A Predictive Visual Analytics System for Studying Neurodegenerative Disease Based on DTI Fiber Tracts.

Diffusion tensor imaging (DTI) has been used to study the effects of neurodegenerative diseases on neural pathways, which may lead to more reliable and early diagnosis of these diseases as well as a better understanding of how they affect the brain. We introduce a predictive visual analytics system for studying patient groups based on their labeled DTI fiber tract data and corresponding statistics. The system's machine-learning-augmented interface guides the user through an organized and holistic analysis space, including the statistical feature space, the physical space, and the space of patients over different groups. We use a custom machine learning pipeline to help narrow down this large analysis space and then explore it pragmatically through a range of linked visualizations. We conduct several case studies using DTI and T1-weighted images from the research database of Parkinson's Progression Markers Initiative.

Post-Stroke Microglia Induce Sirtuin2 Expression to Suppress the Anti-inflammatory Function of Infiltrating Regulatory T Cells.

Ischemic stroke is among the leading causes of death and disability across the globe. Post-stroke neuroinflammation contributes to the pathophysiology of ischemic stroke in the acute phase through damaging neurons in the penumbra region. Infiltrating regulatory T cells (Treg cells) provide neuronal protection in ischemic brains. In the current study using a mouse-transient middle cerebral artery occlusion (MCAO) model, we characterized the changes of sirtuin expression in infiltrating Treg cells in the acute phase of ischemia. We found that Sirt2 was remarkably upregulated in infiltrating Treg cells at day 3 post-MCAO. In vitro inhibition of Sirt2 activity enhanced the expression of immunosuppression-associated molecules including forkhead box P3 (Foxp3) in Treg cells. Using a lentiviral system to express exogenous Sirt2 in Treg cells, we found that Sirt2 weakened the anti-inflammatory effect of Treg cells on pro-inflammatory macrophages. Additionally, post-MCAO microglia increased Sirt2 expression in Treg cells in a cell-to-cell contact manner. We further found that microglia remarkably induced hypoxia-inducible factor 1-alpha (HIF-1α) expression in Treg cells, and inhibition of HIF-1α abolished microglia-induced Sirt2 upregulation. Collectively, we discovered a novel mechanism by which the immunoregulatory activity of infiltrating Treg cells is modulated after ischemia.