Atomic insight into prion disorder: An intricate detail gained by 0.5 μs molecular dynamics simulation of preventive G127V and deleterious D178V mutation in prion protein.

In this study we are looking into two contradicting mutations found in prion protein (PrP) viz G127V and D178V, that are reportedly protective and pathogenic, respectively. Despite significant advances in comprehension of the role of pathogenic mutations, the role of protective mutation in amyloid fold inhibition still lacks a substantial basis. To understand the structural basis of protective mutation, molecular dynamics simulation coupled with protein-protein docking and molecular mechanics/Poisson-Boltzmann surface area analysis was used to understand the instant structural variability brought about by these mutations alone and in combination on PrP and prion-prion complex.

D224V and S128Y mutation in FSHR influence thumb movement differentially: An intricate insight gained by short-term molecular dynamics simulation.

Follicle-stimulating hormone-follicle-stimulating hormone receptor (FSH-FSHR) interaction is one of the most thoroughly studied signaling pathways primarily because of being implicated in sexual reproduction in mammals by way of maintaining gonadal function and sexual fertility. Despite material advances in understanding the role of point mutations, their mechanistic basis in FSH-FSHR signaling is still confined to mystically altered behavior of sTYS335 (sulfated tyrosine) yet lacking a substantial theory. To understand the structural basis of receptor modulation, we choose two behaviorally contradicting mutations, namely S128Y (activating) and D224Y (inactivating), found in FSH receptor responsible for ovarian hyperstimulation syndrome and ovarian dysgenesis, respectively.

CCL22 and CCR4 Gene Polymorphisms in Myocardial Infarction: Risk Assessment of rs4359426 and rs2228428 in Iranian Population.

Background: Myocardial infarction (MI) is an irreversible damage of myocardial tissue caused by prolonged ischemia and hypoxia. A local hypoxia-induced inflammation causes recruitment of leukocytes to the inflammatory site to aid cardiac remodeling and tissue healing. Among various chemokines involved in the process, CCL22 plays an essential role in cardiac cell migrations.

Structural discordance in HIV-1 Vpu from brain isolate alarms amyloid fibril forming behavior- a computational perspective.

HIV-1 being the most widespread type worldwide, its accounts for almost 95% of all infections including HIV associated dementia (HAD) that triggers neurological dysfunction and neurodegeneration in patients. The common features associated with HAD and other neurodegenerative diseases are accumulation of amyloid plaques, neuronal loss and deterioration of cognitive abilities, amongst which amyloid fibrillation is considered to be a hallmark. The success of effective therapeutics lies in the understanding of mechanisms leading to neurotoxicity.

Irigenin, a novel lead from Western Himalayan chemiome inhibits Fibronectin-Extra Domain A induced metastasis in Lung cancer cells.

Several lines of evidence indicate that Fibronectin Extra Domain A (EDA) promotes metastatic capacity of tumor cells by engaging cell surface α9β1 integrins. This interaction mediated by the C-C loop of EDA activates pro-oncogenic signaling pathways leading to epithelial to mesenchymal transition (EMT) of tumor cells, thus signifying its importance in control of metastatic progression. In this context the present study was designed to explore the active compounds from selected ethno-medicinal plants of western Himalayan region for targeting EDA of Fibronectin in lung carcinoma cells.