A Salmonella Typhimurium-Typhi genomic chimera: a model to study Vi polysaccharide capsule function in vivo.

The Vi capsular polysaccharide is a virulence-associated factor expressed by Salmonella enterica serotype Typhi but absent from virtually all other Salmonella serotypes. In order to study this determinant in vivo, we characterised a Vi-positive S. Typhimurium (C5.507 Vi(+)), harbouring the Salmonella pathogenicity island (SPI)-7, which encodes the Vi locus. S. Typhimurium C5.507 Vi(+) colonised and persisted in mice at similar levels compared to the parent strain, S. Typhimurium C5. However, the innate immune response to infection with C5.507 Vi(+) and SGB1, an isogenic derivative not expressing Vi, differed markedly. Infection with C5.507 Vi(+) resulted in a significant reduction in cellular trafficking of innate immune cells, including PMN and NK cells, compared to SGB1 Vi(-) infected animals. C5.507 Vi(+) infection stimulated reduced numbers of TNF-α, MIP-2 and perforin producing cells compared to SGB1 Vi(-). The modulating effect associated with Vi was not observed in MyD88(-/-) and was reduced in TLR4(-/-) mice. The presence of the Vi capsule also correlated with induction of the anti-inflammatory cytokine IL-10 in vivo, a factor that impacted on chemotaxis and the activation of immune cells in vitro.

Phase-variable surface structures are required for infection of Campylobacter jejuni by bacteriophages.

This study characterizes the interaction between Campylobacter jejuni and the 16 phages used in the United Kingdom typing scheme by screening spontaneous mutants of the phage-type strains and transposon mutants of the sequenced strain NCTC 11168. We show that the 16 typing phages fall into four groups based on their patterns of activity against spontaneous mutants. Screens of transposon and defined mutants indicate that the phage-bacterium interaction for one of these groups appears to involve the capsular polysaccharide (CPS), while two of the other three groups consist of flagellatropic phages. The expression of CPS and flagella is potentially phase variable in C. jejuni, and the implications of these findings for typing and intervention strategies are discussed.

Dasher - A data entry interface using continuous gestures and language models

Existing devices for communicating information to computers are bulky, slow to use, or unreliable. Dasher is a new interface incorporating language modelling and driven by continuous two-dimensional gestures, e.g. a mouse, touchscreen, or eye-tracker. Tests have shown that this device can be used to enter text at a rate of up to 34 words per minute, compared with typical ten-finger keyboard typing of 40-60 words per minute. Although the interface is slower than a conventional keyboard, it is small and simple, and could be used on personal data assistants and by motion-impaired computer users.

Epigenetic remodeling of meiotic crossover frequency in Arabidopsis thaliana DNA methyltransferase mutants.

Meiosis is a specialized eukaryotic cell division that generates haploid gametes required for sexual reproduction. During meiosis, homologous chromosomes pair and undergo reciprocal genetic exchange, termed crossover (CO). Meiotic CO frequency varies along the physical length of chromosomes and is determined by hierarchical mechanisms, including epigenetic organization, for example methylation of the DNA and histones. Here we investigate the role of DNA methylation in determining patterns of CO frequency along Arabidopsis thaliana chromosomes. In A. thaliana the pericentromeric regions are repetitive, densely DNA methylated, and suppressed for both RNA polymerase-II transcription and CO frequency. DNA hypomethylated methyltransferase1 (met1) mutants show transcriptional reactivation of repetitive sequences in the pericentromeres, which we demonstrate is coupled to extensive remodeling of CO frequency. We observe elevated centromere-proximal COs in met1, coincident with pericentromeric decreases and distal increases. Importantly, total numbers of CO events are similar between wild type and met1, suggesting a role for interference and homeostasis in CO remodeling. To understand recombination distributions at a finer scale we generated CO frequency maps close to the telomere of chromosome 3 in wild type and demonstrate an elevated recombination topology in met1. Using a pollen-typing strategy we have identified an intergenic nucleosome-free CO hotspot 3a, and we demonstrate that it undergoes increased recombination activity in met1. We hypothesize that modulation of 3a activity is caused by CO remodeling driven by elevated centromeric COs. These data demonstrate how regional epigenetic organization can pattern recombination frequency along eukaryotic chromosomes.

A computational fluid-structure interaction study of inflation cycles of a tension cone decelerator

Inflatable aerodynamic decelerators present potential advantages for planetary entry in missions of robotic and human exploration. The design of these structures face many engineering challenges, including complex deformable geometries, anisotropic material response, and coupled shockturbulence interactions. In this paper, we describe a comprehensive computational fluid-structure interaction study of an inflation cycle of a tension cone decelerator in supersonic flow and compare the simulations with earlier published experimental results. The aeroshell design and flow conditions closely match recent experiments conducted at Mach 2.5. The structural model is a 16-sided polygonal tension cone with seams between each segment. The computational model utilizes adaptive mesh refinement, large-eddy simulation, and shell mechanics with self-contact modeling to represent the flow and structure interaction. This study focuses on the dynamics of the structure as the inflation pressure varies gradually, and the behavior of forces experienced by the flexible and rigid (the payload capsule) structures. © 2011 by the American Institute of Aeronautics and Astronautics, Inc. All rights reserved.