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181.
Genetics and pathogenesis of inflammatory bowel disease 总被引:1,自引:0,他引:1
Recent advances have provided substantial insight into the maintenance of mucosal immunity and the pathogenesis of inflammatory bowel disease. Cellular programs responsible for intestinal homeostasis use diverse intracellular and intercellular networks to promote immune tolerance, inflammation or epithelial restitution. Complex interfaces integrate local host and microbial signals to activate appropriate effector programs selectively and even drive plasticity between these programs. In addition, genetic studies and mouse models have emphasized the role of genetic predispositions and how they affect interactions with microbial and environmental factors, leading to pro-colitogenic perturbations of the host-commensal relationship. 相似文献
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Cho J Jeon S Wilson SA Liu LV Kang EA Braymer JJ Lim MH Hedman B Hodgson KO Valentine JS Solomon EI Nam W 《Nature》2011,478(7370):502-505
Oxygen-containing mononuclear iron species--iron(III)-peroxo, iron(III)-hydroperoxo and iron(IV)-oxo--are key intermediates in the catalytic activation of dioxygen by iron-containing metalloenzymes. It has been difficult to generate synthetic analogues of these three active iron-oxygen species in identical host complexes, which is necessary to elucidate changes to the structure of the iron centre during catalysis and the factors that control their chemical reactivities with substrates. Here we report the high-resolution crystal structure of a mononuclear non-haem side-on iron(III)-peroxo complex, [Fe(III)(TMC)(OO)](+). We also report a series of chemical reactions in which this iron(III)-peroxo complex is cleanly converted to the iron(III)-hydroperoxo complex, [Fe(III)(TMC)(OOH)](2+), via a short-lived intermediate on protonation. This iron(III)-hydroperoxo complex then cleanly converts to the ferryl complex, [Fe(IV)(TMC)(O)](2+), via homolytic O-O bond cleavage of the iron(III)-hydroperoxo species. All three of these iron species--the three most biologically relevant iron-oxygen intermediates--have been spectroscopically characterized; we note that they have been obtained using a simple macrocyclic ligand. We have performed relative reactivity studies on these three iron species which reveal that the iron(III)-hydroperoxo complex is the most reactive of the three in the deformylation of aldehydes and that it has a similar reactivity to the iron(IV)-oxo complex in C-H bond activation of alkylaromatics. These reactivity results demonstrate that iron(III)-hydroperoxo species are viable oxidants in both nucleophilic and electrophilic reactions by iron-containing enzymes. 相似文献
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Limited heterogeneity of rearranged T-cell receptor V alpha transcripts in brains of multiple sclerosis patients 总被引:49,自引:0,他引:49
J R Oksenberg S Stuart A B Begovich R B Bell H A Erlich L Steinman C C Bernard 《Nature》1990,345(6273):344-346
190.
Alkaline phosphatase binds to collagen; a hypothesis on the mechanism of extravesicular mineralization in epiphyseal cartilage 总被引:1,自引:0,他引:1
F. Vittur N. Stagni L. Moro B. de Bernard 《Cellular and molecular life sciences : CMLS》1984,40(8):836-837
Summary Affinity chromatography on Sepharose 4B-collagen gels was used to test the affinity of alkaline phosphatase for collagen. Results indicate that 1) alkaline phosphatase of preosseous cartilage binds to collagen probably by electrostatic interactions, 2) this interaction is inhibited by proteoglycan subunits. These results suggest that, in vivo, the formation of a collagen-alkaline phosphatase complex may be a step of the process leading to cartilage calcification.This investigation was supported by research grants of C.N.R. (C.T. 82.02437.04), of Ministero della Pubblica Istruzione and of the University of Trieste.To whom correspondence and reprint requests should be addressed. 相似文献