mTOR-related cell-clearing systems in epileptic seizures, an update

Recent evidence suggests that autophagy impairment is implicated in the epileptogenic mechanisms downstream of mTOR hyperactivation. This holds true for a variety of genetic and acquired epileptic syndromes besides malformations of cortical development which are classically known as mTORopathies. Autophagy suppression is sufficient to induce epilepsy in experimental models, while rescuing autophagy prevents epileptogenesis, improves behavioral alterations, and provides neuroprotection in seizure-induced neuronal damage. The implication of autophagy in epileptogenesis and maturation phenomena related to seizure activity is supported by evidence indicating that autophagy is involved in the molecular mechanisms which are implicated in epilepsy. In general, mTOR-dependent autophagy regulates the proliferation and migration of inter-/neuronal cortical progenitors, synapse development, vesicular release, synaptic plasticity, and importantly, synaptic clustering of GABAA receptors and subsequent excitatory/inhibitory balance in the brain. Similar to autophagy, the ubiquitin–proteasome system is regulated downstream of mTOR, and it is implicated in epileptogenesis. Thus, mTOR-dependent cell-clearing systems are now taking center stage in the field of epilepsy. In the present review, we discuss such evidence in a variety of seizure-related disorders and models. This is expected to provide a deeper insight into the molecular mechanisms underlying seizure activit

Nanomedicine and graphene-based materials: advanced technologies for potential treatments of diseases in the developing nervous system

Abstract: The interest in graphene-based nanomaterials (GBNs) application in nanomedicine, in particular in neurology, steadily increased in the last decades. GBNs peculiar physical–chemical properties allow the design of innovative therapeutic tools able to manipulate biological structures with subcellular resolution. In this review, we report GBNs applications to the central nervous system (CNS) when these nanomaterials are engineered as potential therapeutics to treat brain pathologies, with a focus on those of the pediatric age. We revise the state-of-the art studies addressing the impact of GBNs in the CNS, showing that the design of GBNs with different dimensions and chemical compositions or the use of specific administration routes and doses can limit unwanted side effects, exploiting GBNs efficacy in therapeutic approaches. These features favor the development of GBNs-based multifunctional devices that may find applications in the field of precision medicine for the treatment of disorders in the developing CNS. In this framework, we address the suitability of GBNs to become successful therapeutic tools, such as drug nano-delivery vectors when being chemically decorated with pharmaceutical agents and/or other molecules to obtain a high specific targeting of the diseased area and to achieve a controlled release of active molecules. Impact: The translational potential of graphene-based nanomaterials (GBNs) can be used for the design of novel therapeutic approaches to treat pathologies affecting the brain with a focus on the pediatric age.GBNs can be chemically decorated with pharmaceutical agents and molecules to obtain a highly specific targeting of the diseased site and a controlled drug release.The type of GBNs, the selected functionalization, the dose, and the way of administration are factors that should be considered to potentiate the therapeutic efficacy of GBNs, limiting possible side effects.GBNs-based multifunctional devices might find applications in the precision medicine and theranostics fields

The crystal structure of alstonite, BaCa(CO3)2: An extraordinary example of 'hidden' complex twinning in large single crystals

Alstonite, BaCa(CO3)2, is a mineral described almost two centuries ago. It is widespread in Nature and forms magnificent cm-sized crystals. Notwithstanding, its crystal structure was still unknown. Here, we report the crystal-structure determination of the mineral and discuss it in relationship to other polymorphs of BaCa(CO3)2. Alstonite is trigonal, space group P31m, with unit-cell parameters a = 17.4360(6), c = 6.1295(2) Å, V = 1613.80(9) Å3 and Z = 12. The crystal structure was solved and refined to R1 = 0.0727 on the basis of 4515 reflections with Fo > 4σ(Fo) and 195 refined parameters. Alstonite is formed by the alternation, along c, of Ba-dominant and Ca-dominant layers, separated by CO3 groups parallel to {0001}. The main take-home message is to show that not all structure determinations of minerals/compounds can be solved routinely. Some crystals, even large ones displaying excellent diffraction quality, can be twinned in complex ways, thus making their study a crystallographic challenge

Combining electrostatic, hindrance and diffusive effects for predicting particle transport and separation efficiency in deterministic lateral displacement microfluidic devices

Microfluidic separators based on Deterministic Lateral Displacement (DLD) constitute a promising technique for the label-free detection and separation of mesoscopic objects of biological interest, ranging from cells to exosomes. Owing to the simultaneous presence of different forces contributing to particle motion, a feasible theoretical approach for interpreting and anticipating the performance of DLD devices is yet to be developed. By combining the results of a recent study on electrostatic effects in DLD devices with an advection-diffusion model previously developed by our group, we here propose a fully predictive approach (i.e., ideally devoid of adjustable parameters) that includes the main physically relevant effects governing particle transport on the one hand, and that is amenable to numerical treatment at affordable computational expenses on the other. The approach proposed, based on ensemble statistics of stochastic particle trajectories, is validated by comparing/contrasting model predictions to available experimental data encompassing different particle dimensions. The comparison suggests that at low/moderate values of the flowrate the approach can yield an accurate prediction of the separation performance, thus making it a promising tool for designing device geometries and operating conditions in nanoscale applications of the DLD technique

Fractionation of a three-particle mixture by Brownian sieving hydrodynamic chromatography

Particles ranging in size from a few nanometers (exosomes or viruses) to a few micrometers (bacteria or red blood cells) can be sorted using a size-based separation process. One of the simplest techniques is provided by hydrodynamic chromatography (HDC) which typically requires long channels to achieve adequate resolution. A new separation mechanism based on a Brownian sieving effect coupled with HDC has recently been proposed to overcome these limitations. An efficiency improvement of up to 2000 % has been predicted for a two-size mixture. The aim of this work is to study and optimize a modified geometry useful for obtaining the simultaneous separation of a three-size diluted suspension. The results suggest a significant performance improvement, up to 3000 %, over the standard HDC

Tuning the polarization states of optical spots at the nanoscale on the poincar´e sphere using a plasmonic nanoantenna

It is shown that the polarization states of optical spots at the nanoscale can be manipulated to various points on the Poincar´e sphere using a plasmonic nanoantenna. Linearly, circularly, and elliptically polarized near-field optical spots at the nanoscale are achieved with various polarization states on the Poincar´e sphere using a plasmonic nanoantenna. A novel plasmonic nanoantenna is illuminated with diffraction-limited linearly polarized light. It is demonstrated that the plasmonic resonances of perpendicular and longitudinal components of the nanoantenna and the angle of incident polarization can be tuned to obtain optical spots beyond the diffraction limit with a desired polarization and handedness

Characterization of polyaniline-detonation nanodiamond nanocomposite fibers by atomic force microscopy based technique

Polyaniline (PANI) fibers were synthesized in presence of detonantion nanodiamond (DND) particles by precipitation polymerization technique. Morphological, electrical and mechanical characterizations of the obtained PANI/DND nanocomposited have been performed by different either standard or advanced atomic force microscopy (AFM) based techniques. Morphological characterization by tapping mode AFM supplied information about the structure of fibers and ribbons forming the PANI/DND network. An AFM based technique that takes advantage of an experimental configuration specifically devised for the purpose was used to assess the electrical properties of the fibers, in particular to verify their conductivity. Finally, mechanical characterization was carried out synergically using two different and recently proposed AFM based techniques, one based on AFM tapping mode and the other requiring AFM contact mode, which probed the nanocomposited nature of PANI/DND fiber sample down to different depths. © 2013 Elsevier Ltd. All rights reserved