Interferon regulatory factor 6 (IRF6) determines intestinal epithelial cell development and immunity.

Intestinal epithelial cell (IEC) responses to interferon (IFN) favor antiviral defense with minimal cytotoxicity, but IEC-specific factors that regulate these responses remain poorly understood. Interferon regulatory factors (IRFs) are a family of nine related transcription factors, and IRF6 is preferentially expressed by epithelial cells, but its roles in IEC immunity are unknown. In this study, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) screens found that Irf6 deficiency enhanced IFN-stimulated antiviral responses in transformed mouse IECs but not macrophages.

Role of type-I and type-III interferons in gastrointestinal homeostasis and pathogenesis.

Interferon (IFN) was discovered based on interference with virus production, and three types of IFN are now defined. Since its discovery, IFN's roles have expanded beyond viruses to diverse pathogen types, tissue homeostasis, and inflammatory disease. The gastrointestinal (GI) tract is arguably the tissue where the roles of IFN types are most distinct, with a particularly prominent role for type-III IFN in antiviral protection of the intestinal epithelium.

The gut protist Tritrichomonas arnold restrains virus-mediated loss of oral tolerance by modulating dietary antigen-presenting dendritic cells.

Loss of oral tolerance (LOT) to gluten, driven by dendritic cell (DC) priming of gluten-specific T helper 1 (Th1) cell immune responses, is a hallmark of celiac disease (CeD) and can be triggered by enteric viral infections. Whether certain commensals can moderate virus-mediated LOT remains elusive. Here, using a mouse model of virus-mediated LOT, we discovered that the gut-colonizing protist Tritrichomonas (T.

Alteration history of Séítah formation rocks inferred by PIXL x-ray fluorescence, x-ray diffraction, and multispectral imaging on Mars.

Collocated crystal sizes and mineral identities are critical for interpreting textural relationships in rocks and testing geological hypotheses, but it has been previously impossible to unambiguously constrain these properties using in situ instruments on Mars rovers. Here, we demonstrate that diffracted and fluoresced x-rays detected by the PIXL instrument (an x-ray fluorescence microscope on the Perseverance rover) provide information about the presence or absence of coherent crystalline domains in various minerals. X-ray analysis and multispectral imaging of rocks from the Séítah formation on the floor of Jezero crater shows that they were emplaced as coarsely crystalline igneous phases.

Homeostatic interferon-lambda response to bacterial microbiota stimulates preemptive antiviral defense within discrete pockets of intestinal epithelium.

Interferon-lambda (IFN-λ) protects intestinal epithelial cells (IECs) from enteric viruses by inducing expression of antiviral IFN-stimulated genes (ISGs). Here, we find that bacterial microbiota stimulate a homeostatic ISG signature in the intestine of specific pathogen-free mice. This homeostatic ISG expression is restricted to IECs, depends on IEC-intrinsic expression of IFN-λ receptor (), and is associated with IFN-λ production by leukocytes.

A small RNA is functional in despite containing a large insertion.

Bacterial small RNAs (sRNAs) are important regulators of gene expression; however, the impact of natural mutations on sRNA functions has not been studied extensively. Here we show that the sRNA MgrR contains a unique 53 bp insertion in , a close relative of and . The insertion is a repetitive extragenic palindromic (REP) sequence that could block transcription, but full-length MgrR is produced in , showing that the insertion has not affected sRNA production.

NeuroCartography: Scalable Automatic Visual Summarization of Concepts in Deep Neural Networks.

Existing research on making sense of deep neural networks often focuses on neuron-level interpretation, which may not adequately capture the bigger picture of how concepts are collectively encoded by multiple neurons. We present Neurocartography, an interactive system that scalably summarizes and visualizes concepts learned by neural networks. It automatically discovers and groups neurons that detect the same concepts, and describes how such neuron groups interact to form higher-level concepts and the subsequent predictions.

Detection of emerging drugs involved in overdose via diachronic word embeddings of substances discussed on social media.

Substances involved in overdose deaths have shifted over time and continue to undergo transition. Early detection of emerging drugs involved in overdose is a major challenge for traditional public health data systems. While novel social media data have shown promise, there is a continued need for robust natural language processing approaches that can identify emerging substances.