Diabetic β-Cells Can Achieve Self-Protection against Oxidative Stress through an Adaptive Up-Regulation of Their Antioxidant Defenses

Background Oxidative stress (OS), through excessive and/or chronic reactive oxygen species (ROS), is a mediator of diabetes-related damages in various tissues including pancreatic β-cells. Here, we have evaluated islet OS status and β-cell response to ROS using the GK/Par rat as a model of type 2 diabetes. Methodology/Principal Findings Localization of OS markers was performed on whole pancreases. Using islets isolated from 7-day-old or 2.5-month-old male GK/Par and Wistar control rats, 1) gene expression was analyzed by qRT-PCR; 2) insulin secretion rate was measured; 3) ROS accumulation and mitochondrial polarization were assessed by fluorescence methods; 4) antioxidant contents were quantified by HPLC. After diabetes onset, OS markers targeted mostly peri-islet vascular and inflammatory areas, and not islet cells. GK/Par islets revealed in fact protected against OS, because they maintained basal ROS accumulation similar or even lower than Wistar islets. Remarkably, GK/Par insulin secretion also exhibited strong resistance to the toxic effect of exogenous H2O2 or endogenous ROS exposure. Such adaptation was associated to both high glutathione content and overexpression (mRNA and/or protein levels) of a large set of genes encoding antioxidant proteins as well as UCP2. Finally, we showed that such a phenotype was not innate but spontaneously acquired after diabetes onset, as the result of an adaptive response to the diabetic environment. Conclusions The GK/Par model illustrates the effectiveness of adaptive response to OS by beta-cells to achieve self-tolerance. It remains to be determined to what extend such islet antioxidant defenses upregulation might contribute to GK/Par beta-cell secretory dysfunction

HIV-1 Protease and Reverse Transcriptase Control the Architecture of Their Nucleocapsid Partner

The HIV-1 nucleocapsid is formed during protease (PR)-directed viral maturation, and is transformed into pre-integration complexes following reverse transcription in the cytoplasm of the infected cell. Here, we report a detailed transmission electron microscopy analysis of the impact of HIV-1 PR and reverse transcriptase (RT) on nucleocapsid plasticity, using in vitro reconstitutions. After binding to nucleic acids, NCp15, a proteolytic intermediate of nucleocapsid protein (NC), was processed at its C-terminus by PR, yielding premature NC (NCp9) followed by mature NC (NCp7), through the consecutive removal of p6 and p1. This allowed NC co-aggregation with its single-stranded nucleic-acid substrate. Examination of these co-aggregates for the ability of RT to catalyse reverse transcription showed an effective synthesis of double-stranded DNA that, remarkably, escaped from the aggregates more efficiently with NCp7 than with NCp9. These data offer a compelling explanation for results from previous virological studies that focused on i) Gag processing leading to nucleocapsid condensation, and ii) the disappearance of NCp7 from the HIV-1 pre-integration complexes. We propose that HIV-1 PR and RT, by controlling the nucleocapsid architecture during the steps of condensation and dismantling, engage in a successive nucleoprotein-remodelling process that spatiotemporally coordinates the pre-integration steps of HIV-1. Finally we suggest that nucleoprotein remodelling mechanisms are common features developed by mobile genetic elements to ensure successful replication

Islet Endothelial Activation and Oxidative Stress Gene Expression Is Reduced by IL-1Ra Treatment in the Type 2 Diabetic GK Rat

Inflammation followed by fibrosis is a component of islet dysfunction in both rodent and human type 2 diabetes. Because islet inflammation may originate from endothelial cells, we assessed the expression of selected genes involved in endothelial cell activation in islets from a spontaneous model of type 2 diabetes, the Goto-Kakizaki (GK) rat. We also examined islet endotheliuml/oxidative stress (OS)/inflammation-related gene expression, islet vascularization and fibrosis after treatment with the interleukin-1 (IL-1) receptor antagonist (IL-1Ra)

Influence of the texturing quality consecutive to Abrasive Water Jet machining on the adhesive properties in mode I of 3D woven composite assemblies

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Influence of the damage generated by abrasive water jet texturing on the tensile static and fatigue behaviour of 3D woven composite in the context of repair

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Parallel implementation of a relativistic semi-Lagrangian Vlasov–Maxwell solver

We describe the parallel implementation of a semi-Lagrangian relativistic VLasov ElectroMagnetic (VLEM) code for the numerical investigation of the dynamics of charged particle distribution in their self-consistent electromagnetic fields. This paper introduces the numerical solution of the Vlasov–Maxwell system in two spatial dimensions, and two or three momentum dimensions. Accuracy, stability, efficiency properties and the implementation of a new algorithm of charge conservation when solving Maxwell equations are discussed. The performances of the code are tested by studying the evolution of Weibel-type instabilities in the relativistic regime. Application to the coupling between Current Filamentation (CFI) and Two-Stream (TSI) instabilities is presented showing the importance of pair-wise vortex merging scenario in the saturation mechanism

Organ donation after out-of-hospital cardiac arrest: a population-based study of data from the Paris Sudden Death Expertise Center

International audienceAbstract Background Organ shortage is a major public health issue, and patients who die after out-of-hospital cardiac arrest (OHCA) could be a valuable source of organs. Here, our objective was to identify factors associated with organ donation after brain death complicating OHCA, in unselected patients entered into a comprehensive real-life registry covering a well-defined geographic area. Methods We prospectively analyzed consecutive adults with OHCA who were successfully resuscitated, but died in intensive care units in the Paris region in 2011–2018. The primary outcome was organ donation after brain death. Independent risk factors were identified using logistic regression analysis. One-year graft survival was assessed using Cox and log-rank tests. Results Of the 3061 included patients, 136 (4.4%) became organ donors after brain death, i.e., 28% of the patients with brain death. An interaction between admission pH and post-resuscitation shock was identified. By multivariate analysis, in patients with post-resuscitation shock, factors associated with organ donation were neurological cause of OHCA (odds ratio [OR], 14.5 [7.6–27.4], P < 0.001), higher pH (OR/0.1 increase, 1.3 [1.1–1.6], P < 0.001); older age was negatively associated with donation (OR/10-year increase, 0.7 [0.6–0.8], P < 0.001). In patients without post-resuscitation shock, the factor associated with donation was neurological cause of OHCA (OR, 6.9 [3.0–15.9], P < 0.001); higher pH (OR/0.1 increase, 0.8 [0.7–1.0], P = 0.04) and OHCA at home (OR, 0.4 [0.2–0.7], P = 0.006) were negatively associated with organ donation. One-year graft survival did not differ according to Utstein characteristics of the donor. Conclusions 4% of patients who died in ICU after OHCA led to organ donation. Patients with OHCA constitute a valuable source of donated organs, and special attention should be paid to young patients with OHCA of neurological cause

Sudden Cardiac Arrest in Young Women

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