Issues

Summary: Epithelial cells in diverse tissues have an innate plasticity program (recently dubbed ‘paligenosis’) such that differentiated cells can become regenerative upon large-scale insults to an organ. Thus, the proliferating, regenerative cells in an organ may not always derive directly from stem cells, which invites us to refine theories about the cell of origin of cancer such as the multi-hit model of tumorigenesis.

Summary: This Review discusses the host factors that influence the outcomes of in vivo probiotic interventions in allergy, focusing on genetics, sex, age and microbiological status in mouse models of allergic disease.

Summary: Orthotopic and heterotopic allograft locations confer unique microenvironments that influence growth kinetics, desmoplasia and angiogenesis. These differences translate to differential sensitivities to FOLFIRINOX and should inform future preclinical study design.

Summary: The elongator subunit IKBKAP/ELP1 is not required for development, but is essential for maintaining mitochondrial function and retina morphology. Loss of this subunit causes progressive, selective degeneration of retinal ganglion cells.

Summary: The nervous system of Schistosoma mansoni has been mapped and the widespread presence of octopamine revealed. The identification of agonists and antagonists of tyrosine-derivative signaling might provide opportunities for drug repurposing.

Summary: We challenged myeloid-specific knockout mice targeting the hypoxia-inducible factor (HIF) pathway to dextran sodium sulfate-induced colitis, demonstrating that HIF-1α, but not HIF-2α, activation in myeloid cells regulates colitis severity in mice.

Editor's choice: The first medium-scale pharmacological in vivo screen on a Drosophila cardiac model identified 11 compounds with protective effects on Friedreich's ataxia cardiomyopathy.

Summary: Using experimental kidney transplantation, we dissected donor graft from recipient environment effects, focusing on the endothelium and inflammation. These results can direct strategies to improve graft survival after suboptimal transplantation.

Summary: The zinc metalloprotease ZMPSTE24 performs the final step of prelamin A processing. Here, a yeast-based system shows differences in protein stability and activity for alleles of ZMPSTE24 that cause progeria disease.

Summary: Dp71 is the most prominent dystrophin gene product in the adult brain. Here, multiple approaches including behavioral tests and electrophysiology are adopted to explore the role of Dp71 in the cerebellum.

Summary: Increased transcriptional activation of the tension-mediated autophagy factor Bag3 is shown to be a consistent molecular hallmark of KY deficiency in animal models.

Summary: Secretome proteomics identifies differential regulation of inflammation modulators during fetal and adult articular cartilage defect healing, offering novel strategies for therapy.

Summary: The authors introduce a new syngeneic mouse model of spontaneous breast cancer brain metastasis, demonstrate its phenotypic, functional and transcriptomic relevance to human TNBC brain metastasis, and test novel therapies.

Summary: COL4A1 mutations cause a multisystem disorder by impairing secretion of COL4A1/A2 heterotrimers. We define parameters for reducing stroke and myopathy in Col4a1 mutant mice by pharmacologically promoting heterotrimer secretion.

Summary: This work provides proof of principle for the use of myotonic dystrophy 1 patient-specific induced pluripotent stem cells to model muscle pathology in vitro and in drug discovery.