A Quadruple Knockout of lasIR and rhlIR of Pseudomonas aeruginosa PAO1 That Retains Wild-Type Twitching Motility Has Equivalent Infectivity and Persistence to PAO1 in a Mouse Model of Lung Infection

It has been widely reported that quorum-sensing incapable strains of Pseudomonas aeruginosa are less virulent than wild type strains. However, quorum sensing mutants of P. aeruginosa have been shown to develop other spontaneous mutations under prolonged culture conditions, and one of the phenotypes of P. aeruginosa that is frequently affected by this phenomenon is type IV pili-dependent motility, referred to as twitching motility. As twitching motility has been reported to be important for adhesion and colonisation, we aimed to generate a quorum-sensing knockout for which the heritage was recorded and the virulence factor production in areas unrelated to quorum sensing was known to be intact. We created a lasIRrhlIR quadruple knockout in PAO1 using a published technique that allows for the deletion of antibiotic resistance cartridges following mutagenesis, to create an unmarked QS knockout of PAO1, thereby avoiding the need for use of antibiotics in culturing, which can have subtle effects on bacterial phenotype. We phenotyped this mutant demonstrating that it produced reduced levels of protease and elastase, barely detectable levels of pyoverdin and undetectable levels of the quorum sensing signal molecules N-3-oxododecanoly-L-homoserine lactone and N-butyryl homoserine lactone, but retained full twitching motility. We then used a mouse model of acute lung infection with P. aeruginosa to demonstrate that the lasIRrhlIR knockout strain showed equal persistence to wild type parental PAO1, induced equal or greater neutrophil infiltration to the lungs, and induced similar levels of expression of inflammatory cytokines in the lungs and similar antibody responses, both in terms of magnitude and isotype. Our results suggest, in contrast to previous reports, that lack of quorum sensing alone does not significantly affect the immunogenicity, infectiveness and persistence of P. aeruginosa in a mouse model of acute lung infection. © 2013 Lazenby et al

Stigmergy co-ordinates multicellular collective behaviours during Myxococcus xanthus surface migration

Surface translocation by the soil bacterium Myxococcus xanthus is a complex multicellular phenomenon that entails two motility systems. However, the mechanisms by which the activities of individual cells are coordinated to manifest this collective behaviour are currently unclear. Here we have developed a novel assay that enables detailed microscopic examination of M. xanthus motility at the interstitial interface between solidified nutrient medium and a glass coverslip. Under these conditions, M. xanthus motility is characterised by extensive micro-morphological patterning that is considerably more elaborate than occurs at an air-surface interface. We have found that during motility on solidified nutrient medium, M. xanthus forges an interconnected furrow network that is lined with an extracellular matrix comprised of exopolysaccharides, extracellular lipids, membrane vesicles and an unidentified slime. Our observations have revealed that M. xanthus motility on solidified nutrient medium is a stigmergic phenomenon in which multi-cellular collective behaviours are co-ordinated through trail-following that is guided by physical furrows and extracellular matrix materials

Construction and analysis of causally dynamic hybrid bond graphs

Engineering systems are frequently abstracted to models with discontinuous behaviour (such as a switch or contact), and a hybrid model is one which contains continuous and discontinuous behaviours. Bond graphs are an established physical modelling method, but there are several methods for constructing switched or ‘hybrid’ bond graphs, developed for either qualitative ‘structural’ analysis or efficient numerical simulation of engineering systems. This article proposes a general hybrid bond graph suitable for both. The controlled junction is adopted as an intuitive way of modelling a discontinuity in the model structure. This element gives rise to ‘dynamic causality’ that is facilitated by a new bond graph notation. From this model, the junction structure and state equations are derived and compared to those obtained by existing methods. The proposed model includes all possible modes of operation and can be represented by a single set of equations. The controlled junctions manifest as Boolean variables in the matrices of coefficients. The method is more compact and intuitive than existing methods and dispenses with the need to derive various modes of operation from a given reference representation. Hence, a method has been developed, which can reach common usage and form a platform for further study

Development and initial validation of the bronchiectasis exacerbation and symptom tool (BEST)

BACKGROUND: Recurrent bronchiectasis exacerbations are related to deterioration of lung function, progression of the disease, impairment of quality of life, and to an increased mortality. Improved detection of exacerbations has been accomplished in chronic obstructive pulmonary disease through the use of patient completed diaries. These tools may enhance exacerbation reporting and identification. The aim of this study was to develop a novel symptom diary for bronchiectasis symptom burden and detection of exacerbations, named the BEST diary. METHODS: Prospective observational study of patients with bronchiectasis conducted at Ninewells Hospital, Dundee. We included patients with confirmed bronchiectasis by computed tomography, who were symptomatic and had at least 1 documented exacerbation of bronchiectasis in the previous 12\u2009months to participate. Symptoms were recorded daily in a diary incorporating cough, sputum volume, sputum colour, dyspnoea, fatigue and systemic disturbance scored from 0 to 26. RESULTS: Twenty-one patients were included in the study. We identified 29 reported (treated exacerbations) and 23 unreported (untreated) exacerbations over 6-month follow-up. The BEST diary score showed a good correlation with the established and validated questionnaires and measures of health status (COPD Assessment Test, r =\u20090.61, p =\u20090.0037, Leicester Cough Questionnaire, r =\u2009-\u20090.52,p =\u20090.0015, St Georges Respiratory Questionnaire, r =\u20090.61,p <\u20090.0001 and 6\u2009min walk test, r =\u2009-\u20090.46,p =\u20090.037). The mean BEST score at baseline was 7.1 points (SD 2.2). The peak symptom score during exacerbation was a mean of 16.4 (3.1), and the change from baseline to exacerbation was a mean of 9.1 points (SD 2.5). Mean duration of exacerbations based on time for a return to baseline symptoms was 15.3\u2009days (SD 5.7). A minimum clinically important difference of 4 points is proposed. CONCLUSIONS: The BEST symptom diary has shown concurrent validity with current health questionnaires and is responsive at onset and recovery from exacerbation. The BEST diary may be useful to detect and characterise exacerbations in bronchiectasis clinical trials

First order parent formulation for generic gauge field theories

We show how a generic gauge field theory described by a BRST differential can systematically be reformulated as a first order parent system whose spacetime part is determined by the de Rham differential. In the spirit of Vasiliev's unfolded approach, this is done by extending the original space of fields so as to include their derivatives as new independent fields together with associated form fields. Through the inclusion of the antifield dependent part of the BRST differential, the parent formulation can be used both for on and off-shell formulations. For diffeomorphism invariant models, the parent formulation can be reformulated as an AKSZ-type sigma model. Several examples, such as the relativistic particle, parametrized theories, Yang-Mills theory, general relativity and the two dimensional sigma model are worked out in details.Comment: 36 pages, additional sections and minor correction

New Fe-based superconductors: properties relevant for applications

Less than two years after the discovery of high temperature superconductivity in oxypnictide LaFeAs(O,F) several families of superconductors based on Fe layers (1111, 122, 11, 111) are available. They share several characteristics with cuprate superconductors that compromise easy applications, such as the layered structure, the small coherence length, and unconventional pairing, On the other hand the Fe-based superconductors have metallic parent compounds, and their electronic anisotropy is generally smaller and does not strongly depend on the level of doping, the supposed order parameter symmetry is s wave, thus in principle not so detrimental to current transmission across grain boundaries. From the application point of view, the main efforts are still devoted to investigate the superconducting properties, to distinguish intrinsic from extrinsic behaviours and to compare the different families in order to identify which one is the fittest for the quest for better and more practical superconductors. The 1111 family shows the highest Tc, huge but also the most anisotropic upper critical field and in-field, fan-shaped resistive transitions reminiscent of those of cuprates, while the 122 family is much less anisotropic with sharper resistive transitions as in low temperature superconductors, but with about half the Tc of the 1111 compounds. An overview of the main superconducting properties relevant to applications will be presented. Upper critical field, electronic anisotropy parameter, intragranular and intergranular critical current density will be discussed and compared, where possible, across the Fe-based superconductor families

The role of asymmetric interactions on the effect of habitat destruction in mutualistic networks

Plant-pollinator mutualistic networks are asymmetric in their interactions: specialist plants are pollinated by generalist animals, while generalist plants are pollinated by a broad involving specialists and generalists. It has been suggested that this asymmetric ---or disassortative--- assemblage could play an important role in determining the equal susceptibility of specialist and generalist plants under habitat destruction. At the core of the argument lies the observation that specialist plants, otherwise candidates to extinction, could cope with the disruption thanks to their interaction with generalist pollinators. We present a theoretical framework that supports this thesis. We analyze a dynamical model of a system of mutualistic plants and pollinators, subject to the destruction of their habitat. We analyze and compare two families of interaction topologies, ranging from highly assortative to highly disassortative ones, as well as real pollination networks. We found that several features observed in natural systems are predicted by the mathematical model. First, there is a tendency to increase the asymmetry of the network as a result of the extinctions. Second, an entropy measure of the differential susceptibility to extinction of specialist and generalist species show that they tend to balance when the network is disassortative. Finally, the disappearance of links in the network, as a result of extinctions, shows that specialist plants preserve more connections than the corresponding plants in an assortative system, enabling them to resist the disruption.Comment: 14 pages, 7 figure

The Void Galaxy Survey

The Void Galaxy Survey (VGS) is a multi-wavelength program to study $\sim$60 void galaxies. Each has been selected from the deepest interior regions of identified voids in the SDSS redshift survey on the basis of a unique geometric technique, with no a prior selection of intrinsic properties of the void galaxies. The project intends to study in detail the gas content, star formation history and stellar content, as well as kinematics and dynamics of void galaxies and their companions in a broad sample of void environments. It involves the HI imaging of the gas distribution in each of the VGS galaxies. Amongst its most tantalizing findings is the possible evidence for cold gas accretion in some of the most interesting objects, amongst which are a polar ring galaxy and a filamentary configuration of void galaxies. Here we shortly describe the scope of the VGS and the results of the full analysis of the pilot sample of 15 void galaxies.Comment: 9 pages, 6 figures. This is an extended version of a paper to appear in "Environment and the Formation of Galaxies: 30 years later", Proceedings of Symposium 2 of JENAM 2010, eds. I. Ferreras, A. Pasquali, ASSP, Springer. Version with highres figures at http://www.astro.rug.nl/~weygaert/vgs_jenam_weygaert.col.pd

Accreting Neutron Stars in Low-Mass X-Ray Binary Systems

Using the Rossi X-ray Timing Explorer (RossiXTE), astronomers have discovered that disk-accreting neutron stars with weak magnetic fields produce three distinct types of high-frequency X-ray oscillations. These oscillations are powered by release of the binding energy of matter falling into the strong gravitational field of the star or by the sudden nuclear burning of matter that has accumulated in the outermost layers of the star. The frequencies of the oscillations reflect the orbital frequencies of gas deep in the gravitational field of the star and/or the spin frequency of the star. These oscillations can therefore be used to explore fundamental physics, such as strong-field gravity and the properties of matter under extreme conditions, and important astrophysical questions, such as the formation and evolution of millisecond pulsars. Observations using RossiXTE have shown that some two dozen neutron stars in low-mass X-ray binary systems have the spin rates and magnetic fields required to become millisecond radio-emitting pulsars when accretion ceases, but that few have spin rates above about 600 Hz. The properties of these stars show that the paucity of spin rates greater than 600 Hz is due in part to the magnetic braking component of the accretion torque and to the limited amount of angular momentum that can be accreted in such systems. Further study will show whether braking by gravitational radiation is also a factor. Analysis of the kilohertz oscillations has provided the first evidence for the existence of the innermost stable circular orbit around dense relativistic stars that is predicted by strong-field general relativity. It has also greatly narrowed the possible descriptions of ultradense matter.Comment: 22 pages, 7 figures, updated list of sources and references, to appear in "Short-period Binary Stars: Observation, Analyses, and Results", eds. E.F. Milone, D.A. Leahy, and D. Hobill (Dordrecht: Springer, http://www.springerlink.com

A systematic review of randomised controlled trials on the effectiveness of exercise programs on lumbo pelvic pain among postnatal women

Background: A substantial number of women tend to be affected by Lumbo Pelvic Pain (LPP) following child birth. Physical exercise is indicated as a beneficial method to relieve LPP, but individual studies appear to suggest mixed findings about its effectiveness. This systematic review aimed to synthesise evidence from randomised controlled trials on the effectiveness of exercise on LPP among postnatal women to inform policy, practice and future research. Methods: A systematic review was conducted of all randomised controlled trials published between January 1990 and July 2014, identified through a comprehensive search of following databases: PubMed, PEDro, Embase, Cinahl, Medline, SPORTDiscus, Cochrane Pregnancy and Childbirth Group’s Trials Register, and electronic libraries of authors’institutions. Randomised controlled trials were eligible for inclusion if the intervention comprised of postnatal exercise for women with LPP onset during pregnancy or within 3 months after delivery and the outcome measures included changes in LPP. Selected articles were assessed using the PEDro Scale for methodological quality and findings were synthesised narratively as meta-analysis was found to be inappropriate due to heterogeneity among included studies. Results: Four randomised controlled trials were included, involving 251 postnatal women. Three trials were rated as of ‘good’ methodological quality. All trials, except one, were at low risk of bias. The trials included physical exercise programs with varying components, differing modes of delivery, follow up times and outcome measures. Intervention in one trial, involving physical therapy with specific stabilising exercises, proved to be effective in reducing LPP intensity. An improvement in gluteal pain on the right side was reported in another trial and a significant difference in pain frequency in another. Conclusion: Our review indicates that only few randomised controlled trials have evaluated the effectiveness of exercise on LPP among postnatal women. There is also a great amount of variability across existing trials in the components of exercise programs, modes of delivery, follow up times and outcome measures. While there is some evidence to indicate the effectiveness of exercise for relieving LPP, further good quality trials are needed to ascertain the most effective elements of postnatal exercise programs suited for LPP treatment