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排序方式: 共有89条查询结果,搜索用时 15 毫秒
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63.
Elena Rapizzi Maria Letizia Taddei Tania Fiaschi Chiara Donati Paola Bruni Paola Chiarugi 《Cellular and molecular life sciences : CMLS》2009,66(19):3207-3218
Sphingosine 1-phosphate (S1P) is a bioactive lipid that acts through a family of G-protein-coupled receptors. Herein, we report
evidence of a novel redox-based cross-talk between S1P and insulin signaling pathways. In skeletal muscle cells S1P, through
engagement of its S1P2 receptor, is found to produce a transient burst of reactive oxygen species through a calcium-dependent activation of the
small GTPase Rac1. S1P-induced redox-signaling is sensed by protein tyrosine phosphatase-1B, the main negative regulator of
insulin receptor phosphorylation, which undergoes oxidation and enzymatic inhibition. This redox-based inhibition of the phosphatase
provokes a ligand-independent trans-phosphorylation of insulin receptor and a strong increase in glucose uptake. Our results propose a new role of S1P, recognizing
the lipid as an insulin-mimetic cue and pointing at reactive oxygen species as critical regulators of the cross-talk between
S1P and insulin pathways. Any possible implication of S1P-directed insulin signaling in diabetes and insulin resistance remains
to be established. 相似文献
64.
Berger T Testa P Hillier A Boerner P Low BC Shibata K Schrijver C Tarbell T Title A 《Nature》2011,472(7342):197-200
Coronal cavities are large low-density regions formed by hemispheric-scale magnetic flux ropes suspended in the Sun's outer atmosphere. They evolve over time, eventually erupting as the dark cores of coronal mass ejections. Although coronal mass ejections are common and can significantly affect planetary magnetospheres, the mechanisms by which cavities evolve to an eruptive state remain poorly understood. Recent optical observations of high-latitude 'polar crown' prominences within coronal cavities reveal dark, low-density 'bubbles' that undergo Rayleigh-Taylor instabilities to form dark plumes rising into overlying coronal cavities. These observations offered a possible mechanism for coronal cavity evolution, although the nature of the bubbles, particularly their buoyancy, was hitherto unclear. Here we report simultaneous optical and extreme-ultraviolet observations of polar crown prominences that show that these bubbles contain plasma at temperatures in the range (2.5-12)?×?10(5) kelvin, which is 25-120 times hotter than the overlying prominence. This identifies a source of the buoyancy, and suggests that the coronal cavity-prominence system supports a novel form of magneto-thermal convection in the solar atmosphere, challenging current hydromagnetic concepts of prominences and their relation to coronal cavities. 相似文献
65.
Paola Gramatica P. Manitto B. Maria Ranzi A. Delbianco Maria Francavilla 《Cellular and molecular life sciences : CMLS》1982,38(7):775-776
Summary (R)-(+)-citronellol, a useful C10 chiral synthon for natural terpenoid products, can be obtained in enantiomerically pure form and satisfactory yield by yeast reduction of geraniol. 相似文献
66.
Neuronal polarization occurs shortly after mitosis. In neurons differentiating in vitro, axon formation follows the segregation of growth-promoting activities to only one of the multiple neurites that form after mitosis. It is unresolved whether such spatial restriction makes use of an intrinsic program, like during C. elegans embryo polarization, or is extrinsic and cue-mediated, as in migratory cells. Here we show that in hippocampal neurons in vitro, the axon consistently arises from the neurite that develops first after mitosis. Centrosomes, the Golgi apparatus and endosomes cluster together close to the area where the first neurite will form, which is in turn opposite from the plane of the last mitotic division. We show that the polarized activities of these organelles are necessary and sufficient for neuronal polarization: (1) polarized microtubule polymerization and membrane transport precedes first neurite formation, (2) neurons with more than one centrosome sprout more than one axon and (3) suppression of centrosome-mediated functions precludes polarization. We conclude that asymmetric centrosome-mediated dynamics in the early post-mitotic stage instruct neuronal polarity, implying that pre-mitotic mechanisms with a role in division orientation may in turn participate in this event. 相似文献
67.
Deng X Hofmann ER Villanueva A Hobert O Capodieci P Veach DR Yin X Campodonico L Glekas A Cordon-Cardo C Clarkson B Bornmann WG Fuks Z Hengartner MO Kolesnick R 《Nature genetics》2004,36(8):906-912
c-Abl, a conserved nonreceptor tyrosine kinase, integrates genotoxic stress responses, acting as a transducer of both pro- and antiapoptotic effector pathways. Nuclear c-Abl seems to interact with the p53 homolog p73 to elicit apoptosis. Although several observations suggest that cytoplasmic localization of c-Abl is required for antiapoptotic function, the signals that mediate its antiapoptotic effect are largely unknown. Here we show that worms carrying an abl-1 deletion allele, abl-1(ok171), are specifically hypersensitive to radiation-induced apoptosis in the Caenorhabditis elegans germ line. Our findings delineate an apoptotic pathway antagonized by ABL-1, which requires sequentially the cell cycle checkpoint genes clk-2, hus-1 and mrt-2; the C. elegans p53 homolog, cep-1; and the genes encoding the components of the conserved apoptotic machinery, ced-3, ced-9 and egl-1. ABL-1 does not antagonize germline apoptosis induced by the DNA-alkylating agent ethylnitrosourea. Furthermore, worms treated with the c-Abl inhibitor STI-571 (Gleevec; used in human cancer therapy), two newly synthesized STI-571 variants or PD166326 had a phenotype similar to that generated by abl-1(ok171). These studies indicate that ABL-1 distinguishes proapoptotic signals triggered by two different DNA-damaging agents and suggest that C. elegans might provide tissue models for development of anticancer drugs. 相似文献
68.
Paola Megazzini Giuseppina Bernardi Paola L. Ballotti 《Cellular and molecular life sciences : CMLS》1965,21(7):406-408
Riassunto L'eserina 0.2–5 mg/kg aumenta la ACh totale del cervello di cavia soprattutto nel telencefalo. Dopo trattamento sub-acuto, l'attività colinoacetilasica aumenta, forse per stimolazione mediata dei neuroni colinergici. 相似文献
69.
Genetic Analysis of Psoriasis Consortium & the Wellcome Trust Case Control Consortium Strange A Capon F Spencer CC Knight J Weale ME Allen MH Barton A Band G Bellenguez C Bergboer JG Blackwell JM Bramon E Bumpstead SJ Casas JP Cork MJ Corvin A Deloukas P Dilthey A Duncanson A Edkins S Estivill X Fitzgerald O Freeman C Giardina E Gray E Hofer A Hüffmeier U Hunt SE Irvine AD Jankowski J Kirby B Langford C Lascorz J Leman J Leslie S Mallbris L Markus HS Mathew CG McLean WH McManus R 《Nature genetics》2010,42(11):985-990
To identify new susceptibility loci for psoriasis, we undertook a genome-wide association study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified associations at eight previously unreported genomic loci. Seven loci harbored genes with recognized immune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These associations were replicated in 9,079 European samples (six loci with a combined P < 5 × 10?? and two loci with a combined P < 5 × 10??). We also report compelling evidence for an interaction between the HLA-C and ERAP1 loci (combined P = 6.95 × 10??). ERAP1 plays an important role in MHC class I peptide processing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk allele. Our findings implicate pathways that integrate epidermal barrier dysfunction with innate and adaptive immune dysregulation in psoriasis pathogenesis. 相似文献
70.
Stevanin G Santorelli FM Azzedine H Coutinho P Chomilier J Denora PS Martin E Ouvrard-Hernandez AM Tessa A Bouslam N Lossos A Charles P Loureiro JL Elleuch N Confavreux C Cruz VT Ruberg M Leguern E Grid D Tazir M Fontaine B Filla A Bertini E Durr A Brice A 《Nature genetics》2007,39(3):366-372
Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is a common and clinically distinct form of familial spastic paraplegia that is linked to the SPG11 locus on chromosome 15 in most affected families. We analyzed 12 ARHSP-TCC families, refined the SPG11 candidate interval and identified ten mutations in a previously unidentified gene expressed ubiquitously in the nervous system but most prominently in the cerebellum, cerebral cortex, hippocampus and pineal gland. The mutations were either nonsense or insertions and deletions leading to a frameshift, suggesting a loss-of-function mechanism. The identification of the function of the gene will provide insight into the mechanisms leading to the degeneration of the corticospinal tract and other brain structures in this frequent form of ARHSP. 相似文献