Parvalbumin interneuron impairment causes synaptic transmission deficits and seizures in SCN8A developmental and epileptic encephalopathy.

SCN8A developmental and epileptic encephalopathy (DEE) is a severe epilepsy syndrome resulting from mutations in the voltage-gated sodium channel Nav1.6, encoded by the gene SCN8A. Nav1.

Microenvironment T-Type calcium channels regulate neuronal and glial processes to promote glioblastoma growth.

Background: Glioblastoma (GBM) is the most common primary malignant brain tumor. The aim of this study was to elucidate the role of microenvironment and intrinsic T-type calcium channels (Cav3) in regulating tumor growth and progression.

Methods: We grafted syngeneic GBM cells into Cav3.

Effect of cold arid high-altitude environment on bioactive phytochemical compounds of organically grown Brassicaceae vegetables for nutri-health security in mountainous regions.

High-altitude (HA) environment presents immense physiological adversities for humans that have been overcome by supplementing bio-active phytochemicals from functional foods that support and accelerate acclimatization under these extreme environmental conditions. Several agricultural interventions have been investigated to enhance the phytochemical content in vegetables however; these studies have been limited to low-altitude (LA) regions only. In view of an existing knowledge gap, current work is designed to compare the phytochemical compositions of HA and LA-grown Brassicaceae vegetables (cabbage, cauliflower, knol-khol, and radish) using organic treatments via farm yard manure (FYM) and Azotobacter.

Quality evaluation of strawberries coated with water-in-oil based emulsion using an advanced electrostatic spray coating system.

In this study, the impact of formulated emulsion was studied on strawberries which were coated using dip and electrostatic spray coating methods. The coated strawberries were kept at room temperature for a period of 12 days. A significant level of chargeability of w/o emulsion was achieved in terms of charge-to-mass ratio of 2.

Parvalbumin Interneuron Impairment Leads to Synaptic Transmission Deficits and Seizures in Epileptic Encephalopathy.

epileptic encephalopathy (EE) is a severe epilepsy syndrome resulting from mutations in the voltage-gated sodium channel Na 1.6, encoded by the gene . Na 1.

Unveiling a robust and high-temperature-stable two-dimensional ZnAl layered double hydroxide nanosheet based flexible triboelectric nanogenerator.

Triboelectric nanogenerators have the ability to harvest low- and mid-frequency vibrational energy from the environment; however, achieving stable performance of the nanogenerator device in high-temperature conditions remains challenging. In this work, a flexible and temperature-stable polyvinyl alcohol (PVA)/layered double hydroxides (LDH) nanocomposite-based triboelectric nanogenerator was developed to harvest unexploited vibrational energy for the first time. Crystalline ZnAl LDH nanosheets grown by a hydrothermal route are used to fabricate the high-performance flexible nanogenerator.

Emergence of selectivity and specificity in a coarse-grained model of the nuclear pore complex with sequence-agnostic FG-Nups.

The role of hydrophobicity of phenylalanine-glycine nucleoporins (FG-Nups) in determining the transport of receptor-bound cargo across the nuclear pore complex (NPC) is investigated using Langevin dynamics simulations. A coarse-grained, minimal model of the NPC, comprising a cylindrical pore and hydrophobic-hydrophilic random copolymers for FG-Nups was employed. Karyopherin-bound receptor-cargo complexes (Kaps) were modeled as rigid, coarse-grained spheres without (inert) and with (patchy) FG-binding hydrophobic domains.

EpiPro, a Novel, Synthetic, Activity-Regulated Promoter That Targets Hyperactive Neurons in Epilepsy for Gene Therapy Applications.

Epileptogenesis is characterized by intrinsic changes in neuronal firing, resulting in hyperactive neurons and the subsequent generation of seizure activity. These alterations are accompanied by changes in gene transcription networks, first with the activation of early-immediate genes and later with the long-term activation of genes involved in memory. Our objective was to engineer a promoter containing binding sites for activity-dependent transcription factors upregulated in chronic epilepsy (EpiPro) and validate it in multiple rodent models of epilepsy.

Chargeability study of disinfectants and the optimization of design parameters of a handheld electrostatic disinfection device for small scale applications.

Apart from aerosols, contaminated surfaces with SARS-CoV-2 virus are the significant carriers of virus transmission. The disinfection and sanitization of the indoor and outdoor places are one among the powerful and effective strategies to avoid the surface-to-human transmission of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) through frequent touch and physical contact. Electrostatic spraying is one of the effective and efficient methods to apply the liquid-based sprays on surfaces to be disinfected or sanitized.

A wideband hybrid combiner design for ITER ion cyclotron radio frequency source.

The high-power radio frequency source for ion cyclotron heating and current drive of ITER tokamak consists of two identical 1.5 MW amplifier chains. These two chains will be combined using a wideband hybrid combiner with adequate coupling flatness, phase balance, return loss, and isolation response to generate 2.

Potent Long-Acting Inhibitors Targeting the HIV-1 Capsid Based on a Versatile Quinazolin-4-one Scaffold.

Long-acting (LA) human immunodeficiency virus-1 (HIV-1) antiretroviral therapy characterized by a ≥1 month dosing interval offers significant advantages over daily oral therapy. However, the criteria for compounds that enter clinical development are high. Exceptional potency and low plasma clearance are required to meet dose size requirements; excellent chemical stability and/or crystalline form stability is required to meet formulation requirements, and new antivirals in HIV-1 therapy need to be largely free of side effects and drug-drug interactions.

Validation of traditional claims of anti-arthritic efficacy of trans-Himalayan snow mountain garlic (Allium ampeloprasum L.) extract using adjuvant-induced arthritis rat model: A comparative evaluation with normal garlic (Allium sativum L.) and dexamethasone.

Ethnopharmacological Relevance: Snow Mountain Garlic (SMG) (Allium ampeloprasum L.) is a wild trans-Himalayan member of the genus Allium, valued for its anti-inflammatory and anti-arthritic properties in the mountain folk medicinal system (Sowa-Rigpa). Despite its age-old medicinal usage by traditional therapists and the native population for various ailments including rheumatism, there is no scientific validation of its phyto-pharmaceutical merits.

Seed coat colour of Indian mustard [ (L.) Czern. and Coss.] is associated with homologs identifiable by targeted functional markers.

Seed coat colour is an important trait in Indian mustard. Breeding for seed coat colour needs precise knowledge of mode of inheritance and markers linked to it. The present study was focussed on genetics and development of functional markers for seed coat colour.

Forebrain epileptiform activity is not required for seizure-induced apnea in a mouse model of epilepsy.

Sudden unexpected death in epilepsy (SUDEP) accounts for the deaths of 8-17% of patients with epilepsy. Although the mechanisms of SUDEP are essentially unknown, one proposed mechanism is respiratory arrest initiated by a convulsive seizure. In mice, we have previously observed that extended apnea occurs during the tonic phase of seizures.

Deciphering the Genetic Inheritance of Tocopherols in Indian Mustard ( L. Czern and Coss).

Tocopherol is vital for the nutritional value and stability of Indian mustard ( L. Czern and Coss) oil; nonetheless, the lack of information on genetic control is hampering its improvement. In this study, six populations (P, P, F, F, BCP, and BCP) of RLC3 × NPJ203 were evaluated in a family block design to evaluate the inheritance pattern, gene effects, and various other genetic parameters of tocopherol content (α, γ, and total), using generation mean analysis.

Discovery and Preclinical Profiling of GSK3839919, a Potent HIV-1 Allosteric Integrase Inhibitor.

Allosteric HIV-1 integrase inhibitors (ALLINIs) have been of interest recently because of their novel mechanism of action. Strategic modifications to the C5 moiety of a class of 4-(4,4-dimethylpiperidinyl)-2,6-dimethylpyridinyl ALLINIs led to the identification of a tetrahydroisoquinoline heterocycle as a suitable spacer element to project the distal hydrophobic aryl ring. Subsequent optimization of the aryl substitutions identified as an ALLINI with single-digit nanomolar inhibitory potency and low clearance across preclinical species.

Scaffold modifications to the 4-(4,4-dimethylpiperidinyl) 2,6-dimethylpyridinyl class of HIV-1 allosteric integrase inhibitors.

Allosteric integrase inhibitors (ALLINIs) of HIV-1 may hold promise as a novel mechanism for HIV therapeutics and cure. Scaffold modifications to the 4-(4,4-dimethylpiperidinyl) 2,6-dimethylpyridinyl class of ALLINIs provided a series of potent compounds with differentiated 5/6 fused ring systems. Notably, inhibitors containing the 1,2,4-triazolopyridine and imidazopyridine core exhibited single digit nM antiviral potency and low to moderate clearance after intravenous (IV) dosing in rat pharmacokinetic (PK) studies.

A comparative study of in-vitro and in-silico anti-candidal activity and GC-MS profiles of snow mountain garlic vs. normal garlic.

Aim: The study aimed to profile the volatile phytocomposition of snow mountain garlic (SMG) compared to normal garlic and investigate the anti-Candida efficacy against clinically relevant multi-drug resistant isolates of Candida species.

Methods And Results: Herein, SMG has shown significantly superior fungicidal power at 2x-MIC dose against C. albicans and C.

Design, Synthesis, and Preclinical Profiling of GSK3739936 (BMS-986180), an Allosteric Inhibitor of HIV-1 Integrase with Broad-Spectrum Activity toward 124/125 Polymorphs.

Allosteric HIV-1 integrase inhibitors (ALLINIs) have garnered special interest because of their novel mechanism of action: they inhibit HIV-1 replication by promoting aberrant integrase multimerization, leading to the production of replication-deficient viral particles. The binding site of ALLINIs is in a well-defined pocket formed at the interface of two integrase monomers that is characterized by conserved residues along with two polymorphic amino acids at residues 124 and 125. The design, synthesis, and optimization of pyridine-based allosteric integrase inhibitors are reported here.