Long-lasting beneficial effects of central serotonin receptor 7 stimulation in female mice modeling Rett syndrome.

Rett syndrome (RTT) is a rare neurodevelopmental disorder, characterized by severe behavioral and physiological symptoms. Mutations in the methyl CpG binding protein 2 gene (MECP2) cause more than 95% of classic cases, and currently there is no cure for this devastating disorder. Recently we have demonstrated that specific behavioral and brain molecular alterations can be rescued in MeCP2-308 male mice, a RTT mouse model, by pharmacological stimulation of the brain serotonin receptor 7 (5-HT7R). This member of the serotonin receptor family-crucially involved in the regulation of brain structural plasticity and cognitive processes-can be stimulated by systemic repeated treatment with LP-211, a brain-penetrant selective 5-HT7R agonist. The present study extends previous findings by demonstrating that the LP-211 treatment (0.25 mg/kg, once per day for 7 days) rescues RTT-related phenotypic alterations, motor coordination (Dowel test), spatial reference memory (Barnes maze test) and synaptic plasticity (hippocampal long-term-potentiation) in MeCP2-308 heterozygous female mice, the genetic and hormonal milieu that resembles that of RTT patients. LP-211 also restores the activation of the ribosomal protein (rp) S6, the downstream target of mTOR and S6 kinase, in the hippocampus of RTT female mice. Notably, the beneficial effects on neurobehavioral and molecular parameters of a seven-day long treatment with LP-211 were evident up to 2 months after the last injection, thus suggesting long-lasting effects on RTT-related impairments. Taken together with our previous study, these results provide compelling preclinical evidence of the potential therapeutic value for RTT of a pharmacological approach targeting the brain 5-HT7R

Structural and Compositional Factors That Control the Li-Ion Conductivity in LiPON Electrolytes

Amorphous Li-ion conductors are important solid-state electrolytes. However, Li transport in these systems is much less understood than for crystalline materials. We investigate amorphous LiPON electrolytes via ab initio molecular dynamics, providing atomistic-level insight into the mechanisms underlying the Li mobility. We find that the latter is strongly influenced by the chemistry and connectivity of phosphate polyanions near Li . Amorphization generates edge-sharing polyhedral connections between Li(O,N) and P(O,N) , and creates under- and overcoordinated Li sites, which destabilizes the Li and enhances their mobility. N substitution for O favors conductivity in two ways: (1) excess Li accompanying 1(N):1(O) substitutions introduces extra carriers; (2) energetically favored N-bridging substitutions condense phosphate units and densify the structure, which, counterintuitively, corresponds to higher Li mobility. Finally, bridging N is not only less electronegative than O but also engaged in strong covalent bonds with P. This weakens interactions with neighboring Li smoothing the way for their migration. When condensation of PO polyhedra leads to the formation of isolated O anions, the Li mobility is reduced, highlighting the importance of oxygen partial pressure control during synthesis. This detailed understanding of the structural mechanisms affecting Li mobility is the key for optimizing the conductivity of LiPON and other amorphous Li-ion conductors. + + + + + + + 4 4

Ab initio investigation of the stability of electrolyte/electrode interfaces in all-solid-state Na batteries

All-solid-state batteries show great potential for achieving high energy density with less safety problems; however, (electro)chemical issues at the solid electrolyte/electrode interface may severely limit their performance. In this work, the electrochemical stability and chemical reactivity of a wide range of potential Na solid-state electrolyte chemistries were investigated using density functional theory calculations. In general, lower voltage limits are predicted for both the reduction and oxidation of Na compounds compared with those of their Li counterparts. The lower reduction limits for the Na compounds indicate their enhanced cathodic stability as well as the possibility of stable sodium metal cycling against a number of oxides and borohydrides. With increasing Na content (or chemical potential), improved cathodic stability but also reduced anodic stability are observed. An increase in the oxidation voltage is shown for Na polyanion systems, including borohydrides, NaSICON-type oxides, and aluminates, due to the covalent stabilization of the anions. In addition, the oxides exhibit remarkable chemical stability when in contact with various cathode materials (layered transition metal oxides and fluorophosphates), whereas the chalcogenides predictably display narrow electrochemical windows and high chemical reactivity. Our findings indicate some promising candidates for solid-state conductors and/or protective coating materials to enable the operation of high-energy-density all-solid-state Na batteries

Advances and challenges in multiscale characterizations and analyses for battery materials

Rechargeable ion batteries are efficient energy storage devices widely employed in portable to large-scale applications such as electric vehicles and grids. Electrochemical reactions within batteries are complex phenomena, and they are strongly dependent on the battery materials and systems used. These electrochemical reactions often include detrimental irreversible reactions at various length scales from atomic- to macro-scales, which ultimately determine the overall electrochemical behavior of the system. Understanding such reaction mechanisms is a critical component to improve battery performance. To help this effort, this review article discusses recent advances and remaining challenges in both computational and experimental approaches to better understand dynamic electrochemical reactions in batteries across multiple length scales. Important related findings from this focus issue will also be highlighted. The aim of our focus issue is to contribute to the battery community towards having better understanding of complex reactions occurring in battery devices and of computational and experimental methods to investigate them. Graphical abstract: [Figure not available: see fulltext.

Study on the influence of visible molds on primary and secondary shelf life of pasteurized gnocchi

Primary (PSL) and secondary shelf life (SSL) of pasteurized fresh gnocchi were assessed. The dependence of the SSL on the extent of deteriorative reactions at the package opening was also predicted. To the aim, industrial gnocchi samples were produced, packaged, pasteurized, transported to the lab, and then stored at room temperature (20 degrees C) for more than 1 year. During this storage period, some samples were opened at five increasing times form the production and stored under different storage conditions to monitor microbiological and sensory quality, pH, moisture content and appearance of visible molds. Results demonstrate that packaged gnocchi remained acceptable for about 12 months and then were refused for appearance of visible molds. Results on SSL assessment demonstrate that temperature after package opening plays a key role on the appearance of fungal rot on the product surface. Unsealed samples stored at 4 degrees C remained acceptable for maximum 4 weeks, whereas samples at 20 degrees C were refused within 1 week from the opening. The data obtained in this study were also used to test the predictive ability of the proposed mathematical model. Considering the simplicity of the hypothesis used to derive the model, its predictive ability can be considered quite acceptable