Bacterial toxins: Offensive, defensive, or something else altogether?

The secretion of proteins that damage host tissue is well established as integral to the infectious processes of many bacterial pathogens. However, recent advances in our understanding of the activity of toxins suggest that the attributes we have assigned to them from early in vitro experimentation have misled us into thinking of them as merely destructive tools. Here, we will discuss the multifarious ways in which toxins contribute to the lifestyle of bacteria and, by considering their activity from an evolutionary perspective, demonstrate how this extends far beyond their ability to destroy host tissue

Risky bodies, risky spaces, maternal ‘instincts’: swimming and motherhood

Swimming and aquatic activity are fields in which gendered, embodied identities are brought to the fore, and the co-presence of other bodies can have a significant impact upon lived experiences. To date, however, there has been little research on sport and physical cultures that investigates how meanings associated with space impact upon women’s embodied experiences of participating in swimming, specifically in the presence of their young children. Using semi-structured interviews and non-participant observations, this qualitative study employed a Foucauldian-feminist framework to explore self-perceptions and embodied experiences of aquatic activity amongst 20 women, who were swimming with children aged under 4. Results highlight that through ‘felt’ maternal responsibilities, the co-presence of babies’ and children’s bodies shifted women’s intentionality away from the self towards their child. Mothers’ embodied experiences were grounded in perceptions of space-specific ‘maternal instincts’ and focused upon disciplining their children’s bodies in the lived-space of the swimming pool. Key findings cohere around mothers’ felt concerns about hygiene, water temperature and safety, and elements of intercorporeality and ‘somatic empathy’

The Third Gravitational Lensing Accuracy Testing (GREAT3) Challenge Handbook

The GRavitational lEnsing Accuracy Testing 3 (GREAT3) challenge is the third in a series of image analysis challenges, with a goal of testing and facilitating the development of methods for analyzing astronomical images that will be used to measure weak gravitational lensing. This measurement requires extremely precise estimation of very small galaxy shape distortions, in the presence of far larger intrinsic galaxy shapes and distortions due to the blurring kernel caused by the atmosphere, telescope optics, and instrumental effects. The GREAT3 challenge is posed to the astronomy, machine learning, and statistics communities, and includes tests of three specific effects that are of immediate relevance to upcoming weak lensing surveys, two of which have never been tested in a community challenge before. These effects include realistically complex galaxy models based on high-resolution imaging from space; spatially varying, physically-motivated blurring kernel; and combination of multiple different exposures. To facilitate entry by people new to the field, and for use as a diagnostic tool, the simulation software for the challenge is publicly available, though the exact parameters used for the challenge are blinded. Sample scripts to analyze the challenge data using existing methods will also be provided. See http://great3challenge.info and http://great3.projects.phys.ucl.ac.uk/leaderboard/ for more information.Comment: 30 pages, 13 figures, submitted for publication, with minor edits (v2) to address comments from the anonymous referee. Simulated data are available for download and participants can find more information at http://great3.projects.phys.ucl.ac.uk/leaderboard

Mapping Soils in Ireland

peer-reviewedThis project is jointly funded by Teagasc and EPA STRIVE funding.Harmonised soil data across Europe with a 1:250 000 geo-referenced soil database will allow for exchange of data across member states and the provide the information needed for reporting on issues re-lating to soil quality under a future Soil Framework Directive. The current status of soils data available in Eu-rope is inconsistent at best. The Irish Soil Information System (ISIS) project is currently developing a national soil map of 1:250,000 and an associated digital soil information system, providing both spatial and quantita-tive information on soil types and properties across Ireland. Both the map and the information system will be freely available to the public through a designated website.This project is jointly funded by Teagasc and EPA STRIVE funding

Manipulation of autophagy in phagocytes facilitates <i>Staphylococcus aureus</i> bloodstream infection

The capacity for intracellular survival within phagocytes is likely a critical factor facilitating the dissemination of Staphylococcus aureus in the host. To date, the majority of work on S. aureus-phagocyte interactions has focused on neutrophils and, to a lesser extent, macrophages, yet we understand little about the role played by dendritic cells (DCs) in the direct killing of this bacterium. Using bone marrow-derived DCs (BMDCs), we demonstrate for the first time that DCs can effectively kill S. aureus but that certain strains of S. aureus have the capacity to evade DC (and macrophage) killing by manipulation of autophagic pathways. Strains with high levels of Agr activity were capable of causing autophagosome accumulation, were not killed by BMDCs, and subsequently escaped from the phagocyte, exerting significant cytotoxic effects. Conversely, strains that exhibited low levels of Agr activity failed to accumulate autophagosomes and were killed by BMDCs. Inhibition of the autophagic pathway by treatment with 3-methyladenine restored the bactericidal effects of BMDCs. Using an in vivo model of systemic infection, we demonstrated that the ability of S. aureus strains to evade phagocytic cell killing and to survive temporarily within phagocytes correlated with persistence in the periphery and that this effect is critically Agr dependent. Taken together, our data suggest that strains of S. aureus exhibiting high levels of Agr activity are capable of blocking autophagic flux, leading to the accumulation of autophagosomes. Within these autophagosomes, the bacteria are protected from phagocytic killing, thus providing an intracellular survival niche within professional phagocytes, which ultimately facilitates dissemination

Targeted control of pneumolysin production by a mobile genetic element in Streptococcus pneumoniae

Streptococcus pneumoniae is a major human pathogen that can cause severe invasive diseases such as pneumonia, septicaemia and meningitis. Young children are at a particularly high risk, with an estimated 3–4 million cases of severe disease and between 300 000 and 500 000 deaths attributable to pneumococcal disease each year. The haemolytic toxin pneumolysin (Ply) is a primary virulence factor for this bacterium, yet despite its key role in pathogenesis, immune evasion and transmission, the regulation of Ply production is not well defined. Using a genome-wide association approach, we identified a large number of potential affectors of Ply activity, including a gene acquired horizontally on the antibiotic resistance-conferring Integrative and Conjugative Element (ICE) ICESp23FST81. This gene encodes a novel modular protein, ZomB, which has an N-terminal UvrD-like helicase domain followed by two Cas4-like domains with potent ATP-dependent nuclease activity. We found the regulatory effect of ZomB to be specific for the ply operon, potentially mediated by its high affinity for the BOX repeats encoded therein. Using a murine model of pneumococcal colonization, we further demonstrate that a ZomB mutant strain colonizes both the upper respiratory tract and lungs at higher levels when compared to the wild-type strain. While the antibiotic resistance-conferring aspects of ICESp23FST81 are often credited with contributing to the success of the S. pneumoniae lineages that acquire it, its ability to control the expression of a major virulence factor implicated in bacterial transmission is also likely to have played an important role

Better maternity care pathways in pregnancies after stillbirth or neonatal death: a feasibility study

Background Around 1 in 150 babies are stillborn or die in the first month of life in the UK. Most women conceive again, and subsequent pregnancies are often characterised by feelings of stress and anxiety, persisting beyond the birth. Psychological distress increases the risk of poor pregnancy outcomes and longer-term parenting difficulties. Appropriate emotional support in subsequent pregnancies is key to ensure the wellbeing of women and families. Substantial variability in existing care has been reported, including fragmentation and poor communication. A new care package improving midwifery continuity and access to emotional support during subsequent pregnancy could improve outcomes. However, no study has assessed the feasibility of a full-scale trial to test effectiveness in improving outcomes and cost-effectiveness for the National Health Service (NHS). Methods A prospective, mixed-methods pre-and post-cohort study, in two Northwest England Maternity Units. Thirty-eight women, (≤ 20 weeks’ gestation, with a previous stillbirth, or neonatal death) were offered the study intervention (allocation of a named midwife care coordinator and access to group and online support). Sixteen women receiving usual care were recruited in the 6 months preceding implementation of the intervention. Outcome data were collected at 2 antenatal and 1 postnatal visit(s). Qualitative interviews captured experiences of care and research processes with women (n = 20), partners (n = 5), and midwives (n = 8). Results Overall recruitment was 90% of target, and 77% of women completed the study. A diverse sample reflected the local population, but non-English speaking was a barrier to participation. Study processes and data collection methods were acceptable. Those who received increased midwifery continuity valued the relationship with the care coordinator and perceived positive impacts on pregnancy experiences. However, the anticipated increase in antenatal continuity for direct midwife contacts was not observed for the intervention group. Take-up of in-person support groups was also limited. Conclusions Women and partners welcomed the opportunity to participate in research. Continuity of midwifery care was supported as a beneficial strategy to improve care and support in pregnancy after the death of a baby by both parents and professionals. Important barriers to implementation included changes in leadership, service pressures and competing priorities

International evidence-based medicine survey of the veterinary profession: information sources used by veterinarians

Veterinarians are encouraged to use evidence to inform their practice, but it is unknown what resources (e.g. journals, electronic sources) are accessed by them globally. Understanding the key places veterinarians seek information can inform where new clinically relevant evidence should most effectively be placed. An international survey was conducted to gain understanding of how veterinary information is accessed by veterinarians worldwide. There were 2137 useable responses to the questionnaire from veterinarians in 78 countries. The majority of respondents (n = 1835/2137, 85.9%) undertook clinical work and worked in a high income country (n = 1576/1762, 89.4%). Respondents heard about the survey via national veterinary organisations or regulatory bodies (31.5%), online veterinary forums and websites (22.7%), regional, discipline-based or international veterinary organisations (22.7%) or by direct invitation from the researchers or via friends, colleagues or social media (7.6%). Clinicians and non-clinicians reportedly used journals most commonly (65.8%, n = 1207/1835; 75.6%, n = 216/286) followed by electronic resources (58.7%, n = 1077/1835; 55.9%, n = 160/286), respectively. Respondents listed a total of 518 journals and 567 electronic sources that they read. Differences in veterinarian preference for resources in developed, and developing countries, were found. The nominated journals most read were the Journal of the American Veterinary Medical Association (12.7% of nominations) for clinicians and the Veterinary Record (5.7%) for non-clinicians. The most accessed electronic resource reported was the Veterinary Information Network (25.6%) for clinicians and PubMed (7.4%) for non-clinicians. In conclusion, a wide array of journals and electronic resources appear to be accessed by veterinarians worldwide. Veterinary organisations appear to play an important role in global communication and outreach to veterinarians and consideration should be given to how these channels could be best utilised for effective dissemination of key research findings

Skeletonization of radial and gastroepiploic conduits in coronary artery bypass surgery

The use of a skeletonized internal thoracic artery in coronary artery bypass graft surgery has been shown to confer certain advantages over a traditional pedicled technique, particularly in certain patient groups. Recent reports indicate that radial and gastroepiploic arteries can also be harvested using a skeletonized technique. The aim of this study is to systematically review the available evidence regarding the use of skeletonized radial and gastroepiploic arteries within coronary artery bypass surgery, focusing specifically on it's effect on conduit length and flow, levels of endothelial damage, graft patency and clinical outcome. Four electronic databases were systematically searched for studies reporting the utilisation of the skeletonization technique within coronary revascularisation surgery in humans. Reference lists of all identified studies were checked for any missing publications. There appears to be some evidence that skeletonization may improve angiographic patency, when compared with pedicled vessels in the short to mid-term. We have found no suggestion of increased complication rates or increased operating time. Skeletonization may increase the length of the conduit, and the number of sequential graft sites, but no clear clinical benefits are apparent. Our study suggests that there is not enough high quality or consistent evidence to currently advocate the application of this technique to radial or gastroepiploic conduits ahead of a traditional pedicled technique