Nitric oxide production by Biomphalaria glabrata haemocytes: effects of Schistosoma mansoni ESPs and regulation through the extracellular signal-regulated kinase pathway

BACKGROUND: Schistosoma mansoni uses Biomphalaria glabrata as an intermediate host during its complex life cycle. In the snail, the parasite initially transforms from a miracidium into a mother sporocyst and during this process excretory-secretory products (ESPs) are released. Nitric oxide (NO) and its reactive intermediates play an important role in host defence responses against pathogens. This study therefore aimed to determine the effects of S. mansoni ESPs on NO production in defence cells (haemocytes) from schistosome-susceptible and schistosome-resistant B. glabrata strains. As S. mansoni ESPs have previously been shown to inhibit extracellular signal-regulated kinase (ERK) phosphorylation (activation) in haemocytes from susceptible, but not resistant, B. glabrata the regulation of NO output by ERK in these cells was also investigated. RESULTS: Haemocytes from resistant snails challenged with S. mansoni ESPs (20 mug/ml) over 5 h displayed an increase in NO production that was 3.3 times greater than that observed for unchallenged haemocytes; lower concentrations of ESPs (0.1-10 mug/ml) did not significantly increase NO output. In contrast, haemocytes from susceptible snails showed no significant change in NO output following challenge with ESPs at any concentration used (0.1-20 mug/ml). Western blotting revealed that U0126 (1 muM or 10 muM) blocked the phosphorylation (activation) status of ERK in haemocytes from both snail strains. Inhibition of ERK signalling by U0126 attenuated considerably intracellular NO production in haemocytes from both susceptible and resistant B. glabrata strains, identifying ERK as a key regulator of NO output in these cells. CONCLUSION: S. mansoni ESPs differentially influence intracellular NO levels in susceptible and resistant B. glabrata haemocytes, possibly through modulation of the ERK signalling pathway. Such effects might facilitate survival of S. mansoni in its intermediate host

Hacking through the Gordian Knot: can facilitating operational mentoring untangle the gender research productivity puzzle in higher education?

This is an Accepted Manuscript of an article published by Taylor & Francis in Studies in Higher Education on 30/05/2017, available online: http://www.tandfonline.com/doi/full/10.1080/03075079.2017.1333494In spite of a number of drivers for change in the pursuit of gender equality in higher education in the UK and beyond, the gender gap in research activity is still widely recognised across most subject disciplines. Over recent years, mentoring strategies have often been seen as the Alexandrian sword capable of cutting the gender deficit ‘Gordian Knot’. However, analysis of current practice and dialogue points to a lack of a consistent approach in addressing and implementing HE policy in this area with many initiatives providing standardised non-evidence-based provision aimed at addressing an alleged confidence deficit and exhausting an already fatigued group of successful senior women. This paper seeks to triangulate existing literature with an analysis of data collected from a funded UK-based research project ultimately proposing a five-step institutional mentoring approach aimed at providing some inroads into alleviating the gender deficit in research productivity in the academy

Assessing learning in the early years’ outdoor classroom: examining challenges in practice

The benefit the outdoor environment has for young children’s development is widely documented. However, there is less literature outlining practitioners’ experiences of assessing learning in the outdoors and factors which impact the level and quality of assessments undertaken. This study, based on a pragmatic mixed methods approach, undertaken in 9 early years’ settings in North Wales, reports the findings of 37 practitioners. The research suggests that assessing children in the outdoors is not used to its potential. Factors impeding the use of the outdoor classroom include: lack of appropriate resources; level of staff expertise; child-staff ratio; adverse weather; and changes to curriculum policy which place emphasis on the formal assessment of children. There appears to be assumptions about learners most likely to benefit from outdoor learning and assessment: boys; children in socio-economically deprived areas; and children with additional learning needs. The paper highlights the need for broader training opportunities for practitioners on planning for learning and assessment in the outdoors that go beyond a single course focus. With creative planning, there is no reason why summative assessments of all areas of learning within the early years’ curriculum cannot be done as effectively outdoors as they may be being done indoors

Epistemological differences and new technology in construction

New technology within the construction industry originates from appeals to replicate the efficiencies seen in other sectors such as automation and manufacturing and construction firms are increasingly engaging in collaborative research and development (R&D) projects with sector specialists. These R&D projects create new communities of practice with a shared collection of knowledge, experience, and problem-solving approaches representing the disparate expertise of each member contributing to the development of new and innovative technological solutions. However, fundamental epistemological differences between the collaborating firms can hinder this process. Shared knowledge and experience to develop ideas is not easily communicated across a project team within which each member possesses a differing approach to understanding the common problem. This paper presents early research engagement in an R&D project investigating the potential of utilising Flexible Robotic Assembly Modules in the Built Environment (FRAMBE). Challenges observed to date during the process of developing FRAMBE as a technological solution are described. This paper aims to exemplify communication issues within cross-sector R&D projects to argue that boundary objects offer a means to consider the epistemological differences within communities of practice, establish a common understanding of the problem, and therefore ways in which to resolve issues surrounding technology development

Association between genotypic diversity and biofilm production in group B Streptococcus

Background: Group B Streptococcus (GBS) is a leading cause of sepsis and meningitis and an important factor in premature and stillbirths. Biofilm production has been suggested to be important for GBS pathogenesis alongside many other elements, including phylogenetic lineage and virulence factors, such as pili and capsule type. A complete understanding of the confluence of these components, however, is lacking. To identify associations between biofilm phenotype, pilus profile and lineage, 293 strains from asymptomatic carriers, invasive disease cases, and bovine mastitis cases, were assessed for biofilm production using an in vitro assay. Results: Multilocus sequence type (ST) profile, pilus island profile, and isolate source were associated with biofilm production. Strains from invasive disease cases and/or belonging to the ST-17 and ST-19 lineages were significantly more likely to form weak biofilms, whereas strains producing strong biofilms were recovered more frequently from individuals with asymptomatic colonization. Conclusions: These data suggest that biofilm production is a lineage-specific trait in GBS and may promote colonization of strains representing lineages other than STs 17 and 19. The findings herein also demonstrate that biofilms must be considered in the treatment of pregnant women, particularly for women with heavy GBS colonization

Ultrastructural Distribution of the 7 Nicotinic Acetylcholine Receptor Subunit in Rat Hippocampus

Acetylcholine (ACh) is an important neurotransmitter in the mammalian brain; it is implicated in arousal, learning, and other cognitive functions. Recent studies indicate that nicotinic receptors contribute to these cholinergic effects, in addition to the established role of muscarinic receptors. In the hippocampus, where cholinergic involvement in learning and memory is particularly well documented, 7 nicotinic acetylcholine receptor subunits (7 nAChRs) are highly expressed, but their precise ultrastructural localization has not been determined. Here, we describe the results of immunogold labeling of serial ultrathin sections through stratum radiatum of area CA1 in the rat. Using both anti-7 nAChR immunolabeling and -bungarotoxin binding, we find that 7 nAChRs are present at nearly all synapses in CA1 stratum radiatum, with immunolabeling present at both presynaptic and postsynaptic elements. Morphological considerations and double immunolabeling indicate that GABAergic as well as glutamatergic synapses bear 7 nAChRs, at densities approaching those observed for glutamate receptors in CA1 stratum radiatum. Postsynaptically, 7 nAChRs often are distributed at dendritic spines in a perisynaptic annulus. In the postsynaptic cytoplasm, immunolabeling is associated with spine apparatus and other membranous structures, suggesting that 7 nAChRs may undergo dynamic regulation, with insertion into the synapse and subsequent internalization. The widespread and substantial expression of 7 nAChRs at synapses in the hippocampus is consistent with an important role in mediating and/or modulating synaptic transmission, plasticity, and neurodegeneration

Emulated trial investigating effects of multiple treatments: estimating combined effects of mucoactive nebulisers in cystic fibrosis using registry data

Introduction: People with cystic fibrosis (CF) are often on multiple long-term treatments, including mucoactive nebulisers. In the UK, the most common mucoactive nebuliser is dornase alfa (DNase). A common therapeutic approach for people already on DNase is to add hypertonic saline (HS). The effects of DNase and HS used alone have been studied in randomised trials, but their effects in combination have not. This study investigates whether, for people already prescribed DNase, adding HS has additional benefit for lung function or use of intravenous antibiotics.// Methods: Using UK CF Registry data from 2007 to 2018, we emulated a target trial. We included people aged 6 years and over who were prescribed DNase without HS for 2 years. We investigated the effects of combinations of DNase and HS over 5 years of follow-up. Inverse-probability-of-treatment weighting was used to control confounding. The period predated triple combination CF transmembrane conductance regulator modulators in routine care.// Results: 4498 individuals were included. At baseline, average age and forced expiratory volume in 1 s (FEV1%) predicted were 21.1 years and 69.7 respectively. During first year of follow-up, 3799 individuals were prescribed DNase alone; 426 added HS; 57 switched to HS alone and 216 were prescribed neither. We found no evidence that adding HS improved FEV1% at 1–5 years, or use of intravenous antibiotics at 1–4 years, compared with DNase alone.// Conclusion: For individuals with CF prescribed DNase, we found no evidence that adding HS had an effect on FEV1% or prescription of intravenous antibiotics. Our study illustrates the emulated target trial approach using CF Registry data

Gendered experiences of academic staff in relation to research activity and the REF2014

This report is based on research commissioned by the institutional Research and Knowledge Transfer Office between June 2015 and June 2016. This research has focused on generating qualitative and quantitative data as to the potential reasons why there appears to be a gender disparity in research productivity within the commissioning institution. In particular, the number of women self-selecting for representation in the REF2014 was comparatively low. This research was led by Dr Chantal Davies (as part of her broader remit in relation to the Forum for Research into Equality and Diversity) with Dr Ruth Healey as co-researcher and Anthony Cliffe as research assistant. A Steering Group made up of representatives from across the institution oversaw the process

Using Twitter™ to drive research impact : a discussion of strategies, opportunities and challenges

Researchers have always recognised the importance of disseminating the findings of their work, however, recently the need to proactively plan and drive the impact of those findings on the wider society has become a necessity. Firstly, this is because funders require evidence of return from investment and secondly and crucially because national research assessments are becoming powerful determinants of future funding. In research studies associated with nursing, impact needs to be demonstrated by showing the effect on a range of stakeholders including service users, patients, carers, the nursing workforce and commissioners. Engaging these groups is a well-known challenge influenced by lack of access to academic journals, lack of time to read long complex research papers and lack of opportunities to interact directly with the researchers. This needs to be addressed urgently to enable nursing research to increase the impact that it has on health delivery and the work of clinical practitioners. Social media is potentially a novel way of enabling research teams to both communicate about research as studies progress and to disseminate findings and research funders are increasingly using it to publicise information about research programmes and studies they fund. A search of the healthcare literature reveals that advice and guidance on the use of social media for research studies is not well understood or exploited by the research community. This paper, therefore, explores how using social networking platforms, notably Twitter™ offers potential new ways for communicating research findings, accessing diverse and traditionally hard-to-reach audiences, knowledge exchange at an exponential rate, and enabling new means of capturing and demonstrating research impact. The paper discusses approaches to initiate the setup of social networking platforms in research projects and considers the practical challenges of using Twitter™ in nursing and healthcare research. The discussion is illuminated with examples from our current research. In summary, we suggest that the use of social media micro-blogging platforms is a contemporary, fast, easy and cost effective way to augment existing ways of disseminating research which helps drive impact