A genetically encoded actuator boosts L-type calcium channel function in diverse physiological settings.

L-type Ca channels (Ca1.2/1.3) convey influx of calcium ions that orchestrate a bevy of biological responses including muscle contraction, neuronal function, and gene transcription.

L-type calcium channel regulation of depression, anxiety and anhedonia-related behavioral phenotypes following chronic stress exposure.

Exposure to chronic and unpredictable stressors can precipitate mood-related disorders in humans, particularly in individuals with pre-existing mental health challenges. L-type calcium channels (LTCCs) have been implicated in numerous neuropsychiatric disorders, as LTCC encoding genes have been identified as candidate risk factors for neuropsychiatric illnesses. In these sets of experiments, we sought to examine the ability of LTCC blockade to alter depression, anxiety, and anhedonic-related behavioral responses to chronic unpredictable stress (CUS) exposure in female and male rats.

Elevating levels of the endocannabinoid 2-arachidonoylglycerol blunts opioid reward but not analgesia.

Converging findings have established that the endocannabinoid (eCB) system serves as a possible target for the development of new treatments for pain as a complement to opioid-based treatments. Here we show in male and female mice that enhancing levels of the eCB, 2-arachidonoylglycerol (2-AG), through pharmacological inhibition of its catabolic enzyme, monoacylglycerol lipase (MAGL), either systemically or in the ventral tegmental area (VTA) with JZL184, leads to a substantial attenuation of the rewarding effects of opioids in male and female mice using conditioned place preference and self-administration paradigms, without altering their analgesic properties. These effects are driven by CB1 receptors (CB1Rs) within the VTA as VTA CB1R conditional knockout, counteracts JZL184's effects.

Interneuron FGF13 regulates seizure susceptibility via a sodium channel-independent mechanism.

Developmental and Epileptic Encephalopathies (DEEs), a class of devastating neurological disorders characterized by recurrent seizures and exacerbated by disruptions to excitatory/inhibitory balance in the brain, are commonly caused by mutations in ion channels. Disruption of, or variants in, were implicated as causal for a set of DEEs, but the underlying mechanisms were clouded because is expressed in both excitatory and inhibitory neurons, undergoes extensive alternative splicing producing multiple isoforms with distinct functions, and the overall roles of FGF13 in neurons are incompletely cataloged. To overcome these challenges, we generated a set of novel cell type-specific conditional knockout mice.

A Genetically Encoded Actuator Selectively Boosts L-type Calcium Channels in Diverse Physiological Settings.

L-type Ca channels (Ca 1.2/1.3) convey influx of calcium ions (Ca ) that orchestrate a bevy of biological responses including muscle contraction and gene transcription.

Repeat investigation during social preference behavior is suppressed in male mice with prefrontal cortex (Ca1.2)-deficiency through the dysregulation of neural dynamics.

Impairments in social behavior are observed in a range of neuropsychiatric disorders and several lines of evidence have demonstrated that dysfunction of the prefrontal cortex (PFC) plays a central role in social deficits. We have previously shown that loss of neuropsychiatric risk gene that codes for the Ca1.2 isoform of L-type calcium channels (LTCCs) in the PFC result in impaired sociability as tested using the three-chamber social approach test.

A comparative study of modulatory interaction between cytokines and apoptotic proteins among Scleroderma patients with and without pulmonary involvement.

Background: Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are the most eminent forms of pulmonary involvement in Scleroderma. In this study we investigate the interaction between cytokines and apoptotic proteins in treatment naive Scleroderma (SSc) patients with and without pulmonary involvement.

Methods: Newly diagnosed treatment naïve Scleroderma (SSc) patients (n = 100) and healthy controls (n = 100) were enrolled.

L-type calcium channels and neuropsychiatric diseases: Insights into genetic risk variant-associated genomic regulation and impact on brain development.

Recent human genetic studies have linked a variety of genetic variants in the and genes to neuropsychiatric and neurodevelopmental disorders. This is not surprising given the work from multiple laboratories using cell and animal models that have established that Ca1.2 and Ca1.

Ca1.3 L-type Ca channel-activated CaMKII/ERK2 pathway in the ventral tegmental area is required for cocaine conditioned place preference.

We have previously demonstrated that pharmacological blockade of ventral tegmental area (VTA) Ca1.3 L-type calcium channels (LTCCs) using Ca1.2 dihydropyridine insensitive (Ca1.

Sex differences in the medial prefrontal cortical glutamate system.

Background: Dysregulation in the prefrontal cortex underlies a variety of psychiatric illnesses, including substance use disorder, depression, and anxiety. Despite the established sex differences in prevalence and presentation of these illnesses, the neural mechanisms driving these differences are largely unexplored. Here, we investigate potential sex differences in glutamatergic transmission within the medial prefrontal cortex (mPFC).

A Clinical Profile of Patients with Hyperuricemia and the Relationship between Hyperuricemia and Metabolic Syndrome: A Cross-sectional Study at a Tertiary Hospital in the Indian Population.

Introduction: Metabolic syndrome is a constellation of interrelated risk factors that increase the risk of cardiovascular diseases (CVD) and diabetes mellitus. The increase in prevalence of hyperuricemia was considered to be directly related to increasing incidence of obesity and Metabolic Syndrome in developing and developed countries. Hyperuricemia is defined as serum uric acid of 6.

Mannose Binding Lectin Levels and its Association with Systemic Lupus Erythematosus Disease Severity: An Indian Report.

Background: Dysregulated serum levels of Mannan binding lectin (MBL) has a probable role in Systemic Lupus Erythematosus (SLE) pathogenesis.

Objective: To evaluate the association between serum MBL levels in SLE patients from western India with the severity of disease Methods: SLE patients (n=70) from Western India were included. Based on MBL levels, patients were classified into four categories, viz.

Impact of Autoantibodies to Complement Components on the Disease Activity in SLE.

Introduction: Systemic Lupus Erythematosus (SLE) is a chronic multi-system autoimmune disease with varied clinical presentations. Complement components are the major players in disease pathogenesis. This retrospective cross-sectional study was aimed at assessing the role of autoantibodies to these complement components and their association disease activity in newly diagnosed SLE patients from India.

Scn2a severe hypomorphic mutation decreases excitatory synaptic input and causes autism-associated behaviors.

SCN2A, encoding the neuronal voltage-gated Na+ channel NaV1.2, is one of the most commonly affected loci linked to autism spectrum disorders (ASDs). Most ASD-associated mutations in SCN2A are loss-of-function mutations, but studies examining how such mutations affect neuronal function and whether Scn2a mutant mice display ASD endophenotypes have been inconsistent.

Dual-process brain mitochondria isolation preserves function and clarifies protein composition.

The brain requires continuously high energy production to maintain ion gradients and normal function. Mitochondria critically undergird brain energetics, and mitochondrial abnormalities feature prominently in neuropsychiatric disease. However, many unique aspects of brain mitochondria composition and function are poorly understood.

A Machine Learning Approach to Predicting Autism Risk Genes: Validation of Known Genes and Discovery of New Candidates.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a strong genetic basis. The role of mutations in ASD has been well established, but the set of genes implicated to date is still far from complete. The current study employs a machine learning-based approach to predict ASD risk genes using features from spatiotemporal gene expression patterns in human brain, gene-level constraint metrics, and other gene variation features.

Loss of Cav1.2 channels impairs hippocampal theta burst stimulation-induced long-term potentiation.

CACNA1 C, which codes for the Ca1.2 isoform of L-type Ca channels (LTCCs), is a prominent risk gene in neuropsychiatric and neurodegenerative conditions. A role forLTCCs, and Ca1.

Hypervitaminosis D and Cortical Venous Thrombosis; An Unusual Presentation.

Hypervitaminosis D is rare but potentially serious condition. It occurs most commonly due to excess doses of vitamin D supplementation, most commonly intramuscular. Here we report a case of iatrogenic hypervitaminosis D who presented with altered sensorium, cortical venous thrombosis and acute renal failure.

Cytokine genes multi-locus analysis reveals synergistic influence on genetic susceptibility in Indian SLE - A multifactor-dimensionality reduction approach.

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with unclear etiology. Several loci associated with genetic susceptibility for lupus have been described. However, it lacks reports on cytokine gene-gene interactions among SLE patients from Asian population.

Infections in Systemic Lupus Erythematosus.

Objectives: Infections are a major cause of morbidity and mortality in patients of Systemic Lupus erythematosus (SLE). We therefore aimed to determine the spectrum of infections in patients of SLE, find a correlation between various disease parameters and the severity and outcome of infections and to compare the outcome between different modalities of immunosuppressive therapy.

Methods: A cross-sectional study was carried out by including all the diagnosed patients of Systemic lupus erythematosus (based on SLICC criteria[1]) aged 12 years and above who developed infections during the study period of 18 months.

Cereblon harnesses Myc-dependent bioenergetics and activity of CD8+ T lymphocytes.

Immunomodulatory drugs, such as thalidomide and related compounds, potentiate T-cell effector functions. Cereblon (CRBN), a substrate receptor of the DDB1-cullin-RING E3 ubiquitin ligase complex, is the only molecular target for this drug class, where drug-induced, ubiquitin-dependent degradation of known "neosubstrates," such as IKAROS, AIOLOS, and CK1α, accounts for their biological activity. Far less clear is whether these CRBN E3 ligase-modulating compounds disrupt the endogenous functions of CRBN.

Dopamine D1R-neuron cacna1c deficiency: a new model of extinction therapy-resistant post-traumatic stress.

Post-traumatic stress disorder (PTSD) is characterized by persistent fear memory of remote traumatic events, mental re-experiencing of the trauma, long-term cognitive deficits, and PTSD-associated hippocampal dysfunction. Extinction-based therapeutic approaches acutely reduce fear. However, many patients eventually relapse to the original conditioned fear response.