Inhibition of the GSK3β/Nav1.6 complex suppresses early-stage Alzheimer's hyperexcitability.

Introduction: Network hyperexcitability (NH) is observed in patients with early-stage Alzheimer's disease (AD), emerging decades before cognitive decline. A key molecular determinant of NH is voltage-gated Na+ channel 1.6 (Nav1.

Sensory neuron-expressed FGF13 controls nociceptive signaling in diabetic neuropathy models.

Nociception involves complex signaling, yet intrinsic mechanisms bidirectionally regulating this process remain unexplored. Here, we show that the fibroblast growth factor 13 (FGF13)/Nav1.7 protein-protein interaction (PPI) complex bidirectionally modulates nociception, and that the FGF13/Nav1.

βIV spectrin abundancy, cellular distribution and sensitivity to AKT/GSK3 regulation in schizophrenia.

Schizophrenia (SCZ) is a complex psychiatric disorder with unclear biological mechanisms. Spectrins, cytoskeletal proteins linked to neurodevelopmental disorders, are regulated by the AKT/GSK3 pathway, which is implicated in SCZ. However, the impact of SCZ-related dysregulation of this pathway on spectrin expression and distribution remains unexplored.

Axin-binding domain of glycogen synthase kinase 3β facilitates functional interactions with voltage-gated Na+ channel Na1.6.

Voltage-gated Na+ (Na) channels are the primary determinants of the action potential in excitable cells. Na channels rely on a wide and diverse array of intracellular protein-protein interactions (PPIs) to achieve their full function. Glycogen synthase kinase 3β (GSK3β) has been previously identified as a modulator of Na1.

Environmental exposure to common pesticide induces synaptic deficit and social memory impairment driven by neurodevelopmental vulnerability of hippocampal parvalbumin interneurons.

Environmental exposure to pesticides at levels deemed safe by regulatory agencies has been linked to increased risk for neurodevelopmental disorders. Yet, the mechanisms linking exposure to these disorders remain unclear. Here, we show that maternal exposure to the pesticide deltamethrin (DM) at the no observed adverse effect level (NOAEL) disrupts long-term potentiation (LTP) in the hippocampus of adult male offspring three months after exposure, a phenotype absent in female offspring.

Assessing the accuracy and reliability of satellite-derived precipitation products in the Kosi River basin (India).

The present research endeavors to examine the effectiveness of four gridded precipitation datasets, namely Integrated Multi-satellite Retrievals for GPM (IMERG), Tropical Precipitation Measuring Mission (TRMM), Modern-Era Retrospective Analysis for Research and Applications Version 2 (MERRA-2), and Precipitation Estimation from Remotely Sensed Information using Artificial Neural Networks (PERSIANN), with the observed rainfall data of eight rain gauge stations of India Meteorological Department (IMD) from 2001 to 2019 in Kosi River basin, India. Various statistical metrics, contingency tests, trend analysis, and rainfall anomaly index were utilized at daily, monthly, seasonal, and annual time scales. The categorical metrics namely probability of detection (POD) and false alarm ratio (FAR) indicate that MERRA-2 and IMERG datasets have the highest level of concurrence with the observed daily data.

Fibroblast growth factor 13-mediated regulation of medium spiny neuron excitability and cocaine self-administration.

Cocaine use disorder (CUD) is a prevalent neuropsychiatric disorder with few existing treatments. Thus, there is an unmet need for the identification of new pharmacological targets for CUD. Previous studies using environmental enrichment versus isolation paradigms have found that the latter induces increased cocaine self-administration with correlative increases in the excitability of medium spiny neurons (MSN) of the nucleus accumbens shell (NAcSh).

Selective gas detection of titania nanoparticles via impedance spectroscopy and capacitive measurement.

The present paper demonstrated the impedance analysis of Au/TiOnanoparticles/Si-Al capacitive sensor for selective detection of volatile organic compounds (VOCs) at different frequency regimes. TiOnanoparticles (NP) were synthesized through the solution process and characterized by field-emission scanning electron microscopy , x-ray diffraction analysis, photoluminescence spectroscopy, and atomic force microscopy. The gas sensitivity of Au/TiONP/Si-Al was investigated, with the effect of temperature modulation (25 °C-250 °C) and dielectric variation in the vicinity of nanoparticles.

Pharmacologically Targeting the Fibroblast Growth Factor 14 Interaction Site on the Voltage-Gated Na Channel 1.6 Enables Isoform-Selective Modulation.

Voltage-gated Na (Na) channels are the primary molecular determinant of the action potential. Among the nine isoforms of the Na channel α subunit that have been described (Na1.1-Na1.

Bioluminescence Methodology for Ion Channel Studies.

As key players in cell function, ion channels are important targets for drug discovery and therapeutic development against a wide range of health conditions. Thus, developing assays to reconstitute ion channel macromolecular complexes in physiological conditions and screen for chemical modifiers of protein-protein interactions within these complexes is timely in drug discovery campaigns. For most ion channels, expressing their pore-forming subunit in heterologous mammalian cells has now become a routine procedure.

Mapping of the FGF14:Nav1.6 complex interface reveals FLPK as a functionally active peptide modulating excitability.

The voltage-gated sodium (Nav) channel complex is comprised of pore-forming α subunits (Nav1.1-1.9) and accessory regulatory proteins such as the intracellular fibroblast growth factor 14 (FGF14).

COVID-19 created chaos across the globe: Three novel quarantine epidemic models.

The latest version of human coronavirus said to be COVID-19 came out as a sudden pandemic disease within human population and in the absence of vaccination and proper treatment till date, it daunting threats heavily to human lives, infecting more than 12, 11, 214 people and death more than 67, 666 people in 208 countries across the globe as on April 06, 2020, which is highly alarming. When no treatment or vaccine is available till date and to avoid COVID-19 to be transmitted in the community, social distancing is the only way to prevent the disease, which is well taken into account in our novel epidemic models as a special compartment, that is, home isolation. Based on the transmitting behavior of COVID-19 in the human population, we develop three quarantine models of this pandemic taking into account the compartments: susceptible population, immigrant population, home isolation population, infectious population, hospital quarantine population, and recovered population.

Effects of Deltamethrin Acute Exposure on Nav1.6 Channels and Medium Spiny Neurons of the Nucleus Accumbens.

Exposure to pyrethroids, a popular insecticide class that targets voltage-gated Na+ (Nav) channels, has been correlated to an increase in diagnosis of neurodevelopmental disorders, such as attention deficit hyperactive disorder (ADHD), in children. Dysregulation of medium spiny neurons (MSNs) firing in the nucleus accumbens (NAc) is thought to play a critical role in the pathophysiology of ADHD and other neurodevelopmental disorders. The Nav1.

High-throughput screening against protein:protein interaction interfaces reveals anti-cancer therapeutics as potent modulators of the voltage-gated Na channel complex.

Multiple voltage-gated Na (Nav) channelopathies can be ascribed to subtle changes in the Nav macromolecular complex. Fibroblast growth factor 14 (FGF14) is a functionally relevant component of the Nav1.6 channel complex, a causative link to spinocerebellar ataxia 27 (SCA27) and an emerging risk factor for neuropsychiatric disorders.

Identification of peptidomimetics as novel chemical probes modulating fibroblast growth factor 14 (FGF14) and voltage-gated sodium channel 1.6 (Nav1.6) protein-protein interactions.

The voltage-gated sodium (Nav) channel is the molecular determinant of action potential in neurons. Protein-protein interactions (PPI) between the intracellular Nav1.6 C-tail and its regulatory protein fibroblast growth factor 14 (FGF14) provide an ideal and largely untapped opportunity for development of neurochemical probes.