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The impact of genetic analysis on the early detection of colorectal cancer

Agrawal et al. | Aug 24, 2023

The impact of genetic analysis on the early detection of colorectal cancer

Although the 5-year survival rate for colorectal cancer is below 10%, it increases to greater than 90% if it is diagnosed early. We hypothesized from our research that analyzing non-synonymous single nucleotide variants (SNVs) in a patient's exome sequence would be an indicator for high genetic risk of developing colorectal cancer.

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Can the nucleotide content of a DNA sequence predict the sequence accessibility?

Balachandran et al. | Mar 10, 2023

Can the nucleotide content of a DNA sequence predict the sequence accessibility?
Image credit: Warren Umoh

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.

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Toxicity of aminomethylphosphonic acid via the Wnt signaling pathway as a novel mechanism

Zhuang et al. | Mar 08, 2023

Toxicity of aminomethylphosphonic acid via the Wnt signaling pathway as a novel mechanism
Image credit: Image credit: Dapur Melodi

The Wnt signaling pathway, known to coordinate important aspects of cellular homeostasis ranging from differentiation, proliferation, migration, and much more, is dysregulated in many human diseases. This study demonstrates that aminomethylphosphonic acid, which is the main metabolite found in the common herbicide Glyphosate, is toxic to planaria and capable of binding to canonical Wnt proteins.

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Deciphering correlation and causation in risk factors for heart disease with Mendelian randomization

Singh et al. | Feb 08, 2023

Deciphering correlation and causation in risk factors for heart disease with Mendelian randomization
Image credit: Robina Weermeijer

Here, seeking to identify the risk of coronary artery disease (CAD), a major cause of cardiovascular disease, the authors used Mendelian randomization. With this method they identified several traits such as blood pressure readings, LDL cholesterol and BMI as significant risk factors. While other traits were not found to be significant risk factors.

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Reactivity-informed design, synthesis, and Michael addition kinetics of C-ring andrographolide analogs

Zhou et al. | Nov 17, 2022

Reactivity-informed design, synthesis, and Michael addition kinetics of C-ring andrographolide analogs

Here, based on the identification of androgapholide as a potential therapeutic treatment against cancer, Alzheimer's disease, diabetes, and multiple sclerosis, due to its ability to inhibit a signaling pathway in immune system function, the authors sought ways to optimize the natural product human systems by manipulating its chemical structure. Through the semisynthesis of a natural product along with computational studies, the authors developed an understanding of the kinetic mechanisms of andrographolide and semisynthetic analogs in the context of Michael additions.

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Assessing CDK5 as a Nanomotor for Chemotactic Drug Delivery

Jiang et al. | Sep 08, 2022

Assessing CDK5 as a Nanomotor for Chemotactic Drug Delivery

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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Investigation of unknown causes of uveal melanoma uncovers seven recurrent genetic mutations

Nanda et al. | Aug 25, 2022

Investigation of unknown causes of uveal melanoma uncovers seven recurrent genetic mutations

Uveal melanoma (UM) is a rare subtype of melanoma but the most frequent primary cancer of the eye in adults. The goal of this study was to research the genetic causes of UM through a comprehensive frequency analysis of base-pair mismatches in patient genomes. Results showed a total of 130 genetic mutations, including seven recurrent mutations, with most mutations occurring in chromosomes 3 and X. Recurrent mutations varied from 8.7% to 17.39% occurrence in the UM patient sample, with all mutations identified as missense. These findings suggest that UM is a recessive heterogeneous disease with selective homozygous mutations. Notably, this study has potential wider significance because the seven genes targeted by recurrent mutations are also involved in other cancers.

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