Pure species within a continuum of genetic and morphological variation:Sympatric oaks at the edge of their range

Background and Aims Studies on oaks (Quercus spp.) have often been hampered by taxonomic confusion, a situation further compounded by the occurrence of extensive interspecific hybridization. In the present study, a combination of genetic and morphological analyses was used to examine sympatric populations of Q. petraea and Q. robur at the north-western edge of their ranges in Northern Ireland, since it had previously been suggested that hybridization could facilitate the apparent rapid, long-distance dispersal of oaks following the glaciations. Methods Samples were collected from 24 sites across Northern Ireland that had been previously designated as ancient or semi-natural woodland. Genotypes were obtained from a total of 950 trees using 12 nuclear microsatellite loci, and admixture coefficients were calculated based on a Bayesian clustering approach. Individuals were also classified as Q. petraea, Q. robur or hybrids based on two objective morphometric characters shown previously to delineate pure individuals effectively. Genetically ‘pure’ individuals of both species, as defined by the Bayesian clustering, were also genotyped for five chloroplast microsatellites. Key Results Genetic and morphological analyses both indicated the presence of pure individuals of both species, as well as a continuum of intermediates. There was a good agreement between the molecular and morphological classification, with a generally clear separation between pure individuals. Conclusions Despite millennia of hybridization and introgression, genetically and morphologically pure individuals of both Q. petraea and Q. robur can be found at the edge of their range, where both species occur sympatrically. The high proportion of individuals exhibiting introgression compared with previous studies may reflect the historical role of hybridization in facilitating dispersal following the glaciations. This is further supported by the significantly higher chloroplast diversity in Q. robur compared with Q. petraea

Lack of genetic structure and evidence for long-distance dispersal in ash (Fraxinus excelsior) populations under threat from an emergent fungal pathogen:Implications for restorative planting

Genetic analysis on populations of European ash (Fraxinus excelsior) throughout Ireland was carried out to determine the levels and patterns of genetic diversity in naturally seeded trees in ash woodlands and hedgerows, with the aim of informing conservation and replanting strategies in the face of potential loss of trees as a result of ash dieback. Samples from 33 sites across Northern Ireland and three sites in the Republic of Ireland were genotyped for eight nuclear and ten chloroplast microsatellites. Levels of diversity were (h)igh (mean A(R)=10.53; mean H-O=0.709; mean H-E=0.765) and were similar to those in Great Britain and continental Europe, whilst levels of population genetic differentiation based on nuclear microsatellites were extremely low ((Phi) over bar (ST)=0.0131). Levels of inbreeding (mean F-IS=0.067) were significantly lower than those reported for populations from Great Britain. Fine-scale analysis of seed dispersal indicated potential for dispersal over hundreds of metres. Our results suggest that ash woodlands across Ireland could be treated as a single management unit, and thus native material from anywhere in Ireland could be used as a source for replanting. In addition, high potential for dispersal has implications for recolonization processes post-ash dieback (Chalara fraxinea) infection, and could aid in our assessment of the capacity of ash to shift its range in response to global climate change.authorsversionPeer reviewe

Squirrelpox virus: assessing prevalence, transmission and environmental degradation

Red squirrels (Sciurus vulgaris) declined in Great Britain and Ireland during the last century, due to habitat loss and the introduction of grey squirrels (Sciurus carolinensis), which competitively exclude the red squirrel and act as a reservoir for squirrelpox virus (SQPV). The disease is generally fatal to red squirrels and their ecological replacement by grey squirrels is up to 25 times faster where the virus is present. We aimed to determine: (1) the seropositivity and prevalence of SQPV DNA in the invasive and native species at a regional scale; (2) possible SQPV transmission routes; and, (3) virus degradation rates under differing environmental conditions. Grey (n = 208) and red (n = 40) squirrel blood and tissues were sampled. Enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qPCR) techniques established seropositivity and viral DNA presence, respectively. Overall 8% of squirrels sampled (both species combined) had evidence of SQPV DNA in their tissues and 22% were in possession of antibodies. SQPV prevalence in sampled red squirrels was 2.5%. Viral loads were typically low in grey squirrels by comparison to red squirrels. There was a trend for a greater number of positive samples in spring and summer than in winter. Possible transmission routes were identified through the presence of viral DNA in faeces (red squirrels only), urine and ectoparasites (both species). Virus degradation analyses suggested that, after 30 days of exposure to six combinations of environments, there were more intact virus particles in scabs kept in warm (25°C) and dry conditions than in cooler (5 and 15°C) or wet conditions. We conclude that SQPV is present at low prevalence in invasive grey squirrel populations with a lower prevalence in native red squirrels. Virus transmission could occur through urine especially during warm dry summer conditions but, more notably, via ectoparasites, which are shared by both species

Seasonal and predator-prey effects on circadian activity of free-ranging mammals revealed by camera traps

Endogenous circadian and seasonal activity patterns are adapted to facilitate effective utilisation of environmental resources. Activity patterns are shaped by physiological constraints, evolutionary history, circadian and seasonal changes and may be influenced by other factors, including ecological competition and interspecific interactions. Remote-sensing camera traps allow the collection of species presence data throughout the 24 h period and for almost indefinite lengths of time. Here, we collate data from 10 separate camera trap surveys in order to describe circadian and seasonal activity patterns of 10 mammal species, and, in particular, to evaluate interspecific (dis)associations of five predator-prey pairs. We recorded 8,761 independent detections throughout Northern Ireland. Badgers, foxes, pine martens and wood mice were nocturnal; European and Irish hares and European rabbits were crepuscular; fallow deer and grey and red squirrels were diurnal. All species exhibited significant seasonal variation in activity relative to the timing of sunrise/sunset. Foxes in particular were more crepuscular from spring to autumn and hares more diurnal. Lagged regression analyses of predator-prey activity patterns between foxes and prey (hares, rabbits and wood mice), and pine marten and prey (squirrel and wood mice) revealed significant annual and seasonal cross-correlations. We found synchronised activity patterns between foxes and hares, rabbits and wood mice and pine marten and wood mice, and asynchrony between squirrels and pine martens. Here, we provide fundamental ecological data on endemic, invasive, pest and commercially valuable species in Ireland, as well as those of conservation importance and those that could harbour diseases of economic and/or zoonotic relevance. Our data will be valuable in informing the development of appropriate species-specific methodologies and processes and associated policies

Hnf4α is a key gene that can generate columnar metaplasia in oesophageal epithelium

AbstractBarrett's metaplasia is the only known morphological precursor to oesophageal adenocarcinoma and is characterized by replacement of stratified squamous epithelium by columnar epithelium. The cell of origin is uncertain and the molecular mechanisms responsible for the change in cellular phenotype are poorly understood. We therefore explored the role of two transcription factors, Cdx2 and HNF4α in the conversion using primary organ cultures. Biopsy samples from cases of human Barrett's metaplasia were analysed for the presence of CDX2 and HNF4α. A new organ culture system for adult murine oesophagus is described. Using this, Cdx2 and HNF4α were ectopically expressed by adenoviral infection. The phenotype following infection was determined by a combination of PCR, immunohistochemical and morphological analyses. We demonstrate the expression of CDX2 and HNF4α in human biopsy samples. Our oesophageal organ culture system expressed markers characteristic of the normal SSQE: p63, K14, K4 and loricrin. Ectopic expression of HNF4α, but not of Cdx2 induced expression of Tff3, villin, K8 and E-cadherin. HNF4α is sufficient to induce a columnar-like phenotype in adult mouse oesophageal epithelium and is present in the human condition. These data suggest that induction of HNF4α is a key early step in the formation of Barrett's metaplasia and are consistent with an origin of Barrett's metaplasia from the oesophageal epithelium

Does intensive management improve remission rates in patients with intermediate rheumatoid arthritis? (the TITRATE trial): study protocol for a randomised controlled trial.

BACKGROUND: Uncontrolled active rheumatoid arthritis can lead to increasing disability and reduced quality of life over time. 'Treating to target' has been shown to be effective in active established disease and also in early disease. However, there is a lack of nationally agreed treatment protocols for patients with established rheumatoid arthritis who have intermediate disease activity. This trial is designed to investigate whether intensive management of disease leads to a greater number of remissions at 12 months. Levels of disability and quality of life, and acceptability and cost-effectiveness of the intervention will also be examined. METHODS: The trial is a 12-month, pragmatic, randomised, open-label, two-arm, parallel-group, multicentre trial undertaken at specialist rheumatology centres across England. Three hundred and ninety-eight patients with established rheumatoid arthritis will be recruited. They will currently have intermediate disease activity (disease activity score for 28 joints assessed using an erythrocyte sedimentation rate of 3.2 to 5.1 with at least three active joints) and will be taking at least one disease-modifying anti-rheumatic drug. Participants will be randomly selected to receive intensive management or standard care. Intensive management will involve monthly clinical reviews with a specialist health practitioner, where drug treatment will be optimised and an individualised treatment support programme delivered based on several principles of motivational interviewing to address identified problem areas, such as pain, fatigue and adherence. Standard care will follow standard local pathways and will be in line with current English guidelines from the National Institute for Health and Clinical Excellence. Patients will be assessed initially and at 6 and 12 months through self-completed questionnaires and clinical evaluation. DISCUSSION: The trial will establish whether the known benefits of intensive treatment strategies in active rheumatoid arthritis are also seen in patients with established rheumatoid arthritis who have moderately active disease. It will evaluate both the clinical and cost-effectiveness of intensive treatment. TRIAL REGISTRATION: Current Controlled Trials, ID: ISRCTN70160382 . Registered on 16 January 2014.MRC Funding: MC_UP_1302/3 NIHR Funding: RP-PG-0610-1006

Innovation in health economic modelling of service improvements for longer-term depression: demonstration in a local health community

Background The purpose of the analysis was to develop a health economic model to estimate the costs and health benefits of alternative National Health Service (NHS) service configurations for people with longer-term depression. Method Modelling methods were used to develop a conceptual and health economic model of the current configuration of services in Sheffield, England for people with longer-term depression. Data and assumptions were synthesised to estimate cost per Quality Adjusted Life Years (QALYs). Results Three service changes were developed and resulted in increased QALYs at increased cost. Versus current care, the incremental cost-effectiveness ratio (ICER) for a self-referral service was £11,378 per QALY. The ICER was £2,227 per QALY for the dropout reduction service and £223 per QALY for an increase in non-therapy services. These results were robust when compared to current cost-effectiveness thresholds and accounting for uncertainty. Conclusions Cost-effective service improvements for longer-term depression have been identified. Also identified were limitations of the current evidence for the long term impact of services