Surface proteins that promote adherence of Staphylococcus aureus to human desquamated nasal epithelial cells

<p>Abstract</p> <p>Background</p> <p>The natural habitat of <it>Staphylococcus aureus </it>is the moist squamous epithelium in the anterior nares. About 20% of the human population carry <it>S. aureus </it>permanently in their noses and another 60% of individuals are intermittent carriers. The ability of <it>S. aureus </it>to colonize the nasal epithelium is in part due to expression of surface proteins clumping factor B (ClfB) and the iron-regulated surface determinant A (IsdA), which promote adhesion to desquamated epithelial cells present in the anterior part of the nasal vestibule. <it>S. aureus </it>strain Newman defective in IsdA and ClfB exhibited reduced but not completely defective adherence to squamous cells in indicating that other cell surface components might also contribute.</p> <p>Results</p> <p>Surface proteins IsdA, ClfB, and the serine-aspartic acid repeat proteins SdrC, SdrD and SdrE were investigated to determine their contribution to the adherence of <it>S. aureus </it>to desquamated nasal epithelial cells. This was achieved by expression of ClfB, IsdA, SdrC, SdrD and SdrE on the surface of the surrogate Gram-positive host <it>Lactococcus lactis </it>and by isolating mutants of <it>S. aureus </it>Newman defective in one or more factor. The level of adherence of strains to squamous cells isolated from the nares of volunteers was measured. Results consistently showed that ClfB, IsdA, SdrC and SdrD each contributed to the ability of <it>S. aureus </it>to adhere to squamous cells. A mutant lacking all four proteins was completely defective in adherence.</p> <p>Conclusion</p> <p>The ability of <it>S. aureus </it>Newman to adhere to desquamated nasal epithelial cells is multifactorial and involves SdrD and SdrC as well as ClfB and IsdA.</p

Using continuous-time spatial capture–recapture models to make inference about animal activity patterns

This work was part‐funded by EPSRC Grant EP/I000917/1, by the research fellowship RF‐2018‐213/9, and the fieldwork was funded by the Summerlee Foundation and Panthera.1. Quantifying the distribution of daily activity is an important component of behavioral ecology. Historically, it has been difficult to obtain data on activity patterns, especially for elusive species. However, the development of affordable camera traps and their widespread usage has led to an explosion of available data from which activity patterns can be estimated. 2. Continuous-time spatial capture?recapture (CT SCR) models drop the occasion structure seen in traditional spatial and nonspatial capture?recapture (CR) models and use the actual times of capture. In addition to estimating density, CT SCR models estimate expected encounters through time. Cyclic splines can be used to allow flexible shapes for modeling cyclic activity patterns, and the fact that SCR models also incorporate distance means that space-time interactions can be explored. This method is applied to a jaguar dataset. 3. Jaguars in Belize are most active and range furthest in the evening and early morning and when they are located closer to the network of trails. There is some evidence that females have a less variable pattern than males. The comparison between sexes demonstrates how CT SCR can be used to explore hypotheses about animal behavior within a formal modeling framework. 4. SCR models were developed primarily to estimate and model density, but the models can be used to explore processes that interact across space and time, especially when using the CT SCR framework that models the temporal dimension at a finer resolution.Publisher PDFPeer reviewe

Open population maximum likelihood spatial capture-recapture

Funding: Part-funded by UK EPSRC grant EP/K041061/1 (DB); Richard Glennie was funded by the Carnegie Trust.Open population capture‐recapture models are widely used to estimate population demographics and abundance over time. Bayesian methods exist to incorporate open population modeling with spatial capture‐recapture (SCR), allowing for estimation of the effective area sampled and population density. Here, open population SCR is formulated as a hidden Markov model (HMM), allowing inference by maximum likelihood for both Cormack‐Jolly‐Seber and Jolly‐Seber models, with and without activity center movement. The method is applied to a 12‐year survey of male jaguars (Panthera onca) in the Cockscomb Basin Wildlife Sanctuary, Belize, to estimate survival probability and population abundance over time. For this application, inference is shown to be biased when assuming activity centers are fixed over time, while including a model for activity center movement provides negligible bias and nominal confidence interval coverage, as demonstrated by a simulation study. The HMM approach is compared with Bayesian data augmentation and closed population models for this application. The method is substantially more computationally efficient than the Bayesian approach and provides a lower root‐mean‐square error in predicting population density compared to closed population models.PostprintPeer reviewe

The association of cycling with all-cause, cardiovascular and cancer mortality: findings from the population-based EPIC-Norfolk cohort.

OBJECTIVES: To investigate associations between modest levels of total and domain-specific (commuting, other utility, recreational) cycling and mortality from all causes, cardiovascular disease and cancer. DESIGN: Population-based cohort study (European Prospective Investigation into Cancer and Nutrition study-Norfolk). SETTING: Participants were recruited from general practices in the east of England and attended health examinations between 1993 and 1997 and again between 1998 and 2000. At the first health assessment, participants reported their average weekly duration of cycling for all purposes using a simple measure of physical activity. At the second health assessment, participants reported a more detailed breakdown of their weekly cycling behaviour using the EPAQ2 physical activity questionnaire. PARTICIPANTS: Adults aged 40-79 years at the first health assessment. PRIMARY OUTCOME MEASURE: All participants were followed for mortality (all-cause, cardiovascular and cancer) until March 2011. RESULTS: There were 22 450 participants with complete data at the first health assessment, of whom 4398 died during follow-up; and 13 346 participants with complete data at the second health assessment, of whom 1670 died during follow-up. Preliminary analyses using exposure data from the first health assessment showed that cycling for at least 60 min/week in total was associated with a 9% reduced risk of all-cause mortality (adjusted HR 0.91, 95% CI 0.84 to 0.99). Using the more precise measures of cycling available from the second health assessment, all types of cycling were associated with greater total moderate-to-vigorous physical activity; however, there was little evidence of an association between overall or domain-specific cycling and mortality. CONCLUSIONS: Cycling, in particular for utility purposes, was associated with greater moderate-to-vigorous and total physical activity. While this study provides tentative evidence that modest levels of cycling may reduce the risk of mortality, further research is required to confirm how much cycling is sufficient to induce health benefits

The immune evasion protein Sbi of Staphylococcus aureus occurs both extracellularly and anchored to the cell envelope by binding lipoteichoic acid

The Sbi protein of Staphylococcus aureus comprises two IgG-binding domains similar to those of protein A and a region that triggers the activation of complement C3. Sbi is expressed on the cell surface but its C-terminal domain lacks motifs associated with wall or membrane anchoring of proteins in Gram-positive bacteria. Cell-associated Sbi fractionates with the cytoplasmic membrane and is not solubilized during protoplast formation. S. aureus expressing Sbi truncates of the C-terminal Y domain allowed identification of residues that are required for association of Sbi with the membrane. Recombinant Sbi bound to purified cytoplasmic membrane material in vitro and to purified lipoteichoic acid. This explains how Sbi partitions with the membrane in fractionation experiments yet is partially exposed on the cell surface. An LTA-defective mutant of S. aureus had reduced levels of Sbi in the cytoplasmic membrane

Capturing the geography of children’s active and sedentary behaviours at home: the HomeSPACE measurement tool

Children spend much of their time at home, indoors and sedentary. This study reports on the development, exploratory factor analysis, validity and reliability of the HomeSPACE Instrument. The instrument assesses features of the home physical environment that influence children’s sedentary behaviour and physical activity, and the family influences that create this environment. The space and equipment audit achieved good to excellent criterion validity and test-retest reliability for equipment, outdoor features and home design measures (Study 1, n = 36 parents). Family influence scales showed acceptable internal consistency and test-retest reliability (Study 2, n = 96 parents). Factor analysis highlighted fifteen scales to assess the importance, preferences and supportiveness of the home environment for activity. The HomeSPACE Instrument extends previous tools to provide a valid and reliable assessment of home influences on children’s sedentary behaviour and physical activity, that is adaptable for varying home physical environments

New Late Cretaceous microvertebrate assemblage from the Campanian-Maastrichtian Williams Fork Formation, northwestern Colorado, USA, and its paleoenvironmental implications

We describe a microvertebrate assemblage from the J&amp;M site, of the Upper Cretaceous (Campanian&ndash;Maastrichtian) Williams Fork Formation. Breakdown of fossil bearing matrix was achieved with the use of heated dimethyl sulfoxide. Nine of the recovered taxa are new to both the J&amp;M site and the Williams Fork Formation. The sharks Lonchidion griffisi, Chiloscyllium sp., and Cantioscyllium markaguntensis are the first non-batoid elasmobranchs reported from the Williams Fork Formation and are all represented by teeth. The rays Cristomylus and Psuedomyledaphus are also newly reported from teeth. The most common identifiable fossils were teeth of indeterminate amiids, most likely belonging to Melvius. Osteichthyan fossils new to the Williams Fork Formation include teeth of Paralbula, an indeterminate pycnodontid tooth plate fragment, and an indeterminate lungfish tooth fragment. A tooth of the teiid Peneteius is also the first reported from within the Williams Fork Formation. Alligatoroid teeth are relatively common and are extremely similar to those of the contemporaneous durophage Brachychampsa but are generically indeterminate. Terrestrial taxa were recovered in much smaller numbers. Theropod dinosaur fossils included isolated tooth fragments belonging to an indeterminate dromaeosaurid and, possibly, to Richardoestesia. We recovered both multituberculate and metatherian fossils in the form of isolated teeth. Some of these taxa are known from marine and estuarine deposits and, given that so many of these marine associated taxa have been recovered together, it seems likely that the J&amp;M site is recording marine or estuarine influence within at least part of its depositional history. The mammalian taxa suggest a Judithian&ndash;Lancian age for the site, while records of the squamate Peneteius and the ray Myledaphus, suggest that the J&amp;M site may be temporally transitional between other late Campanian and late Maastrichtian-aged localities. &nbsp;</p

Security and privacy requirements for a multi-institutional cancer research data grid: an interview-based study

<p>Abstract</p> <p>Background</p> <p>Data protection is important for all information systems that deal with human-subjects data. Grid-based systems – such as the cancer Biomedical Informatics Grid (caBIG) – seek to develop new mechanisms to facilitate real-time federation of cancer-relevant data sources, including sources protected under a variety of regulatory laws, such as HIPAA and 21CFR11. These systems embody new models for data sharing, and hence pose new challenges to the regulatory community, and to those who would develop or adopt them. These challenges must be understood by both systems developers and system adopters. In this paper, we describe our work collecting policy statements, expectations, and requirements from regulatory decision makers at academic cancer centers in the United States. We use these statements to examine fundamental assumptions regarding data sharing using data federations and grid computing.</p> <p>Methods</p> <p>An interview-based study of key stakeholders from a sample of US cancer centers. Interviews were structured, and used an instrument that was developed for the purpose of this study. The instrument included a set of problem scenarios – difficult policy situations that were derived during a full-day discussion of potentially problematic issues by a set of project participants with diverse expertise. Each problem scenario included a set of open-ended questions that were designed to elucidate stakeholder opinions and concerns. Interviews were transcribed verbatim and used for both qualitative and quantitative analysis. For quantitative analysis, data was aggregated at the individual or institutional unit of analysis, depending on the specific interview question.</p> <p>Results</p> <p>Thirty-one (31) individuals at six cancer centers were contacted to participate. Twenty-four out of thirty-one (24/31) individuals responded to our request- yielding a total response rate of 77%. Respondents included IRB directors and policy-makers, privacy and security officers, directors of offices of research, information security officers and university legal counsel. Nineteen total interviews were conducted over a period of 16 weeks. Respondents provided answers for all four scenarios (a total of 87 questions). Results were grouped by broad themes, including among others: governance, legal and financial issues, partnership agreements, de-identification, institutional technical infrastructure for security and privacy protection, training, risk management, auditing, IRB issues, and patient/subject consent.</p> <p>Conclusion</p> <p>The findings suggest that with additional work, large scale federated sharing of data within a regulated environment is possible. A key challenge is developing suitable models for authentication and authorization practices within a federated environment. Authentication – the recognition and validation of a person's identity – is in fact a global property of such systems, while authorization – the permission to access data or resources – mimics data sharing agreements in being best served at a local level. Nine specific recommendations result from the work and are discussed in detail. These include: (1) the necessity to construct separate legal or corporate entities for governance of federated sharing initiatives on this scale; (2) consensus on the treatment of foreign and commercial partnerships; (3) the development of risk models and risk management processes; (4) development of technical infrastructure to support the credentialing process associated with research including human subjects; (5) exploring the feasibility of developing large-scale, federated honest broker approaches; (6) the development of suitable, federated identity provisioning processes to support federated authentication and authorization; (7) community development of requisite HIPAA and research ethics training modules by federation members; (8) the recognition of the need for central auditing requirements and authority, and; (9) use of two-protocol data exchange models where possible in the federation.</p

A π-Extended Donor-Acceptor-Donor Triphenylene Twin linked via a Pyrazine-bridge

Beta-amino triphenylenes can be accessed via palladium catalyzed amination of the corresponding triflate using benzophe-none imine. Transformation of amine 6 to benzoyl amide 18 is also straightforward and its wide mesophase range demon-strates that the new linkage supports columnar liquid crystal formation. Amine 6 also undergoes clean aerobic oxidation to give a new twinned structure linked through an electron-poor pyrazine ring. The new discotic liquid crystal motif contains donor and acceptor fragments, and is more oval in shape rather than disk-like. It forms a wide range columnar mesophase. Absorption spectra are strong and broad; emission is also broad and occurs with a Stokes shift of ca. 0.7 eV, indicative of charge-transfer characte

The impact of hypoxia on the host-pathogen interaction between neutrophils and staphylococcus aureus

Neutrophils are key to host defence, and impaired neutrophil function predisposes to infection with an array of pathogens, with Staphylococcus aureus a common and sometimes life-threatening problem in this setting. Both infiltrating immune cells and replicating bacteria consume oxygen, contributing to the profound tissue hypoxia that characterises sites of infection. Hypoxia in turn has a dramatic effect on both neutrophil bactericidal function and the properties of S. aureus, including the production of virulence factors. Hypoxia thereby shapes the host–pathogen interaction and the progression of infection, for example promoting intracellular bacterial persistence, enabling local tissue destruction with the formation of an encaging abscess capsule, and facilitating the establishment and propagation of bacterial biofilms which block the access of host immune cells. Elucidating the molecular mechanisms underlying host–pathogen interactions in the setting of hypoxia will enable better understanding of persistent and recalcitrant infections due to S. aureus and may uncover novel therapeutic targets and strategies