The structure of the PapD-PapGII pilin complex reveals an open and flexible P5 pocket

P pili are hairlike polymeric structures that mediate binding of uropathogenic Escherichia coli to the surface of the kidney via the PapG adhesin at their tips. PapG is composed of two domains: a lectin domain at the tip of the pilus followed by a pilin domain that comprises the initial polymerizing subunit of the 1,000-plus-subunit heteropolymeric pilus fiber. Prior to assembly, periplasmic pilin domains bind to a chaperone, PapD. PapD mediates donor strand complementation, in which a beta strand of PapD temporarily completes the pilin domain's fold, preventing premature, nonproductive interactions with other pilin subunits and facilitating subunit folding. Chaperone-subunit complexes are delivered to the outer membrane usher where donor strand exchange (DSE) replaces PapD's donated beta strand with an amino-terminal extension on the next incoming pilin subunit. This occurs via a zip-in-zip-out mechanism that initiates at a relatively accessible hydrophobic space termed the P5 pocket on the terminally incorporated pilus subunit. Here, we solve the structure of PapD in complex with the pilin domain of isoform II of PapG (PapGIIp). Our data revealed that PapGIIp adopts an immunoglobulin fold with a missing seventh strand, complemented in parallel by the G1 PapD strand, typical of pilin subunits. Comparisons with other chaperone-pilin complexes indicated that the interactive surfaces are highly conserved. Interestingly, the PapGIIp P5 pocket was in an open conformation, which, as molecular dynamics simulations revealed, switches between an open and a closed conformation due to the flexibility of the surrounding loops. Our study reveals the structural details of the DSE mechanism

Barriers-enablers-ownership approach: A mixed methods analysis of a social intervention to improve surgical antibiotic prescribing in hospitals

Objectives To assess an intervention for surgical antibiotic prophylaxis (SAP) improvement within surgical teams focused on addressing barriers and fostering enablers and ownership of guideline compliance. Design The Queensland Surgical Antibiotic Prophylaxis (QSAP) study was a multicentre, mixed methods study designed to address barriers and enablers to SAP compliance and facilitate engagement in self-directed audit/feedback and assess the efficacy of the intervention in improving compliance with SAP guidelines. The implementation was assessed using a 24-month interrupted time series design coupled with a qualitative evaluation. Setting The study was undertaken at three hospitals (one regional, two metropolitan) in Australia. Participants SAP-prescribing decisions for 1757 patients undergoing general surgical procedures from three health services were included. Six bimonthly time points, pre-implementation and post implementation of the intervention, were measured. Qualitative interviews were performed with 29 clinical team members. SAP improvements varied across site and time periods. Intervention QSAP embedded ownership of quality improvement in SAP within surgical teams and used known social influences to address barriers to and enablers of optimal SAP prescribing. Results The site that reported senior surgeon engagement showed steady and consistent improvement in prescribing over 24 months (prestudy and poststudy). Multiple factors, including resource issues, influenced engagement and sites/time points where these were present had no improvement in guideline compliance. Conclusions The barriers-enablers-ownership model shows promise in its ability to facilitate prescribing improvements and could be expanded into other areas of antimicrobial stewardship. Senior ownership was a predictor of success (or failure) of the intervention across sites and time periods. The key role of senior leaders in change leadership indicates the critical need to engage other specialties in the stewardship agenda. The influence of contextual factors in limiting engagement clearly identifies issues of resource distributions/inequalities within health systems as limiting antimicrobial optimisation potential

Undular tidal bores: Effect of channel constriction and bridge piers

A tidal bore may occur in a macro-tidal estuary when the tidal range exceeds 4.5-6 m and the estuary bathymetry amplifies the tidal wave. Its upstream propagation induces a strong mixing of the estuarine waters. The propagation of undular tidal bores was investigated herein to study the effect of bridge piers on the bore propagation and characteristics. Both the tidal bore profile and the turbulence generated by the bore were recorded. The free-surface undulation profiles exhibited a quasi-periodic shape, and the potential energy of the undulations represented up to 30% of the potential energy of the tidal bore. The presence of the channel constriction had a major impact on the free-surface properties. The undular tidal bore lost nearly one third of its potential energy per surface area as it propagated through the channel constriction. The detailed instantaneous velocity measurements showed a marked effect of the tidal bore passage suggesting the upstream advection of energetic events and vorticity "clouds" behind the bore front in both channel configurations: prismatic and with constriction. The turbulence patches were linked to some secondary motions and the proposed mechanisms were consistent with some field observations in the Daly River tidal bore. The findings emphasise the strong mixing induced by the tidal bore processes, and the impact of bridge structures on the phenomenon. © 2010 Springer Science+Business Media B.V

Predicting the Impact of Climate Change on Threatened Species in UK Waters

Global climate change is affecting the distribution of marine species and is thought to represent a threat to biodiversity. Previous studies project expansion of species range for some species and local extinction elsewhere under climate change. Such range shifts raise concern for species whose long-term persistence is already threatened by other human disturbances such as fishing. However, few studies have attempted to assess the effects of future climate change on threatened vertebrate marine species using a multi-model approach. There has also been a recent surge of interest in climate change impacts on protected areas. This study applies three species distribution models and two sets of climate model projections to explore the potential impacts of climate change on marine species by 2050. A set of species in the North Sea, including seven threatened and ten major commercial species were used as a case study. Changes in habitat suitability in selected candidate protected areas around the UK under future climatic scenarios were assessed for these species. Moreover, change in the degree of overlap between commercial and threatened species ranges was calculated as a proxy of the potential threat posed by overfishing through bycatch. The ensemble projections suggest northward shifts in species at an average rate of 27 km per decade, resulting in small average changes in range overlap between threatened and commercially exploited species. Furthermore, the adverse consequences of climate change on the habitat suitability of protected areas were projected to be small. Although the models show large variation in the predicted consequences of climate change, the multi-model approach helps identify the potential risk of increased exposure to human stressors of critically endangered species such as common skate (Dipturus batis) and angelshark (Squatina squatina)

Parents’ Beliefs about and Associations to their Elementary Children’s Home Technology Usage

This study sought to gather information through a survey of how newcomer parents’ beliefs about technology usage and how they engage with technology as they support their children with twenty-first century literacies. Parent respondents (N = 70) were drawn from two publicly funded schools in the Niagara Region, Ontario, Canada, where the population tends to be immigrant, visible minority, with post-secondary education, but unemployed and low income. Descriptive statistics quantified daily technology activities as being communication-oriented with the majority of parents holding distinct beliefs about the amount and type of their children’s technology usage. Chi-square tests indicated significant associations for demographic characteristics such as the gender, age, education, first language, and ethnicity of the parents as determinants of their beliefs about their children’s technology usage (e.g., social media, mobile phones, television). As well, levels of access and use varied in terms of the number of new technologies and the types of literacy practices that families engage in. Immigrant parents might hold misconceptions about twenty-first century literacies, therefore there should be an attempt to assist them to provide responsive twenty-first century literacy and technology support for their children

Male reproductive health and environmental xenoestrogens

EHP is a publication of the U.S. government. Publication of EHP lies in the public domain and is therefore without copyright. Research articles from EHP may be used freely; however, articles from the News section of EHP may contain photographs or figures copyrighted by other commercial organizations and individuals that may not be used without obtaining prior approval from both the EHP editors and the holder of the copyright. Use of any materials published in EHP should be acknowledged (for example, "Reproduced with permission from Environmental Health Perspectives") and a reference provided for the article from which the material was reproduced.Male reproductive health has deteriorated in many countries during the last few decades. In the 1990s, declining semen quality has been reported from Belgium, Denmark, France, and Great Britain. The incidence of testicular cancer has increased during the same time incidences of hypospadias and cryptorchidism also appear to be increasing. Similar reproductive problems occur in many wildlife species. There are marked geographic differences in the prevalence of male reproductive disorders. While the reasons for these differences are currently unknown, both clinical and laboratory research suggest that the adverse changes may be inter-related and have a common origin in fetal life or childhood. Exposure of the male fetus to supranormal levels of estrogens, such as diethlylstilbestrol, can result in the above-mentioned reproductive defects. The growing number of reports demonstrating that common environmental contaminants and natural factors possess estrogenic activity presents the working hypothesis that the adverse trends in male reproductive health may be, at least in part, associated with exposure to estrogenic or other hormonally active (e.g., antiandrogenic) environmental chemicals during fetal and childhood development. An extensive research program is needed to understand the extent of the problem, its underlying etiology, and the development of a strategy for prevention and intervention.Supported by EU Contract BMH4-CT96-0314

Aptamers for respiratory syncytial virus detection.

The identification of the infectious agents is pivotal for appropriate care of patients with viral diseases. Current viral diagnostics rely on selective detection of viral nucleic acid or protein components. In general, detection of proteins rather than nucleic acids is technically more suitable for rapid tests. However, protein-based virus identification methods depend on antibodies limiting the practical applicability of these approaches. Aptamers rival antibodies in target selectivity and binding affinity, and excel in terms of robustness and cost of synthesis. Although aptamers have been generated for virus identification in laboratory settings, their introduction into routine virus diagnostics has not been realized, yet. Here, we demonstrate that the rationally designed SELEX protocol can be applied on whole virus to select aptamers, which can potentially be applied for viral diagnostics. This approach does not require purified virus protein or complicated virus purification. The presented data also illustrate that corroborating the functionality of aptamers with various approaches is essential to pinpoint the most appropriate aptamer amongst the panel of candidates obtained by the selection. Our protocol yielded aptamers capable of detecting respiratory syncytial virus (RSV), an important pathogen causing severe disease especially in young infants, at clinically relevant concentrations in complex matrices

Experimental study of a positive surge. Part 1: Basic flow patterns and wave attenuation

A positive surge results from a sudden change in flow that increases the depth. It is the unsteady flow analogy of the stationary hydraulic jump and a geophysical application is the tidal bore. Positive surges are commonly studied using the method of characteristics and the Saint-Venant equations. The paper presents the results from new experimental investigations conducted in a large rectangular channel. Detailed unsteady velocity measurements were performed with a high temporal resolution using acoustic Doppler velocimetry and non-intrusive free-surface measurement devices. Several experiments were conducted with the same initial discharge (Q=0.060 m³/s) and 6 different gate openings after closure resulting in both non-breaking undular and breaking bores. The analysis of undular surges revealed wave amplitude attenuation with increasing distance of surge propagation were in agreement with Ippen and Kulin theory. Also, undular wave period and wave length data were relatively close to the values predicted by the wave dispersion theory for gravity waves in intermediate water depths

Spatial variation in prostate cancer survival in the Northern and Yorkshire region of England using Bayesian relative survival smoothing

Primary Care Trust (PCT) estimates of survival lack robustness as there are small numbers of deaths per year in each area, even when incidence is high. We assess PCT-level spatial variation in prostate cancer survival using Bayesian spatial models of excess mortality. We extracted data on men diagnosed with prostate cancer between 1990 and 1999 from the Northern and Yorkshire Cancer Registry and Information Service database. Models were adjusted for age at diagnosis, period of diagnosis and deprivation. All covariates had a significant association with excess mortality; men from more deprived areas, older age at diagnosis and diagnosed in 1990–1994 had higher excess mortality. The unadjusted relative excess risks (RER) of death by PCT ranged from 0.75 to 1.66. After adjustment, areas of high and low excess mortality were smoothed towards the mean, and the RERs ranged from 0.74 to 1.49. Using Bayesian smoothing techniques to model cancer survival by geographic area offers many advantages over traditional methods; estimates in areas with small populations or low incidence rates are stabilised and shrunk towards local and global risk estimates improving reliability and precision, complex models are easily handled and adjustment for covariates can be made