Muthusamy, A. | bioRxiv Science

bioRxiv2023

Unraveling the Potential of Epicatechin Gallate in Targeting Aberrant Cardiac Ca2+ Signaling Protein

The cardiovascular sarcoplasmic reticulum (SR) calcium (Ca2+) ATPase is an imperative determinant of cardiac functionality. In addition, anomalies in Ca2+ handling protein and atypical energy metabolism are inherent in heart failure (HF). Moreover, Ca2+ overload in SR leads to mitochondrial matrix Ca2+ overload, which can trigger the generation of Reactive Oxygen Species (ROS), culminating in the triggering of the Permeability Transition Pore (PTP) and Cytochrome C release, resulting in apoptosis that leads to arrhythmias and numerous disorders. Although proteins involved in the molecular mechanism of Ca2+ dysfunction regarding mitochondrial dysfunction remains elusive, this study aims to assess the major Ca2+ handling proteins which may be involved in the Ca2+ malfunction that causes mitochondrial dysfunction and predicting the most effective drug by targeting the analyzed Ca2+ handling proteins through various insilico analyses.Thirteen proteins absorbed from interaction analysis were docked with four optimal phytochemicals from Crataegus oxyacantha (COC) to identify the potential agonist/antagonist against those anomalies causing Ca2+ handling signaling proteins. Furthermore,The ADMET profile of tyramine, vitexin, epicatechin, and epicatechin gallate was acclimated to evaluate potential drugability utilizing QikProp by Schrodinger.Keeping this in view, critical molecular docking evaluations were performed using Glide (Maestro), autodock, and autodock vina.Based on the results of 156 dockings by Maestro, auto-dock, and auto-dock vina, PKA C with epicatechin gallate exhibits good interaction. Therefore, a 2000ns molecular dynamics (MD) simulation was utilized to assess the feasible phytochemical epicatechin gallate - PKA C complex binding stability utilizing Desmond. As a result, the molecular dynamics simulation study confirmed that epicatechin gallate from COC has high possibilities to inhibit the aberrant cardiac Ca2+ signaling proteins due to its conformational rigidity.

bioinformatics↗

bioRxiv2017

Responses To Mechanically And Visually Cued Water Waves In The Nervous System Of The Medicinal Leech

Summary statementCues from water movement help aquatic predators find their prey. We study how the nervous system of the medicinal leech processes visual and mechanical information derived from surface waves.\n\nAbstractSensitivity to water waves is a key modality by which aquatic predators can detect and localize their prey. For one such predator, the medicinal leech, Hirudo verbana, behavioral responses to visual and mechanical cues from water waves are well documented. Here, we quantitatively characterized the response patterns of a multisensory interneuron, the S cell, to mechanically and visually cued water waves. The frequency dependence of the S-cell response matched the behavioral response well, in that sensitivity was higher for low frequencies in the visual modality and for high frequencies in the mechanical modality. We demonstrated that neither the cephalic ganglia nor the tail brain is required for the S cell to respond to visually cued water waves. The direction of spike propagation within the S- cell system did follow the direction of wave propagation under certain circumstances, but it is unlikely that downstream neuronal targets can use this information. In terms of overall firing rate, the S cell response was not direction selective. Accordingly we propose a role for the S cell in the detection of waves but not in the localization of their source.

neuroscience↗