Issues

Summary: Disease Models & Mechanisms announces the launch of a new Outstanding Resource Paper Prize. To mark the occasion, we highlight exciting recent Resource articles and discuss their importance for biomedical research.

Summary: Lack of reproducibility in animal studies continues to be a challenge, and improving this is a National Institutes of Health priority. Key strategies to enhance translatability are offered and discussed by The Jackson Laboratory investigators.

Summary: This Review discusses the unique enrichment of variants causing Finnish disease heritage disorders and the discovery of novel genotype–phenotype associations underlying monogenic and common complex diseases.

Summary: Cell therapies for Parkinson's disease have entered into first-in-human clinical trials. Here, we discuss pertinent outstanding questions that require consideration before widespread adoption of this therapeutic intervention and remain to be further explored.

Summary: This Review critically discusses the links between RAS signalling and ageing, and how RAS inhibitors could extend lifespan and enhance healthspan.

Summary: Metabolomic analysis of Huntington disease (HD) patients and of a HD yeast model identified deregulated metabolic pathways. We used the yeast model to investigate their role in the aggregation of huntingtin protein and their implications in HD.

Summary: Cell migration patterns are abnormal in neural precursors derived from bipolar disorder patients, which could contribute to the already known structural changes in the brain.

Summary: Using single-cell RNA sequencing to measure the induced pluripotent stem cell-derived microglia response, we find convergence between ATPγS and lipopolysaccharide (LPS)+IFN-γ; however, comparison to genetic mouse models indicates LPS as a better model for Alzheimer's disease.

Summary: Targeted Exoc5 deletion in embryonic ureter urothelial progenitor cells impairs autophagy, causing Fn14 activation and urothelial cell death, with a lethal congenital obstructive uropathy rescuable by administration of a caspase inhibitor.

Summary: A pre-clinical model of acute respiratory distress syndrome (ARDS) in human-sized swine, which recapitulates the clinical, radiographic and histopathologic manifestations of ARDS, providing a tool to study therapies for this highly morbid lung disease.

Editor's choice: Epilepsy remains challenging to treat. In this study, we show that manipulating endogenous mechanisms that maintain stability of neuronal activity represents a possible route to better manage this disorder.

Summary: Nicotinamide riboside rescues the exercise capacity and mitochondrial function of a Drosophila model of Barth syndrome in a Sir2/Spargel-dependent manner.

Summary: Adherent-invasive Escherichia coli (AIEC)-colonized transgenic mouse ‘Vill-hCC6’ reproducing ileal colonization by AIEC observed in Crohn's disease is proposed as a new tool to evaluate AIEC-targeting strategies.