Spatial dysregulation of T follicular helper cells impairs vaccine responses in aging.

The magnitude and quality of the germinal center (GC) response decline with age, resulting in poor vaccine-induced immunity in older individuals. A functional GC requires the co-ordination of multiple cell types across time and space, in particular across its two functionally distinct compartments: the light and dark zones. In aged mice, there is CXCR4-mediated mislocalization of T follicular helper (TFH) cells to the dark zone and a compressed network of follicular dendritic cells (FDCs) in the light zone. Here we show that TFH cell localization is critical for the quality of the antibody response and for the expansion of the FDC network upon immunization. The smaller GC and compressed FDC network in aged mice were corrected by provision of TFH cells that colocalize with FDCs using CXCR5. This demonstrates that the age-dependent defects in the GC response are reversible and shows that TFH cells support stromal cell responses to vaccines

Brain energy rescue:an emerging therapeutic concept for neurodegenerative disorders of ageing

The brain requires a continuous supply of energy in the form of ATP, most of which is produced from glucose by oxidative phosphorylation in mitochondria, complemented by aerobic glycolysis in the cytoplasm. When glucose levels are limited, ketone bodies generated in the liver and lactate derived from exercising skeletal muscle can also become important energy substrates for the brain. In neurodegenerative disorders of ageing, brain glucose metabolism deteriorates in a progressive, region-specific and disease-specific manner — a problem that is best characterized in Alzheimer disease, where it begins presymptomatically. This Review discusses the status and prospects of therapeutic strategies for countering neurodegenerative disorders of ageing by improving, preserving or rescuing brain energetics. The approaches described include restoring oxidative phosphorylation and glycolysis, increasing insulin sensitivity, correcting mitochondrial dysfunction, ketone-based interventions, acting via hormones that modulate cerebral energetics, RNA therapeutics and complementary multimodal lifestyle changes

Dataset to run examples in SmartPLS 3 (teaching and learning)

This zip file contains: - 3 .zip files = projects to be imported into SmartPLS 3 >>> DLOQ-A model with 7 dimensions >>> DLOQ-A model with second-order latent variable >>> ECSI model (Tenenhaus et al., 2005) to exemplify direct, indirect and total effects, as well as importance-performance map and moderation with continuous variables. >>> ECSI Model (Sanches, 2013) to exemplify MGA (multi-group analysis) - 5 files (csv, txt) with data to run 7 examples in SmartPLS 3 Note: - DLOQ-A = new dataset (ours) - ECSI-Tenenhaus et al. [model for mediation and moderation] = available at: http://www.smartpls.com > Resources > SmartPLS Project Examples - ECSI-Sanches [dataset for MGA] = available in the software R > library(plspm) > data(satisfaction