Cell-to-Cell Communication in Learning and Memory: From Neuro- and Glio-Transmission to Information Exchange Mediated by Extracellular Vesicles

Most aspects of nervous system development and function rely on the continuous crosstalk between neurons and the variegated universe of non-neuronal cells surrounding them. The most extraordinary property of this cellular community is its ability to undergo adaptive modifications in response to environmental cues originating from inside or outside the body. Such ability, known as neuronal plasticity, allows long-lasting modifications of the strength, composition and efficacy of the connections between neurons, which constitutes the biochemical base for learning and memory. Nerve cells communicate with each other through both wiring (synaptic) and volume transmission of signals. It is by now clear that glial cells, and in particular astrocytes, also play critical roles in both modes by releasing different kinds of molecules (e.g., D-serine secreted by astrocytes). On the other hand, neurons produce factors that can regulate the activity of glial cells, including their ability to release regulatory molecules. In the last fifteen years it has been demonstrated that both neurons and glial cells release extracellular vesicles (EVs) of different kinds, both in physiologic and pathological conditions. Here we discuss the possible involvement of EVs in the events underlying learning and memory, in both physiologic and pathological condition

IMMIGRATION AND RESILIENCE: THE CASE-STUDY OF INNER ITALIAN AREAS

The immigration phenomenon is involving the whole national territory with particular effect on small inland areas of the Italian regions and it happens for various reasons. The case-study will concern the observation of the town of Palazzo San Gervasio (Potenza) that, as a reality endowed with an identification and expulsion center (CIE), is evolving into a reality that not only intends to tighten solid and strong alliance for mutual growth, with immigrants, but aims to achieve a level of resilience that can avoid depopula-tion and the consequent disappearance of the same city. The community of Palazzo San Gervasio has found in the migrants a lifeblood able to trigger processes of “improve-ment” of the Community heritage of welcome and tolerance. This allowed the development of an European project designed to identify the causes of the problems before putting reception to discuss with each other, outside of institutional as well as administrative settings, doctors, prefecture, re-gional representatives and state organs with simple citizens, associations and, especially migrants. The first working tables have already shown some problematic processes, for example, in the allocation of recognition documents, beyond, the possibility to move in Europe, would give migrants the possibility to integrate, without legal problems, in the communities cozy and, on the other hand, they have shown that, especially the younger boys have received a non-charitable but absolutely time integration from peers. Therefore, contrary to what one might imagine, it is the youngest and the residents in the inland community to show greater sensitivity to the phenomenon. Of course much remains: to know the needs (housing, the social spaces, prayer space, market areas, etc.) of migrants but the case of small indoor areas, not only, shows a real aptitude of the same to a inherent resiliency, but also, such a sensitivity that you feel “ready to sail” each of the elements of conscious welcoming community that today we could all be forced to become migrants

Lidstone–Euler Second-Type Boundary Value Problems: Theoretical and Computational Tools

AbstractGeneral nonlinear high odd-order differential equations with Lidstone–Euler boundary conditions of second type are treated both theoretically and computationally. First, the associated interpolation problem is considered. Then, a theorem of existence and uniqueness of the solution to the Lidstone–Euler second-type boundary value problem is given. Finally, for a numerical solution, two different approaches are illustrated and some numerical examples are included to demonstrate the validity and applicability of the proposed algorithms

Lidstone–Euler interpolation and related high even order boundary value problem

AbstractWe consider the Lidstone–Euler interpolation problem and the associated Lidstone–Euler boundary value problem, in both theoretical and computational aspects. After a theorem of existence and uniqueness of the solution to the Lidstone–Euler boundary value problem, we present a numerical method for solving it. This method uses the extrapolated Bernstein polynomials and produces an approximating convergent polynomial sequence. Particularly, we consider the fourth-order case, arising in various physical models. Finally, we present some numerical examples and we compare the proposed method with a modified decomposition method for a tenth-order problem. The numerical results confirm the theoretical and computational ones

Relationship between Interpolation and Differential Equations: A Class of Collocation Methods

In this chapter, the connection between general linear interpolation and initial, boundary and multipoint value problems is explained. First, a result of a theoretical nature is given, which highlights the relationship between the interpolation problem and the Fredholm integral equation for high-order differential problems. After observing that the given problem is equivalent to a Fredholm integral equation, this relation is used in order to determine a general procedure for the numerical solution of high-order differential problems by means of appropriate collocation methods based on the integration of the Fredholm integral equation. The classical analysis of the class of the obtained methods is carried out. Some particular cases are illustrated. Numerical examples are given in order to illustrate the efficiency of the method

Regulation of mRNA transport, localization and translation in the nervous system of mammals (Review).

Post-transcriptional control of mRNA trafficking and metabolism plays a critical role in the actualization and fine tuning of the genetic program of cells, both in development and in differentiated tissues. Cis-acting signals, responsible for post-transcriptional regulation, reside in the RNA message itself, usually in untranslated regions, 5' or 3' to the coding sequence, and are recognized by trans-acting factors: RNA-binding proteins (RBPs) and/or non-coding RNAs (ncRNAs). ncRNAs bind short mRNA sequences usually present in the 3'-untranslated (3'-UTR) region of their target messages. RBPs recognize specific nucleotide sequences and/or secondary/tertiary structures. Most RBPs assemble on mRNA at the moment of transcription and shepherd it to its destination, somehow determining its final fate. Regulation of mRNA localization and metabolism has a particularly important role in the nervous system where local translation of pre-localized mRNAs has been implicated in developing axon and dendrite pathfinding, and in synapse formation. Moreover, activity-dependent mRNA trafficking and local translation may underlie long-lasting changes in synaptic efficacy, responsible for learning and memory. This review focuses on the role of RBPs in neuronal development and plasticity, as well as possible connections between ncRNAs and RBPs

Aurora-A inactivation causes mitotic spindle pole fragmentation by unbalancing microtubule-generated forces

<p>Abstract</p> <p>Background</p> <p>Aurora-A is an oncogenic kinase playing well-documented roles in mitotic spindle organisation. We previously found that Aurora-A inactivation yields the formation of spindles with fragmented poles that can drive chromosome mis-segregation. Here we have addressed the mechanism through which Aurora-A activity regulates the structure and cohesion of spindle poles.</p> <p>Results</p> <p>We inactivated Aurora-A in human U2OS osteosarcoma cells either by RNA-interference-mediated silencing or treating cultures with the specific inhibitor MLN8237. We show that mitotic spindle pole fragmentation induced by Aurora-A inactivation is associated with microtubule hyperstabilisation. Silencing of the microtubule-stabilising factor ch-TOG prevents spindle pole fragmentation caused by inactivation of Aurora-A alone and concomitantly reduces the hyperstabilisation of microtubules. Furthermore, decreasing pole-directed spindle forces by inhibition of the Eg5 kinesin, or by destabilisation of microtubule-kinetochore attachments, also prevents pole fragmentation in Aurora-A-inactivated mitoses.</p> <p>Conclusions</p> <p>Our findings indicate that microtubule-generated forces are imbalanced in Aurora-A-defective cells and exert abnormal pressure at the level of spindle poles, ultimately causing their fragmentation. This study therefore highlights a novel role of the Aurora-A kinase in regulating the balance between microtubule forces during bipolar spindle assembly.</p

Genomic and non-genomic mechanisms of action of thyroid hormones and their catabolite 3,5-diiodo-l-thyronine in Mammals

Since the realization that the cellular homologs of a gene found in the retrovirus that contributes to erythroblastosis in birds (v-erbA), i.e. the proto-oncogene c-erbA encodes the nuclear receptors for thyroid hormones (THs), most of the interest for THs focalized on their ability to control gene transcription. It was found, indeed, that, by regulating gene expression in many tissues, these hormones could mediate critical events both in development and in adult organisms. Among their eects, much attention was given to their ability to increase energy expenditure, and they were early proposed as anti-obesity drugs. However, their clinical use has been strongly challenged by the concomitant onset of toxic eects, especially on the heart. Notably, it has been clearly demonstrated that, besides their direct action on transcription (genomic eects), THs also have non-genomic eects, mediated by cell membrane and/or mitochondrial binding sites, and sometimes triggered by their endogenous catabolites. Among these latter molecules, 3,5-diiodo-L-thyronine (3,5-T2) has been attracting increasing interest because some of its metabolic eects are similar to those induced by T3, but it seems to be safer. The main target of 3,5-T2 appears to be the mitochondria, and it has been hypothesized that, by acting mainly on mitochondrial function and oxidative stress, 3,5-T2 might prevent and revert tissue damages and hepatic steatosis induced by a hyper-lipid diet, while concomitantly reducing the circulating levels of low density lipoproteins (LDL) and triglycerides. Besides a summary concerning general metabolism of THs, as well as their genomic and non-genomic eects, herein we will discuss resistance to THs and the possible mechanisms of action of 3,5-T2, also in relation to its possible clinical use as a drug

Involvement of the H3.3 Histone Variant in the Epigenetic Regulation of Gene Expression in the Nervous System, in Both Physiological and Pathological Conditions

All the cells of an organism contain the same genome. However, each cell expresses only a minor fraction of its potential and, in particular, the genes encoding the proteins necessary for basal metabolism and the proteins responsible for its specific phenotype. The ability to use only the right and necessary genes involved in specific functions depends on the structural organization of the nuclear chromatin, which in turn depends on the epigenetic history of each cell, which is stored in the form of a collection of DNA and protein modifications. Among these modifications, DNA methylation and many kinds of post-translational modifications of histones play a key role in organizing the complex indexing of usable genes. In addition, non-canonical histone proteins (also known as histone variants), the synthesis of which is not directly linked with DNA replication, are used to mark specific regions of the genome. Here, we will discuss the role of the H3.3 histone variant, with particular attention to its loading into chromatin in the mammalian nervous system, both in physiological and pathological conditions. Indeed, chromatin modifications that mark cell memory seem to be of special importance for the cells involved in the complex processes of learning and memory