Contribution of S6K1/MAPK signaling pathways in the response to oxidative stress: activation of RSK and MSK by hydrogen peroxide

Trobareu correccions de l'article a: http://dx.doi.org/10.1371/annotation/0b485bd9-b1b2-4c60-ab22-3ac5d271dc59Cells respond to different kind of stress through the coordinated activation of signaling pathways such as MAPK or p53. To find which molecular mechanisms are involved, we need to understand their cell adaptation. The ribosomal protein, S6 kinase 1 (S6K1), is a common downstream target of signaling by hormonal or nutritional stress. Here, we investigated the initial contribution of S6K1/MAPK signaling pathways in the cell response to oxidative stress produced by hydrogen peroxide (H2O2). To analyze S6K1 activation, we used the commercial anti-phospho-Thr389-S6K1 antibody most frequently mentioned in the bibliography. We found that this antibody detected an 80-90 kDa protein that was rapidly phosphorylated in response to H2O2 in several human cells. Unexpectedly, this phosphorylation was insensitive to both mTOR and PI3K inhibitors, and knock-down experiments showed that this protein was not S6K1. RSK and MSK proteins were candidate targets of this phosphorylation. We demonstrated that H2O2 stimulated phosphorylation of RSK and MSK kinases at residues that are homologous to Thr389 in S6K1. This phosphorylation required the activity of either p38 or ERK MAP kinases. Kinase assays showed activation of RSK and MSK by H2O2. Experiments with mouse embryonic fibroblasts from p38 animals" knockout confirmed these observations. Altogether, these findings show that the S6K1 signaling pathway is not activated under these conditions, clarify previous observations probably misinterpreted by non-specific detection of proteins RSK and MSK by the anti-phospho-Thr389-S6K1 antibody, and demonstrate the specific activation of MAPK signaling pathways through ERK/p38/RSK/MSK by H2O2

Insights into the Interconnection of the Electrodes and Electrolyte Species in Lithium–Sulfur Batteries Using Spatially Resolved <i>Operando</i> X‑ray Absorption Spectroscopy and X‑ray Fluorescence Mapping

The lithium–sulfur (Li–S) battery chemistry has attracted great interest in the last decade because of its outstanding theoretical gravimetric energy density compared to the state-of-the-art lithium-ion battery technology. However, practically achieved energy density is still far below the theoretical value, even in small laboratory-scale batteries. The problems seen in laboratory-scale batteries will inevitably increase during scale-up to large application-format cells, as the electrolyte to active material (AM) ratio will need to be reduced in these cells to achieve high gravimetric energy density on cell-level basis. Our study shows the unique possibility of X-ray fluorescence (XRF) mapping to visualize the spatial distribution of the AM inside operating Li–S batteries in all cell components [working electrode (WE), separator, and counter electrode (CE)]. Through a combination of <i>operando</i> XRF mapping and X-ray absorption spectroscopy, we show that unless self-discharge is efficiently prevented, the AM can completely dissolve and distribute throughout the cell stack within a time frame of 2 h, causing poor capacity retention. Using a polysulfide diffusion barrier between the WE and the CE, we successfully suppress these processes and thereby establish a tool for examining the sealed cathode electrode compartment, enabling sophisticated studies for future optimization of the WE processes

Naringin processing using GAS antisolvent technique and in vivo applications

Naringin is a flavanone glycoside with various pharmacological activities, including neuroprotective and antipsychotic-like effects. However, it has poor solubility in water and oral bioavailability. This study aims to investigate the influence of gas antisolvent operational parameters (pressure, temperature, antisolvent flow rate, and initial concentration of solute) on particle diameter using a 24 Central Composite Design. Naringin particles produced were analyzed for dissolution rate and then applied to ketamine-induced hyperlocomotion in mice. Results for run with C= 5 mg•mL 1, P = 12 MPa, T = 308 K, CO2 flow rate= 15 mL.min 1 showed amorphous particles while run with C= 10 mg.mL 1, P = 8 MPa, T = 318 K, CO2 flow rate= 15 mL.min 1 kept the crystalline structure of naringin. In vivo assays showed promising results for run with crystalline particles, probably due to the increased bioavailability, and amorphous particles had similar effects to commercial naringin because of the recrystallization when in contact with the aqueous medium