Vikrant Singh

Dr. A.P.J. Abdul Kalam Technical University · Department of Mechanical Engineering

Hexahydro-1,3,5-trinitro-1,3,5-triazine, or Royal Demolition Explosive (RDX), is a major component of plastic explosives such as C-4. Acute exposures from intentional or accidental ingestion are a documented clinical concern, especially among young male U.S. service members in the armed forces. When ingested in large enough quantity, RDX causes ton...

21 The voltage-gated sodium Na V 1.7 channel plays a key role as a mediator of action 22 potential propagation in C-fiber nociceptors and is an established molecular target for 23 pain therapy. ProTx-II is a potent and moderately selective peptide toxin from tarantula 24 venom that inhibits human Na V 1.7 activation. Here we used available structur...

21 The voltage-gated sodium Na V 1.7 channel plays a key role as a mediator of action 22 potential propagation in C-fiber nociceptors and is an established molecular target for 23 pain therapy. ProTx-II is a potent and moderately selective peptide toxin from tarantula 24 venom that inhibits human Na V 1.7 activation. Here we used available structur...

Epileptogenic seizures, or status epilepticus (SE), leads to excitotoxic injury in hippocampal and limbic neurons in the kainic acid (KA) animal model of temporal lobe epilepsy (TLE). Here, we have further characterized neural activity regulated methylaminoisobutryic acid (MeAIB)/glutamine transport activity in mature rat hippocampal neurons in vit...

Objective: Royal demolition explosive (RDX) can induce seizures in wildlife and humans following release into the environment or after voluntary consumption. During the Vietnam War, RDX intoxication was the most common cause of generalized seizures in US service personnel, and in some sections of the armed forces, eating of RDX has continued as "a...

Uncontrolled fibrous aggregation of proteins in the human brain implicates a range of anomalous biological phenomena, ultimately leading to Alzheimer's Disease (AD). Aggregates of β-Amyloid(1-42) (AB42) have been considered the most viable biomarker for early diagnosis of AD; therefore, it is highly essential to detect AB42 peptides in easily acces...

Thyroid hormones (THs) are essential for normal vertebrate development and diverse environmental chemicals are hypothesized to cause developmental toxicity by disrupting TH-mediated signaling. The larval zebrafish (Danio rerio) is an emerging in vivo model of developmental TH disruption; however, the effects of TR antagonism have not yet been studi...

The capsaicin receptor TRPV1 is an outstanding representative of ligand-gated ion channels in ligand selectivity and sensitivity. However, molecular interactions that stabilize the ligand-binding pocket in its permissive conformation, and how many permissive conformations the ligand-binding pocket may adopt, remain unclear. To answer these question...

Characterization of the key cellular targets contributing to sustained microglial activation in neurodegenerative diseases, including Parkinson's disease (PD), and optimal modulation of these targets can provide potential treatments to halt disease progression. Here, we demonstrated that microglial Kv1.3, a voltage-gated potassium channel, was tran...

Ion channels have recently attracted attention as potential mediators of skin disease. Here, we explored the consequences of genetically encoded induction of the cell volume-regulating Ca²⁺-activated KCa3.1 channel (Kcnn4) for murine epidermal homeostasis. Doxycycline-treated mice harboring the KCa3.1+-transgene under the control of the reverse tet...

Ion channels have recently attracted attention as potential mediators of skin disease. Here, we explored the consequences of genetically encoded induction of the cell volume-regulating Ca 2+ -activated KCa3.1 channel ( Kcnn4 ) for murine epidermal homeostasis. Doxycycline-treated mice harboring the KCa3.1+-transgene under the control of the reverse...

Calcium-activated K⁺ channels constitute attractive targets for the treatment of neurological and cardiovascular diseases. To explain why certain 2-aminobenzothiazole/oxazole-type KCa activators (SKAs) are KCa3.1 selective we previously generated homology models of the C-terminal calmodulin-binding domain (CaM-BD) of KCa3.1 and KCa2.3 in complex wi...

Chronic neuroinflammation characterized by the sustained activation of microglia and subsequent release of pro‐inflammatory mediators is concomitant with the progressive neurodegeneration observed in Parkinson's disease (PD). Microglial potassium channels have a well‐developed pharmacology and constitute attractive targets for reducing neuroinflamm...

Figure S1. Microglial KCa3.1 expression is elevated in brains of 4‐month‐old 5xFAD mice. Figure S2. Microglial KCa3.1 expression in human AD brains is located to microglia but not astrocytes. Figure S3. Treatment with senicapoc‐medicated diet resulted in therapeutically active brain levels. Figure S4. The effect of chronic oral senicapoc treatme...

Objective Purkinje neuron dysfunction is associated with cerebellar ataxia. In a mouse model of spinocerebellar ataxia type 1 (SCA1), reduced potassium channel function contributes to altered membrane excitability resulting in impaired Purkinje neuron spiking. We sought to determine the relationship between altered membrane excitability and motor d...

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and...

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and...

The Hv1 voltage-gated proton channel is a dimeric complex consisting of two voltage-sensing domains (VSDs), each containing a gated proton permeation pathway. Dimerization is controlled by a cytoplasmic coiled-coil domain. The transitions from the closed to the open state in the two VSDs are known to occur cooperatively; however, the underlying mec...

Unlabelled: Neuronal atrophy in neurodegenerative diseases is commonly viewed as an early event in a continuum that ultimately results in neuronal loss. In a mouse model of the polyglutamine disorder spinocerebellar ataxia type 1 (SCA1), we tested the hypothesis that cerebellar Purkinje neuron atrophy serves an adaptive role rather than being simp...

Small-conductance (KCa2) and intermediate-conductance (KCa3.1) calcium-activated K+ channels are voltage-independent and share a common calcium/calmodulin-mediated gating mechanism. Existing positive gating modulators like EBIO, NS309 or SKA-31 activate both KCa2 and KCa3.1 channels with similar potency or, as in the case of CyPPA and NS13001, sele...