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Biology subjects

Gleave, E.

Publications and source records attributed to Gleave, E..

2 recordsLinked to original sources

Comparison of Explainable AI Models for MRI-based Alzheimer's Disease Classification

Deep learning models based on convolutional neural networks (CNNs) have been used to classify Alzheimers disease or infer dementia severity from 3D T1-weighted brain MRI scans. Here, we examine the value of adding occlusion sensitivity analysis (OSA) and gradient-weighted class activation mapping (Grad-CAM) to these models to make the results more interpretable. Much research in this area focuses on specific datasets such as the Alzheimers Disease Neuroimaging Initiative (ADNI) or National Alzheimers Coordinating Center (NACC), which assess people of North American, predominantly European ancestry, so we examine how well models trained on these data generalize to a new population dataset from India (NIMHANS cohort). We also evaluate the benefit of using a combined dataset to train the CNN models. Our experiments show feature localization consistent with knowledge of AD from other methods. OSA and Grad-CAM resolve features at different scales to help interpret diagnostic inferences made by CNNs.

neuroscience↗

Stepping dynamics of dynein characterized by MINFLUX

Cytoplasmic dynein is the principal motor for minus-end-directed motility and force generation functions along microtubules (MTs)1. Dynein converts the chemical energy of ATP hydrolysis into coordinated structural changes to step processively along MTs, but how dynein couples ATP hydrolysis to a minus-end-directed step remains controversial2, 3. The dynamics of dynein stepping have previously been characterized by tracking flexible regions of the motor with limited resolution4-6. Here, we site-specifically labeled yeast dynein at its MT-binding domain by developing a cysteine-light mutant and tracked its stepping at sub-millisecond and nanometer resolution at physiological ATP concentrations using MINFLUX7. We show that dynein hydrolyzes one ATP per step and takes multiples of 8 nm steps. Steps are preceded by a transient movement towards the plus end. These backward "dips" correspond to MT release upon ATP binding and subsequent diffusion of the stepping monomer around its MT-bound partner. Functional assays showed that dips terminate with a minus-end-directed movement upon ATP hydrolysis. These results provide critical insights into the order of mechanochemical events that result in a productive step of dynein.

biophysics↗