Induction of p73, Δ133p53, Δ160p53, pAKT lead to neuroprotection via DNA repair by 5-LOX inhibition

Molecular Biology Reports - The inflammatory process plays a key role in neurodegenerative disorder. The inflammatory molecule, 5-lipooxygenase (5-LOX), protein is involved in the pathologic...     

Fog computing in enabling 5G-driven emerging technologies for development of sustainable smart city infrastructures

Cluster Computing - The usage of 5G-enabled IoT devices is rising exponentially as humans tend to shift towards a more automated lifestyle. A significant amount of IoT devices is expected to join...     

A novel dual luciferase based high throughput assay to monitor autophagy in real time in yeast S. cerevisiae

BackgroundMacroautophagy is a cellular response to starvation wherein superfluous and damaged cytoplasmic constituents are degraded to provide energy for survival and to maintain cellular homeostasis. Dysfunctional autophagy is attributed to disease progression in several pathological conditions and therefore, autophagy has appeared as a potential pharmacological target for such conditions.ObjectiveIn search of potential drugs that modulate autophagy, identifying small molecule effectors of autophagy is the primary step. The conventional autophagy assays have a limitation that they cannot be scaled down to a high throughput format, therefore, novel sensitive assays are needed to discover new candidate molecules. Keeping this rationale in mind, a dual luciferase based assay was developed in the yeast S. cerevisiae that could measure both selective and general autophagy in real time.MethodsFirefly and Renilla luciferase reporter genes were cloned under POT-1 promoter. Using fatty acid medium the promoter was induced and the luciferase cargo was allowed to build up. The cells were then transferred to starvation conditions to stimulate autophagy and the degradation of luciferase markers was followed with time.Results and conclusionThe assay was more sensitive than conventional assays and could be scaled down to a 384 well format using an automated system. A good Z-factor score indicated that the assay is highly suitable for High Throughput Screening (HTS) of small molecule libraries. Screening of a small molecule library with our assay identified several known and novel modulators of autophagy.     

A mechanics-based perspective on the function of the esophagogastric junction during functional luminal imaging probe manometry

Biomechanics and Modeling in Mechanobiology - The esophagogastric junction (EGJ) is located at the distal end of the esophagus and acts as a valve allowing swallowed food to enter the stomach and...     

5-LOX in Alzheimer’s Disease: Potential Serum Marker and In Vitro Evidences for Rescue of Neurotoxicity by Its Inhibitor YWCS

The inflammatory process plays a key role in neurodegenerative disorder. The inflammatory molecule, 5-lipooxygenase (5-LOX), protein is involved in the pathologic phenotype of Alzheimer’s disease (AD) which includes Aβ amyloid deposition and tau hyperphosphorylation. This study determined the level of 5-LOX in serum of AD patients, mild cognitive impairment (MCI) patients, and the normal elderly, and the rescue effect by YWCS, a peptide inhibitor of 5-LOX on neurotoxicity by Aβ amyloid_25–35 (Aβ_25–35) in neuroblastoma cells. The concentration of serum 5-LOX was estimated by surface plasmon resonance and western blot. The neuroprotective effect of 5-LOX peptide inhibitor YWCS in Aβ_25–35-induced neurotoxicity was analyzed by MTT assay and western blotting. We found significant upregulated serum 5-LOX in AD patients and also in MCI patients compared to the normal control group. The peptide inhibitor of 5-LOX, YWCS, prevented the neurotoxic effect of Aβ_25–35 by reducing the expression of γ-secretase as well as p-Tau₁₈₁ in SH-SY5Y cells. However, YWCS was nontoxic towards normal HEK cells. The differential expression of serum 5-LOX among the study groups suggests it can be one of potential serum protein marker and a therapeutic regimen for AD and MCI. The negative correlation with neuropsychological parameters, i.e., MoCA and HMSE, increases its importance and makes it useful during the clinical setup which is very needful in developing countries. Peptide YWCS can serve as a new platform as a 5-LOX inhibitor which can prevent neurotoxicity developed in AD.     

Simulation of glioblastoma growth using a 3D multispecies tumor model with mass effect

Journal of Mathematical Biology - In this article, we present a multispecies reaction–advection–diffusion partial differential equation coupled with linear elasticity for modeling tumor...     

The infant gut resistome associates with E. coli,environmental exposures,gut microbiome maturity,and asthma-associated bacterial composition

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Synthesis and SAR of 4-aminocyclopentapyrrolidines as orally active N-type calcium channel inhibitors for inflammatory and neuropathic pain

A novel series of N-type calcium channel inhibitors have been discovered. Optimization of potency and HT-ADME properties provides 4-aminocyclopentapyrrolidines with analgesic efficacy after oral dosing.     

SUMO fosters assembly and functionality of the MutSγ complex to facilitate meiotic crossing over

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