Beyond buttons: Explorations in creative storytelling

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Counteraction of HCV-induced oxidative stress concurs to establish chronic infection in liver cell cultures

Hepatitis C virus (HCV) is a blood-borne pathogen causing acute and chronic hepatitis. A significant number of people chronically infected with HCV develop cirrhosis and/or liver cancer. The pathophysiologic mechanisms of hepatocyte damage associated with chronic HCV infection are not fully understood yet, mainly due to the lack of an in vitro system able to recapitulate the stages of infection in vivo. Several studies underline that HCV virus replication depends on redox-sensitive cellular pathways; in addition, it is known that virus itself induces alterations of the cellular redox state. However, the exact interplay between HCV replication and oxidative stress has not been elucidated. In particular, the role of reduced glutathione (GSH) in HCV replication and infection is still not clear. We set up an in vitro system, based on low m.o.i. of Huh7.5 cell line with a HCV infectious clone (J6/JFH1), that reproduced the acute and persistent phases of HCV infection up to 76 days of culture. We demonstrated that the acute phase of HCV infection is characterized by the elevated levels of reactive oxygen species (ROS) associated in part with an increase of NADPH-oxidase transcripts and activity and a depletion of GSH accompanied by high rates of viral replication and apoptotic cell death. Conversely, the chronic phase is characterized by a reestablishment of reduced environment due to a decreased ROS production and increased GSH content in infected cells that might concur to the establishment of viral persistence. Treatment with the prooxidant auranofin of the persistently infected cultures induced the increase of viral RNA titer, suggesting that a prooxidant state could favor the reactivation of HCV viral replication that in turn caused cell damage and death. Our results suggest that targeting the redox-sensitive host-cells pathways essential for viral replication and/or persistence may represent a promising option for contrasting HCV infection

A few key theoretical issues of importance in modern molecular electrochemistry

International audienceThis opinion paper details three typical cases in which new theoretical concepts need to be implemented in molecular electrochemistry in order to rationalize experimental results obtained in nanoscale cells or performed in new electrolytic media such as RTILs

The long-time chronoamperometric current at an inlaid disk electrode

Existing analytical solutions for the long-time chronoamperometric current response at an inlaid disk electrode are restricted to diffusion-limited currents due to extreme polarisation or reversible kinetics at the electrode surface. In this article, we derive an approximate analytical solution for the long-time-dependent current when the kinetics of the redox reaction at the electrode surface are quasi-reversible and the diffusion coefficients of the oxidant and reductant are different. We also detail a novel method for calculating the steady-state current. We show that our new method encapsulates and extends the existing solutions, and agrees with numerically simulated currents. © 2012 Elsevier B.V. All rights reserved

Glutathione increase by the n-butanoyl glutathione derivative (GSH-C4) inhibits viral replication and induces a predominant Th1 immune profile in old mice infected with influenza virus

During aging, glutathione (GSH) content declines and the immune system undergoes a deficiency in the induction of Th1 response. Reduced secretion of Th1 cytokines, which is associated with GSH depletion, could weaken the host defenses against viral infections. We first evaluated the concentration of GSH and cysteine in organs of old mice; then, the effect of the administration of the N-butanoyl GSH derivative (GSH-C4) on the response of aged mice infected with influenza A PR8/H1N1 virus was studied through the determination of GSH concentration in organs, lung viral titer, IgA and IgG1/IgG2a production and Th1/Th2 cytokine profile. Old mice had lower GSH than young mice in organs. Also the gene expression of endoplasmic reticulum (ER) stress markers involved in GSH metabolism and folding of proteins, i.e. Nrf2 and PDI, was reduced. Following infection, GSH content remained low and neither infection nor GSH-C4 treatment affected Nrf2 expression. In contrast, PDI expression was upregulated during infection and appeared counterbalanced by GSH-C4. Moreover, the treatment with GSH-C4 increased GSH content in organs, reduced viral replication and induced a predominant Th1 response. In conclusion, GSH-C4 treatment could be used in the elderly to contrast influenza virus infection by inducing immune response, in particular the Th1 profile

Mathematical Modelling of Nitric Oxide Release Caused by Exocytosis and Determination of a Stellate Neuron Activity Function in Rat Brain

In this work we report the results of the mathematical modelling of NO◦ -release by neurons considering a series of Gaussian bursts, together with its transport in the brain by diffusion. Our analysis relies on the NO◦ -release from a neuron monitored before, during and after its patch-clamp stimulation as detected by an ultramicroelectrode introduced into a slice of living rat’s brain. The parameters of the neuron activity function have been obtained by numerical fitting of experimental data with simulated theoretical results. Within our initial hypothesis about the Gaussian decomposition of NO◦ -release that allowed drawing qualitative and quantitative conclusions about the considered neuron activity function. It is noted that since the activity function can be readily modified this signal processing may be adapted to the treatment of other and maybe more physiologically relevant hypotheses

Electron Transfer Catalysis of The Hydrogenolysis of Acyl Dicarbonyl Cyclopentadienyliron Complexes by Tributyltin Hydride

The conversion of acyl dicarbonyl cyclopentadienyliron compounds Cp(CO)2Fe(COR) into aldehydes is not straightforward. It is shown here, mainly from electrochemical results, that the hydrogenolysis of the metal acyl bond can be efficiently achieved by trialkytin hydrides under very mild conditions, according to a chain reaction process initiated by an electron transfer to the acyl complex. The expected aldehyde is formed together with the heterobinuclear iron-tin complex

Electron Transfer Catalysis of The Hydrogenolysis of Acyl Dicarbonyl Cyclopentadienyliron Complexes by Tributyltin Hydride

The conversion of acyl dicarbonyl cyclopentadienyliron compounds Cp(CO)2Fe(COR) into aldehydes is not straightforward. It is shown here, mainly from electrochemical results, that the hydrogenolysis of the metal acyl bond can be efficiently achieved by trialkytin hydrides under very mild conditions, according to a chain reaction process initiated by an electron transfer to the acyl complex. The expected aldehyde is formed together with the heterobinuclear iron-tin complex