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Intestinal Epithelial and Intraepithelial T Cell Crosstalk Mediates a Dynamic Response to Infection.

Cell | Nov 2, 2017

Intestinal intraepithelial lymphocytes (IELs) are located at the critical interface between the intestinal lumen, which is chronically exposed to food and microbes, and the core of the body. Using high-resolution microscopy techniques and intersectional genetic tools, we investigated the nature of IEL responses to luminal microbes. We observed that TCRγδ IELs exhibit unique microbiota-dependent location and movement patterns in the epithelial compartment. This behavioral pattern quickly changes upon exposure to different enteric pathogens, resulting in increased interepithelial cell (EC) scanning, expression of antimicrobial genes, and glycolysis. Both dynamic and metabolic changes to γδ IEL depend on pathogen sensing by ECs. Direct modulation of glycolysis is sufficient to change γδ IEL behavior and susceptibility to early pathogen invasion. Our results uncover a coordinated EC-IEL response to enteric infections that modulates lymphocyte energy utilization and dynamics and supports maintenance of the intestinal epithelial barrier. VIDEO ABSTRACT.

Pubmed ID: 28942917 RIS Download

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Gene Set Enrichment Analysis

A computational software that determines whether an a priori defined set of genes shows statistically significant, concordant differences between two biological states (e.g. phenotypes). Additional resources to analyze, annotate and interpret enrichment results are also available including the Molecular Signatures Database (MSigDB), a collection of annotated gene sets for use with GSEA software.

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Imaris

Interactive Vision In The Life SciencesCombining speed, precision and ease-of-use, Imaris provides an impressive range of capabilities for working with three-dimensional images. Move easily between simple and advanced 3D views. Use flexible editing and processing functions, such as interactive surface rendering and object slicing capabilities. And output to standard TIFF, Quicktime and AVI formats. Imaris accepts virtually all image formats that are used in confocal microscopy and many of those used in wide-field image acquisition.BitPlane, Inc. also releases the following companion products:- ImarisXT is a multi-functional two-way interface from Imaris to both classic programming languages and to Matlab.- Imaris MeasurementPro and Imaris Track provide the ability to segment and follow the movement of independent objects in a 3D image over time. Objects can either be Surface Objects or Spots, created automatically or manually.- ImarisColoc enables users to easily isolate, visualize, and quantify regional overlap in 3D and 4D images and automates the process of selecting colocalized image areas.

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SciPy

A Python-based environment of open-source software for mathematics, science, and engineering. The core packages of SciPy include: NumPy, a base N-dimensional array package; SciPy Library, a fundamental library for scientific computing; and IPython, an enhanced interactive console.

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Graphpad Prism

Statistical software package for data analysis, hypothesis testing, and modeling. The software can capable perform mathematical calculations (including biostatistics) and graphical plotting such as curve fitting (nonlinear regression) and scientific graphing.

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Cufflinks

A software which is used for transcriptome assembly and differential expression analysis for RNA-Seq. This software includes a script called cuffmerge that can be used to merge together several Cufflinks assemblies. It also handles running Cuffcompare as well as automatically filtering a number of transfrags that are likely to be artifacts. If the researcher has a reference GTF file, the researcher can provide it to the script to more effectively merge novel isoforms and maximize overall assembly quality.

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PANTHER

Classification system that classifies genes by their functions, using published scientific experimental evidence and evolutionary relationships to predict function even in the absence of direct experimental evidence. Proteins are classified by expert biologists according to: * Gene families and subfamilies, including annotated phylogenetic trees * Gene Ontology classes: molecular function, biological process, cellular component * PANTHER Protein Classes * Pathways, including diagrams The PANTHER Classifications are the result of human curation as well as sophisticated bioinformatics algorithms. Details of the methods can be found in (Thomas et al., Genome Research 2003; Mi et al. NAR 2005). Version 8.1 contains 7729 protein families, each with a phylogenetic tree relating modern-day genes in 48 organisms.) PANTHER contains the complete sets of protein coding genes for 48 organisms, obtained from definitive sources. PANTHER uses the Gene Ontology for classifications by molecular function, biological process and cellular component. The PANTHER Protein Class ontology was adapted from the PANTHER/X molecular function ontology, and includes commonly used classes of protein functions, many of which are not covered by GO molecular function. You may download the classes and relationship information. PANTHER uses only a subset of GO terms (GO slim) to facilitate browsing. You may download the PANTHER GO slim. You may Score proteins against the PANTHER HMM library and download PANTHER tools and data. PANTHER Pathway consists of over 176, primarily signaling, pathways, each with subfamilies and protein sequences mapped to individual pathway components. Pathways are drawn using CellDesigner software, capturing molecular level events in both signaling and metabolic pathways, and can be exported in SBML format. The SBGN view of the diagram can also be exported. Pathway diagrams are interactive and include tools for visualizing gene expression data in the context of the diagrams.

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FlowJo

Software for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.

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