THE VARIABLE GENOMIC ARCHITECTURE OF ISOLATION BETWEEN HYBRIDIZING SPECIES OF HOUSE MICE

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75350/1/EVO_846_sm_FigS3A.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/75350/2/EVO_846_sm_legend.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/75350/3/EVO_846_sm_FigS4.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/75350/4/j.1558-5646.2009.00846.x.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/75350/5/EVO_846_sm_FigS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/75350/6/EVO_846_sm_FigS2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/75350/7/EVO_846_sm_FigS3B.pd

A Common Dominant TLR5 Stop Codon Polymorphism Abolishes Flagellin Signaling and Is Associated with Susceptibility to Legionnaires' Disease

Although Toll-like receptors (TLRs) are critical mediators of the immune response to pathogens, the influence of polymorphisms in this gene family on human susceptibility to infection is poorly understood. We demonstrated recently that TLR5 recognizes flagellin, a potent inflammatory stimulus present in the flagellar structure of many bacteria. Here, we show that a common stop codon polymorphism in the ligand-binding domain of TLR5 (TLR5392STOP) is unable to mediate flagellin signaling, acts in a dominant fashion, and is associated with susceptibility to pneumonia caused by Legionella pneumophila, a flagellated bacterium. We also show that flagellin is a principal stimulant of proinflammatory cytokine production in lung epithelial cells. Together, these observations suggest that TLR5392STOP increases human susceptibility to infection through an unusual dominant mechanism that compromises TLR5's essential role as a regulator of the lung epithelial innate immune response

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements