VHF-UHF phased array techniques

http://deepblue.lib.umich.edu/bitstream/2027.42/6411/3/bad0627.0001.001.txthttp://deepblue.lib.umich.edu/bitstream/2027.42/6411/5/VHF-UHF Phased Array Techniques.pd

Hyperinduction of Host Beta Interferon by a Listeria monocytogenes Strain Naturally Overexpressing the Multidrug Efflux Pump MdrT

Many pathogens regulate or modify their immune-stimulating ligands to avoid detection by their infected hosts. Listeria monocytogenes, a facultative intracellular bacterial pathogen, interacts with multiple components of mammalian innate immunity during its infection cycle. During replication within the cytosol of infected cells, L. monocytogenes utilizes two multidrug efflux pumps, MdrM and MdrT, to secrete the small nucleic acid second messenger cyclic-di-AMP (c-di-AMP). Host recognition of c-di-AMP triggers the production of type I interferons, including beta interferon (IFN-β), which, surprisingly, promote L. monocytogenes virulence. In this study, we have examined the capacity of multiple laboratory and clinical isolates of L. monocytogenes to stimulate host production of IFN-β. We have identified the L. monocytogenes strain LO28 as able to hyperinduce IFN-β production in infected cells ∼30-fold more than the common laboratory clone L. monocytogenes strain 10403S. Genomic analyses determined that LO28 contains a naturally occurring loss-of-function allele of the transcriptional regulator BrtA and correspondingly derepresses expression of MdrT. Surprisingly, while derepression of MdrT resulted in hyperstimulation of IFN-β, it results in significant attenuation in multiple mouse models of infection. While type I interferons may promote L. monocytogenes virulence, this study demonstrates that unregulated expression of the c-di-AMP-secreting efflux pump MdrT significantly restricts virulence in vivo by an unknown mechanism

Recent progress in the genetics of common obesity

The genetic contribution to interindividual variation in common obesity has been estimated at 40–70%. Yet, despite a relatively high heritability, the search for obesity susceptibility genes has been an arduous task. This paper reviews recent progress made in the obesity genetics field with an emphasis on established obesity susceptibility loci identified through candidate gene as well as genome-wide studies. For the last 15 years, candidate gene and genome-wide linkage studies have been the two main genetic epidemiological approaches to identify genetic loci for common traits, yet progress has been slow and success limited. Only recently have candidate gene studies started to succeed; by means of large-scale studies and meta-analyses at least five variants in four candidate genes have been found to be robustly associated with obesity-related traits. Genome-wide linkage studies, however, have so far not been able to pinpoint genetic loci for common obesity. The genome-wide association approach, which has become available in recent years, has dramatically changed the pace of gene discoveries for common disease, including obesity. Three waves of large-scale high-density genome-wide association studies have already discovered at least 15 previously unanticipated genetic loci incontrovertibly associated with body mass index and extreme obesity risk. Although the combined contribution of these loci to the variation in obesity risk at the population level is small and their predictive value is typically low, these recently discovered loci are set to improve fundamentally our insights into the pathophysiology of obesity