Phylogeographic reconstruction of a bacterial species with high levels of lateral gene transfer

Background Phylogeographic reconstruction of some bacterial populations is hindered by low diversity coupled with high levels of lateral gene transfer. A comparison of recombination levels and diversity at seven housekeeping genes for eleven bacterial species, most of which are commonly cited as having high levels of lateral gene transfer shows that the relative contributions of homologous recombination versus mutation for Burkholderia pseudomallei is over two times higher than for Streptococcus pneumoniae and is thus the highest value yet reported in bacteria. Despite the potential for homologous recombination to increase diversity, B. pseudomallei exhibits a relative lack of diversity at these loci. In these situations, whole genome genotyping of orthologous shared single nucleotide polymorphism loci, discovered using next generation sequencing technologies, can provide very large data sets capable of estimating core phylogenetic relationships. We compared and searched 43 whole genome sequences of B. pseudomallei and its closest relatives for single nucleotide polymorphisms in orthologous shared regions to use in phylogenetic reconstruction. Results Bayesian phylogenetic analyses of >14,000 single nucleotide polymorphisms yielded completely resolved trees for these 43 strains with high levels of statistical support. These results enable a better understanding of a separate analysis of population differentiation among >1,700 B. pseudomallei isolates as defined by sequence data from seven housekeeping genes. We analyzed this larger data set for population structure and allele sharing that can be attributed to lateral gene transfer. Our results suggest that despite an almost panmictic population, we can detect two distinct populations of B. pseudomallei that conform to biogeographic patterns found in many plant and animal species. That is, separation along Wallace's Line, a biogeographic boundary between Southeast Asia and Australia. Conclusion We describe an Australian origin for B. pseudomallei, characterized by a single introduction event into Southeast Asia during a recent glacial period, and variable levels of lateral gene transfer within populations. These patterns provide insights into mechanisms of genetic diversification in B. pseudomallei and its closest relatives, and provide a framework for integrating the traditionally separate fields of population genetics and phylogenetics for other bacterial species with high levels of lateral gene transfer.

Plantar fasciitis : are pain and fascial thickness associated with arch shape and loading?

Background and Purpose Although plantar fascial thickening is a sonographic criterion for the diagnosis of plantar fasciitis, the effect of local loading and structural factors on fascial morphology are unknown. The purposes of this study were to compare sonographic measures of fascial thickness and radiographic measures of arch shape and regional loading of the foot during gait in individuals with and without unilateral plantar fasciitis and to investigate potential relationships between these loading and structural factors and the morphology of the plantar fascia in individuals with and without heel pain. Subjects The participants were 10 subjects with unilateral plantar fasciitis and 10 matched asymptomatic controls. Methods Heel pain on weight bearing was measured by a visual analog scale. Fascial thickness and static arch angle were determined from bilateral sagittal sonograms and weight-bearing lateral foot roentgenograms. Regional plantar loading was estimated from a pressure plate. Results On average, the plantar fascia of the symptomatic limb was thicker than the plantar fascia of the asymptomatic limb (6.1±1.4 mm versus 4.2±0.5 mm), which, in turn, was thicker than the fascia of the matched control limbs (3.4±0.5 mm and 3.5±0.6 mm). Pain was correlated with fascial thickness, arch angle, and midfoot loading in the symptomatic foot. Fascial thickness, in turn, was positively correlated with arch angle in symptomatic and asymptomatic feet and with peak regional loading of the midfoot in the symptomatic limb. Discussion and Conclusion The findings indicate that fascial thickness and pain in plantar fasciitis are associated with the regional loading and static shape of the arch.

Streptococcus pneumoniae infection suppresses allergic airways disease by inducing regulatory T cells

An inverse association exists between some bacterial infections and the prevalence of asthma. We investigated whether Streptococcus pneumoniae infection protects against asthma using mouse models of ovalbumin (OVA)-induced allergic airway disease (AAD). Mice were intratracheally infected or treated with killed S. pneumoniae before, during or after OVA sensitisation and subsequent challenge. The effects of S. pneumoniae on AAD were assessed. Infection or treatment with killed S. pneumoniae suppressed hallmark features of AAD, including antigen-specific T-helper cell (Th) type 2 cytokine and antibody responses, peripheral and pulmonary eosinophil accumulation, goblet cell hyperplasia, and airway hyperresponsiveness. The effect of infection on the development of specific features of AAD depended on the timing of infection relative to allergic sensitisation and challenge. Infection induced significant increases in regulatory T-cell (Treg) numbers in lymph nodes, which correlated with the degree of suppression of AAD. Tregs reduced T-cell proliferation and Th2 cytokine release. The suppressive effects of infection were reversed by anti-CD25 treatment. Respiratory infection or treatment with S. pneumoniae attenuates allergic immune responses and suppresses AAD. These effects may be mediated by S. pneumoniae-induced Tregs. This identifies the potential for the development of therapeutic agents for asthma from S. pneumoniae.

State convergence in the initialisation of stream ciphers

An initialisation process is a key component in modern stream cipher design. A well-designed initialisation process should ensure that each key-IV pair generates a different key stream. In this paper, we analyse two ciphers, A5/1 and Mixer, for which this does not happen due to state convergence. We show how the state convergence problem occurs and estimate the effective key-space in each case.