CTLA-4 expressing innate lymphoid cells modulate mucosal homeostasis in a microbiota dependent manner.

The maintenance of intestinal homeostasis is a fundamental process critical for organismal integrity. Sitting at the interface of the gut microbiome and mucosal immunity, adaptive and innate lymphoid populations regulate the balance between commensal micro-organisms and pathogens. Checkpoint inhibitors, particularly those targeting the CTLA-4 pathway, disrupt this fine balance and can lead to inflammatory bowel disease and immune checkpoint colitis.

PRC2-RNA interactions: Viewpoint from Tom Cech, Chen Davidovich, and Richard Jenner.

Diverse biochemical, structural, and in vivo data support models for the regulation of polycomb repressive complex 2 (PRC2) activity by RNAs, which may contribute to the maintenance of epigenetic states. Here, we summarize this research and also suggest why it can be difficult to capture biologically relevant PRC2-RNA interactions in living cells.

Paediatric mass casualty response through the lens of Functional Resonance Analytical Methodology- lessons learned.

Background: Mass Casualty Incidents are rare but can significantly stress healthcare systems. Functional Resonance Analytical Methodology (FRAM) is a systematic approach to model and explore how complex systems adapt to variations and to understand resilient properties in the face of perturbations. The aim of this study was to use FRAM to create a model of a paediatric trauma system during the initial response to the Manchester Arena Attack to provide resilience-based insights for the management of future Mass Casualty Incidents (MCI).

Apparent RNA bridging between PRC2 and chromatin is an artifact of non-specific chromatin precipitation upon RNA degradation.

Polycomb repressive complex 2 (PRC2) modifies chromatin to maintain repression of genes specific for other cell lineages. In vitro, RNA inhibits PRC2 activity, but the effect of RNA on PRC2 in cells is less clear, with studies concluding that RNA either antagonizes or promotes PRC2 chromatin association. The addition of RNase A to chromatin immunoprecipitation reactions has been reported to reduce detection of PRC2 target sites, suggesting the existence of RNA bridges connecting PRC2 to chromatin.

CD90 is not constitutively expressed in functional innate lymphoid cells.

Huge progress has been made in understanding the biology of innate lymphoid cells (ILC) by adopting several well-known concepts in T cell biology. As such, flow cytometry gating strategies and markers, such as CD90, have been applied to indentify ILC. Here, we report that most non-NK intestinal ILC have a high expression of CD90 as expected, but surprisingly a sub-population of cells exhibit low or even no expression of this marker.

Cohesin-independent STAG proteins interact with RNA and R-loops and promote complex loading.

Most studies of cohesin function consider the Stromalin Antigen (STAG/SA) proteins as core complex members given their ubiquitous interaction with the cohesin ring. Here, we provide functional data to support the notion that the SA subunit is not a mere passenger in this structure, but instead plays a key role in the localization of cohesin to diverse biological processes and promotes loading of the complex at these sites. We show that in cells acutely depleted for RAD21, SA proteins remain bound to chromatin, cluster in 3D and interact with CTCF, as well as with a wide range of RNA binding proteins involved in multiple RNA processing mechanisms.

Safety profile of a multimodal fail-safe model to minimize postoperative complications in oncologic colorectal resections-a cohort study.

Background: Despite innovations in surgical techniques, major complications following colorectal surgery still lead to a significant morbidity and mortality. There is no standard protocol for perioperative management of patients with colorectal cancer. This study evaluates the effectiveness of a multimodal fail-safe model in minimizing severe surgical complications following colorectal resections.

Family-centred practice in speech-language pathology practice with children and young people in out-of-home care in Australia: A scoping review.

: Communication difficulties are more common in children or young people (CYP) who have lived in out-of-home care (OOHC) compared to the general population. Principles of family-centred practice (FCP) are frequently utilised by speech-language pathologists (SLPs) when working with CYP with communication difficulties. The aim of this scoping review was to describe how the principles of FCP are applied in the literature to speech-language pathology practice with CYP aged 0-18 in OOHC in Australia.

Cyclin-dependent Kinase 9 as a Potential Target for Anti-TNF-resistant Inflammatory Bowel Disease.

Background & Aims: Resistance to single cytokine blockade, namely anti-tumor necrosis factor (TNF) therapy, is a growing concern for patients with inflammatory bowel disease (IBD). The transcription factor T-bet is a critical regulator of intestinal homeostasis, is genetically linked to mucosal inflammation and controls the expression of multiples genes such as the pro-inflammatory cytokines interferon (IFN)-γ and TNF. Inhibiting T-bet may therefore offer a more attractive prospect for treating IBD but remains challenging to target therapeutically.

JAZF1-SUZ12 dysregulates PRC2 function and gene expression during cell differentiation.

Polycomb repressive complex 2 (PRC2) methylates histone H3 lysine 27 (H3K27me3) to maintain gene repression and is essential for cell differentiation. In low-grade endometrial stromal sarcoma (LG-ESS), the PRC2 subunit SUZ12 is often fused with the NuA4/TIP60 subunit JAZF1. We show that JAZF1-SUZ12 dysregulates PRC2 composition, genome occupancy, histone modification, gene expression, and cell differentiation.

The TH1 cell lineage-determining transcription factor T-bet suppresses TH2 gene expression by redistributing GATA3 away from TH2 genes.

Lineage-determining transcription factors (LD-TFs) drive the differentiation of progenitor cells into a specific lineage. In CD4+ T cells, T-bet dictates differentiation of the TH1 lineage, whereas GATA3 drives differentiation of the alternative TH2 lineage. However, LD-TFs, including T-bet and GATA3, are frequently co-expressed but how this affects LD-TF function is not known.

The Th1 cell regulatory circuitry is largely conserved between human and mouse.

Gene expression programs controlled by lineage-determining transcription factors are often conserved between species. However, infectious diseases have exerted profound evolutionary pressure, and therefore the genes regulated by immune-specific transcription factors might be expected to exhibit greater divergence. T-bet (Tbx21) is the immune-specific, lineage-specifying transcription factor for T helper type I (Th1) immunity, which is fundamental for the immune response to intracellular pathogens but also underlies inflammatory diseases.

A Pseudoscorpion's Promising Pinch: The venom of Chelifer cancroides contains a rich source of novel compounds.

With pedipalps modified for venom injection, some pseudoscorpions possess a unique venom delivery system, which evolved independently from those of other arachnids like scorpions and spiders. Up to now, only a few studies have been focused on pseudoscorpion venom, which either identified a small fraction of venom compounds, or were based on solely transcriptomic approaches. Only one study addressed the bioactivity of pseudoscorpion venom.

Nascent RNA antagonizes the interaction of a set of regulatory proteins with chromatin.

A number of regulatory factors are recruited to chromatin by specialized RNAs. Whether RNA has a more general role in regulating the interaction of proteins with chromatin has not been determined. We used proteomics methods to measure the global impact of nascent RNA on chromatin in embryonic stem cells.

A Crohn's Disease-associated IL2RA Enhancer Variant Determines the Balance of T Cell Immunity by Regulating Responsiveness to IL-2 Signalling.

Background And Aims: Differential responsiveness to interleukin [IL]-2 between effector CD4+ T cells [Teff] and regulatory T cells [Treg] is a fundamental mechanism of immunoregulation. The single nucleotide polymorphism [SNP] rs61839660, located within IL2RA [CD25], has been associated with the development of Crohn's disease [CD]. We sought to identify the T cell immune phenotype of IBD patients who carry this SNP.

The Study of Protein-DNA Interactions in CD4 T-Cells Using ChIPmentation.

Chromatin immunoprecipitation (ChIP) coupled with high-throughput sequencing (ChIP-seq) is an invaluable method to profile of enrichment of histone modifications and transcription factor binding sites across the genome. However, standard ChIP-seq protocols require large numbers of cells (>10) as starting material, which are often impossible to obtain for rare immune populations. Here we describe a streamlined ChIP protocol optimised for small cell numbers in conjunction with transposon-tagging mediated sequencing library preparation (ChIPmentation) which allows the analysis of samples of as low as 10 cells.