A New Result Concerning the Solvability of a Class of General Systems of Variational Equations with Nonmonotone Operators: Applications to Dirichlet and Neumann Nonlinear Problems

A new result of solvability for a wide class of systems of variational equations depending on parameters and governed by nonmonotone operators is found in a Banach real and reflexive space with applications to Dirichlet and Neumann problems related to nonlinear elliptic systems

The serotonin receptor 7 and the structural plasticity of brain circuits

Serotonin (5-hydroxytryptamine, 5-HT) modulates numerous physiological processes in the nervous system. Together with its function as neurotransmitter, 5-HT regulates neurite outgrowth, dendritic spine shape and density, growth cone motility and synapse formation during development. In the mammalian brain 5-HT innervation is virtually ubiquitous and the diversity and specificity of its signaling and function arise from at least 20 different receptors, grouped in 7 classes. Here we will focus on the role 5-HT7 receptor (5-HT7R) in the correct establishment of neuronal cytoarchitecture during development, as also suggested by its involvement in several neurodevelopmental disorders. The emerging picture shows that this receptor is a key player contributing not only to shape brain networks during development but also to remodel neuronal wiring in the mature brain, thus controlling cognitive and emotional responses. The activation of 5-HT7R might be one of the mechanisms underlying the ability of the CNS to respond to different stimuli by modulation of its circuit configuration

Activation of 5-HT7 receptor stimulates neurite elongation through mTOR, Cdc42 and actin filaments dynamics.

Recent studies have indicated that the serotonin receptor subtype 7 (5-HT7R) plays a crucial role in shaping neuronal morphology during embryonic and early postnatal life. Here we show that pharmacological stimulation of 5-HT7R using a highly selective agonist, LP-211, enhances neurite outgrowth in neuronal primary cultures from the cortex, hippocampus and striatal complex of embryonic mouse brain, through multiple signal transduction pathways. All these signaling systems, involving mTOR, the Rho GTPase Cdc42, Cdk5, and ERK, are known to converge on the reorganization of cytoskeletal proteins that subserve neurite outgrowth. Indeed, our data indicate that neurite elongation stimulated by 5-HT7R is modulated by drugs affecting actin polymerization. In addition, we show, by 2D Western blot analyses, that treatment of neuronal cultures with LP-211 alters the expression profile of cofilin, an actin binding protein involved in microfilaments dynamics. Furthermore, by using microfluidic chambers that physically separate axons from the soma and dendrites, we demonstrate that agonist-dependent activation of 5-HT7R stimulates axonal elongation. Our results identify for the first time several signal transduction pathways, activated by stimulation of 5-HT7R, that converge to promote cytoskeleton reorganization and consequent modulation of axonal elongation. Therefore, the activation of 5-HT7R might represent one of the key elements regulating CNS connectivity and plasticity during development

Algae as food in Europe: an overview of species diversity and their application

ABSTRACT: Algae have been consumed for millennia in several parts of the world as food, food supplements, and additives, due to their unique organoleptic properties and nutritional and health benefits. Algae are sustainable sources of proteins, minerals, and fiber, with well-balanced essential amino acids, pigments, and fatty acids, among other relevant metabolites for human nutrition. This review covers the historical consumption of algae in Europe, developments in the current European market, challenges when introducing new species to the market, bottlenecks in production technology, consumer acceptance, and legislation. The current algae species that are consumed and commercialized in Europe were investigated, according to their status under the European Union (EU) Novel Food legislation, along with the market perspectives in terms of the current research and development initiatives, while evaluating the interest and potential in the European market. The regular consumption of more than 150 algae species was identified, of which only 20% are approved under the EU Novel Food legislation, which demonstrates that the current legislation is not broad enough and requires an urgent update. Finally, the potential of the European algae market growth was indicated by the analysis of the trends in research, technological advances, and market initiatives to promote algae commercialization and consumption.info:eu-repo/semantics/publishedVersio

miR-218 promotes dopaminergic differentiation and controls neuron excitability and neurotransmitter release through the regulation of a synaptic-related genes network

In the brain microRNAs (miRNAs) are believed to play a role in orchestrating synaptic plasticity at a higher-level by acting as an additional mechanism of translational regulation, alongside the mRNAs/polysome system. Despite extensive research, our understanding of the specific contribution of individual miRNA to the function of dopaminergic neurons (DAn) remains limited. By performing a dopaminergic-specific miRNA screening, we have identified miR-218 as a critical regulator of DAn activity in male and female mice. We have found that miR-218 is specifically expressed in mesencephalic DAn and is able to promote dopaminergic differentiation of embryonic stem cells and functional maturation of transdifferentiated induced DA neurons. Midbrain-specific deletion of both genes encoding for miR-218 (referred to as miR-218-1 and mir218-2) affects the expression of a cluster of synaptic-related mRNAs and alters the intrinsic excitability of DAn, as it increases instantaneous frequencies of evoked action potentials, reduces rheobase current, affects the ionic current underlying the action potential after hyperpolarization phase and reduces dopamine efflux in response to a single electrical stimulus. Our findings provide a comprehensive understanding of the involvement of miR-218 in the dopaminergic system and highlight its role as a modulator of dopaminergic transmission

Proceedings of the Fifth Italian Conference on Computational Linguistics CLiC-it 2018

On behalf of the Program Committee, a very warm welcome to the Fifth Italian Conference on Computational Linguistics (CLiC-­‐it 2018). This edition of the conference is held in Torino. The conference is locally organised by the University of Torino and hosted into its prestigious main lecture hall “Cavallerizza Reale”. The CLiC-­‐it conference series is an initiative of the Italian Association for Computational Linguistics (AILC) which, after five years of activity, has clearly established itself as the premier national forum for research and development in the fields of Computational Linguistics and Natural Language Processing, where leading researchers and practitioners from academia and industry meet to share their research results, experiences, and challenges

The Serotonin Receptor 7: a key regulator of neuronal cytoarchitecture in the Central Nervous System

In the last decade, a number of results show the involvement of 5-HT7 receptor in many aspects of neuronal development, such as neurite outgrowth, modulation of neuronal morphology and changes of dendritic spine shape and density. In particular, it was demonstrated that stimulation of endogenous receptor in embryonic hippocampal neurons resulted in a marked elongation of neurites (Kvanchina et al., 2005). In addition, the activation of 5-HT7R/G12 signaling pathway in postnatal hippocampal cultures promotes formation of dendritic protrusion, synaptogenesis and modulates synaptic plasticity (Kobe et al., 2012). In line with these results, my PhD project aims at characterizing the role of 5-HT7 receptor in remodeling neuronal cyto-architecture and connectivity during the early and late development, in behavioral relevant CNS circuits. The comprehension of the molecular basis of 5-HT7 receptor involvement in modulation of neuronal connectivity is important to understand whether the pharmacological modulation of this receptor may improve a number of neurodevelopmental diseases carachterized by altered connectivity (e.g., X-fragile, ADHD, Rett syndrome). Here I show that stimulation of 5-HT7R with the selective agonist LP-211 promotes extensive neurite elongation in striatal, cortical and hippocampal embryonic primary cultures. These effects are inhibited by the selective 5-HT7 receptor antagonist SB-269970. This neurite outgrowth requires the activation of ERK1/2 and Cdk5 and is sustained by qualitative and quantitative changes of selected neuronal cytoskeletal proteins (i.e. actin, MAP1B, cofilin). In addition, using specifically designed microfluidic chambers, I also demonstrate that stimulation of hippocampal neurons with LP-211 significantly enhances axonal elongation. Furthermore, preliminary results show that stimulation of 5-HT7 receptor, in vivo in adult mice, modulates dendritic spine morphology in the CNS. Finally, the 5-HT7 receptor stimulation partially rescues the morphological alterations of mouse cortical embryonic primary cultures obtained from Mecp2-/y animal model, which recapitulates a severe form of mental retardation characterized by altered cerebral connectivity, the Rett syndrome. Taken together, these results highlight the key role played by 5-HT7 receptor in the regulation of neuronal cytoarchitecture and may provide insights for innovative pharmacological treatments of neurodevelopmental disorders characterized by altered brain connectivity

Dirichlet and Neumann Problems Related to Nonlinear Elliptic Systems: Solvability, Multiple Solutions, Solutions with Positive Components

We study the solvability of Dirichlet and Neumann problems for different classes of nonlinear elliptic systems depending on parameters and with nonmonotone operators, using existence theorems related to a general system of variational equations in a reflexive Banach space. We also point out some regularity properties and the sign of the found solutions components. We often prove the existence of at least two different solutions with positive components

Dirichlet and Neumann Problems Related to Nonlinear Elliptic Systems: Solvability, Multiple Solutions, Solutions with Positive Components

We study the solvability of Dirichlet and Neumann problems for different classes of nonlinear elliptic systems depending on parameters and with nonmonotone operators, using existence theorems related to a general system of variational equations in a reflexive Banach space. We also point out some regularity properties and the sign of the found solutions components. We often prove the existence of at least two different solutions with positive components