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High-throughput virtual screening of novel dihydropyrimidine monastrol analogs reveals robust structure-activity relationship to kinesin Eg5 binding thermodynamics

Shern et al. | Jan 20, 2021

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.

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Effect of Natural Compounds Curcumin and Nicotinamide on α-synuclein Accumulation in a C. elegans Model of Parkinson’s Disease

Mehrotra et al. | Jan 29, 2018

Effect of Natural Compounds Curcumin and Nicotinamide on α-synuclein Accumulation in a C. elegans Model of Parkinson’s Disease

Parkinson's disease is a neurodegenerative disorder that affects over 10 million people worldwide. It is caused by destruction of dopamine-producing neurons, which results in severe motor and movement symptoms. In this study, the authors investigated the anti-Parkinsonian effects of two natural compounds curcumin and nicotinamide using C. elegans as a model organism.

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Starts and Stops of Rhythmic and Discrete Movements: Modulation in the Excitability of the Corticomotor Tract During Transition to a Different Type of Movement

Lim et al. | Aug 27, 2018

Starts and Stops of Rhythmic and Discrete Movements: Modulation in the Excitability of the Corticomotor Tract During Transition to a Different Type of Movement

Control of voluntary and involuntary movements is one of the most important aspects of human neurological function, but the mechanisms of motor control are not completely understood. In this study, the authors use transcranial magnetic stimulation (TMS) to stimulate a portion of the motor cortex while subjects performed either discrete (e.g. throwing) or rhythmic (e.g. walking) movements. By recording electrical activity in the muscles during this process, the authors showed that motor evoked potentials (MEPs) measured in the muscles during TMS stimulation are larger in amplitude for discrete movements than for rhythmic movements. Interestingly, they also found that MEPs during transitions between rhythmic and discrete movements were nearly identical and larger in amplitude than those recorded during either rhythmic or discrete movements. This research provides important insights into the mechanisms of neurological control of movement and will serve as the foundation for future studies to learn more about temporal variability in neural activity during different movement types.

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A Novel Alzheimer's Disease Therapeutic Model: Attenuating Hyperphosphorylated Tau and Amyloid β (Aβ) Aggregates by Characterizing Antioxidative, Anti-Inflammatory, and Neuroprotective Properties of Natural Extracts

Pokkunuri et al. | Jul 25, 2022

A Novel Alzheimer's Disease Therapeutic Model: Attenuating Hyperphosphorylated Tau and Amyloid β (Aβ) Aggregates by Characterizing Antioxidative, Anti-Inflammatory, and Neuroprotective Properties of Natural Extracts

Oxidative damage and neuro-inflammation were the key pathways implicated in the pathogenesis of Alzheimer’s disease. In this study, 30 natural extracts from plant roots and leaves with extensive anti-inflammatory and anti-oxidative properties were consumed by Drosophila melanogaster. Several assays were performed to evaluate the efficacy of these combinational extracts on delaying the progression of Alzheimer’s disease. The experimental group showed increased motor activity, improved associative memory, and decreased lifespan decline relative to the control group.

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Utilizing the Magnus effect to produce more downforce than a standard wing

Angiras et al. | Aug 15, 2022

Utilizing the Magnus effect to produce more downforce than a standard wing

Here, seeking a better solution to produce downforce that keeps a vehicle grounded at high speeds than wings which tend to result in degraded car performance due to increased air resistance, the authors considered using the Magnus effect as a replacement. The authors found that a spinning cylinder generated significantly more downforce through the Magnus effect than a standard wing at all wind speeds as simulated through the use of a leaf blower. They suggest that a cylinder could be a potential replacement for a wing when downforce is a priority.

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