Kalirin is a guanine nucleotide exchange factor (GEF) for the GTPase RAC1, linked to schizophrenia and Alzheimer’s Disease. It plays a crucial role in synaptic plasticity by regulating dendritic spine formation and actin cytoskeleton remodeling, which are essential for creating new synapses. Authors developed two novel compounds targeting kalirin, confirming that predictive modeling can indicate biological activity.
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Studying the effects of different anesthetics on quasi-periodic patterns in rat fMRI
The authors looked at the effects of commonly used anesthetics in rodents on brain activity (specifically quasi-periodic patterns). Understanding effects on brain activity is important for researchers to understand when choosing rodent models for disease.
Read More...Testing Simarouba amara’s therapeutic effects against weedicide-induced tumor-like morphology in planarians
According to the World Health Organization, cancer is a leading cause of death globally. The disease’s prevalence is rapidly increasing in association with factors including the increased use of pesticides and herbicides, such as glyphosate, which is one of the most widely used herbicide ingredients. Natural antioxidants and phytochemicals are being tested as anti-cancer agents due to their antiproliferative, antioxidative, and pro-apoptotic properties. Thus, we aimed to investigate the potential role of S. amara extract as a therapeutic agent against glyphosate-induced toxicity and tumor-like morphologies in regenerating and homeostatic planaria (Dugesia dorotocephala).
Read More...Analyzing breath sounds by using deep learning in diagnosing bronchial blockages with artificial lung
Many common respiratory illnesses like bronchitis, asthma, and chronic obstructive pulmonary disease (COPD) lead to bronchial inflammation and, subsequently, a blockage. However, there are many difficulties in measuring the severity of the blockage. A numeric metric to determine the degree of the blockage severity is necessary. To tackle this demand, we aimed to develop a novel human respiratory model and design a deep-learning program that can constantly monitor and report bronchial blockage by recording breath sounds in a non-intrusive way.
Read More...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.
Read More...Effect of environment factors on the expression of soluble PDE8A1 in E. coli
PDE8, a type of phosphodiesterase (PDE), is proven to be crucial in various cellular activities and physiological activities by influencing second messenger systems. It is involved in a wide range of diseases, including Alzheimer’s disease and various heart diseases. However, there is limited information about PDE8 selective inhibitors. This work aimed to improve the solubility and yield of PDE8 in the supernatant by exploring suitable culture conditions, including temperatures and different additives.
Read More...Societal awareness regarding viral Hepatitis in developed and developing countries
Many cases of viral hepatitis are easily preventable if caught early; however, a lack of public awareness regarding often leads to diagnoses near the final stages of disease when it is most lethal. Thus, we wanted to understand to what extent an individual's sex, age, education and country of residence (India or Singapore) impacts disease identification. We sent out a survey and quiz to residents in India (n = 239) and Singapore (n = 130) with questions that test their knowledge and awareness of the disease. We hypothesized that older and more educated individuals would score higher because they are more experienced, but that the Indian population will not be as knowledgeable as the Singaporean population because they do not have as many resources, such as socioeconomic access to schools and accessibility to healthcare, available to them. Additionally, we predicted that there would not be any notable differences between make and females. The results revealed that the accuracy for all groups we looked at was primarily below 50%, demonstrating a severe knowledge gap. Therefore, we concluded that if more medical professionals discussed viral hepatitis during hospital visits and in schools, patients can avoid the end stages of the disease in notable cases.
Read More...Contrasting role of ASCC3 and ALKBH3 in determining genomic alterations in Glioblastoma Multiforme
Glioblastoma Multiforme (GBM) is the most malignant brain tumor with the highest fraction of genome alterations (FGA), manifesting poor disease-free status (DFS) and overall survival (OS). We explored The Cancer Genome Atlas (TCGA) and cBioportal public dataset- Firehose legacy GBM to study DNA repair genes Activating Signal Cointegrator 1 Complex Subunit 3 (ASCC3) and Alpha-Ketoglutarate-Dependent Dioxygenase AlkB Homolog 3 (ALKBH3). To test our hypothesis that these genes have correlations with FGA and can better determine prognosis and survival, we sorted the dataset to arrive at 254 patients. Analyzing using RStudio, both ASCC3 and ALKBH3 demonstrated hypomethylation in 82.3% and 61.8% of patients, respectively. Interestingly, low mRNA expression was observed in both these genes. We further conducted correlation tests between both methylation and mRNA expression of these genes with FGA. ASCC3 was found to be negatively correlated, while ALKBH3 was found to be positively correlated, potentially indicating contrasting dysregulation of these two genes. Prognostic analysis showed the following: ASCC3 hypomethylation is significant with DFS and high ASCC3 mRNA expression to be significant with OS, demonstrating ASCC3’s potential as disease prediction marker.
Read More...High-throughput virtual screening of novel dihydropyrimidine monastrol analogs reveals robust structure-activity relationship to kinesin Eg5 binding thermodynamics
As cancer continues to take millions of lives worldwide, the need to create effective therapeutics for the disease persists. The kinesin Eg5 assembly motor protein is a promising target for cancer therapeutics as inhibition of this protein leads to cell cycle arrest. Monastrol, a small dihydropyrimidine-based molecule capable of inhibiting the kinesin Eg5 function, has attracted the attention of medicinal chemists with its potency, affinity, and specificity to the highly targeted loop5/α2/α3 allosteric binding pocket. In this work, we employed high-throughput virtual screening (HTVS) to identify potential small molecule Eg5 inhibitors from a designed set of novel dihydropyrimidine analogs structurally similar to monastrol.
Read More...The Effect of the Human MeCP2 gene on Drosophila melanogaster behavior and p53 inhibition as a model for Rett Syndrome
In this study, the authors observe if the symptoms of Rett Syndrome, a neurodegenerative disease in humans, are reflected in Drosophila melanogaster. This was achieved by differentiating the behavior and physical aspects of wild-type flies from flies expressing the full-length MeCP2 gene and the mutated MeCP2 gene (R106W). After conducting these experiments, some of the Rett Syndrome symptoms were recapitulated in Drosophila, and a subset of those were partially ameliorated by the introduction of pifithrin-alpha.
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