Enzyme chemotaxis is a thermodynamic phenomenon in which enzymes move along a substrate concentration gradient towards regions with higher substrate concentrations and can be used to steer nanovehicles towards targets along natural substrate concentrations. In patients with Alzheimer’s disease, a gradient of tau protein forms in the bloodstream. Tau protein is a substrate of the enzyme CDK5, which catalyzes the phosphorylation of tau protein and can travel using chemotaxis along tau protein gradients to increasing concentrations of tau and amyloid-beta proteins. The authors hypothesized that CDK5 would be able to overcome these barriers of Brownian motion and developed a quantitative model using Michaelis-Menten kinetics to define the necessary parameters to confirm and characterize CDK5’s chemotactic behavior to establish its utility in drug delivery and other applications.
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Design and in silico screening of analogs of rilpivirine as novel non-nucleoside reverse transcriptase inhibitors (NNRTIs) for antiretroviral therapy
In this study, the authors use high-throughput virtual screening to design and evaluate a set of non-nucleoside reverse transcriptase inhibitors for binding affinity to the protein reverse transcriptase. These studies have important applications toward HIV therapies.
Read More...Can the nucleotide content of a DNA sequence predict the sequence accessibility?
Sequence accessibility is an important factor affecting gene expression. Sequence accessibility or openness impacts the likelihood that a gene is transcribed and translated into a protein and performs functions and manifests traits. There are many potential factors that affect the accessibility of a gene. In this study, our hypothesis was that the content of nucleotides in a genetic sequence predicts its accessibility. Using a machine learning linear regression model, we studied the relationship between nucleotide content and accessibility.
Read More...Prediction of preclinical Aβ deposit in Alzheimer’s disease mice using EEG and machine learning
Alzheimer’s disease (AD) is a common disease affecting 6 million people in the U.S., but no cure exists. To create therapy for AD, it is critical to detect amyloid-β protein in the brain at the early stage of AD because the accumulation of amyloid-β over 20 years is believed to cause memory impairment. However, it is difficult to examine amyloid-β in patients’ brains. In this study, we hypothesized that we could accurately predict the presence of amyloid-β using EEG data and machine learning.
Read More...A new therapy against MDR bacteria by in silico virtual screening of Pseudomonas aeruginosa LpxC inhibitors
Here, seeking to address the growing threat of multidrug-resistant bacteria (MDR). the authors used in silico virtual screening to target MDR Pseudomonas aeruginosa. They considered a key protein in its biosynthesis and virtually screened 20,000 candidates and 30 derivatives of brequinar. In the end, they identified a possible candidate with the highest degree of potential to inhibit the pathogen's lipid A synthesis.
Read More...RNAi-based Gene Therapy Targeting ZGPAT Promotes EGF-dependent Wound Healing
Wound-healing involves a sequence of events, such as inflammation, proliferation, and migration of different cell types like fibroblasts. Zinc Finger CCCH-type with G-Patch Domain Containing Protein (ZGPAT), encodes a protein that has its main role as a transcription repressor by binding to a specific DNA sequence. The aim of the study was to find out whether inhibiting ZGPAT will expedite the wound healing process by accelerating cell migration. This treatment strategy can provide a key to the development of wound healing strategies in medicine and cellular biology.
Read More...String analysis of exon 10 of the CFTR gene and the use of Bioinformatics in determination of the most accurate DNA indicator for CF prediction
Cystic fibrosis is a genetic disease caused by mutations in the CFTR gene. In this paper, the authors attempt to identify variations in stretches of up to 8 nucleotides in the protein-coding portions of the CFTR gene that are associated with disease development. This would allow screening of newborns or even fetuses in utero to determine the likelihood they develop cystic fibrosis.
Read More...How Ethanol Concentration Affects Catalase Catalysis of Hydrogen Peroxide
Catalase is a critical enzyme in the human body because it is capable of converting potentially dangerous hydrogen peroxide into water and oxygen. This work asks whether ethanol affects catalase activity, as alcohol consumption has been often linked to hepatitis occurring in the liver, where catalase level is especially high, and ethanol is known to be capable of denaturing proteins. Testing different concentrations of ethanol found that higher concentrations reduced the activity of catalase. This work has important implications on the negative effects of ethanol on metabolism, in which catalase plays an important role, and protein function more broadly.
Read More...Down-regulation of CD44 inhibits Wnt/β-catenin mediated cancer cell migration and invasion in gastric cancer
In this study, we aimed to characterize CD44-mediated regulation of the Wnt/β-catenin signaling pathway, which promotes cancer invasion and metastasis. We hypothesized that CD44 down-regulation will inhibit gastric cancer cell migration and invasion by leading to down-regulation of Wnt/β-catenin signaling. We found that CD44 up-regulation was significantly related to poor prognosis in gastric cancer patients. We demonstrated the CD44 down-regulation decreased β-catenin protein expression level. Our results suggest that CD44 down-regulation inhibits cell migration and invasion by down-regulating β-catenin expression level.
Read More...Synthesis of a novel CCR1 antagonist for treatment of glioblastoma
Glioblastoma is a brain cancer caused by the presence of a fast-growing, malignant tumor in the brain. As of now, this cancer is universally lethal due to lack of efficacious treatment options. C-C chemokine receptor 1 (CCR1) is a G-protein coupled receptor that controls chemotaxis, the movement of cells in response to chemical stimuli. This research aims to synthesize potential CCR1 antagonists by coupling carboxylic acids with a triazole core. We synthesized these compounds using a simple carboxylic acid coupling and confirmed the identity of the final compounds using nuclear magnetic resonance (NMR) spectroscopy.
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