoris expression system. To test the validity of this approach, the BGLU44-encoded hydrolase was expressed in P. pastoris and purified to homogeneity. When tested against a wide range of natural and synthetic substrates, this enzyme showed a preference for -mannosides including 1,4--D-mannooligosaccharides, suggesting that it may be involved in A. thaliana in degradation of mannans, galactomannans, or glucogalactomannans. Supporting this notion, BGLU44 shared high sequence identity and similar gene organization with tomato endosperm -mannosidase and barley seed -glucosidase/-mannosidase BGQ60. 相似文献
106.
107.
A mixture model for estimating the local false discovery rate in DNA microarray analysis 总被引:3,自引:0,他引:3
MOTIVATION: Statistical methods based on controlling the false discovery rate (FDR) or positive false discovery rate (pFDR) are now well established in identifying differentially expressed genes in DNA microarray. Several authors have recently raised the important issue that FDR or pFDR may give misleading inference when specific genes are of interest because they average the genes under consideration with genes that show stronger evidence for differential expression. The paper proposes a flexible and robust mixture model for estimating the local FDR which quantifies how plausible each specific gene expresses differentially. RESULTS: We develop a special mixture model tailored to multiple testing by requiring the P-value distribution for the differentially expressed genes to be stochastically smaller than the P-value distribution for the non-differentially expressed genes. A smoothing mechanism is built in. The proposed model gives robust estimation of local FDR for any reasonable underlying P-value distributions. It also provides a single framework for estimating the proportion of differentially expressed genes, pFDR, negative predictive values, sensitivity and specificity. A cervical cancer study shows that the local FDR gives more specific and relevant quantification of the evidence for differential expression that can be substantially different from pFDR. AVAILABILITY: An R function implementing the proposed model is available at http://www.geocities.com/jg_liao/software 相似文献
108.
109.
Neuronal transplantation has provided a promising approach for treating neurodegenerative diseases. Recently, efforts have been directed at in vitro induction of various stem cells to transform into neurons. We report the first successful quantities in an in vitro attempt at directing the transformation into neurons of human umbilical mesenchymal cells, which are capable of rapid proliferation in vitro and are easily available. When cultured in neuronal conditioned medium, human umbilical mesenchymal cells started to express neuron-specific proteins such as NeuN and neurofilament (NF) on the 3rd day and exhibited retraction of the cell body, elaboration of processes, clustering of cells and expression of functional mRNA responsible for the synthesis of subunits of the kainate receptor and glutamate decarboxylase on the 6th day. Between the 9th and 12th days, the percentage of human umbilical mesenchymal cells expressing NF was as high as 87%, while functionality was demonstrated by glutamate invoking an inward current. At this stage, cells were differentiated into mature neurons in the postmitosis phase. 相似文献
110.
Goto Y Hogg JC Shih CH Ishii H Vincent R van Eeden SF 《American journal of physiology. Lung cellular and molecular physiology》2004,287(1):L79-L85
Exposure to air pollution [particulate matter, particles <10 microm (PM(10))] causes a systemic inflammatory response that includes stimulation of the bone marrow (BM) and progression of atherosclerosis. Monocytes are known to play a key role in atherogenesis by migration into subendothelial lesions where they appear as foam cells. The present study was designed to quantify the BM monocyte response in Watanabe heritable hyperlipidemic (WHHL) rabbits after PM(10) exposure. WHHL rabbits were given twice weekly intrapharyngeal instillations of 5 mg of PM(10) for 4 wk to a total of 40 mg and compared with control WHHL or New Zealand White (NZW) rabbits. The thymidine analog 5'-bromo-2'-deoxyuridine was used to label dividing cells in the BM and a monoclonal antibody to identify monocytes in peripheral blood. The transit time of monocytes through the BM was faster in WHHL than in NZW rabbits (30.4 +/- 1.9 h vs. 35.2 +/- 0.9 h, WHHL vs. NZW; P < 0.05). PM(10) instillation exposure increased circulating band cell counts, caused rapid release of monocytes from the BM, and further shortened their transit time through the BM to 23.2 +/- 1.6 h (P < 0.05). The percentage of alveolar macrophages containing particles in the lung correlated with the BM transit time of monocytes (r(2) = 0.45, P <0.05). We conclude that atherosclerosis increases the release of monocytes from the BM, and PM(10) exposure accelerates this process in relation to the amount of particles phagocytosed by alveolar macrophages. 相似文献