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Cerebral cavernous malformations (CCMs) are a cause of stroke and seizure for which no effective medical therapies yet exist. CCMs arise from the loss of an adaptor complex that negatively regulates MEKK3-KLF2/4 signalling in brain endothelial cells, but upstream activators of this disease pathway have yet to be identified. Here we identify endothelial Toll-like receptor 4 (TLR4) and the gut microbiome as critical stimulants of CCM formation. Activation of TLR4 by Gram-negative bacteria or lipopolysaccharide accelerates CCM formation, and genetic or pharmacologic blockade of TLR4 signalling prevents CCM formation in mice. Polymorphisms that increase expression of the TLR4 gene or the gene encoding its co-receptor CD14 are associated with higher CCM lesion burden in humans. Germ-free mice are protected from CCM formation, and a single course of antibiotics permanently alters CCM susceptibility in mice. These studies identify unexpected roles for the microbiome and innate immune signalling in the pathogenesis of a cerebrovascular disease, as well as strategies for its treatment.
Pubmed ID: 28489816
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A collection of tools for flow cytometer and application setup, data acquisition, and data analysis that help streamline flow cytometry workflows. It provides features to help users integrate flow systems into new application areas, including index sorting for stem cell and single-cell applications, as well as automation protocols for high-throughput and robotic laboratories.
View all literature mentionsOpen source whole genome association analysis toolset, designed to perform range of basic, large scale analyses in computationally efficient manner. Used for analysis of genotype/phenotype data. Through integration with gPLINK and Haploview, there is some support for subsequent visualization, annotation and storage of results. PLINK 1.9 is improved and second generation of the software.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on February 23,2023.Software package for comparison and analysis of microbial communities, primarily based on high-throughput amplicon sequencing data, but also supporting analysis of other types of data. QIMME analyzes and transforms raw sequencing data generated on Illumina or other platforms to publication quality graphics and statistics.
View all literature mentionsBiotechnology company in San Diego, California. Provides life scientists with innovative research reagents including immunity and cell culture products.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsMus musculus with name DBA/2J from IMSR.
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