Neurite outgrowth inhibitory levels of organophosphates induce tissue transglutaminase activity in differentiating N2a cells: evidence for covalent adduct formation

Organophosphate compounds (OPs) induce both acute and delayed neurotoxic effects, the latter of which is believed to involve their interaction with proteins other than acetylcholinesterase. However, few OP-binding proteins have been identified that may have a direct role in OP-induced delayed neurotoxicity. Given their ability to disrupt Ca2+ homeostasis, a key aim of the current work was to investigate the effects of sub-lethal neurite outgrowth inhibitory levels of OPs on the Ca2+-dependent enzyme tissue transglutaminase (TG2). At 1–10 µM, the OPs phenyl saligenin phosphate (PSP) and chlorpyrifos oxon (CPO) had no effect cell viability but induced concentration-dependent decreases in neurite outgrowth in differentiating N2a neuroblastoma cells. The activity of TG2 increased in cell lysates of differentiating cells exposed for 24 h to PSP and chlorpyrifos oxon CPO (10 µM), as determined by biotin-cadaverine incorporation assays. Exposure to both OPs (3 and/or 10 µM) also enhanced in situ incorporation of the membrane permeable substrate biotin-X-cadaverine, as indicated by Western blot analysis of treated cell lysates probed with ExtrAvidin peroxidase and fluorescence microscopy of cell monolayers incubated with FITC-streptavidin. Both OPs (10 µM) stimulated the activity of human and mouse recombinant TG2 and covalent labelling of TG2 with dansylamine-labelled PSP was demonstrated by fluorescence imaging following SDS-PAGE. A number of TG2 substrates were tentatively identified by mass spectrometry, including cytoskeletal proteins, chaperones and proteins involved protein synthesis and gene regulation. We propose that the elevated TG2 activity observed is due to the formation of a novel covalent adduct between TG2 and OPs

Room temperature magnetic phase transition in an electrically-tuned van der Waals ferromagnet

Finding tunable van der Waals (vdW) ferromagnets that operate at above room temperature is an important research focus in physics and materials science. Most vdW magnets are only intrinsically magnetic far below room temperature and magnetism with square-shaped hysteresis at room-temperature has yet to be observed. Here, we report magnetism in a quasi-2D magnet Cr1.2Te2 observed at room temperature (290 K). This magnetism was tuned via a protonic gate with an electron doping concentration up to 3.8 * 10^21 cm^-3. We observed non-monotonic evolutions in both coercivity and anomalous Hall resistivity. Under increased electron doping, the coercivities and anomalous Hall effects (AHEs) vanished, indicating a doping-induced magnetic phase transition. This occurred up to room temperature. DFT calculations showed the formation of an antiferromagnetic (AFM) phase caused by the intercalation of protons which induced significant electron doping in the Cr1.2Te2. The tunability of the magnetic properties and phase in room temperature magnetic vdW Cr1.2Te2 is a significant step towards practical spintronic devices.Comment: 18 pages, 4 figure

Recent trends in the use of electrical neuromodulation in Parkinson's disease

Purpose of Review: This review aims to survey recent trends in electrical forms of neuromodulation, with a specific application to Parkinson’s disease (PD). Emerging trends are identified, highlighting synergies in state-of-the-art neuromodulation strategies, with directions for future improvements in stimulation efficacy suggested. Recent Findings: Deep brain stimulation remains the most common and effective form of electrical stimulation for the treatment of PD. Evidence suggests that transcranial direct current stimulation (tDCS) most likely impacts the motor symptoms of the disease, with the most prominent results relating to rehabilitation. However, utility is limited due to its weak effects and high variability, with medication state a key confound for efficacy level. Recent innovations in transcranial alternating current stimulation (tACS) offer new areas for investigation. Summary: Our understanding of the mechanistic foundations of electrical current stimulation is advancing and as it does so, trends emerge which steer future clinical trials towards greater efficacy

An extended random-sets model for fusion-based text feature selection

Selecting features that represent a specific corpus is important for the success of many machine learning and text mining applications. In information retrieval (IR), fusion-based techniques have shown remarkable performance compared to traditional models. However, in text feature selection (FS), popular models do not consider the fusion of the taxonomic features of the corpus. This research proposed an innovative and effective extended random-sets model for fusion-based FS. The model fused scores of different hierarchal features to accurately weight the representative words based on their appearance across the documents in the corpus and in several latent topics. The model was evaluated for information filtering (IF) using TREC topics and the standard RCV1 dataset. The results showed that the proposed model significantly outperformed eleven state-of-the-art baseline models in six evaluation metrics