Can glial cells save neurons in epilepsy?

Epilepsy is a neurological disorder caused by the pathological hyper-synchronization of neuronal discharges. The fundamental research of epilepsy mechanisms and the targets of drug design options for its treatment have focused on neurons. However, approximately 30% of patients suffering from epilepsy show resistance to standard anti-epileptic chemotherapeutic agents while the symptoms of the remaining 70% of patients can be alleviated but not completely removed by the current medications. Thus, new strategies for the treatment of epilepsy are in urgent demand. Over the past decades, with the increase in knowledge on the role of glia in the genesis and development of epilepsy, glial cells are receiving renewed attention. In a normal brain, glial cells maintain neuronal health and in partnership with neurons regulate virtually every aspect of brain function. In epilepsy, however, the supportive roles of glial cells are compromised, and their interaction with neurons is altered, which disrupts brain function. In this review, we will focus on the role of glia-related processes in epileptogenesis and their contribution to abnormal neuronal activity, with the major focus on the dysfunction of astroglial potassium channels, water channels, gap junctions, glutamate transporters, purinergic signaling, synaptogenesis, on the roles of microglial inflammatory cytokines, microglia-astrocyte interactions in epilepsy, and on the oligodendroglial potassium channels and myelin abnormalities in the epileptic brain. These recent findings suggest that glia should be considered as the promising next-generation targets for designing anti-epileptic drugs that may improve epilepsy and drug-resistant epilepsy.kategorija casopsisa M2

Room-temperature multiferroic hexagonal LuFeO3_3 films

The crystal and magnetic structures of single-crystalline hexagonal LuFeO$_3$ films have been studied using x-ray, electron and neutron diffraction methods. The polar structure of these films are found to persist up to 1050 K; and the switchability of the polar behavior is observed at room temperature, indicating ferroelectricity. An antiferromagnetic order was shown to occur below 440 K, followed by a spin reorientation resulting in a weak ferromagnetic order below 130 K. This observation of coexisting multiple ferroic orders demonstrates that hexagonal LuFeO$_3$ films are room-temperature multiferroics

PEGylated Red-Emitting Calcium Probe with Improved Sensing Properties for Neuroscience.

Monitoring calcium concentration in the cytosol is of main importance as this ion drives many biological cascades within the cell. To this end, molecular calcium probes are widely used. Most of them, especially the red emitting probes, suffer from nonspecific interactions with inner membranes due to the hydrophobic nature of their fluorophore. To circumvent this issue, calcium probes conjugated to dextran can be used to enhance the hydrophilicity and reduce the nonspecific interaction and compartmentalization. However, dextran conjugates also feature important drawbacks including lower affinity, lower dynamic range, and slow diffusion. Herein, we combined the advantage of molecular probes and dextran conjugate without their drawbacks by designing a new red emitting turn-on calcium probe based on PET quenching, Rhod-PEG, in which the rhodamine fluorophore bears four PEG4 units. This modification led to a high affinity calcium probe (Kd = 748 nM) with reduced nonspecific interactions, enhanced photostability, two-photon absorbance, and brightness compared to the commercially available Rhod-2. After spectral characterizations, we showed that Rhod-PEG quickly and efficiently diffused through the dendrites of pyramidal neurons with an enhanced sensitivity (ΔF/F0) at shorter time after patching compared to Rhod-2.journal article2017 Nov 222017 10 24imported"Supporting information" disponible sur le site de l'éditeur à l'adresse suivante : http://pubs.acs.org/doi/suppl/10.1021/acssensors.7b0066

Room-Temperature Multiferroic Hexagonal LuFeO\u3csub\u3e3\u3c/sub\u3e Films

The crystal and magnetic structures of single-crystalline hexagonal LuFeO3 films have been studied using x-ray, electron, and neutron diffraction methods. The polar structure of these films are found to persist up to 1050 K; and the switchability of the polar behavior is observed at room temperature, indicating ferroelectricity. An antiferromagnetic order was shown to occur below 440 K, followed by a spin reorientation resulting in a weak ferromagnetic order below 130 K. This observation of coexisting multiple ferroic orders demonstrates that hexagonal LuFeO3 films are room-temperature multiferroics

Response theory for time-resolved second-harmonic generation and two-photon photoemission

A unified response theory for the time-resolved nonlinear light generation and two-photon photoemission (2PPE) from metal surfaces is presented. The theory allows to describe the dependence of the nonlinear optical response and the photoelectron yield, respectively, on the time dependence of the exciting light field. Quantum-mechanical interference effects affect the results significantly. Contributions to 2PPE due to the optical nonlinearity of the surface region are derived and shown to be relevant close to a plasmon resonance. The interplay between pulse shape, relaxation times of excited electrons, and band structure is analyzed directly in the time domain. While our theory works for arbitrary pulse shapes, we mainly focus on the case of two pulses of the same mean frequency. Difficulties in extracting relaxation rates from pump-probe experiments are discussed, for example due to the effect of detuning of intermediate states on the interference. The theory also allows to determine the range of validity of the optical Bloch equations and of semiclassical rate equations, respectively. Finally, we discuss how collective plasma excitations affect the nonlinear optical response and 2PPE.Comment: 27 pages, including 11 figures, version as publishe

NGDEEP Epoch 1: Spatially Resolved Hα\alpha Observations of Disk and Bulge Growth in Star-Forming Galaxies at z∼z \sim 0.6-2.2 from JWST NIRISS Slitless Spectroscopy

We study the H$\alpha$ equivalent width, EW(H$\alpha$), maps of 19 galaxies at $0.6 < z < 2.2$ in the Hubble Ultra Deep Field (HUDF) derived from NIRISS slitless spectroscopy as part of the Next Generation Deep Extragalactic Exploratory Public (NGDEEP) Survey. Our galaxies mostly lie on the star-formation main sequence with a stellar mass range of $\mathrm{10^9 - 10^{11} M_\odot}$, and are therefore characteristic of "typical" star-forming galaxies at these redshifts. Leveraging deep HST and JWST broad-band images, spanning 0.4-4 $\mu$m, we perform spatially-resolved fitting of the spectral energy distributions (SEDs) for these galaxies and construct specific star formation rate (sSFR) and stellar-mass-weighted age maps. We compare these to the EW(H$\alpha$) maps with a spatial resolution of $\sim$1 kpc. The pixel-to-pixel EW(H$\alpha$) increases with increasing sSFR and with decreasing age, with the average trend slightly different from the relations derived from integrated fluxes of galaxies from the literature. Quantifying the radial profiles of EW(H$\alpha$), sSFR, and age, the majority (84%) of galaxies show positive EW(H$\alpha$) gradients, positive sSFR gradients, and negative age gradients, in line with the the inside-out quenching scenario. A few galaxies (16%) show inverse (and flat) trends possibly due to merging or starbursts. Comparing the distributions of EW(H$\alpha$) and sSFR to the star formation history models as a function of galactocentric radius, the central region of galaxies (e.g., their bulges) have experienced, at least one, rapid star-formation episodes, which leads to the formation of bulge, while their outer regions (e.g., disks) grow in a more steady-state. These results demonstrate the ability to study resolved star formation in distant galaxies with JWST NIRISS.Comment: 22 pages, 11 figure

Cross-Platform Comparison of Microarray-Based Multiple-Class Prediction

High-throughput microarray technology has been widely applied in biological and medical decision-making research during the past decade. However, the diversity of platforms has made it a challenge to re-use and/or integrate datasets generated in different experiments or labs for constructing array-based diagnostic models. Using large toxicogenomics datasets generated using both Affymetrix and Agilent microarray platforms, we carried out a benchmark evaluation of cross-platform consistency in multiple-class prediction using three widely-used machine learning algorithms. After an initial assessment of model performance on different platforms, we evaluated whether predictive signature features selected in one platform could be directly used to train a model in the other platform and whether predictive models trained using data from one platform could predict datasets profiled using the other platform with comparable performance. Our results established that it is possible to successfully apply multiple-class prediction models across different commercial microarray platforms, offering a number of important benefits such as accelerating the possible translation of biomarkers identified with microarrays to clinically-validated assays. However, this investigation focuses on a technical platform comparison and is actually only the beginning of exploring cross-platform consistency. Further studies are needed to confirm the feasibility of microarray-based cross-platform prediction, especially using independent datasets