Novel cyclic di-GMP effectors of the YajQ protein family control bacterial virulence

Bis-(3 ',5 ') cyclic di-guanylate (cyclic di-GMP) is a key bacterial second messenger that is implicated in the regulation of many critical processes that include motility, biofilm formation and virulence. Cyclic di-GMP influences diverse functions through interaction with a range of effectors. Our knowledge of these effectors and their different regulatory actions is far from complete, however. Here we have used an affinity pull-down assay using cyclic di-GMP-coupled magnetic beads to identify cyclic di-GMP binding proteins in the plant pathogen Xanthomonas campestris pv. campestris (Xcc). This analysis identified XC_3703, a protein of the YajQ family, as a potential cyclic di-GMP receptor. Isothermal titration calorimetry showed that the purified XC_3703 protein bound cyclic di-GMP with a high affinity (K-d similar to 2 mu M). Mutation of XC_3703 led to reduced virulence of Xcc to plants and alteration in biofilm formation. Yeast two-hybrid and far-western analyses showed that XC_3703 was able to interact with XC_2801, a transcription factor of the LysR family. Mutation of XC_2801 and XC_3703 had partially overlapping effects on the transcriptome of Xcc, and both affected virulence. Electromobility shift assays showed that XC_3703 positively affected the binding of XC_2801 to the promoters of target virulence genes, an effect that was reversed by cyclic di-GMP. Genetic and functional analysis of YajQ family members from the human pathogens Pseudomonas aeruginosa and Stenotrophomonas maltophilia showed that they also specifically bound cyclic di-GMP and contributed to virulence in model systems. The findings thus identify a new class of cyclic di-GMP effector that regulates bacterial virulence

Sex-Specific Differences in Shoaling Affect Parasite Transmission in Guppies

Background: Individuals have to trade-off the costs and benefits of group membership during shoaling behaviour. Shoaling can increase the risk of parasite transmission, but this cost has rarely been quantified experimentally. Guppies (Poecilia reticulata) are a model system for behavioural studies, and they are commonly infected by gyrodactylid parasites, notorious fish pathogens that are directly transmitted between guppy hosts. Methodology/Principal Findings:Parasite transmission in single sex shoals of male and female guppies were observed using an experimental infection of Gyrodactylus turnbulli. Parasite transmission was affected by sex-specific differences in host behaviour, and significantly more parasites were transmitted when fish had more frequent and more prolonged contact with each other. Females shoaled significantly more than males and had a four times higher risk to contract an infection. Conclusions/Significance: Intersexual differences in host behaviours such as shoaling are driven by differences in natural and sexual selection experienced by both sexes. Here we show that the potential benefits of an increased shoaling tendency are traded off against increased risks of contracting an infectious parasite in a group-living species

Proposed changes to the function of the Mental Health Act will erode patient rights

Imagine for a moment you ind yourself arrested in some foreign clime – Queensland, for example. You are told you have transgressed some northern law and are looking at several weeks inside. You are anxious, to be sure, but not dismayed. You know you are innocent and you’re sure you’ll be able to persuade a judge that there has been a miscarriage of justice. You also know that under Queensland law the police must present you to court “as soon as reasonably practicable” and you know that, like all Australian jurisdictions, this time frame is normally interpreted as being within 24 hours, 365 days of the year. All Australians enjoy a basic right to freedom of movement. Australians who ind themselves detained against their will have a right to be brought before a court to ensure that the terms of the detention are lawful. This ancient right is protected in the civil law through habeas corpus and is also relected in the prompt review of criminal procedure. Timely independent review of restrictions on liberty is also applied in the medico-legal context. For example, while the NSW Guardianship Act allows a person responsible or guardian to consent for a patient who lacks capacity, if that patient objects to the treatment, the Act stipulates that, a quasijudicial body - the Guardianship Tribunal – must authorise this consent to check that this deprivation of freedom is justiied. The Tribunal is available to hear urgent matters around the clock and urgent orders are usually made within a week

Mechanical Properties of Plant Underground Storage Organs and Implications for Dietary Models of Early Hominins

The diet of early human ancestors has received renewed theoretical interest since the discovery of elevated d13C values in the enamel of Australopithecus africanus and Paranthropus robustus. As a result, the hominin diet is hypothesized to have included C4 grass or the tissues of animals which themselves consumed C4 grass. On mechanical grounds, such a diet is incompatible with the dental morphology and dental microwear of early hominins. Most inferences, particularly for Paranthropus, favor a diet of hard or mechanically resistant foods. This discrepancy has invigorated the longstanding hypothesis that hominins consumed plant underground storage organs (USOs). Plant USOs are attractive candidate foods because many bulbous grasses and cormous sedges use C4 photosynthesis. Yet mechanical data for USOs—or any putative hominin food—are scarcely known. To fill this empirical void we measured the mechanical properties of USOs from 98 plant species from across sub-Saharan Africa. We found that rhizomes were the most resistant to deformation and fracture, followed by tubers, corms, and bulbs. An important result of this study is that corms exhibited low toughness values (mean = 265.0 J m-2) and relatively high Young’s modulus values (mean = 4.9 MPa). This combination of properties fits many descriptions of the hominin diet as consisting of hard-brittle objects. When compared to corms, bulbs are tougher (mean = 325.0 J m-2) and less stiff (mean = 2.5 MPa). Again, this combination of traits resembles dietary inferences, especially for Australopithecus, which is predicted to have consumed soft-tough foods. Lastly, we observed the roasting behavior of Hadza hunter-gatherers and measured the effects of roasting on the toughness on undomesticated tubers. Our results support assumptions that roasting lessens the work of mastication, and, by inference, the cost of digestion. Together these findings provide the first mechanical basis for discussing the adaptive advantages of roasting tubers and the plausibility of USOs in the diet of early hominins

Burden of Illness in UK Subjects with Reported Respiratory Infections Vaccinated or Unvaccinated against Influenza: A Retrospective Observational Study

<div><p>Objective</p><p>Detailed data are lacking on influenza burden in the United Kingdom (UK). The objective of this study was to estimate the disease burden associated with influenza-like illness (ILI) in the United Kingdom stratified by age, risk and influenza vaccination status.</p><p>Methods</p><p>This retrospective, cross-sectional, exploratory, observational study used linked data from the General Practice Research Database and the Hospital Episode Statistics databases to estimate resource use and cost associated with ILI in the UK.</p><p>Results</p><p>Data were included from 156,193 patients with ≥1 general practitioner visit with ILI. There were 21,518 high-risk patients, of whom 12,514 (58.2%) were vaccinated and 9,004 (41.8%) were not vaccinated, and 134,675 low-risk patients, of whom 17,482 (13.0%) were vaccinated and 117,193 (87.0%) were not vaccinated. High-risk vaccinated patients were older (p<0.001) and had more risk conditions (p<0.001). High-risk (odds ratio [OR] 2.16) or vaccinated (OR 1.19) patients had a higher probability of >1 general practitioner visit compared with low-risk and unvaccinated patients. Patients who were high-risk and vaccinated had a reduced risk of >1 general practitioner visit (OR 0.82; p<0.001). High-risk individuals who were also vaccinated had a lower probability of ILI-related hospitalisation than individuals who were high-risk or vaccinated alone (OR 0.59). In people aged ≥65 years, the mortality rate was lower in vaccinated than unvaccinated individuals (OR 0.75). The cost of ILI-related GP visits and hospital admissions in the UK over the study period in low-risk vaccinated patients was £27,391,142 and £141,932,471, respectively. In low-risk unvaccinated patients the corresponding values were £168,318,709 and £112,534,130, respectively.</p><p>Conclusions</p><p>Although vaccination rates in target groups have increased, many people are still not receiving influenza vaccination, and the burden of ILI in the United Kingdom remains substantial. Improving influenza vaccination uptake may have the potential to reduce this burden.</p></div

Invasion speeds for structured populations in fluctuating environments

We live in a time where climate models predict future increases in environmental variability and biological invasions are becoming increasingly frequent. A key to developing effective responses to biological invasions in increasingly variable environments will be estimates of their rates of spatial spread and the associated uncertainty of these estimates. Using stochastic, stage-structured, integro-difference equation models, we show analytically that invasion speeds are asymptotically normally distributed with a variance that decreases in time. We apply our methods to a simple juvenile-adult model with stochastic variation in reproduction and an illustrative example with published data for the perennial herb, \emph{Calathea ovandensis}. These examples buttressed by additional analysis reveal that increased variability in vital rates simultaneously slow down invasions yet generate greater uncertainty about rates of spatial spread. Moreover, while temporal autocorrelations in vital rates inflate variability in invasion speeds, the effect of these autocorrelations on the average invasion speed can be positive or negative depending on life history traits and how well vital rates ``remember'' the past

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Young people’s perceptions of smartphone-enabled self-testing and online care for sexually transmitted infections: qualitative interview study

Background Control of sexually transmitted infections (STI) is a global public health priority. Despite the UK’s free, confidential sexual health clinical services, those at greatest risk of STIs, including young people, report barriers to use. These include: embarrassment regarding face-to-face consultations; the time-commitment needed to attend clinic; privacy concerns (e.g. being seen attending clinic); and issues related to confidentiality. A smartphone-enabled STI self-testing device, linked with online clinical care pathways for treatment, partner notification, and disease surveillance, is being developed by the eSTI2 consortium. It is intended to benefit public health, and could do so by increasing testing among populations which underutilise existing services and/or by enabling rapid provision of effective treatment. We explored its acceptability among potential users. Methods In-depth interviews were conducted in 2012 with 25 sexually-experienced 16–24 year olds, recruited from Further Education colleges in an urban, high STI prevalence area. Thematic analysis was undertaken. Results Nine females and 16 males participated. 21 self-defined as Black; three, mixed ethnicity; and one, Muslim/Asian. 22 reported experience of STI testing, two reported previous STI diagnoses, and all had owned smartphones. Participants expressed enthusiasm about the proposed service, and suggested that they and their peers would use it and test more often if it were available. Utilizing sexual healthcare was perceived to be easier and faster with STI self-testing and online clinical care, which facilitated concealment of STI testing from peers/family, and avoided embarrassing face-to-face consultations. Despite these perceived advantages to privacy, new privacy concerns arose regarding communications technology: principally the risk inherent in having evidence of STI testing or diagnosis visible or retrievable on their phone. Some concerns arose regarding the proposed self-test’s accuracy, related to self-operation and the technology’s novelty. Several expressed anxiety around the possibility of being diagnosed and treated without any contact with healthcare professionals. Conclusions Remote STI self-testing and online care appealed to these young people. It addressed barriers they associated with conventional STI services, thus may benefit public health through earlier detection and treatment. Our findings underpin development of online care pathways, as part of ongoing research to create this complex e-health intervention

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