Category Health/Medical

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...

The picture shows toxic Alzheimer’s amyloid beta molecules landing on a fake cell membrane, wrapped around a silver nanoparticle. A laser, with help from the silver particle, lights up the molecule to reveal its structure. Credit: Copyright Debanjan Bhowmik; Credit to Debanjan Bhowmik, TIFR, Mumbai

The elusive toxic form of the Alzheimer’s molecule has now been observed, during its attempt to bore into the outer covering of a cell decoy, using a new method involving laser light and fat-coated silver nanoparticles.

“Everybody wants to make the key to solve Alzheimer’s Disease, but we don’t know what the lock looks like. We now have a glimpse of something which could be the lock...