12 research outputs found
Differential relevance of NF-κB and JNK in the pathophysiology of hemorrhage/resususcitation-induced liver injury after chronic ethanol feeding
No full textBackground: Chronic ethanol (EtOH) abuse worsens pathophysiological derangements after hemorrhagic shock and resuscitation (H/R) that induce hepatic injury and strong inflammatory changes via JNK and NF-κB activation. Inhibiting JNK with a cell-penetrating, protease-resistant peptide D-JNKI-1 after H/R in mice with healthy livers ameliorated these effects. Here, we studied if JNK inhibition by D-JNKI-1 in chronically EtOH-fed mice after hemorrhagic shock prior to the onset of resuscitation also confers protection.
Methods: Male mice were fed a Lieber-DeCarli diet containing EtOH or an isocaloric control (ctrl) diet for 4 weeks. Animals were hemorrhaged for 90 min (32 ± 2 mm Hg) and randomly received either D-JNKI-1 (11 mg/kg, intraperitoneally, i. p.) or sterile saline as vehicle (veh) immediately before the onset of resuscitation. Sham animals underwent surgical procedures without H/R and were either D-JNKI-1 or veh treated. Two hours after resuscitation, blood samples and liver tissue were harvested.
Results: H/R induced hepatic injury with increased systemic interleukin (IL)-6 levels, and enhanced local gene expression of NF-κB-controlled genes such as intercellular adhesion molecule (ICAM)-1 and matrix metallopeptidase (MMP)9. c-Jun and NF-κB phosphorylation were increased after H/R. These effects were further increased in EtOH-fed mice after H/R. D-JNKI-1 application inhibited the proinflammatory changes and reduced significantly hepatic injury after H/R in ctrl-fed mice. Moreover, D-JNKI-1 reduces in ctrl-fed mice the H/R-induced c-Jun and NF-κB phosphorylation. However, in chronically EtOH-fed mice, JNK inhibition did not prevent the H/R-induced hepatic damage and proinflammatory changes nor c-Jun and NF-κB phosphorylation after H/R.
Conclusions: These results indicate, that JNK inhibition is protective only in not pre-harmed liver after H/R. In contrast, the pronounced H/R-induced liver damage in mice being chronically fed with ethanol cannot be prevented by JNK inhibition after H/R and seems to be under the control of NF-κB
Chronische Alkoholbelastung geht mit erhöhter Leberschädigung und Mortalität nach hämorrhagischem Schock und anschließender Reperfusion (H/R) in transgenen cis-NF-kappaBEGFP Reportermäusen einher
No full textLa croissance économique turque entre 1980 et 1995 s’explique-t-elle par les dépenses publiques, le travail informel ou le capital humain ?.
No full textCet article tente d’identifier empiriquement les déterminants de la croissance turque à partir de données annuelles de 1980 à 1995. L’analyse empirique s’appuie sur un modèle théorique "canonique" de croissance qui nous sert à élaborer des résultats empiriques. Il nous invite à construire un résidu de Solow, à partir des parts des rémunérations des facteurs, dont on cherche ensuite les déterminants empiriquement. Après avoir effectué une première sélection de variables économiques, dont les résultats ne sont pas présentés ici, deux modèles concurrents peuvent expliquer le résidu de Solow. Un premier modèle dans lequel les dépenses publiques joueraient un rôle essentiel et un second modèle dans lequel le travail informel (approximé par le taux de chômage) et le capital humain (approximé par des variables d’éducation) joueraient, indépendamment, un rôle important, sont acceptables a priori en se basant sur des critères statistiques standards. Une comparaison des deux modèles à partir des tests de modèles, conclut cependant en faveur de la première explication. Les résultats doivent être néanmoins considérés avec beaucoup de précautions.Dépenses publiques; résidu de Solow; Croissance économique;
Activation of NF-κB after chronic ethanol intake and haemorrhagic shock/resuscitation in mice: NF-κB after chronic ethanol and H/R
No full textChronic ethanol abuse and haemorrhagic shock are major causes of global mortality and, separately, induce profound hepato- and immune-toxic effects via activation of NF-κB. Here, we assessed the effects of chronic ethanol intake upon the pathophysiological derangements after haemorrhagic shock with subsequent resuscitation (H/R), with particular attention to the contribution of NF-κB
A novel N-ethyl-N-nitrosourea-induced mutation in phospholipase Cγ2 causes inflammatory arthritis, metabolic defects, and male infertility in vitro in a murine model
No full textA novel N-ethyl-N-nitrosourea-induced mutation in phospholipase C?2 causes inflammatory arthritis, metabolic defects, and male infertility in vitro in a murine model.
No full textIt is difficult to identify a single causative factor for inflammatory arthritis because of the multifactorial nature of the disease. This study was undertaken to dissect the molecular complexity of systemic inflammatory disease, utilizing a combined approach of mutagenesis and systematic phenotype screening in a murine model.In a large-scale N-ethyl-N-nitrosourea mutagenesis project, the Ali14 mutant mouse strain was established because of dominant inheritance of spontaneous swelling and inflammation of the hind paws. Genetic mapping and subsequent candidate gene sequencing were conducted to find the causative gene, and systematic phenotyping of Ali14/+ mice was performed in the German Mouse Clinic.A novel missense mutation in the phospholipase C?2 gene (Plcg2) was identified in Ali14/+ mice. Because of the hyperreactive external entry of calcium observed in cultured B cells and other in vitro experiments, the Ali14 mutation is thought to be a novel gain-of-function allele of Plcg2. Findings from systematic screening of Ali14/+ mice demonstrated various phenotypic changes: an abnormally high T cell:B cell ratio, up-regulation of Ig, alterations in body composition, and a reduction in cholesterol and triglyceride levels in peripheral blood. In addition, spermatozoa from Ali14/+ mice failed to fertilize eggs in vitro, despite the normal fertility of the Ali14/+ male mice in vivo.These results suggest that the Plcg2-mediated pathways play a crucial role in various metabolic and sperm functions, in addition to initiating and maintaining the immune system. These findings may indicate the importance of the Ali14/+ mouse strain as a model for systemic inflammatory diseases and inflammation-related metabolic changes in humans
A Novel N-ethyl-N-nitrosourea-Induced Mutation in Phospholipase C gamma 2 Causes Inflammatory Arthritis, Metabolic Defects, and Male Infertility In Vitro in a Murine Model
No full textObjective. It is difficult to identify a single causative factor for inflammatory arthritis because of the multifactorial nature of the disease. This study was undertaken to dissect the molecular complexity of systemic inflammatory disease, utilizing a combined approach of mutagenesis and systematic phenotype screening in a murine model. Methods. In a large-scale N-ethyl-N-nitrosourea mutagenesis project, the Ali14 mutant mouse strain was established because of dominant inheritance of spontaneous swelling and inflammation of the hind paws. Genetic mapping and subsequent candidate gene sequencing were conducted to find the causative gene, and systematic phenotyping of Ali14/+ mice was performed in the German Mouse Clinic. Results. A novel missense mutation in the phospholipase C gamma 2 gene (Plcg2) was identified in Ali14/+ mice. Because of the hyperreactive external entry of calcium observed in cultured B cells and other in vitro experiments, the Ali14 mutation is thought to be a novel gain-of-function allele of Plcg2. Findings from systematic screening of Ali14/+ mice demonstrated various phenotypic changes: an abnormally high T cell: B cel
A novel <em>N</em>-ethyl-<em>N</em>-nitrosourea-induced mutation in <em>phospholipase Cγ2</em> causes inflammatory arthritis, metabolic defects, and male infertility <em>in vitro</em> in a murine model.
No full textOBJECTIVE: It is difficult to identify a single causative factor for inflammatory arthritis because of the multifactorial nature of the disease. This study was undertaken to dissect the molecular complexity of systemic inflammatory disease, utilizing a combined approach of mutagenesis and systematic phenotype screening in a murine model. METHODS: In a large-scale N-ethyl-N-nitrosourea mutagenesis project, the Ali14 mutant mouse strain was established because of dominant inheritance of spontaneous swelling and inflammation of the hind paws. Genetic mapping and subsequent candidate gene sequencing were conducted to find the causative gene, and systematic phenotyping of Ali14/+ mice was performed in the German Mouse Clinic. RESULTS: A novel missense mutation in the phospholipase Cγ2 gene (Plcg2) was identified in Ali14/+ mice. Because of the hyperreactive external entry of calcium observed in cultured B cells and other in vitro experiments, the Ali14 mutation is thought to be a novel gain-of-function allele of Plcg2. Findings from systematic screening of Ali14/+ mice demonstrated various phenotypic changes: an abnormally high T cell:B cell ratio, up-regulation of Ig, alterations in body composition, and a reduction in cholesterol and triglyceride levels in peripheral blood. In addition, spermatozoa from Ali14/+ mice failed to fertilize eggs in vitro, despite the normal fertility of the Ali14/+ male mice in vivo. CONCLUSION: These results suggest that the Plcg2-mediated pathways play a crucial role in various metabolic and sperm functions, in addition to initiating and maintaining the immune system. These findings may indicate the importance of the Ali14/+ mouse strain as a model for systemic inflammatory diseases and inflammation-related metabolic changes in humans
Stratification strength and light climate explain variation in chlorophyll a at the continental scale in a European multilake survey in a heatwave summer
No full textTo determine the drivers of phytoplankton biomass, we collected standardized morphometric, physical, and
biological data in 230 lakes across the Mediterranean, Continental, and Boreal climatic zones of the European
continent. Multilinear regression models tested on this snapshot of mostly eutrophic lakes (median total phosphorus
[TP] = 0.06 and total nitrogen [TN] = 0.7 mg L-1), and its subsets (2 depth types and 3 climatic zones),
show that light climate and stratification strength were the most significant explanatory variables for chlorophyll
a (Chl a) variance. TN was a significant predictor for phytoplankton biomass for shallow and continental
lakes, while TP never appeared as an explanatory variable, suggesting that under high TP, light, which partially
controls stratification strength, becomes limiting for phytoplankton development. Mediterranean lakes were the
warmest yet most weakly stratified and had significantly less Chl a than Boreal lakes, where the temperature
anomaly from the long-term average, during a summer heatwave was the highest (+4 C) and showed a significant,
exponential relationship with stratification strength. This European survey represents a summer snapshot
of phytoplankton biomass and its drivers, and lends support that light and stratification metrics, which are both
affected by climate change, are better predictors for phytoplankton biomass in nutrient-rich lakes than nutrient
concentrations and surface temperature.The authors acknowledge COST Action ES 1105 “CYANOCOST – Cyanobacterial blooms and toxins in water resources: Occurrence impacts and management” and COST Action Global Change Biology ES 1201 NETLAKE – Networking Lake Observatories in Europe” for contributing to this study through networking and knowledge sharing with European experts in the field. We acknowledge the members of the Global Lake Ecological Observatory Network (GLEON) for their collaborative spirit and enthusiasm that inspired the grassroots effort of the EMLS. E.M. was supported by a grant from the Swiss State Secretariat for Education, Research and Innovation to Bas Ibelings and by supplementary funding from University of Geneva. We thank Wendy Beekman for the nutrient analysis. We thank Pieter Slot for assisting with the pigment analysis. We thank Dr. Ian Jones for valuable feedback on an earlier version of the manuscript. We thank the Leibniz Institute of Freshwater Ecology and the Aquatic Microbial Ecology Group for logistic and technical support of J. Fonvielle and H.‐P. Grossart, and the Leibniz Association for financial support. H.P. was supported by the US National Science Foundation (1840715, 1831096). A.C.’s work was funded by the Spanish Agencia Estatal de Investigacion and EU funds through the project CLIMAWET (CGL2015‐69557‐R). The collection of data for Lough Erne and Lough Neagh were funded by the Department of Agriculture, Environment and Rural Affairs, Northern Ireland. We are grateful to Kristiina Vuorio from the Freshwater Centre of the Finnish Environment institute for her help in organizing, collecting and analysing samples by the University of Jyväskylä and to Gerald Dörflinger from the Water Development Department of Cyprus for his assistance with the sampling in Cyprus and for granting the CUT team permission to use WDD’s equipment. Finally, we would like to thank the numerous other assistants that helped realizing each local survey. Open access funding provided by Universite de Geneve.info:eu-repo/semantics/publishedVersio
