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Computational development of aryl sulfone compounds as potential NNRTIs

Zhang et al. | Oct 12, 2022

Computational development of aryl sulfone compounds as potential NNRTIs

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are allosteric inhibitors that bind to the HIV reverse transcriptase and prevent replication. Indolyl aryl sulfones (IAS) and IAS derivatives have been found to be highly effective against mutant strains of HIV-1 reverse transcriptase. Here, we analyzed molecules designed using aryl sulfone scaffolds paired to cyclic compounds as potential NNRTIs through the computational design and docking of 100 novel NNRTI candidates. Moreover, we explored the specific combinations of functional groups and aryl sulfones that resulted in the NNRTI candidates with the strongest binding affinity while testing all compounds for carcinogenicity. We hypothesized that the combination of an IAS scaffold and pyrimidine would produce the compounds with the best binding affinity. Our hypothesis was correct as the series of molecules with an IAS scaffold and pyrimidine exhibited the best average binding affinity. Additionally, this study found 32 molecules designed in this procedure with higher or equal binding affinities to the previously successful IAS derivative 5-bromo-3-[(3,5-dimethylphenyl)sulfonyl]indole-2-carboxyamide when docked to HIV-1 reverse transcriptase.

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Analyzing honey’s ability to inhibit the growth of Rhizopus stolonifer

Johnecheck et al. | Jun 06, 2023

Analyzing honey’s ability to inhibit the growth of <i>Rhizopus stolonifer</i>
Image credit: Johnecheck et al. 2023

Rhizopus stolonifer is a mold commonly found growing on bread that can cause many negative health effects when consumed. Preservatives are the well-known answer to this problem; however, many preservatives are not naturally found in food, and some have negative health effects of their own. We focused on honey as a possible solution because of its natural origin and self-preservation ability. We hypothesized that honey would decrease the growth rate of R. stolonifer . We evaluated the honey with a zone of inhibition (ZOI) test on agar plates. Sabouraud dextrose agar was mixed with differing volumes of honey to generate concentrations between 10.0% and 30.0%. These plates were then inoculated with a solution of spores collected from the mold. The ZOI was measured to determine antifungal effectiveness. A statistically significant difference was found between the means of all concentrations except for 20.0% and 22.5%. Our findings support the hypothesis as we showed a positive correlation between the honey concentration and growth rate of mold. By using this data, progress could be made on an all-natural, honey-based preservative.

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The influence of music on lexical decision-making in adolescents

Fisher et al. | Apr 28, 2024

The influence of music on lexical decision-making in adolescents

The lexical decision task is designed to test aspects of vocabulary retrieval from short-term and long-term memory by prompting the subject to differentiate between words and non-words. From this task, researchers can determine the effects of certain stimuli on linguistic processing. Numerous studies have investigated the effects of music on various cognitive capacities, like memory and vocabulary. In the current study, we hypothesized that participants would show greater accuracy rates on the lexical decision task when exposed to a selected piece of classical music while completing the task, as compared to completing the task in silence. We tested this hypothesis on a group of 25 participants who completed the lexical decision task once in silence and once while listening to Beethoven's “Moonlight Sonata, 1st Movement”. The results suggest a positive association between the effects of classical background music and improved accuracy. Our results indicate that listening to certain types of music may enhance linguistic processes such as reading and writing. Further research with a larger group of participants is necessary to better understand the association between music and linguistic processing abilities.

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Contrasting role of ASCC3 and ALKBH3 in determining genomic alterations in Glioblastoma Multiforme

Sriram et al. | Sep 27, 2022

Contrasting role of <i>ASCC3</i> and <i>ALKBH3</i> 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.

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Reduce the harm of acid rain to plants by producing nitrogen fertilizer through neutralization

Xu et al. | Apr 25, 2023

Reduce the harm of acid rain to plants by producing nitrogen fertilizer through neutralization
Image credit: Ave Calvar Martinez, pexels.com

The phenomenon of dying trees and plants in areas affected by acid rain has become increasingly problematic in recent times. Is there any method to efficiently utilize the rainwater and reduce the harmfulness of acid rain or make it beneficial to plants? This study aimed to investigate the potential of neutralizing acid rainwater infiltrating the soil to increase soil pH, produce beneficial salts for plants, and support better plant growth. To test this hypothesis, precipitation samples were collected from six states in the U.S. in 2022, and the pH of the acid rain was measured to obtain a representative pH value for the country. Experiments were then conducted to simulate the neutralization of acid rain and the subsequent change in soil pH levels. To evaluate the effectiveness and feasibility of this method, cat grass was planted in pots of soil soaked with solutions mimicking acid rain, with control and experimental groups receiving neutralizing agents (ammonium hydroxide) or not. Plant growth was measured by analyzing the height of the plants. Results demonstrated that neutralizing agents were effective in improving soil pH levels and that the resulting salts produced were beneficial to the growth of the grass. The findings suggest that this method could be applied on a larger agricultural scale to reduce the harmful effects of acid rain and increase agricultural efficiency.

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Association of agenesis of the corpus callosum with epilepsy and anticonvulsant drug treatment

Steger et al. | Feb 21, 2023

Association of agenesis of the corpus callosum with epilepsy and anticonvulsant drug treatment
Image credit: Robina Weermeijer on Unsplash

Agenesis of the Corpus Callosum (ACC) is a birth defect where an infant’s corpus callosum, the structure linking the brain’s two hemispheres to allow interhemispheric communication, fails to develop in a typical manner during pregnancy. Existing research on the connection between ACC and epilepsy leaves significant gaps, due to the lack of focused investigation. One important gap is the degree to which ACC may impact the course of epilepsy treatment and outcomes. The present study was conducted to test the hypotheses that epilepsy is highly prevalent among individuals with ACC, and that those with both ACC and epilepsy have a lower response rate to anticonvulsant drugs than other patients treated with anticonvulsant drugs. A weighted average of epilepsy rates was calculated from a review of existing literature, which supported the hypothesis that epilepsy was more common among individuals with ACC (25.11%) than in the general population (1.2%). An empirical survey administered to 57 subjects or parents of subjects showed that rate of intractable epilepsy among study subjects with both ACC and epilepsy was substantially higher than the rate found in the general population, indicating that individuals with both conditions had a lower response rate to the anticonvulsant drugs. This study contributes novel results regarding the potential for concurrence of ACC and epilepsy to interfere with anticonvulsant drug treatment. We also discuss implications for how medical professionals may use the findings of this study to add depth to their treatment decisions.

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The role of xpa-1 and him-1 in UV protection of Caenorhabditis elegans

Tung et al. | Feb 25, 2022

The role of <em>xpa-1</em> and <em>him-1</em> in UV protection of <em>Caenorhabditis elegans</em>

Caenorhabditis elegans xpa-1 and him-1 are orthologs of human XPA and human SMC1A, respectively. Mutations in the XPA are correlated with Xeroderma pigmentosum, a condition that induces hypersensitivity to ultraviolet (UV) radiation. Alternatively, SMC1A mutations may lead to Cornelia de Lange Syndrome, a multi-organ disorder that makes patients more sensitive to UVinduced DNA damage. Both C. elegans genes have been found to be involved in protection against UV radiation, but their combined effects have not been tested when they are both knocked down. The authors hypothesized that because these genes are involved in separate pathways, the simultaneous knockdown of both of these genes using RNA interference (RNAi) in C. elegans will cause them to become more sensitive to UV radiation than either of them knocked down individually. UV protection was measured via the percent survival of C. elegans post 365 nm and 5.4x10-19 joules of UV radiation. The double xpa-1/him-1 RNAi knockdown showed a significantly reduced percent survival after 15 and 30 minutes of UV radiation relative to wild-type and xpa-1 and him-1 single knockdowns. These measurements were consistent with their hypothesis and demonstrated that xpa-1 and him-1 genes play distinct roles in resistance against UV stress in C. elegans. This result raises the possibility that the xpa-1/him-1 double knockdown could be useful as an animal model for studying the human disease Xeroderma pigmentosum and Cornelia de Lange Syndrome.

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Conversion of Mesenchymal Stem Cells to Cancer-Associated Fibroblasts in a Tumor Microenvironment: An in vitro Study

Ramesh et al. | Feb 18, 2020

Conversion of Mesenchymal Stem Cells to Cancer-Associated Fibroblasts in a Tumor Microenvironment: An <em>in vitro</em> Study

Mesenchymal stem cells(MSCs) play a role in tumor formation by differentiating into cancer associated fibroblasts (CAFs) which enable metastasis of tumors. The process of conversion of MSCs into CAFs is not clear. In this study, authors tested the hypothesis that cancers cells secrete soluble factors that induce differentiation by culturing bone marrow mesenchymal stem cells in media conditioned by a breast cancer cell line.

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Analysis of biofertilization impacts on Pisum sativum

Holden et al. | May 18, 2023

Analysis of biofertilization impacts on <i>Pisum sativum</i>
Image credit: David Boozer

This study explored the various effects of three different produce-based biofertilizers on pea plant growth, using red apple, pear, strawberry, and control treatments. It was hypothesized that the application of fruit biomatter would increase the growth of pea plants, with the application of strawberry biomatter having the most significant effect due to strawberries containing a higher nutrient content compared to pears and apples. Analysis confirmed the hypothesis. The application of strawberry biomatter could prove to be an effective way to increase plant growth in commercial agriculture.

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