A review of the experimental protocol and motivation for DYAMOND, the first intercomparison project of global storm-resolving models, is presented. Nine models submitted simulation output for a 40-day (1 August–10 September 2016) intercomparison period. Eight of these employed a tiling of the sphere that was uniformly less than 5 km. By resolving the transient dynamics of convective storms in the tropics, global storm-resolving models remove the need to parameterize tropical deep convection, providing a fundamentally more sound representation of the climate system and a more natural link to commensurately high-resolution data from satellite-borne sensors. The models and some basic characteristics of their output are described in more detail, as is the availability and planned use of this output for future scientific study. Tropically and zonally averaged energy budgets, precipitable water distributions, and precipitation from the model ensemble are evaluated, as is their representation of tropical cyclones and the predictability of column water vapor, the latter being important for tropical weather.

N-formyl peptide receptors (FPRs) are critical regulators of host defense in phagocytes and are also expressed in epithelia. FPR signaling and function have been extensively studied in phagocytes, yet their functional biology in epithelia is poorly understood. We describe a novel intestinal epithelial FPR signaling pathway that is activated by an endogenous FPR ligand, annexin A1 (ANXA1), and its cleavage product Ac2-26, which mediate activation of ROS by an epithelial NADPH oxidase, NOX1. We show that epithelial cell migration was regulated by this signaling cascade through oxidative inactivation of the regulatory phosphatases PTEN and PTP-PEST, with consequent activation of focal adhesion kinase (FAK) and paxillin. In vivo studies using intestinal epithelial specific Nox1 -/-IEC and AnxA1 -/-mice demonstrated defects in intestinal mucosal wound repair, while systemic administration of ANXA1 promoted wound recovery in a NOX1-dependent fashion. Additionally, increased ANXA1 expression was observed in the intestinal epithelium and infiltrating leukocytes in the mucosa of ulcerative colitis patients compared with normal intestinal mucosa. Our findings delineate a novel epithelial FPR1/NOX1-dependent redox signaling pathway that promotes mucosal wound repair.

Esophageal wall defects of different etiology in the upper gastrointestinal tract can be treated successfully with EVT, considering that indication for EVT should be weighed carefully. EVT can be regarded as a novel life-saving therapeutic tool.

Interleukin-1 family members are central mediators of host defense. Here we show that the novel IL-1 family member, IL-36γ, was expressed during experimental colitis and human inflammatory bowel disease (IBD). In response to dextran sodium sulfate (DSS)-induced damage, germ-free (GF) mice failed to induce IL-36γ, suggesting that gut microbiota are involved in its induction. Surprisingly, IL-36R-deficient (Il1rl2−/−) mice exhibited defective recovery following DSS-induced damage and impaired closure of colonic mucosal biopsy wounds, which coincided with impaired neutrophil accumulation in the wound bed. Failure of Il1rl2−/− mice to recover from DSS-induced damage was associated with a profound reduction in IL-22 expression, particularly by colonic neutrophils. Defective recovery of Il1rl2−/− mice could be rescued an aryl hydrocarbon receptor (AhR) agonist, which was sufficient to restore IL-22 expression and promote full recovery from DSS-induced damage. These findings implicate the IL-36/IL-36R axis in the resolution of intestinal mucosal wounds.

Impaired or excessive growth of endothelial cells contributes to several diseases. However, the functional involvement of regulatory long non-coding RNAs in these processes is not well defined. Here, we show that the long non-coding antisense transcript of GATA6 (GATA6-AS) interacts with the epigenetic regulator LOXL2 to regulate endothelial gene expression via changes in histone methylation. Using RNA deep sequencing, we find that GATA6-AS is upregulated in endothelial cells during hypoxia. Silencing of GATA6-AS diminishes TGF-β2-induced endothelial–mesenchymal transition in vitro and promotes formation of blood vessels in mice. We identify LOXL2, known to remove activating H3K4me3 chromatin marks, as a GATA6-AS-associated protein, and reveal a set of angiogenesis-related genes that are inversely regulated by LOXL2 and GATA6-AS silencing. As GATA6-AS silencing reduces H3K4me3 methylation of two of these genes, periostin and cyclooxygenase-2, we conclude that GATA6-AS acts as negative regulator of nuclear LOXL2 function.

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We discuss scientific features and computational performance of kilometre-scale global weather and climate simulations, considering the Icosahedral Non-hydrostatic (ICON) model and the Integrated Forecast System (IFS). Scalability measurements and a performance modelling approach are used to derive performance estimates for these models on upcoming exascale supercomputers. This is complemented by preliminary analyses of the model data that illustrate the importance of high-resolution models to gain improvements in the accuracy of convective processes, a better understanding of physics dynamics interactions and poorly resolved or parametrized processes, such as gravity waves, convection and boundary layer. This article is part of the theme issue ‘Multiscale modelling, simulation and computing: from the desktop to the exascale’.

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