Reduced AKT/mTOR signaling and protein synthesis dysregulation in a Rett syndrome animal model.

Rett syndrome (RTT) is a neurodevelopmental disorder with no efficient treatment that is caused in the majority of cases by mutations in the gene methyl-CpG binding-protein 2 (MECP2). RTT becomes manifest after a period of apparently normal development and causes growth deceleration, severe psychomotor impairment and mental retardation. Effective animal models for RTT are available and show morphofunctional abnormalities of synaptic connectivity. However, the molecular consequences of MeCP2 disruption leading to neuronal and synaptic alterations are not known. Protein synthesis regulation via the mammalian target of the rapamycin (mTOR) pathway is crucial for synaptic organization, and its disruption is involved in a number of neurodevelopmental diseases. We investigated the phosphorylation of the ribosomal protein (rp) S6, whose activation is highly dependent from mTOR activity. Immunohistochemistry showed that rpS6 phosphorylation is severely affected in neurons across the cortical areas of Mecp2 mutants and that this alteration precedes the severe symptomatic phase of the disease. Moreover, we found a severe defect of the initiation of protein synthesis in the brain of presymptomatic Mecp2 mutant that was not restricted to a specific subset of transcripts. Finally, we provide evidence for a general dysfunction of the Akt/mTOR, but not extracellular-regulated kinase, signaling associated with the disease progression in mutant brains. Our results indicate that defects in the AKT/mTOR pathway are responsible for the altered translational control in Mecp2 mutant neurons and disclosed a novel putative biomarker of the pathological process. Importantly, this study provides a novel context of therapeutic interventions that can be designed to successfully restrain or ameliorate the development of RTT

Sugar-and-acid profile of Penjar tomatoes and its evolution during storage

The alcobaca mutation in the Penjar tomato (Solanum lycopersicum L.) variety alters the ripening process and confers a long shelf life (more than four months). Storage of Penjar tomatoes leads to a distinctive sensory profile valued by local consumers, who prefer aged tomatoes to fresh ones. To study chemical changes occurring during storage, we characterized the complete sugar-and-acid profile of 25 accessions at harvest and at 2 and 4 months after harvest. We found considerable variability in the sugar-and-acid profile within the Penjar variety, especially for fructose and glucose. Some accessions presented exceptionally high values for sugars, making them especially interesting for breeding programs. During postharvest, the concentration of glucose, fructose, and citric acid decreased, whereas the concentration of malic and glutamic acids increased. Data from this study offer novel insights into postharvest changes in tomato quality parameters and help elucidate the reasons for the appreciation of this variety by consumers.Postprint (published version