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1.
S. Wehmeier A. S. Varghese S. S. Gurcha B. Tissot M. Panico P. Hitchen H. R. Morris G. S. Besra A. Dell M. C. M. Smith 《Molecular microbiology》2009,71(2):421-433
Previously mutations in a putative protein O -mannosyltransferase (SCO3154, Pmt) and a polyprenol phosphate mannose synthase (SCO1423, Ppm1) were found to cause resistance to phage, φC31, in the antibiotic producing bacteria Streptomyces coelicolor A3(2). It was proposed that these two enzymes were part of a protein O-glycosylation pathway that was necessary for synthesis of the phage receptor. Here we provide the evidence that Pmt and Ppm1 are indeed both required for protein O-glycosylation. The phosphate binding protein PstS was found to be glycosylated with a trihexose in the S. coelicolor parent strain, J1929, but not in the pmt − derivative, DT1025. Ppm1 was necessary for the transfer of mannose to endogenous polyprenol phosphate in membrane preparations of S. coelicolor . A mutation in ppm1 that conferred an E218V substitution in Ppm1 abolished mannose transfer and glycosylation of PstS. Mass spectrometry analysis of extracted lipids showed the presence of a glycosylated polyprenol phosphate (PP) containing nine repeated isoprenyl units (C45 -PP). S. coelicolor membranes were also able to catalyse the transfer of mannose to peptides derived from PstS, indicating that these could be targets for Pmt in vivo . 相似文献
2.
During the progression of malignant peritoneal mesothelioma (MPeM), tumor nodules propagate diffusely within the abdomen and tumors are characterized by distinct phenotypic sub-types. Recent studies in solid organ cancers have shown that cancer stem cells (CSCs) play a pivotal role in the initiation and progression of tumors. However, it is not known whether tumorigenic stem cells exist and whether they promote tumor growth in MPeM. In this study, we developed and characterized a CSC model for MPeM using stably expandable tumorigenic stem cells derived from patient tumors. We found morphologically distinct populations of CSCs that divide asymmetrically or symmetrically in MPeM in vitro cell culture. The MPeM stem cells (MPeMSCs) express stem cell markers c-MYC, NES and VEGFR2 and in the presence of matrix components cells form colony spheres. MPeMSCs are multipotent, differentiate into neuronal, vascular and adipose progeny upon defined induction and the differentiating cells express lineage-specific markers such as TUBB3, an early neuronal marker; vWF, VEGFA, VEGFC and IL-8, endothelial markers; and PPARγ and FABP4, adipose markers. Xenotransplantation experiments using MPeMSCs demonstrated early tumor growth compared with parental cells. Limiting dilution experiments using MPeMSCs and endothelial lineage-induced cells derived from a single MPeMSC resulted in early tumor growth in the latter group indicating that endothelial differentiation of MPeMSCs is important for MPeM tumor initiation. Our observation that the MPeM tumors contain stem cells with tumorigenic potential has important implications for understanding the cells of origin and tumor progression in MPeM and hence targeting CSCs may be a useful strategy to inhibit malignant progression. 相似文献
3.
R G Webster G M Air D W Metzger P M Colman J N Varghese A T Baker W G Laver 《Journal of virology》1987,61(9):2910-2916
We previously determined, by X-ray crystallography, the three-dimensional structure of a complex between influenza virus N9 neuraminidase (NA) and the Fab fragments of monoclonal antibody NC-41 [P. M. Colman, W. G. Laver, J. N. Varghese, A. T. Baker, P. A. Tulloch, G. M. Air, and R. G. Webster, Nature (London) 326:358-363, 1987]. This antibody binds to an epitope on the upper surface of the NA which is made up of four polypeptide loops over an area of approximately 600 A2 (60 nm2). We now describe properties of NC-41 and other monoclonal antibodies to N9 NA and the properties of variants selected with these antibodies (escape mutants). All except one of the escape mutants had single amino acid sequence changes which affected the binding of NC-41 and which therefore are located within the NC-41 epitope. The other one had a change outside the epitope which did not affect the binding of any of the other antibodies. All the antibodies which selected variants inhibited enzyme activity with fetuin (molecular weight, 50,000) as the substrate, but only five, including NC-41, also inhibited enzyme activity with the small substrate N-acetylneuramin-lactose (molecular weight, 600). These five probably inhibited enzyme activity by distorting the catalytic site of the NA. Isolated, intact N9 NA molecules form rosettes in the absence of detergent, and these possess high levels of hemagglutinin activity (W.G. Laver, P.M. Colman, R.G. Webster, V.S. Hinshaw, and G.M. Air, Virology 137:314-323, 1984). The enzyme activity of N9 NA was inhibited efficiently by 2-deoxy-2,3-dehydro-N-acetylneuraminic acid, whereas hemagglutinin activity was unaffected. The NAs of several variants with sequence changes in the NC-41 epitope lost hemagglutinin activity without any loss of enzyme activity, suggesting that the two activities are associated with separate sites on the N9 NA head. 相似文献
4.
Dale L. Birkle Pawels Kurian Pierre Braquet Nicolas G. Bazan 《Journal of neurochemistry》1988,51(6):1900-1905
We have investigated the effects of the specific platelet-activating factor (PAF; 1-alkyl-2-acetyl-glycerophosphocholine) antagonist BN52021 on free fatty acid (FFA) and diacylglycerol (DG) accumulation and on the loss of fatty acids from phosphatidylinositol-4,5-bisphosphate (PIP2) in mouse brain. Mice were pretreated with BN52021 (10 mg/kg, i.p.) 30 min before electroconvulsive shock (ECS) or postdecapitation ischemia. These procedures cause rapid breakdown of PIP2 and accumulation of FFA and DG. Lipid extracts were prepared from microwave-fixed cerebrum and fractionated by TLC, and the fatty acid methyl esters were prepared by methanolysis and quantified by capillary GLC. In saline or vehicle (dimethyl sulfoxide)-treated mice, ECS caused marked accumulation of FFA and DG and loss of mainly stearic (18:0) and arachidonic (20:4) acids from PIP2. BN52021 pretreatment of ECS-treated mice decreased the accumulation of free palmitic (16:0), 18:0, 20:4, and docosahexaenoic (22:6) acids with no effect on the fatty acids in DG or the loss of PIP2. BN52021 had no effect on basal levels of FFA, DG, or PIP2. One minute of postdecapitation ischemia induced PIP2 loss and accumulation of FFA and DG. BN52021 attenuated the accumulation of free 20:4 and 22:6 acids, decreased the content of oleic (18:1), 20:4, and 22:6 acids in DG, but had no effect on PIP2 loss. These data indicate that BN52021 reduces the injury-induced activation of phospholipase A2 and lysophospholipase, which mediate the accumulation of FFA in brain, while having a negligible effect on phospholipase C-mediated degradation of PIP2. 相似文献
5.
Effect of saffron on thymocyte proliferation, intracellular glutathione levels and its antitumor activity. 总被引:1,自引:0,他引:1
S C Nair M J Salomi C D Varghese B Panikkar K R Panikkar 《BioFactors (Oxford, England)》1992,4(1):51-54
Liposome encapsulation of saffron effectively enhanced its antitumor activity towards Sarcoma-180 (S-180) and Ehrlich ascites carcinoma solid tumors in mice. Significant inhibition (P < 0.001) in the growth of these tumors was observed as compared with vehicle (control) mice. In the presence of phytohemagglutinin (PHA), a T cell mitogen, saffron stimulated non-specific proliferation of lymphocytes in vitro. The intracellular reduced glutathione and related enzymes, i.e. glutathione reductase and glutathione-S-transferase, of S-180 tumor cells were significantly elevated when incubated with saffron, possibly acting to maintain functional levels of other antioxidants. Our studies indicate the antioxidant activity of saffron. 相似文献
6.
Properties of 2-hydroxylaminoimidazoles and their implications for the biological effects of 2-nitroimidazoles 总被引:1,自引:0,他引:1
In aqueous solution, in the presence of ammonium chloride, N1-substituted 2-nitroimidazoles are readily reduced to the corresponding hydroxylamines. In air, under neutral conditions, analogous to the reactions of aromatic hydroxylamines, 2-hydroxylaminoimidazoles are converted to the azoxy derivatives via a base-catalyzed condensation reaction between the hydroxylamine and its oxidation product, the nitroso derivative. In nitrogen, rearrangement to form the 2-amino-4(5)hydroxyimidazole derivative followed by addition of water across the C4-C5 double bond to yield isomers of a 4,5-dihydro-4,5-dihydroxy derivative appears to be a major reaction. 2-hydroxylaminoimidazoles undergo a complex series of reactions with glutathione. The initial reaction is the formation of a labile conjugate involving an N-S-linkage. Subsequently in the presence of excess GSH, under neutral conditions, two stable conjugates identified as 2-amino-4-S-glutathionyl- and 2-amino-5-S-glutathionyl imidazoles are formed. Nucleophilic attack by GSH on the imidazole ring of a nitrenium ion is postulated as the initial step in the formation of the stable GSH conjugates as well as the 2-amino-4,5-dihydro dihydroxy derivative. The results provide a molecular mechanism for many of the biological effects of N1-substituted 2-nitroimidazoles in hypoxic mammalian cells. 相似文献
7.
Hormonal sex reversal of wild-spawned tilapia in India 总被引:1,自引:0,他引:1
The effectiveness of methyltestosterone (MT) for sex reversal and growth promotion in Oreochromis mossambicus was studied in culture experiments in India. Wild-spawned fry were treated with 30 μg MT g−1 diet for 30 or 60 days at two feeding levels (initially 20% or 10% of body weight daily). The fish were grown on for 66–96 days after the hormone treatment period in fertilized cement ponds without supplementary feeding. Tilapia treated with MT for 60 days attained an average weight of 29.0 g compared to 18.8 g for untreated fish reared under similar conditions. The percentage of males among the untreated tilapia was 58%, MT treatment for 30 days significantly increased this percentage at the higher feeding level (79% male), but not at the lower feeding level (51%). More than 90% of the tilapia in both 60 day MT treatment groups were male; 3% of all the fish reared showed an intersex condition. The experiments demonstrated that the anabolic and sex reversal effects of MT on tilapia are proportional to the duration of treatment and quantity of hormone administered. The possible application of monosex tilapia culture in tropical countries is noted. 相似文献
8.
Dr. Y. W. Ho Professor G. Varghese Dr. G. S. T. Aylor 《Journal of Phytopathology》1985,114(3):193-202
Pathogenicity tests with Fusarium oxysporum isolated form Malaysian oil palm were made with oil palms seedlings raised form Malaysian seed as well s with wilt-susceptible seedlings gown from African seed. Oil palm seedlings grown form Malaysian seed were also inoculated with African isolates of F. oxysporum f. sp. elaeidis and F. oxysporum var. redolens. The experiments were made under normal soil moisture conditions and under water stress. F. oxysporum f. sp. elaeidis isolates form Africa were pathogenic to oil palm seedlings from Malaysian seeds but the Malaysian F oxysporum isolates were non-pathogenic to plams grown from Malaysian seed or the wilt-susceptible palms from African seed. Seedlings from Malaysian seed proved to be highly susceptible to the vascular wilt disease caused by F. oxysporum f. sp. elaeidis as 75–90% of the palms were infected. The susceptibility of the palms from Malaysian seed varied with different African isolates tested. The Yaligimba isolate from Zaire which was found to be F. oxysporum var. redolens was the most virulent. Disease was more severe when oil palm seedlings were subjected to a period of water stress. The incidence of death in the seedlings under stress conditions was 45% as compared with only 15% for palms grown under normal conditions. 相似文献
9.
Summary Corn plants were grown in pots to study the effect of post-planting loosening of an unstable sandy loam soil on the anatomy
of roots. Roots from compact soil had more elaborate production of sclerified cells in the cortical and vascular tissue which
may be considered as traits developed in such roots to resist external forces to prevent the deformation of interior cells.
It appears that the compact layer that developes on unstable soils after irrigation, hinders the normal development of root
structure. Its loosening decreases soil resistance and permits normal development of root anatomy. 相似文献
10.
Induction of anchorage-independent growth in human diploid fibroblasts by the cyclopenta-polycyclic aromatic hydrocarbon, benz[l]aceanthrylene 总被引:1,自引:0,他引:1
Cyclopenta-fused polycyclic aromatic hydrocarbons are a class of environmental PAH that have been recently identified. Many of these chemicals have been found to be more active than benzo[a]pyrene in tests for genetic toxicity using bacterial and rodent cells. Benz[l]aceanthrylene, a cyclopenta-polycyclic aromatic hydrocarbon related to benz[a]anthracene, and benzo[a]pyrene were compared for their activity to induce cytotoxicity and anchorage-independent growth with normal human diploid fibroblasts. Both benz[l]aceanthrylene and benzo[a]pyrene were relatively non-cytotoxic to normal human diploid fibroblasts. However, benz[l]aceanthrylene was twice as active compared to benzo[a]pyrene over the concentration range examined as an inducer of anchorage-independent growth. The ability of benz[l]aceanthrylene to induce anchorage-independent colony growth in normal human cells, in combination with its demonstrated ability as a mouse-skin tumorigen, suggests this PAH to be a potential multi-species carcinogen. 相似文献