Category Health/Medical

Highlights •Early neural stem cell NSC impairment in 3xTg-AD mice correlates with SVZ subventricular zone niche lipid accumulations •Similar lipid accumulations are found in the SVZ in postmortem human AD brains •Accumulating SVZ lipids are locally generated, oleic acid-enriched triglycerides •Inhibiting oleic acid signaling or synthesis rescues NSC defects in 3xTg-AD mice Credit: Fernandes et al. Aberrant Lipid Metabolism in the Forebrain Niche Suppresses Adult Neural Stem Cell Proliferation in an Animal Model of Alzheimer’s Disease. Cell Stem Cell, 27 August 2015 DOI: 10.1016/j.stem.2015.08.001

For the 1st time since the disease was described 109 years ago, researchers have discovered accumulations of fat droplets/ lipids in the brain of patients who died from the disease and h...

Tom1 Modulates Binding of Tollip to Phosphatidylinositol 3-Phosphate via a Coupled Folding and Binding Mechanism •Tollip TBD is a disordered domain that partially folds when bound to Tom1 GAT •Tom1 GAT also directly binds to the Tollip C2 domain •Binding of Tom1 to Tollip inhibits binding of Tollip to PtdIns(3)P •Tollip TBD plays a major role in Tom1’s inhibitory function

It has important implications for Rx of allergies, heart disease, cancer types. The discovery explains how 2 particular proteins, Tollip and Tom1, work together to contribute to the turnover of cell-surface receptor proteins that trigger inflammation...

This is a three-dimensional model of a tumor showing cell types in varying colors. Credit: Bartek Waclaw and Martin Nowak

The new model explains why cancer cells have a surprising number of genetic mutations in common, how driver mutations spread through the whole tumor and how drug resistance evolves. “Previously, we and others have mostly used non-spatial models to study cancer evolution,” Nowak said. “But those models do not describe the spatial characteristics of solid tumors. Now, for the first time, we have a computational model that can do that.”

A key insight of the new model, Nowak said, is the ability for cells to migrate locally. “Cellular mobility makes cancers grow fast, and it makes cancers homogenous in the sense that cancer cells share a common set of mutations...

Neurons, red, created from ALS patients bearing the C9orf72 mutation, show clumps of the RanGAP protein, yellow, in their nuclei, white. The nuclei of other cells are in blue.
Credit: Jeffrey Rothstein laboratory, Johns Hopkins Medicine

The 1st steps in how a common gene mutation causes brain damage associated with both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have been found by Johns Hopkins researchers. Altered C9orf72 gene on human chromosome 9, causes RNA molecules to block critical pathways for protein transport, causing a molecular traffic jam outside brain cell nuclei and affecting their operations and survival. In a proof-of-concept experiment, a molecular therapy eased the jam and restored molecular flow into the cell’s core.

The mutation, the most comm...