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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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Grammatical Gender and Politics: A Comparison of French and English in Political Discourse

Zhang et al. | Jul 07, 2021

Grammatical Gender and Politics: A Comparison of French and English in Political Discourse

Grammatical gender systems are prevalent across many languages, and when comparing French and English the existence of this system becomes a strong distinction. There have been studies that attribute assigned grammatical gender with the ability to influence conceptualization (attributing gender attributes) of all nouns, thus affecting people's thoughts on a grand scale. We hypothesized that due to the influence of a grammatical gender system, French political discourse would have a large difference between the number of masculine and feminine nouns used. Specifically, we predicted there would be a larger ratio of feminine to masculine nouns in French political discourse than in non-political discourse when compared to English discourse. Through linguistic analysis of gendered nouns in French political writing, we found that there is a clear difference between the number of feminine versus masculine nouns, signaling a preference for a more “effeminate” language.

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Comparative singlet oxygen photosensitizer efficiency of berberine, rose bengal, and methylene blue by time course nuclear magnetic resonance (NMR) monitoring of a photochemical 4+2 cycloaddition endoperoxide formation

Su et al. | May 14, 2021

Comparative singlet oxygen photosensitizer efficiency of berberine, rose bengal, and methylene blue by time course nuclear magnetic resonance (NMR) monitoring of a photochemical 4+2 cycloaddition endoperoxide formation

Berberine, a natural product alkaloid, has been shown to exert biological activity via in situ production of singlet oxygen when photo irradiated. Berberine utilizes singlet oxygen in its putative mechanism of action, wherein it forms an activated complex with DNA and photosensitizes triplet oxygen to singlet oxygen to specifically oxidize guanine residues, thereby halting cell replication and leading to cell death. This has potential application in photodynamic therapy, alongside other such compounds which also act as photosensitizers and produce singlet oxygen in situ. The quantification of singlet oxygen in various photosensitizers, including berberine, is essential for determining their photosensitizer efficiencies. We postulated that the singlet oxygen produced by photoirradiation of berberine would be superior in terms of singlet oxygen production to the aforementioned photosensitizers when irradiated with UV light, but inferior under visible light conditions, due to its strong absorbance of UV wavelengths.

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The characterization of quorum sensing trajectories of Vibrio fischeri using longitudinal data analytics

Abdel-Azim et al. | Dec 16, 2023

The characterization of quorum sensing trajectories of <i>Vibrio fischeri</i> using longitudinal data analytics

Quorum sensing (QS) is the process in which bacteria recognize and respond to the surrounding cell density, and it can be inhibited by certain antimicrobial substances. This study showed that illumination intensity data is insufficient for evaluating QS activity without proper statistical modeling. It concluded that modeling illumination intensity through time provides a more accurate evaluation of QS activity than conventional cross-sectional analysis.

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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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Improving Wound Healing by Breaking Down Biofilm Formation and Reducing Nosocomial Infections

DiStefano et al. | Jul 09, 2019

Improving Wound Healing by Breaking Down Biofilm Formation and Reducing Nosocomial Infections

In a 10-year period in the early 2000’s, hospital-based (nosocomial) infections increased by 123%, and this number is increasing as time goes on. The purpose of this experiment was to use hyaluronic acid, silver nanoparticles, and a bacteriophage cocktail to create a hydrogel that promotes wound healing by increasing cell proliferation while simultaneously disrupting biofilm formation and breaking down Staphylococcus aureus and Pseudomonas aeruginosa, which are two strains of bacteria that attribute to nosocomial infections and are increasing in antibiotic resistance.

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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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Developing anticholinergic drugs for the treatment of asthma with improved efficacy

Wong et al. | Jul 05, 2023

Developing anticholinergic drugs for the treatment of asthma with improved efficacy
Image credit: Wong et al.

Anticholinergics are used in treating asthma, a chronic inflammation of the airways. These drugs block human M1 and M2 muscarinic acetylcholine receptors, inhibiting bronchoconstriction. However, studies have reported complications of anticholinergic usage, such as exacerbated eosinophil production and worsened urinary retention. Modification of known anticholinergics using bioisosteric replacements to increase efficacy could potentially minimize these complications. The present study focuses on identifying viable analogs of anticholinergics to improve binding energy to the receptors compared to current treatment options. Glycopyrrolate (G), ipratropium (IB), and tiotropium bromide (TB) were chosen as parent drugs of interest, due to the presence of common functional groups within the molecules, specifically esters and alcohols. Docking score analysis via AutoDock Vina was used to evaluate the binding energy between drug analogs and the muscarinic acetylcholine receptors. The final results suggest that G-A3, IB-A3, and TB-A1 are the most viable analogs, as binding energy was improved when compared to the parent drug. G-A4, IB-A4, IB-A5, TB-A3, and TB-A4 are also potential candidates, although there were slight regressions in binding energy to both muscarinic receptors for these analogs. By researching the effects of bioisosteric replacements of current anticholinergics, it is evident that there is a potential to provide asthmatics with more effective treatment options.

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