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C Condé X Rambout M Lebrun A Lecat E Di Valentin F Dequiedt J Piette G Gloire S Legrand 《PloS one》2012,7(7):e41005
SHIP-1 is an inositol phosphatase predominantly expressed in hematopoietic cells. Over the ten past years, SHIP-1 has been described as an important regulator of immune functions. Here, we characterize a new inhibitory function for SHIP-1 in NOD2 signaling. NOD2 is a crucial cytoplasmic bacterial sensor that activates proinflammatory and antimicrobial responses upon bacterial invasion. We observed that SHIP-1 decreases NOD2-induced NF-κB activation in macrophages. This negative regulation relies on its interaction with XIAP. Indeed, we observed that XIAP is an essential mediator of the NOD2 signaling pathway that enables proper NF-κB activation in macrophages. Upon NOD2 activation, SHIP-1 C-terminal proline rich domain (PRD) interacts with XIAP, thereby disturbing the interaction between XIAP and RIP2 in order to decrease NF-κB signaling. 相似文献
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Lucy I. Crouch Aurore Labourel Paul H. Walton Gideon J. Davies Harry J. Gilbert 《The Journal of biological chemistry》2016,291(14):7439-7449
Lignocellulosic biomass is a sustainable industrial substrate. Copper-dependent lytic polysaccharide monooxygenases (LPMOs) contribute to the degradation of lignocellulose and increase the efficiency of biofuel production. LPMOs can contain non-catalytic carbohydrate binding modules (CBMs), but their role in the activity of these enzymes is poorly understood. Here we explored the importance of CBMs in LPMO function. The family 2a CBMs of two monooxygenases, CfLPMO10 and TbLPMO10 from Cellulomonas fimi and Thermobispora bispora, respectively, were deleted and/or replaced with CBMs from other proteins. The data showed that the CBMs could potentiate and, surprisingly, inhibit LPMO activity, and that these effects were both enzyme-specific and substrate-specific. Removing the natural CBM or introducing CtCBM3a, from the Clostridium thermocellum cellulosome scaffoldin CipA, almost abolished the catalytic activity of the LPMOs against the cellulosic substrates. The deleterious effect of CBM removal likely reflects the importance of prolonged presentation of the enzyme on the surface of the substrate for efficient catalytic activity, as only LPMOs appended to CBMs bound tightly to cellulose. The negative impact of CtCBM3a is in sharp contrast with the capacity of this binding module to potentiate the activity of a range of glycoside hydrolases including cellulases. The deletion of the endogenous CBM from CfLPMO10 or the introduction of a family 10 CBM from Cellvibrio japonicus LPMO10B into TbLPMO10 influenced the quantity of non-oxidized products generated, demonstrating that CBMs can modulate the mode of action of LPMOs. This study demonstrates that engineered LPMO-CBM hybrids can display enhanced industrially relevant oxygenations. 相似文献
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G protein-dependent CCR5 signaling is not required for efficient infection of primary T lymphocytes and macrophages by R5 human immunodeficiency virus type 1 isolates
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Amara A Vidy A Boulla G Mollier K Garcia-Perez J Alcamí J Blanpain C Parmentier M Virelizier JL Charneau P Arenzana-Seisdedos F 《Journal of virology》2003,77(4):2550-2558
The requirement of human immunodeficiency virus (HIV)-induced CCR5 activation for infection by R5 HIV type 1 (HIV-1) strains remains controversial. Ectopic CCR5 expression in CD4(+)-transformed cells or pharmacological inhibition of G(alpha)i proteins coupled to CCR5 left unsolved whether CCR5-dependent cell activation is necessary for the HIV life cycle. In this study, we investigated the role played by HIV-induced CCR5-dependent cell signaling during infection of primary CD4-expressing leukocytes. Using lentiviral vectors, we restored CCR5 expression in T lymphocytes and macrophages from individuals carrying the homozygous 32-bp deletion of the CCR5 gene (ccr5 Delta32/Delta32). Expression of wild-type (wt) CCR5 in ccr5 Delta32/Delta32 cells permitted infection by R5 HIV isolates. We assessed the capacity of a CCR5 derivative carrying a mutated DRY motif (CCR5-R126N) in the second intracellular loop to work as an HIV-1 coreceptor. The R126N mutation is known to disable G protein coupling and agonist-induced signal transduction through CCR5 and other G protein-coupled receptors. Despite its inability to promote either intracellular calcium mobilization or cell chemotaxis, the inactive CCR5-R126N mutant provided full coreceptor function to several R5 HIV-1 isolates in primary cells as efficiently as wt CCR5. We conclude that in a primary, CCR5-reconstituted CD4(+) cell environment, G protein signaling is dispensable for R5 HIV-1 isolates to actively infect primary CD4(+) T lymphocytes or macrophages. 相似文献
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Anne Lorrain Heidi Pethybridge Nicolas Cassar Aurore Receveur Valrie Allain Nathalie Bodin Laurent Bopp C. Anela Choy Leanne Duffy Brian Fry Nicolas Goi Brittany S. Graham Alistair J. Hobday John M. Logan Frederic Mnard Christophe E. Menkes Robert J. Olson Dan E. Pagendam David Point Andrew T. Revill Christopher J. Somes Jock W. Young 《Global Change Biology》2020,26(2):458-470
Considerable uncertainty remains over how increasing atmospheric CO2 and anthropogenic climate changes are affecting open‐ocean marine ecosystems from phytoplankton to top predators. Biological time series data are thus urgently needed for the world's oceans. Here, we use the carbon stable isotope composition of tuna to provide a first insight into the existence of global trends in complex ecosystem dynamics and changes in the oceanic carbon cycle. From 2000 to 2015, considerable declines in δ13C values of 0.8‰–2.5‰ were observed across three tuna species sampled globally, with more substantial changes in the Pacific Ocean compared to the Atlantic and Indian Oceans. Tuna recorded not only the Suess effect, that is, fossil fuel‐derived and isotopically light carbon being incorporated into marine ecosystems, but also recorded profound changes at the base of marine food webs. We suggest a global shift in phytoplankton community structure, for example, a reduction in 13C‐rich phytoplankton such as diatoms, and/or a change in phytoplankton physiology during this period, although this does not rule out other concomitant changes at higher levels in the food webs. Our study establishes tuna δ13C values as a candidate essential ocean variable to assess complex ecosystem responses to climate change at regional to global scales and over decadal timescales. Finally, this time series will be invaluable in calibrating and validating global earth system models to project changes in marine biota. 相似文献
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Giron-Michel J Azzi S Khawam K Mortier E Caignard A Devocelle A Ferrini S Croce M François H Lecru L Charpentier B Chouaib S Azzarone B Eid P 《PloS one》2012,7(2):e31624
The ability of Interleukin-15 (IL-15) to activate many immune antitumor mechanisms renders the cytokine a good candidate for the therapy of solid tumors, particularly renal cell carcinoma. Although IL-15 is being currently used in clinical trials, the function of the cytokine on kidney's components has not been extensively studied; we thus investigated the role of IL-15 on normal and tumor renal epithelial cells. Herein, we analyzed the expression and the biological functions of IL-15 in normal renal proximal tubuli (RPTEC) and in their neoplastic counterparts, the renal clear cell carcinomas (RCC). This study shows that RPTEC express a functional heterotrimeric IL-15Rαβγc complex whose stimulation with physiologic concentrations of rhIL-15 is sufficient to inhibit epithelial mesenchymal transition (EMT) commitment preserving E-cadherin expression. Indeed, IL-15 is not only a survival factor for epithelial cells, but it can also preserve the renal epithelial phenotype through the γc-signaling pathway, demonstrating that the cytokine possess a wide range of action in epithelial homeostasis. In contrast, in RCC in vitro and in vivo studies reveal a defect in the expression of γc-receptor and JAK3 associated kinase, which strongly impacts IL-15 signaling. Indeed, in the absence of the γc/JAK3 couple we demonstrate the assembly of an unprecedented functional high affinity IL-15Rαβ heterodimer, that in response to physiologic concentrations of IL-15, triggers an unbalanced signal causing the down-regulation of the tumor suppressor gene E-cadherin, favoring RCC EMT process. Remarkably, the rescue of IL-15/γc-dependent signaling (STAT5), by co-transfecting γc and JAK3 in RCC, inhibits EMT reversion. In conclusion, these data highlight the central role of IL-15 and γc-receptor signaling in renal homeostasis through the control of E-cadherin expression and preservation of epithelial phenotype both in RPTEC (up-regulation) and RCC (down-regulation). 相似文献
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Hubert du Pontavice Didier Gascuel Gabriel Reygondeau Aurore Maureaud William W. L. Cheung 《Global Change Biology》2020,26(3):1306-1318
Sea water temperature affects all biological and ecological processes that ultimately impact ecosystem functioning. In this study, we examine the influence of temperature on global biomass transfers from marine secondary production to fish stocks. By combining fisheries catches in all coastal ocean areas and life‐history traits of exploited marine species, we provide global estimates of two trophic transfer parameters which determine biomass flows in coastal marine food web: the trophic transfer efficiency (TTE) and the biomass residence time (BRT) in the food web. We find that biomass transfers in tropical ecosystems are less efficient and faster than in areas with cooler waters. In contrast, biomass transfers through the food web became faster and more efficient between 1950 and 2010. Using simulated changes in sea water temperature from three Earth system models, we project that the mean TTE in coastal waters would decrease from 7.7% to 7.2% between 2010 and 2100 under the ‘no effective mitigation’ representative concentration pathway (RCP8.5), while BRT between trophic levels 2 and 4 is projected to decrease from 2.7 to 2.3 years on average. Beyond the global trends, we show that the TTEs and BRTs may vary substantially among ecosystem types and that the polar ecosystems may be the most impacted ecosystems. The detected and projected changes in mean TTE and BRT will undermine food web functioning. Our study provides quantitative understanding of temperature effects on trophodynamic of marine ecosystems under climate change. 相似文献
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Aurore Puymège Stéphane Bertin Sarah Chuzeville Gérard Guédon Sophie Payot 《Journal of bacteriology》2013,195(6):1142-1151
Putative integrative and conjugative elements (ICEs), i.e., genomic islands which could excise, self-transfer by conjugation, and integrate into the chromosome of the bacterial host strain, were previously identified by in silico analysis in the sequenced genomes of Streptococcus agalactiae (M. Brochet et al., J. Bacteriol. 190:6913–6917, 2008). We investigated here the mobility of the elements integrated into the 3′ end of a tRNALys gene. Three of the four putative ICEs tested were found to excise but only one (ICE_515_tRNALys) was found to transfer by conjugation not only to S. agalactiae strains but also to a Streptococcus pyogenes strain. Transfer was observed even if recipient cell already carries a related resident ICE or a genomic island flanked by attL and attR recombination sites but devoid of conjugation or recombination genes (CIs-Mobilizable Element [CIME]). The incoming ICE preferentially integrates into the 3′ end of the tRNALys gene (i.e., the attR site of the resident element), leading to a CIME-ICE structure. Transfer of the whole composite element CIME-ICE was obtained, showing that the CIME is mobilizable in cis by the ICE. Therefore, genomic islands carrying putative virulence genes but lacking the mobility gene can be mobilized by a related ICE after site-specific accretion. 相似文献
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Live animal movements are a major transmission route for the spread of infectious agents such as Mycobacterium bovis, the main agent of bovine Tuberculosis (bTB). France became officially bTB-free in 2001, but M. bovis is still circulating in the cattle population, with about a hundred of outbreaks per year, most located in a few geographic areas. The aim of this study was to analyse the role of cattle movements in bTB spread in France between 2005 and 2014, using social network analysis and logistic regression models. At a global scale, the trade network was studied to assess the association between several centrality measures and bTB infection though a case-control analysis. The bTB infection status was associated with a higher in-degree (odds-ratio [OR] = 2.4 [1.1–5.4]) and with a higher ingoing contact chain (OR = 2.2 [1.0–4.7]). At a more local scale, a second case-control analysis was conducted to estimate the relative importance of cattle movements and spatial neighbourhood. Only direct purchase from infected herds was shown to be associated with bTB infection (OR = 2.9 [1.7–5.2]), spatial proximity to infected herds being the predominant risk factor, with decreasing ORs when distance increases. Indeed, the population attributable fraction was 12% [5%–18%] for cattle movements and 73% [68%–78%] for spatial neighbourhood. Based on these results, networks of potential effective contacts between herds were built and analysed for the three major spoligotypes reported in France. In these networks, the links representing cattle movements were associated with higher edge betweenness than those representing the spatial proximity between infected herds. They were often links connecting distinct communities and sometimes distinct geographical areas. Therefore, although their role was quantitatively lower than the one of spatial neighbourhood, cattle movements appear to have been essential in the French bTB dynamics between 2005 and 2014. 相似文献