Issues

Summary: Insulin resistance drives obesity-related diseases, but it is a complex state featuring loss and gain of insulin action, and dysregulated crosstalk with growth factor signalling. ‘Rebalancing’ signalling may offer a beneficial addition to current therapy.

Summary: Diet-induced models of peripheral neuropathy highlight the importance of diet composition, duration and source, with mouse strain, age and sex, in recapitulating human disease. Improved models will accelerate translation to the clinic and drug development.

Summary: Toxicity of C9ALS/FTD poly-GR in zebrafish embryos is suppressed by Trolox, and poly-GR can be detected and quantified in zebrafish model protein homogenates, and in the frontal cortex of C9FTD/ALS cases.

Summary: A tool for quantitative image analysis of muscle deterioration that allows predicting healthspan in the nematode model Caenorhabditis elegans and may lead to the first C. elegans-based high-throughput sarcopenia screening platform.

Summary: High-grade serous ovarian cancer is defined by TP53 mutation and chromosomal instability (CIN), the cause of which remains poorly understood. We developed a novel model system that implicates cell cycle deregulation upon p53 loss as cause of CIN.

Summary: Expression of truncated KCNQ4 variants lacking the C-terminal tetramerization domain results in cell-death inducing cytotoxicity, providing novel insight into the development of alternative therapeutic strategies for DFNA2 hearing loss.

Summary: The early manifestations of an inherited retinal disease was investigated by means of a transcriptome analysis, and a possible drug-based therapeutic approach (endothelin receptor antagonists) is suggested.

Editor's choice: We report the unexpected finding that systemic administration of diphtheria toxin induces rapid regression of murine lung adenocarcinomas expressing human EGFR^L858R in the absence of a transgenic allele containing human diphtheria toxin receptor.

Summary: Genetic STAT3 ablation in mice and VEGF-inducible zebrafish reveals that VEGF signals through STAT3 to promote vascular permeability. Pyrimethamine reduces VEGF-induced permeability in animal models.

Summary: A zebrafish stk3 mutant line and Wwtr1 overexpression line provide evidence for functions of the Hippo signaling pathway in renal cyst formation and represent potential models for polycystic kidney disease.

Summary: We report the first mouse model of isolated hypoplastic left heart syndrome (HLHS), allowing for the investigation of abnormal cardiac, brain and placental development that is implicated in HLHS.