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Modular mimics of neuroactive alkaloids - design, synthesis, and cholinesterase inhibitory activity of rivastigmine analogs

Yu et al. | Sep 12, 2022

Modular mimics of neuroactive alkaloids - design, synthesis, and cholinesterase inhibitory activity of rivastigmine analogs

Naturally occurring neuroactive alkaloids are often studied for their potential to treat Neurological diseases. This team of students study Rivastigmine, a potent cholinesterase inhibitor that is a synthetic analog of physostigmine, which comes from the Calabar bean plant Physostigma venenosum. By comparing the effects of optimized synthetic analogs to the naturally occurring alkaloid, they determine the most favorable analog for inhibition of acetylcholinesterase (AChE), the enzyme that breaks down the neurotransmitter acetylcholine (ACh) to terminate neuronal transmission and signaling between synapses.

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Machine learning-based enzyme engineering of PETase for improved efficiency in plastic degradation

Gupta et al. | Jan 31, 2023

 Machine learning-based enzyme engineering of PETase for improved efficiency in plastic degradation
Image credit: Markus Spiske

Here, recognizing the recognizing the growing threat of non-biodegradable plastic waste, the authors investigated the ability to use a modified enzyme identified in bacteria to decompose polyethylene terephthalate (PET). They used simulations to screen and identify an optimized enzyme based on machine learning models. Ultimately, they identified a potential mutant PETases capable of decomposing PET with improved thermal stability.

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Assigning Lightning Seasons to Different Regions in the United States

Hawkins et al. | Sep 07, 2020

Assigning Lightning Seasons to Different Regions in the United States

Climate change is predicted to increase the frequency of severe thunderstorm events in coming years. In this study, the authors hypothesized that (i) the majority of severe thunderstorm events will occur in the summer months in all states examined for all years analyzed, (ii) climate change will cause an unusual number of severe thunderstorm events in winter months in all states, (iii) thundersnow would be observed in Colorado, and (iv.) there would be no difference in the number of severe thunderstorm events between states in any given year examined. They classified lightning seasons in all states observed, with the most severe thunderstorm events occurring in May, June, July, and August. Colorado, New Jersey, Washington, and West Virginia were found to have severe thunderstorm events in the winter, which could be explained by increased winter storms due to climate change (1). Overall, they highlight the importance of quantifying when lightning seasons occur to avoid lightning-related injuries or death.

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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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POC-MON: A Novel and Cost-Effective Pocket Lemon Sniff Test (PLST) for Early Detection of Major Depressive Disorder

Cruz et al. | Jul 07, 2020

POC-MON: A Novel and Cost-Effective Pocket Lemon Sniff Test (PLST) for Early Detection of Major Depressive Disorder

Effective treatment of depression requires early detection. Depressive symptoms overlap with olfactory regions, which led to several studies of the correlation between sense of smell and depression. The alarming rise of depression, its related crimes, suicides, and lack of inexpensive, quick tools in detecting early depression — this study aims in demonstrating decreased olfaction and depression correlation. Forty-two subjects (ages 13-83) underwent POC-MON (Pocket Lemon) assessment — an oven-dried lemon peel sniff test, subjected to distance measurement when odor first detected (threshold) and completed Patient Health Questionnaires (PHQ-9). POC-MON and PHQ-9 scores yielded a correlation of 20% and 18% for the right and left nostrils, respectively. Among male (n=17) subjects, the average distance of POC-MON and PHQ-9 scores produced a correlation of 14% and 16% for the right and left nostrils, respectively. Females (n=25) demonstrated a correlation of 28% and 21% for the right and left nostrils, respectively. These results suggest the correlation between olfaction and depression in diagnosing its early-stage, using a quick, inexpensive, and patient-friendly tool — POC-MON.

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Bacteroides thetaiotaomicron Growth Numbers Are Unchanged in the Presence of Yogurt

Phan et al. | Dec 29, 2016

<i>Bacteroides thetaiotaomicron</i> Growth Numbers Are Unchanged in the Presence of Yogurt

Disruptions to the microbiome, specifically the imbalance in the two major phyla, the Firmicutes and the Bacteroidetes, have been linked to the development of obesity. This study explored whether or not Fage plain total 0% Greek yogurt, which contains live and active bacterial cultures belonging to the Firmicute phylum, could decrease the numbers of Bacteroides thetaiotaomicron, an organism found in the human gut that belongs to the Bacteroidetes phylum.

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A Quantitative Assessment of Time, Frequency, and Time-frequency Algorithms for Automated Seizure Detection and Monitoring

Vangal et al. | Sep 28, 2020

A Quantitative Assessment of Time, Frequency, and Time-frequency Algorithms for Automated Seizure Detection and Monitoring

Each year, over 100,000 patients die from Sudden Unexpected Death in Epilepsy (SUDEP). A reliable seizure warning system can help patients stay safe. This work presents a comprehensive, comparative analysis of three different signal processing algorithms for automated seizure/ictal detection. The experimental results show that the proposed methods can be effective for accurate automated seizure detection and monitoring in clinical care.

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