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Transporting epithelia commonly consist of tubes that mediate between the body and its environment. Lumen formation is closely linked to epithelial morphogenesis, but an open question is how luminal symmetry is broken to generate tubes rather than hollow cysts. A report about the biomechanics of intercellular contacts might now provide some answers.
Sander and colleagues discuss recent evidence for and against the roles of stem cells versus the plasticity of mature cell types in response to injury during regeneration of the adult liver and pancreas.
Barker and colleagues review the history and recent developments of organoid cultures derived from pluripotent stem cells and adult epithelia, and discuss how the technology can be used for basic research as well as translational applications.
Receptor-interacting protein kinase 3 (RIPK3) is a key regulator of necroptosis. Seo et al. show that the E3 ligase CHIP mediates ubiquitylation and lysosomal degradation of RIPK3, thus regulating both necrosome formation and necroptosis.
Kornfeld and colleagues identify miRNAs that are dysregulated in brown adipose tissue in mouse models of obesity and ageing, and show that miR-328 targets Bace1 to promote brown adipogenesis.
By culturing rat hepatocyte doublets in microwells with controlled ECM environments, Viasnoff and colleagues show that the lumen between the cells extends anisotropically towards regions of lower intercellular tension.
By proteomics analysis of conditioned media from cells with constitutive mTORC1 activity, Yu and colleagues identify IGF binding protein 5 (IGFBP5) as a protein that is induced by mTORC1 through HIF1 and that blocks IGF-1 signalling.
Eichel et al. show that β-arrestin-mediated MAPK activation by GPCRs involves dissociation of β-arrestin from its activating GPCR, and accumulation of β-arrestin in clathrin-coated structures, where it promotes MAPK signalling.
Durocher and colleagues find that in budding yeast, the movement of chromosomes induced by DNA breaks is due to the loss of attachment of kinetochores to spindle pole bodies and of telomeres to the nuclear periphery, and may promote checkpoint arrest.
An actin filament coat promotes cargo expulsion from large exocytosing vesicles, but the mechanisms of coat formation and force generation have been poorly characterized. Elegant imaging studies of the Drosophila melanogaster salivary gland now reveal how actin and myosin are recruited, and show that myosin II forms a contractile 'cage' that facilitates exocytosis.
The first hours of mammalian embryogenesis are devoted to extensive epigenetic reprogramming. One hallmark is active demethylation of the paternal genome by Tet (ten-eleven translocation) enzymes. However, the process is now shown to be Tet-independent at first, with Tet enzymes only counteracting hitherto underappreciated de novo DNA methylation activity in later zygotic stages.
The control of proteasome-mediated protein degradation is thought to occur mainly at the level of polyubiquitylation of the substrate. However, the proteasome can also be regulated directly, as now demonstrated by a study in which DYRK2-mediated phosphorylation of the 19S subunit Rpt3 is found to increase proteasome activity.
DNA resection is the first step of double-strand break repair by homologous recombination. Broderick et al. find that EXD2 plays a key role in this process by acting as an essential cofactor for the MRN complex.
Boxem and colleagues perform a yeast two-hybrid screen to identify interactions between C. elegans polarity genes, followed by an RNAi screen to identify the functions of interaction pairs in the establishment and maintenance of cell polarity in various tissues.
Nerlov and colleagues show that expression of mKitL by cortical vascular endothelial cells is important for DN1 progenitor maintenance, whereas expression of mKitL by cortical thymic epithelial cells is required for maintaining DN2 progenitor cells.
Lecuit and colleagues show that, depending on its interaction partner, the G-protein-coupled receptor Smog regulates myosin II activation in different locations during Drosophila morphogenesis.
Using ultrasensitive mass spectrometry of wild-type and mutant early mouse zygotes, Hajkova and colleagues show that 5mC loss and 5hmC accumulation are uncoupled during zygotic epigenetic reprogramming.
Yang and colleagues identify a lncRNA that controls HIF1α signalling to stabilize HIF1α under normoxic conditions, and promotes breast cancer tumorigenesis.