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31.
Krishnamurthy B Mariana L Gellert SA Colman PG Harrison LC Lew AM Santamaria P Thomas HE Kay TW 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(7):4458-4464
T cells specific for proinsulin and islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP) induce diabetes in nonobese diabetic (NOD) mice. TCR transgenic mice with CD8(+) T cells specific for IGRP(206-214) (NOD8.3 mice) develop accelerated diabetes that requires CD4(+) T cell help. We previously showed that immune responses against proinsulin are necessary for IGRP(206-214)-specific CD8(+) T cells to expand. In this study, we show that diabetes development is dramatically reduced in NOD8.3 mice crossed to NOD mice tolerant to proinsulin (NOD-PI mice). This indicates that immunity to proinsulin is even required in the great majority of NOD8.3 mice that have a pre-existing repertoire of IGRP(206-214)-specific cells. However, protection from diabetes could be overcome by inducing islet inflammation either by a single dose of streptozotocin or anti-CD40 agonist Ab treatment. This suggests that islet inflammation can substitute for proinsulin-specific CD4(+) T cell help to activate IGRP(206-214)-specific T cells. 相似文献
32.
Oxidative stress causes nuclear factor-kappaB activation in acute hypovolemic hemorrhagic shock 总被引:4,自引:0,他引:4
33.
Local calcium signaling in neurons 总被引:18,自引:0,他引:18
Transient rises in the cytoplasmic concentration of calcium ions serve as second messenger signals that control many neuronal functions. Selective triggering of these functions is achieved through spatial localization of calcium signals. Several qualitatively different forms of local calcium signaling can be distinguished by the location of open calcium channels as well as by the distance between these channels and the calcium binding proteins that serve as the molecular targets of calcium action. Local calcium signaling is especially prominent at presynaptic active zones and postsynaptic densities, structures that are distinguished by highly organized macromolecular arrays that yield precise spatial arrangements of calcium signaling proteins. Similar forms of local calcium signaling may be employed throughout the nervous system, though much remains to be learned about the molecular underpinnings of these events. 相似文献
34.
Campbell DJ Dixon B Kladis A Kemme M Santamaria JD 《American journal of physiology. Regulatory, integrative and comparative physiology》2001,281(4):R1059-R1070
We used cardiopulmonary bypass (CPB) as a model of activation of the contact system and investigated the involvement of the plasma and tissue kallikrein-kinin systems (KKS) in this process. Circulating levels of bradykinin and kallidin and their metabolites, plasma and tissue kallikrein, low and high molecular weight kininogen, and kallistatin were measured before, during, and 1, 4, and 10 h after CPB in subjects undergoing cardiac surgery. Bradykinin peptide levels increased 10- to 20-fold during the first 10 min, returned toward basal levels by 70 min of CPB, and remained 1.2- to 2.5-fold elevated after CPB. Kallidin peptide levels showed little change during CPB, but they were elevated 1.7- to 5.2-fold after CPB. There were reductions of 80 and 60% in plasma and tissue kallikrein levels, respectively, during the first minute of CPB. Kininogen and kallistatin levels were unchanged. Angiotensin-converting enzyme inhibition did not amplify the increase in bradykinin levels during CPB. Aprotinin administration prevented activation of the KKS. The changes in circulating kinin and kallikrein levels indicate activation of both the plasma and tissue KKS during activation of the contact system by CPB. 相似文献
35.
A study of larval Diptera (Chironomidae, Culicidae and Simuliidae) from Spain has been carried out to fulfill a catalogue of species of the genus Smittium (Harpellales: Legeriomycetaceae) present within these hosts. Among the reported taxa, eight are new species: Smittium brevisporum, S. bulbosporo-phorus, S. gracilis, S. hecatei, S. heterosporum, S. inex-pectans, S. prostratum and S. pseudodimorphum. We also report six previously described species, which are new for the Iberian Peninsula: S. alpinum, S. dipterorum, S. megazygosporum, S. pusillum, S. typhellum and S. fecundum. Three other species (S. simulii, S. culicis and S. culisetae) previously were reported from Spain. In two of them (S. fecundum and S. culicis), we describe for the first time the presence of zygospores. Some of the included species have been artificially cultured as well as ultrastructurally studied using scanning electron microscopy (SEM), with the purpose of observing the surface of both trichospores and the trichospore collar and the morphology of the trichospore appendage. 相似文献
36.
Proviral amplification of the Gypsy endogenous retrovirus of Drosophila melanogaster involves env-independent invasion of the female germline 下载免费PDF全文
Chalvet F Teysset L Terzian C Prud'homme N Santamaria P Bucheton A Pélisson A 《The EMBO journal》1999,18(9):2659-2669
Gypsy is an infectious endogenous retrovirus of Drosophila melanogaster. The gypsy proviruses replicate very efficiently in the genome of the progeny of females homozygous for permissive alleles of the flamenco gene. This replicative transposition is correlated with derepression of gypsy expression, specifically in the somatic cells of the ovaries of the permissive mothers. The determinism of this amplification was studied further by making chimeric mothers containing different permissive/restrictive and somatic/germinal lineages. We show here that the derepression of active proviruses in the permissive soma is necessary and sufficient to induce proviral insertions in the progeny, even if the F1 flies derive from restrictive germ cells devoid of active proviruses. Therefore, gypsy endogenous multiplication results from the transfer of some gypsy-encoded genetic material from the soma towards the germen of the mother and its subsequent insertion into the chromosomes of the progeny. This transfer, however, is not likely to result from retroviral infection of the germline. Indeed, we also show here that the insertion of a tagged gypsy element, mutant for the env gene, occurs at high frequency, independently of the production of gypsy Env proteins by any transcomplementing helper. The possible role of the env gene for horizontal transfer to new hosts is discussed. 相似文献
37.
Frdric Tournier Yves Bobinnec Alain Debec Pedro Santamaria Michel Bornens 《Biology of the cell / under the auspices of the European Cell Biology Organization》1999,91(2):99-108
Centrosomes are powerful and exclusive parthenogenetic agents in the Xenopus egg. We have previously shown that heterologous centrosomes from various vertebrate species were able to promote egg cleavage in Xenopus and that human centrosome activity was associated with an insoluble proteinacious structure that is not significantly simpler than the native centrosome. In this work, we have investigated the parthenogenetic capacity of more evolutionary distant centrosomes. We show that centrosomes devoid of centrioles, such as SPBs isolated from Saccharomyces cerevisiae, do not form asters of microtubules in cytoplasmic extracts from Xenopus eggs, and are inactive in the parthenogenetic test. We further show that Drosophila centrosomes which possess a typical centriole architecture, and are quite active to nucleate microtubules in Xenopus cytoplasmic extracts, are unable to trigger egg cleavage. This was observed both with centrosomes isolated from Drosophila syncytial embryos and nucleus-centrosome complexes from the Drosophila Kc23 cell line. We demonstrate that this inability could not be restored after pre-incubation of Drosophila centrosomes in the egg cytoplasm before injection. We conclude that the parthenogenetic activity of a centrosome is not directly linked to its capacity to nucleate microtubules from the egg tubulin, and that the evolutionary conserved nine-fold symmetrical structure of the centriole cannot be considered as sufficient for triggering procentriole assembly. 相似文献
38.
Santamaria R Fiorito F Irace C De Martino L Maffettone C Granato GE Di Pascale A Iovane V Pagnini U Colonna A 《Biochimica et biophysica acta》2011,1813(5):704-712
Cellular iron metabolism is essentially controlled by the binding of cytosolic iron regulatory proteins (IRP1 or IRP2) to iron-responsive elements (IREs) located on mRNAs coding for proteins involved in iron acquisition, utilization and storage. The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is one of the most potent toxins of current interest that occurs as poisonous chemical in the environment. TCDD exposure has been reported to induce a broad spectrum of toxic and biological responses, including significant changes in gene expression for heme and iron metabolism associated with liver injury. Here, we have investigated the molecular effects of TCDD on the iron metabolism providing the first evidence that administration of the toxin TCDD to mammalian cells affects the maintenance of iron homeostasis. We found that exposure of Madin-Darby Bovine Kidney cell to TCDD caused a divergent modulation of IRP1 and IRP2 RNA-binding capacity. Interestingly, we observed a concomitant IRP1 down-regulation and IRP2 up-regulation thus determining a marked enhancement of transferrin receptor 1 (TfR-1) expression and a biphasic response in ferritin content. The changed ferritin content coupled to TfR-1 induction after TCDD exposure impairs the cellular iron homeostasis, ultimately leading to significant changes in the labile iron pool (LIP) extent. Since important iron requirement changes occur during the regulation of cell growth, it is not surprising that the dioxin-dependent iron metabolism dysregulation herein described may be linked to cell-fate decision, supporting the hypothesis of a central connection among exposure to dioxins and the regulation of critical cellular processes. This article is part of a Special Issue entitled: 11th European Symposium on Calcium. 相似文献
39.
Autoimmune islet destruction in spontaneous type 1 diabetes is not beta-cell exclusive 总被引:8,自引:0,他引:8
Winer S Tsui H Lau A Song A Li X Cheung RK Sampson A Afifiyan F Elford A Jackowski G Becker DJ Santamaria P Ohashi P Dosch HM 《Nature medicine》2003,9(2):198-205
Pancreatic islets of Langerhans are enveloped by peri-islet Schwann cells (pSC), which express glial fibrillary acidic protein (GFAP) and S100beta. pSC-autoreactive T- and B-cell responses arise in 3- to 4-week-old diabetes-prone non-obese diabetic (NOD) mice, followed by progressive pSC destruction before detectable beta-cell death. Humans with probable prediabetes generate similar autoreactivities, and autoantibodies in islet-cell autoantibody (lCA) -positive sera co-localize to pSC. Moreover, GFAP-specific NOD T-cell lines transferred pathogenic peri-insulitis to NOD/severe combined immunodeficient (NOD/SCID) mice, and immunotherapy with GFAP or S100beta prevented diabetes. pSC survived in rat insulin promoter Iymphocytic choriomeningitis virus (rip-LCMV) glycoprotein/CD8+ T-cell receptor(gp) double-transgenic mice with virus-induced diabetes, suggesting that pSC death is not an obligate consequence of local inflammation and beta-cell destruction. However, pSC were deleted in spontaneously diabetic NOD mice carrying the CD8+/8.3 T-cell receptor transgene, a T cell receptor commonly expressed in earliest islet infiltrates. Autoimmune targeting of pancreatic nervous system tissue elements seems to be an integral, early part of natural type 1 diabetes. 相似文献
40.
Destoumieux-Garzón D Thomas X Santamaria M Goulard C Barthélémy M Boscher B Bessin Y Molle G Pons AM Letellier L Peduzzi J Rebuffat S 《Molecular microbiology》2003,49(4):1031-1041
The mechanism of action of microcin E492 (MccE492) was investigated for the first time in live bacteria. MccE492 was expressed and purified to homogeneity through an optimized large-scale procedure. Highly purified MccE492 showed potent antibacterial activity at minimal inhibitory concentrations in the range of 0.02-1.2 microM. The microcin bactericidal spectrum of activity was found to be restricted to Enterobacteriaceae and specifically directed against Escherichia and Salmonella species. Isogenic bacteria that possessed mutations in membrane proteins, particularly of the TonB-ExbB-ExbD complex, were assayed. The microcin bactericidal activity was shown to be TonB- and energy-dependent, supporting the hypothesis that the mechanism of action is receptor mediated. In addition, MccE492 depolarized and permeabilized the E. coli cytoplasmic membrane. The membrane depolarization was TonB dependent. From this study, we propose that MccE492 is recognized by iron-siderophore receptors, including FepA, which promote its import across the outer membrane via a TonB- and energy-dependent pathway. MccE492 then inserts into the inner membrane, whereupon the potential becomes destabilized by pore formation. Because cytoplasmic membrane permeabilization of MccE492 occurs beneath the threshold of the bactericidal concentration and does not result in cell lysis, the cytoplasmic membrane is not hypothesized to be the sole target of MccE492. 相似文献