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排序方式: 共有418条查询结果,搜索用时 15 毫秒
51.
Bettina Couderc Marie Penary Mustapha Tohfe Anne Pradines Antoine Casteignau Danièle Berg Gilles Favre 《BMC biotechnology》2006,6(1):26-11
Background
The use of integrating viral vectors in Gene therapy clinical trials has pointed out the problem of the deleterous effect of the integration of the ectopic gene to the cellular genome and the safety of this strategy. We proposed here a way to induce the death of gene modified cells upon request by acting on a pro-apoptotic protein cellular localization and on the activation of its apoptotic function. 相似文献52.
53.
Foulquier F Amyere M Jaeken J Zeevaert R Schollen E Race V Bammens R Morelle W Rosnoblet C Legrand D Demaegd D Buist N Cheillan D Guffon N Morsomme P Annaert W Freeze HH Van Schaftingen E Vikkula M Matthijs G 《American journal of human genetics》2012,91(1):15-26
Protein glycosylation is a complex process that depends not only on the activities of several enzymes and transporters but also on a subtle balance between vesicular Golgi trafficking, compartmental pH, and ion homeostasis. Through a combination of autozygosity mapping and expression analysis in two siblings with an abnormal serum-transferrin isoelectric focusing test (type 2) and a peculiar skeletal phenotype with epiphyseal, metaphyseal, and diaphyseal dysplasia, we identified TMEM165 (also named TPARL) as a gene involved in congenital disorders of glycosylation (CDG). The affected individuals are homozygous for a deep intronic splice mutation in TMEM165. In our cohort of unsolved CDG-II cases, we found another individual with the same mutation and two unrelated individuals with missense mutations in TMEM165. TMEM165 encodes a putative transmembrane 324 amino acid protein whose cellular functions are unknown. Using a siRNA strategy, we showed that TMEM165 deficiency causes Golgi glycosylation defects in HEK cells. 相似文献
54.
Fahmi L Makran B Pla D Sanz L Oukkache N Lkhider M Harrison RA Ghalim N Calvete JJ 《Journal of Proteomics》2012,75(8):2442-2453
We report the proteomic analysis of the venom of the medically relevant snake, Cerastes cerastes, from Morocco, and the immunoreactivity profile of an experimental monospecific (CcMo_AV against Moroccan C. cerastes venom) and a commercial (Gamma-VIP against Tunisian C. cerastes and M. lebetina venoms) F(ab')(2) antivenoms towards geographic variants of C. cerastes and C. vipera venoms. The venom of C. cerastes is a low-complexity proteome composed of 25-30 toxins belonging to 6 protein families, mainly targetting the hemostatic system. This toxin arsenal explains the clinical picture observed in C. cerastes envenomings. Despite geographic compositional variation, the monospecific CcMo_AV and the Gamma-VIP divalent antivenom produced at Institut Pasteur de Tunis, showed similar immunocapturing capability towards Moroccan, Tunisian, and Egyptian C. cerastes venom proteins. Proteins partially escaping immunorecognition were all identified as PLA(2) molecules. Antivenomic analysis showed low degree of cross-reactivity of Moroccan CcMo_AV and Tunisian Gamma-VIP antivenoms towards C. vipera venom toxins. This study indicates that a more complete therapeutic cover could be achieved by including C. vipera venom in the formulation of venom immunization mixtures, thereby generating a pan-Cerastes antivenom. 相似文献
55.
Makran B Fahmi L Pla D Sanz L Oukkache N Lkhider M Ghalim N Calvete JJ 《Journal of Proteomics》2012,75(8):2431-2441
Proteomic analysis of the venom of the medically relevant snake Macrovipera mauritanica from Morocco revealed a complex proteome composed of at least 45 toxins from 9 protein families targeting the hemostatic system of the prey or victim. The toxin profile of Moroccan M. mauritanica displays great similarity, but also worth noting departures, with the previously reported venom proteome of M. lebetina from Tunisia. Despite fine compositional differences between these Macrovipera taxa, their overall venom phenotypes explain the clinical picture observed in M. mauritanica and M. lebetina envenomings. However, M. mauritanica venom also contains significant amounts of orphan molecules whose presence in the venom seems to be difficult to rationalize in the context of a predator-prey arms race. The paraspecific immunoreactivity of an experimental monospecific (M. mauritanica) antivenom and a commercial bivalent antivenom, anti-C. cerastes and anti-M. lebetina, against the venoms of Moroccan M. mauritanica and Tunisian M. lebetina, was also investigated through an affinity chromatography-based antivenomics approach. Both antivenoms very efficiently immunodepleted homologous venom toxins and displayed a high degree of paraspecificity, suggesting the clinical utility of the two antivenoms for treating bites of both M. mauritanica or M. lebetina. 相似文献
56.
57.
Celia CarrilloAziz Hichami Pierre Andreoletti Mustapha Cherkaoui-Malki María del Mar CaviaSouleymane Abdoul-Azize Sara R. Alonso-Torre Naim Akhtar Khan 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2012,1821(4):618-626
Though most of the studies have focused on the effects of free fatty acids on T-cell activation, fatty acids incorporated into plasma membrane phospholipids may also affect cell signaling via diacylglycerol (DAG), generally produced by phospholipid hydrolysis. In the present study, we have synthesized a DAG-containing oleic acid and studied its implication in the modulation of calcium signaling in human Jurkat T-cells. 1-palmitoyl-2-oleoyl-sn-glycerol (POG) induced a dose-dependent increase in [Ca2+]i. This effect was due to the presence of oleic acid at the sn-2 position as no differences were observed between POG and 1-stearoly-2-oleoyl-sn-glycerol (SOG). However, the substitution of oleic acid with arachidonic acid at the sn-2 position of the DAG moiety exerted a different response on the increases in [Ca2+]i in these cells. POG-evoked increases in [Ca2+]i were not due to its metabolites. Furthermore, POG-induced increases in [Ca2+]i were due to the opening of TRPC3/TRPC6 channels as silencing of TRPC3 and TRPC6 genes by shRNA abolished calcium entry. Moreover, disruption of lipid rafts with methyl-β-cyclodextrin completely abolished POG-evoked increases in [Ca2+]i. In conclusion, our results demonstrate that oleic acid can influence T-lymphocyte functions, in the conjugated form of DAG, via opening TRPC3/6 channels. 相似文献
58.
X Stephenne E Nicastro S Eeckhoudt C Hermans O Nyabi C Lombard M Najimi E Sokal 《PloS one》2012,7(8):e42819
Islet and hepatocyte transplantation are associated with tissue factor-dependent activation of coagulation which elicits instant blood mediated inflammatory reaction, thereby contributing to a low rate of engraftment. The aim of this study was i) to evaluate the procoagulant activity of human adult liver-derived mesenchymal progenitor cells (hALPCs), ii) to compare it to other mesenchymal cells of extra-hepatic (bone marrow mesenchymal stem cells and skin fibroblasts) or liver origin (liver myofibroblasts), and iii) to determine the ways this activity could be modulated. Using a whole blood coagulation test (thromboelastometry), we demonstrated that all analyzed cell types exhibit procoagulant activity. The hALPCs pronounced procoagulant activity was associated with an increased tissue factor and a decreased tissue factor pathway inhibitor expression as compared with hepatocytes. At therapeutic doses, the procoagulant effect of hALPCs was inhibited by neither antithrombin activators nor direct factor Xa inhibitor or direct thrombin inhibitors individually. However, concomitant administration of an antithrombin activator or direct factor Xa inhibitor and direct thrombin inhibitor proved to be a particularly effective combination for controlling the procoagulant effects of hALPCs both in vitro and in vivo. The results suggest that this dual antithrombotic therapy should also improve the efficacy of cell transplantation in humans. 相似文献
59.
Sabour Alaoui S Dessirier V de Araujo E Alexaki VI Pelekanou V Lkhider M Stathopoulos EN Castanas E Bagot M Bensussan A Tsapis A 《PloS one》2012,7(3):e33609
The soluble TNF-like weak inducer of apoptosis (TWEAK, TNFSF12) binds to the fibroblast growth factor-inducible 14 receptor (FN14, TNFRSF12A) on the cell membrane and induces multiple biological responses, such as proliferation, migration, differentiation, angiogenesis and apoptosis. Previous reports show that TWEAK, which does not contain a death domain in its cytoplasmic tail, induces the apoptosis of tumor cell lines through the induction of TNFα secretion. TWEAK induces apoptosis in human keratinocytes. Our experiments clearly demonstrate that TWEAK does not induce the secretion of TNFα or TRAIL proteins. The use of specific inhibitors and the absence of procaspase-3 cleavage suggest that the apoptosis of keratinocytes follows a caspase- and cathepsin B-independent pathway. Further investigation showed that TWEAK induces a decrease in the mitochondrial membrane potential of keratinocytes. Confocal microscopy showed that TWEAK induces the cleavage and the translocation of apoptosis inducing factor (AIF) from the mitochondria to the nucleus, thus initiating caspase-independent apoptosis. Moreover, TWEAK induces FOXO3 and GADD45 expression, cdc2 phosphorylation and cdc2 and cyclinB1 degradation, resulting in the arrest of cell growth at the G2/M phase. Finally, we report that TWEAK and FN14 are normally expressed in the basal layer of the physiological epidermis and are greatly enhanced in benign (psoriasis) and malignant (squamous cell carcinoma) skin pathologies that are characterized by an inflammatory component. TWEAK might play an essential role in skin homeostasis and pathology. 相似文献
60.
Lysy PA Smets F Najimi M Sokal EM 《Differentiation; research in biological diversity》2008,76(10):1057-1067
The current majority of protocols for hepatocyte differentiation of mesenchymal stem cells (MSCs) are conducted using oncostatin M (OSM) as an inducer of hepatocyte-like maturation. As leukemia inhibitory factor (LIF) and OSM share similar signaling pathways, we examined whether LIF could play a role in the hepatocyte differentiation process. A differentiation protocol was designed using LIF as a maturation cytokine and this was compared with standard and control protocols applied to human MSCs of bone marrow origin. We observed that mesenchymal-derived hepatocyte-like cells (MDHLCs) acquired similar morphological changes when exposed to LIF or to OSM. Using protein and gene expression assays, we noticed a comparable hepatic marker expression in both differentiation conditions. Furthermore, LIF and OSM allowed the acquisition of equivalent levels of hepatocyte-like functionality as attested by evaluation of urea secretion and glycogen deposition. However, no increase in the expression of hepatocyte-like features could be observed in MDHLCs after a combined exposition to LIF and OSM. In conclusion, we demonstrated that LIF can play a similar role as OSM in the hepatocyte differentiation process of human MSCs. 相似文献