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101.
Eva A.V. Moelants Anneleen Mortier Karolien Grauwen Isabelle Ronsse Jo Van Damme Paul Proost 《Cytokine》2013,61(1):161-167
Citrullination, a posttranslational modification (PTM) recently discovered on inflammatory chemokines such as interleukin-8 (IL-8/CXCL8) and interferon-γ-inducible protein-10 (IP-10/CXCL10), seriously influences their biological activity. Citrullination or the deimination of arginine to citrulline is dependent on peptidylarginine deiminases (PADs) and has been linked to autoimmune diseases such as multiple sclerosis (MS) and rheumatoid arthritis (RA). Chemokines are to date the first identified PAD substrates with receptor-mediated biological activity. We investigated whether cytokines that play a crucial role in RA, like interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α), may be citrullinated by PAD and whether such a PTM influences the biological activity of these cytokines. IL-1β and TNF-α were first incubated with PAD in vitro and the occurrence of citrullination was examined by Edman degradation and a recently developed detection method for citrullinated proteins. Both techniques confirmed that human TNF-α, but not IL-1β, was citrullinated by PAD. Citrullination of TNF-α reduced its potency to stimulate chemokine production in vitro on human primary fibroblasts. Concentrations of the inflammatory chemokines CXCL8, CXCL10 and monocyte chemotactic protein-1 (MCP-1/CCL2) were significantly lower in supernatants of fibroblasts induced with citrullinated TNF-α compared to unmodified TNF-α. However, upon citrullination TNF-α retained its capacity to induce apoptosis/necrosis of mononuclear cells, its binding potency to Infliximab and its ability to recruit neutrophils to the peritoneal cavity of mice. 相似文献
102.
The aim of this study was to identify groups of travel mode users, based on objective risk estimates, and examine overall differences in demographic characteristics, perceived risk, worry, perceived control when using travel modes, trust in authorities, and safety motivation. The results were based on a self-completion questionnaire survey about risk perception and travel mode use in a representative sample of the Norwegian public (n = 1864). In addition, aggregate-level data on accidents in transport were used to establish the “objective risk” for various travel modes. The respondents were split into two clusters. The first cluster was characterized by a relatively greater objective risk for accidents related to public travel modes as well as related to being a pedestrian, while the second cluster was characterized by a higher risk level related to motorized private modes of transportation. There was a significant overall difference in the risk estimates among the members of the two clusters. There was also an overall difference in risk perception and other risk-related judgments due to which risk estimate-based cluster the respondents belonged. Associations between objective risk estimates, perceived risk, and worry are discussed in relation to cluster differences in objective risk. 相似文献
103.
Isabelle Barber-Peoc'h Muthiah Manoharan P. Dan Cook 《Nucleosides, nucleotides & nucleic acids》2013,32(7-9):1407-1410
Abstract The drug properties of antisense and antigene oligonucleotides can he enhanced by strategic positioning of ligands capable of ameliorating these properties.1,2 Certain ligands may improve the cellular delivery of oligomers and increase their affinity for the target gene and resistance to nucleases. The 2′-O-position is an attractive modification site.3 Oligonucleotides possessing the 2′-O-akyl modifications exhibit higher chemical stability under depurination conditions, higher stability to enzymatic cleavage by both endo- and exonucleases, and increased affinity for target mRNA. In addition, they form highly stable triple helices. Thus they promise to be versatile compounds in controlling gene expression by antisense and antigene technologies. 相似文献
104.
105.
Mélanie Aye Carole Di Giorgio Isabelle Berque-Bestel Ahissan Aime Benoit P. Pichon Yves Jammes Philippe Barthélémy Michel De Méo 《Mutation Research - Genetic Toxicology and Environmental Mutagenesis》2013,750(1-2):129-138
We proposed to evaluate the genotoxicity and mutagenicity of a new quantum dots (QDs) nanoplatform (QDsN), consisting of CdSe/ZnS core–shell QDs encapsulated by a natural fusogenic lipid (1,2-di-oleoyl-sn-glycero-3-phosphocholine (DOPC)) and functionalized by a nucleolipid N-[5′-(2′,3′-di-oleoyl) uridine]-N′,N′,N′-trimethylammoniumtosylate (DOTAU). This QDs nanoplatform may represent a new therapeutic tool for the diagnosis and treatment of human cancers. The genotoxic, mutagenic and clastogenic effects of QDsN were compared to those of cadmium chloride (CdCl2). Three assays were used: (1) the Salmonella/microsome assay with four tester strains, (2) the comet assay and (3) the micronucleus test on CHO cells. The contribution of simulated sunlight was studied in the three assays while oxidative events were only explored in the comet assay in aliquots pretreated with the antioxidant l-ergothioneine. We found that QDsN could enter CHO-K1 cells and accumulate in cytoplasmic vesicles. It was not mutagenic in the Salmonella/mutagenicity test whereas CdCl2 was weakly positive. In the dark, both the QDsN and CdCl2 similarly induced dose-dependent increases in single-strand breaks and micronuclei. Exposure to simulated sunlight significantly potentiated the genotoxic activities of both QDsN and CdCl2, but did not significantly increase micronucleus frequencies. l-Ergothioneine significantly reduced but did not completely suppress the DNA-damaging activity of QDsN and CdCl2. The present results clearly point to the genotoxic properties and the risk of long-term adverse effects of such a nanoplatform if used for human anticancer therapy and diagnosis in the future. 相似文献
106.
Julie Blaising Pierre L. Lévy Claire Gondeau Capucine Phelip Mihayl Varbanov Elodie Teissier Florence Ruggiero Stephen J. Polyak Nicholas H. Oberlies Tijana Ivanovic Eve‐Isabelle Pécheur 《Cellular microbiology》2013,15(11):1866-1882
Hepatitis C virus (HCV) is a global health concern infecting 170 million people worldwide. Previous studies indicate that the extract from milk thistle known as silymarin and its main component silibinin inhibit HCV infection. Here we investigated the mechanism of anti‐HCV action ofsilymarin‐derived compounds at the molecular level. By using live‐cell confocal imaging, single particle tracking, transmission electron microscopy and biochemical approaches on HCV‐infected human hepatoma cells and primary hepatocytes, we show that silibinin potently inhibits HCV infection and hinders HCV entry by slowing down trafficking through clathrin‐coated pits and vesicles. Detailed analyses revealed that silibinin altered the formation of both clathrin‐coated pits and vesicles in cells and caused abnormal uptake and trafficking of transferrin, a well‐known cargo of the clathrin endocytic pathway. Silibinin also inhibited infection by other viruses that enter cells by clathrin‐mediated endocytosis including reovirus, vesicular stomatitis and influenza viruses. Our study demonstrates that silibinin inhibits HCV early steps of infection by affecting endosomal trafficking of virions. It provides new insights into the molecular mechanisms of action of silibinin against HCV entry and also suggests that silibinin is a potential broad‐spectrum antiviral therapy. 相似文献
107.
Mahban Irandoust Julian Alvarez Zarate Isabelle Hubeek Ellen M. van Beek Karin Schornagel Aart J. F. Broekhuizen Mercan Akyuz Arjan A. van de Loosdrecht Ruud Delwel Peter J. Valk Edwin Sonneveld Pamela Kearns Ursula Creutzig Dirk Reinhardt Eveline S. J. M. de Bont Eva A. Coenen Marry M. van den Heuvel-Eibrink C. Michel Zwaan Gertjan J. L. Kaspers Jacqueline Cloos Timo K. van den Berg 《PloS one》2013,8(1)
Background
Recent studies show the importance of interactions between CD47 expressed on acute myeloid leukemia (AML) cells and the inhibitory immunoreceptor, signal regulatory protein-alpha (SIRPα) on macrophages. Although AML cells express SIRPα, its function has not been investigated in these cells. In this study we aimed to determine the role of the SIRPα in acute myeloid leukemia.Design and Methods
We analyzed the expression of SIRPα, both on mRNA and protein level in AML patients and we further investigated whether the expression of SIRPα on two low SIRPα expressing AML cell lines could be upregulated upon differentiation of the cells. We determined the effect of chimeric SIRPα expression on tumor cell growth and programmed cell death by its triggering with an agonistic antibody in these cells. Moreover, we examined the efficacy of agonistic antibody in combination with established antileukemic drugs.Results
By microarray analysis of an extensive cohort of primary AML samples, we demonstrated that SIRPα is differentially expressed in AML subgroups and its expression level is dependent on differentiation stage, with high levels in FAB M4/M5 AML and low levels in FAB M0–M3. Interestingly, AML patients with high SIRPα expression had a poor prognosis. Our results also showed that SIRPα is upregulated upon differentiation of NB4 and Kasumi cells. In addition, triggering of SIRPα with an agonistic antibody in the cells stably expressing chimeric SIRPα, led to inhibition of growth and induction of programmed cell death. Finally, the SIRPα-derived signaling synergized with the activity of established antileukemic drugs.Conclusions
Our data indicate that triggering of SIRPα has antileukemic effect and may function as a potential therapeutic target in AML. 相似文献108.
Agathe Hess Lianchun Yu Isabelle Klein Marine De Mazancourt Gilles Jebrak Hervé Mal Olivier Brugière Michel Fournier Maurice Courbage Gaelle Dauriat Elisabeth Schouman-Clayes Christine Clerici Laurence Mangin 《PloS one》2013,8(10)
Breathing is maintained and controlled by a network of automatic neurons in the brainstem that generate respiratory rhythm and receive regulatory inputs. Breathing complexity therefore arises from respiratory central pattern generators modulated by peripheral and supra-spinal inputs. Very little is known on the brainstem neural substrates underlying breathing complexity in humans. We used both experimental and theoretical approaches to decipher these mechanisms in healthy humans and patients with chronic obstructive pulmonary disease (COPD). COPD is the most frequent chronic lung disease in the general population mainly due to tobacco smoke. In patients, airflow obstruction associated with hyperinflation and respiratory muscles weakness are key factors contributing to load-capacity imbalance and hence increased respiratory drive. Unexpectedly, we found that the patients breathed with a higher level of complexity during inspiration and expiration than controls. Using functional magnetic resonance imaging (fMRI), we scanned the brain of the participants to analyze the activity of two small regions involved in respiratory rhythmogenesis, the rostral ventro-lateral (VL) medulla (pre-Bötzinger complex) and the caudal VL pons (parafacial group). fMRI revealed in controls higher activity of the VL medulla suggesting active inspiration, while in patients higher activity of the VL pons suggesting active expiration. COPD patients reactivate the parafacial to sustain ventilation. These findings may be involved in the onset of respiratory failure when the neural network becomes overwhelmed by respiratory overload We show that central neural activity correlates with airflow complexity in healthy subjects and COPD patients, at rest and during inspiratory loading. We finally used a theoretical approach of respiratory rhythmogenesis that reproduces the kernel activity of neurons involved in the automatic breathing. The model reveals how a chaotic activity in neurons can contribute to chaos in airflow and reproduces key experimental fMRI findings. 相似文献
109.
Céline Hauzy Grégoire Nadin Elsa Canard Isabelle Gounand Nicolas Mouquet Bo Ebenman 《PloS one》2013,8(12)
Resource enrichment can potentially destabilize predator-prey dynamics. This phenomenon historically referred as the "paradox of enrichment" has mostly been explored in spatially homogenous environments. However, many predator-prey communities exchange organisms within spatially heterogeneous networks called metacommunities. This heterogeneity can result from uneven distribution of resources among communities and thus can lead to the spreading of local enrichment within metacommunities. Here, we adapted the original Rosenzweig-MacArthur predator-prey model, built to study the paradox of enrichment, to investigate the effect of regional enrichment and of its spatial distribution on predator-prey dynamics in metacommunities. We found that the potential for destabilization was depending on the connectivity among communities and the spatial distribution of enrichment. In one hand, we found that at low dispersal regional enrichment led to the destabilization of predator-prey dynamics. This destabilizing effect was more pronounced when the enrichment was uneven among communities. In the other hand, we found that high dispersal could stabilize the predator-prey dynamics when the enrichment was spatially heterogeneous. Our results illustrate that the destabilizing effect of enrichment can be dampened when the spatial scale of resource enrichment is lower than that of organismss movements (heterogeneous enrichment). From a conservation perspective, our results illustrate that spatial heterogeneity could decrease the regional extinction risk of species involved in specialized trophic interactions. From the perspective of biological control, our results show that the heterogeneous distribution of pest resource could favor or dampen outbreaks of pests and of their natural enemies, depending on the spatial scale of heterogeneity. 相似文献
110.
Karita Negandhi Isabelle Laurion Michael J. Whiticar Pierre E. Galand Xiaomei Xu Connie Lovejoy 《PloS one》2013,8(11)
Thawing permafrost in the Canadian Arctic tundra leads to peat erosion and slumping in narrow and shallow runnel ponds that surround more commonly studied polygonal ponds. Here we compared the methane production between runnel and polygonal ponds using stable isotope ratios, 14C signatures, and investigated potential methanogenic communities through high-throughput sequencing archaeal 16S rRNA genes. We found that runnel ponds had significantly higher methane and carbon dioxide emissions, produced from a slightly larger fraction of old carbon, compared to polygonal ponds. The methane stable isotopic signature indicated production through acetoclastic methanogenesis, but gene signatures from acetoclastic and hydrogenotrophic methanogenic Archaea were detected in both polygonal and runnel ponds. We conclude that runnel ponds represent a source of methane from potentially older C, and that they contain methanogenic communities able to use diverse sources of carbon, increasing the risk of augmented methane release under a warmer climate. 相似文献