SGK1 mutations in DLBCL generate hyperstable protein neoisoforms that promote AKT independence.

Serum and glucocorticoid-regulated kinase 1 (SGK1) is one of the most frequently mutated genes in diffuse large B-cell lymphoma (DLBCL). However, little is known about its function or the consequence of its mutation. The frequent finding of truncating mutations has led to the widespread assumption that these represent loss-of-function variants and, accordingly, that SGK1 must act as a tumor suppressor. In this study, instead, the most common SGK1 mutations led to production of aberrantly spliced messenger RNA neoisoforms in which translation is initiated from downstream methionines. The resulting N-terminal truncated protein isoforms showed increased expression related to the exclusion of an N-terminal degradation domain. However, they retained a functional kinase domain, the overexpression of which rendered cells resistant to AKT inhibition, in part because of increased phosphorylation of GSK3B. These findings challenge the prevailing assumption that SGK1 is a tumor-suppressor gene in DLBCL and provide the impetus to explore further the pharmacological inhibition of SGK1 as a therapeutic strategy for DLBCL.

Insights into the toxicity of iron oxides nanoparticles in land snails.

The use of manufactured nanoparticles (NPs) is spreading rapidly across technology and medicine fields, posing concerns about their consequence on ecosystems and human health. The present study aims to assess the biological responses triggered by iron oxide NPs (IONPs) and iron oxide NPs incorporated into zeolite (IONPZ) in relation to oxidative stress on the land snail Helix aspersa in order to investigate its use as a biomarker for terrestrial environments. Morphology and structure of both NPs were characterized. Snail food was supplemented with a range of concentrations of IONPs and IONPZ and values of the hemocyte lysosomal membranes' destabilization by 50% were estimated by the neutral red retention (NRRT50) assay. Subsequently, snails were fed with NPs concentrations equal to half of the NRRT50 values, 0.05 mg L-1 for IONPs and 1 mg L-1 for IONPZ, for 1, 5, 10 and 20 days. Both effectors induced oxidative stress in snails' hemocytes compared to untreated animals. The latter was detected by NRRT changes, reactive oxygen species (ROS) production, lipid peroxidation estimation, DNA integrity loss, measurement of protein carbonyl content by an enzyme-linked immunoabsorbent assay (ELISA), determination of ubiquitin conjugates and cleaved caspases conjugates levels. The results showed that the simultaneous use of the parameters tested could constitute possible reliable biomarkers for the evaluation of NPs toxicity. However, more research is required in order to enlighten the disposal and toxic impact of iron oxide NPs on the environment to ensure their safe use in the future.