DLK-dependent axonal mitochondrial fission drives degeneration after axotomy.

Currently there are no effective treatments for an array of neurodegenerative disorders to a large part because cell-based models fail to recapitulate disease. Here we develop a reproducible human iPSC-based model where laser axotomy causes retrograde axon degeneration leading to neuronal cell death. Time-lapse confocal imaging revealed that damage triggers an apoptotic wave of mitochondrial fission proceeding from the site of injury to the soma.

Origins and impact of extrachromosomal DNA.

Extrachromosomal DNA (ecDNA) is a major contributor to treatment resistance and poor outcome for patients with cancer. Here we examine the diversity of ecDNA elements across cancer, revealing the associated tissue, genetic and mutational contexts. By analysing data from 14,778 patients with 39 tumour types from the 100,000 Genomes Project, we demonstrate that 17.

Detection of live attenuated measles virus in the respiratory tract following subcutaneous MMR Vaccination.

The live attenuated measles vaccine is extremely effective in preventing measles and induces mucosal immunity in the respiratory tract, however the mechanism is not known. We show that live attenuated measles virus (LAMV) RNA is frequently detected in the respiratory tract 7-21 days after subcutaneous measles-mumps-rubella (MMR) vaccination in healthy children (n = 5/20) and macaques (n = 6/8). Replicating LAMV was isolated from the lungs of 2 macaques, with no evidence of transmission to unvaccinated individuals.

Differential enrichment of retinal ganglion cells underlies proposed core neurodegenerative transcription programs.

In a published Correction , a revised analysis updated two "core transcription programs" proposed to underlie axon injury-induced retinal ganglion cell (RGC) neurodegeneration. Though extensive, the Correction purported to leave the two principal conclusions of its parent study unaltered. The first of those findings was that a core program mediated by the Activating Transcription Factor-4 (ATF4) and its likely heterodimeric partner does not include numerous canonical ATF4 target genes stimulated by RGC axon injury.

Chemogenetic neuronal silencing decouples c-Jun activation from cell death in the temporal cortex.

Initial symptoms of neurodegenerative diseases are often defined by the loss of the most vulnerable neural populations specific to each disorder. In the early stages of Alzheimer's disease, vulnerable circuits in the temporal lobe exhibit diminished activity prior to overt degeneration. It remains unclear whether these functional changes contribute to regional vulnerability or are simply a consequence of pathology.