Two-component systems required for virulence in Pseudomonas aeruginosa

This is the author accepted manuscript. The final version is available from Oxford University Press via the DOI in this record.Pseudomonas aeruginosa is a versatile opportunistic pathogen capable of infecting a broad range of hosts, in addition to thriving in a broad range of environmental conditions outside of hosts. With this versatility comes the need to tightly regulate its genome to optimise its gene expression and behaviour to the prevailing conditions. Two-component systems (TCSs) comprising sensor kinases and response regulators, play a major role in this regulation. This minireview discusses the growing number of two-component systems that have been implicated in the virulence of Pseudomonas aeruginosa, with a special focus on the emerging theme of multikinase networks, which are networks comprising multiple sensor kinases working together, sensing and integrating multiple signals to decide upon the best response. The networks covered in depth regulate processes such as the switch between acute and chronic virulence (GacS network), the Cup fimbriae (Roc network and Rcs/Pvr network), the aminoarabinose modification of lipopolysaccharide (a network involving the PhoQP and PmrBA TCSs), twitching motility and virulence (a network formed from the Chp chemosensory pathway and the FimS/AlgR TCS), and biofilm formation (Wsp chemosensory pathway). In addition, we highlight the important interfaces between these systems and secondary messenger signals such as cAMP and c-di-GMP.This work was supported by the Medical Research Council (MRC) [grant number MR/M020045/1], the Leverhulme Trust [grant number RPG-2014-228] and the RoseTrees Trust [grant number M328]

Irregular Satellites of the Planets: Products of Capture in the Early Solar System

All four giant planets in the Solar system possess irregular satellites, characterized by large, highly eccentric and/or inclined orbits that are distinct from the nearly circular, uninclined orbits of the regular satellites. This difference can be traced directly to different modes of formation. Whereas the regular satellites grew by accretion within circumplanetary disks the irregular satellites were captured from initially heliocentric orbits at an early epoch. Recently, powerful survey observations have greatly increased the number of known irregular satellites, permitting a fresh look at the group properties of these objects and motivating a re-examination of the mechanisms of capture. None of the suggested mechanisms, including gas-drag, pull-down, and three-body capture, convincingly fit the group characteristics of the irregular satellites. The sources of the satellites also remain unidentified.Comment: 51 pages, 17 figures, 5 tables, to appear in ARAA 200

On the shopfloor: exploring the impact of teacher trade unions on school-based industrial relations

Teachers are highly unionised workers and their trade unions exert an important influence on the shaping and implementation of educational policy. Despite this importance there is relatively little analysis of the impact of teacher trade unions in educational management literature. Very little empirical research has sought to establish the impact of teacher unions at school level. In an era of devolved management and quasi-markets this omission is significant. New personnel issues continue to emerge at school level and this may well generate increased trade union activity at the workplace. This article explores the extent to which devolved management is drawing school-based union representation into a more prominent role. It argues that whilst there can be significant differences between individual schools, increased school autonomy is raising the profile of trade union activity in the workplace, and this needs to be better reflected in educational management research

Bronchoalveolar lavage in infants with recurrent lower respiratory symptoms

Background: Few data are available about the inflammatory cytokine profile of bronchoalveolar lavage (BAL) from young children with frequent wheeze. The first aim was to investigate the BAL cellular and cytokine profiles in infants with recurrent lower respiratory symptoms in whom bronchoscopy was indicated for clinical symptom evaluation. The second aim was to relate the BAL results with the histological findings of the endobronchial carina biopsies. Methods: Thirty-nine infants (median age 0.9 years) underwent lung function testing by whole-body plethysmography prior to the bronchoscopy. The BAL differential cell counts and cytokine levels were quantified. These findings were compared with the histological findings of the endobronchial carina biopsies. Results: The differential cytology reflected mainly that described for healthy infants with lymphocyte counts at the upper range level. A positive association between BAL CD8+ lymphocytes and neutrophils and endobronchial reticular basement membrane was found. Detectable levels of pro-inflammatory cytokine proteins IL-1 beta, IL-17A, IL-18, IL-23, and IL-33 were found, whereas levels of Th2-type cytokine proteins were low. Frequent wheeze was the only clinical characteristic significantly related to detectable combined pro-inflammatory cytokine profile. Lung function did not correlate with any cytokine. Conclusions: A positive association between BAL CD8+ lymphocytes and neutrophils and endobronchial reticular basement thickness was found. Detectable production of pro-inflammatory cytokines associated positively with frequent wheeze.Peer reviewe

A Corpus of Potentially Contradictory Research Claims from Cardiovascular Research Abstracts

Background: Research literature in biomedicine and related fields contains a huge number of claims, such as the effectiveness of treatments. These claims are not always consistent and may even contradict each other. Being able to identify contradictory claims is important for those who rely on the biomedical literature. Automated methods to identify and resolve them are required to cope with the amount of information available. However, research in this area has been hampered by a lack of suitable resources. We describe a methodology to develop a corpus which addresses this gap by providing examples of potentially contradictory claims and demonstrate how it can be applied to identify these claims from Medline abstracts related to the topic of cardiovascular disease. Methods A set of systematic reviews concerned with four topics in cardiovascular disease were identified from Medline and analysed to determine whether the abstracts they reviewed contained contradictory research claims. For each review, annotators were asked to analyse these abstracts to identify claims within them that answered the question addressed in the review. The annotators were also asked to indicate how the claim related to that question and the type of the claim. Results: A total of 259 abstracts associated with 24 systematic reviews were used to form the corpus. Agreement between the annotators was high, suggesting that the information they provided is reliable. Conclusions: The paper describes a methodology for constructing a corpus containing contradictory research claims from the biomedical literature. The corpus is made available to enable further research into this area and support the development of automated approaches to contradiction identification

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

A large scale survey reveals that chromosomal copy-number alterations significantly affect gene modules involved in cancer initiation and progression

Background Recent observations point towards the existence of a large number of neighborhoods composed of functionally-related gene modules that lie together in the genome. This local component in the distribution of the functionality across chromosomes is probably affecting the own chromosomal architecture by limiting the possibilities in which genes can be arranged and distributed across the genome. As a direct consequence of this fact it is therefore presumable that diseases such as cancer, harboring DNA copy number alterations (CNAs), will have a symptomatology strongly dependent on modules of functionally-related genes rather than on a unique "important" gene. Methods We carried out a systematic analysis of more than 140,000 observations of CNAs in cancers and searched by enrichments in gene functional modules associated to high frequencies of loss or gains. Results The analysis of CNAs in cancers clearly demonstrates the existence of a significant pattern of loss of gene modules functionally related to cancer initiation and progression along with the amplification of modules of genes related to unspecific defense against xenobiotics (probably chemotherapeutical agents). With the extension of this analysis to an Array-CGH dataset (glioblastomas) from The Cancer Genome Atlas we demonstrate the validity of this approach to investigate the functional impact of CNAs. Conclusions The presented results indicate promising clinical and therapeutic implications. Our findings also directly point out to the necessity of adopting a function-centric, rather a gene-centric, view in the understanding of phenotypes or diseases harboring CNAs.Spanish Ministry of Science and Innovation (grant BIO2008-04212)Spanish Ministry of Science and Innovation (grant FIS PI 08/0440)GVA-FEDER (PROMETEO/2010/001)Red Temática de Investigación Cooperativa en Cáncer (RTICC) (grant RD06/0020/1019)Instituto de Salud Carlos III (ISCIII)Spanish Ministry of Science and InnovationSpanish Ministry of Health (FI06/00027

Futures trading, spot price volatility and market efficiency: evidence from European real estate securities futures

In 2007 futures contracts were introduced based upon the listed real estate market in Europe. Following their launch they have received increasing attention from property investors, however, few studies have considered the impact their introduction has had. This study considers two key elements. Firstly, a traditional Generalized Autoregressive Conditional Heteroskedasticity (GARCH) model, the approach of Bessembinder & Seguin (1992) and the Gray’s (1996) Markov-switching-GARCH model are used to examine the impact of futures trading on the European real estate securities market. The results show that futures trading did not destabilize the underlying listed market. Importantly, the results also reveal that the introduction of a futures market has improved the speed and quality of information flowing to the spot market. Secondly, we assess the hedging effectiveness of the contracts using two alternative strategies (naïve and Ordinary Least Squares models). The empirical results also show that the contracts are effective hedging instruments, leading to a reduction in risk of 64 %

A change in the optical polarization associated with a gamma-ray flare in the blazar 3C 279

It is widely accepted that strong and variable radiation detected over all accessible energy bands in a number of active galaxies arises from a relativistic, Doppler-boosted jet pointing close to our line of sight. The size of the emitting zone and the location of this region relative to the central supermassive black hole are, however, poorly known, with estimates ranging from light-hours to a light-year or more. Here we report the coincidence of a gamma-ray flare with a dramatic change of optical polarization angle. This provides evidence for co-spatiality of optical and gamma-ray emission regions and indicates a highly ordered jet magnetic field. The results also require a non-axisymmetric structure of the emission zone, implying a curved trajectory for the emitting material within the jet, with the dissipation region located at a considerable distance from the black hole, at about 10^5 gravitational radii.Comment: Published in Nature issued on 18 February 2010. Corresponding authors: Masaaki Hayashida and Greg Madejsk