The prevalence of occult hepatitis B virus (hbv) infection in a large multi-ethnic haemodialysis cohort.

Haemodialysis patients are at increased risk of exposure to blood borne viruses. To reduce transmission in the UK, all haemodialysis patients are regularly screened, and if susceptible to Hepatitis B virus (HBV) infection, vaccinated

Pregnancy-specific glycoprotein function, conservation and receptor investigation

Pregnancy-specific glycoproteins (PSGs) are highly glycosylated secreted proteins encoded by multi-gene families in some placental mammals. They are carcinoembryonic antigen (CEA) family and immunoglobulin (Ig) superfamily members. PSGs are immunomodulatory, and have been demonstrated to possess antiplatelet and pro-angiogenic properties. Low serum levels of these proteins have been correlated with adverse pregnancy outcomes. Objectives: Main research goals of this thesis were: 1). To attempt to replicate previously reported cytokine responses to PSG-treatment of immune cells and subsequently to investigate functionally important amino acids within PSG1. 2). To determine whether candidate receptor, integrin αvβ3, was a binding partner for PSG1 and to investigate whether PSG1 possessed functionality in a leukocyte-endothelial interaction assay. 3). To determine whether proteins generated from recently identified putative PSG genes in the horse shared functional properties with PSGs from other species. Outcomes: 1). Sequential domain deletion of PSG1 as well as mutation of conserved residues within the PSG1 Ndomain did not affect PSG1-induced TGF-β1. The investigated response was subsequently found to be the result of latent TGF-β1 contaminating the recombinant protein. Protein further purified by SEC to remove this showed no induction of TGF-β1. The most N-terminal glycosylation site was demonstrated to have an important role in PSG N domain secretion. PSG1 attenuated LPS-induced IL-6 and TNF-α. Investigations into signalling underpinning this proved inconclusive. 2). Integrin αvβ3 was identified as a novel PSG1 receptor mediating an as yet unknown function. Preliminary investigations into a role for PSGs as inhibitors of leukocyte endothelial interactions showed no effect by PSG1. 3). Horse PSG protein, CEACAM49, was shown to be similarly contaminated by latent TGF-β1 particle and once removed did not demonstrate TGF-β1 release. Interestingly horse PSG did show anti-platelet properties through inhibition of the plateletfibrinogen interaction as previously published for mouse and human PSGs

Skin cancer excision is more efficient and cost effective in a specialist secondary care service

Aim: To compare the relative efficiencies of skin excisions in primary and secondary care. Methods: We compared the benign: malignant ratio for specimens referred by General Practice, General Surgery and the Skin Cancer Service to the regional pathology laboratory over one month. We used cost minimization analysis to compare the relative efficiencies of the services. Results: 620 excisions were received: 139 from General Practice, 118 from General Surgery and 363 from the Skin Cancer Service. The number (%) of malignant lesions was 13 (9.4%) from General Practice, 18 (15.2%) from General Surgery and 137 (37.7%) from the Skin Cancer Service. Excision was cheaper in General Practice at €84.58 as compared to €97.49 in the hospital day surgical unit. However, the cost per malignant lesion excised was €1779.80 in general practice versus €381.78 in the Skin Cancer Service. Conclusion: Our results indicate that moving skin cancer treatment to General Practice may result in an excess of benign excisions and therefore be both less efficient and less cost effective

A direct comparison of 2D versus 3D diffusion analysis at nanowire electrodes: A finite element analysis and experimental study

In electroanalysis, the benefits accrued by miniaturisation are a key driver in sensor development. Finite element simulations of electrochemical processes occurring at ultramicro- and nano-electrodes are used to provide key insight into experimental design in relation to diffusion profiles and expected currents. The most commonly used method, the diffusion domain approach (DDA) offers a means of reducing a three dimensional design to two dimensions to ease computational demands. However, the DDA approach can be limited when using basic assumptions which can be incorrect, for example that all electrodes in an array are equivalent. Consequently, to get a more realistic view of molecular diffusion to nanoelectrodes, it is necessary to undertake simulations in 3D. In this work, two and three dimensional models of electrodes comprising of (i) single nanowires, (ii) arrays of nanowires and (iii) interdigitated arrays of nanowires operating in generator-collector mode, were undertaken and compared to experimental results obtained from fabricated devices. The 3D simulations predicted a higher extracted current for a single nanowires and diffusionally independent nanowire arrays when compared to 2D simulations since, unlike the 2D model, they take into account molecular diffusion to and from nanowire termini. These current differences were observed to increase with increasing electrode width and decrease with electrode length. When the nanowire arrays were diffusionally overlapped, they behaved as an electrode of larger width, and the divergence between both models increased further. By contrast, using interdigitated nanowire arrays in generator-collector mode, the differences between extracted current values obtained using the 2D and 3D models were significantly lower. Simulations indicated however, that a higher collection efficiency was predicted by the 2D model when compared to the 3D model. Electrochemical experiments were undertaken to confirm the simulation study and demonstrated that the extracted currents from 3D simulations more closely mapped onto experimentally measured currents

Brucella abortus Infection of Placental Trophoblasts Triggers Endoplasmic Reticulum Stress-Mediated Cell Death and Fetal Loss via Type IV Secretion System-Dependent Activation of CHOP.

Subversion of endoplasmic reticulum (ER) function is a feature shared by multiple intracellular bacteria and viruses, and in many cases this disruption of cellular function activates pathways of the unfolded protein response (UPR). In the case of infection with Brucella abortus, the etiologic agent of brucellosis, the unfolded protein response in the infected placenta contributes to placentitis and abortion, leading to pathogen transmission. Here we show that B. abortus infection of pregnant mice led to death of infected placental trophoblasts in a manner that depended on the VirB type IV secretion system (T4SS) and its effector VceC. The trophoblast death program required the ER stress-induced transcription factor CHOP. While NOD1/NOD2 expression in macrophages contributed to ER stress-induced inflammation, these receptors did not play a role in trophoblast death. Both placentitis and abortion were independent of apoptosis-associated Speck-like protein containing a caspase activation and recruitment domain (ASC). These studies show that B. abortus uses its T4SS to induce cell-type-specific responses to ER stress in trophoblasts that trigger placental inflammation and abortion. Our results suggest further that in B. abortus the T4SS and its effectors are under selection as bacterial transmission factors.IMPORTANCE Brucella abortus infects the placenta of pregnant cows, where it replicates to high levels and triggers abortion of the calf. The aborted material is highly infectious and transmits infection to both cows and humans, but very little is known about how B. abortus causes abortion. By studying this infection in pregnant mice, we discovered that B. abortus kills trophoblasts, which are important cells for maintaining pregnancy. This killing required an injected bacterial protein (VceC) that triggered an endoplasmic reticulum (ER) stress response in the trophoblast. By inhibiting ER stress or infecting mice that lack CHOP, a protein induced by ER stress, we could prevent death of trophoblasts, reduce inflammation, and increase the viability of the pups. Our results suggest that B. abortus injects VceC into placental trophoblasts to promote its transmission by abortion

Genetic evidence supports recolonisation by Mya arenaria of western Europe from North America

The softshell clam Mya arenaria (L.) is currently widespread on the east and west coasts of North America. This bivalve also occurs on western European shores, where the post-Pleistocene origin of the species, whether introduced or relict, has been debated. We collected 320 M. arenaria from 8 locations in Europe and North America. Clams (n = 84) from 7 of the locations were examined for mitochondrial DNA variation by sequencing a section of the cytochrome oxidase 1 (COX1) gene. These were analysed together with 212 sequences, sourced from GenBank, from the same gene from 12 additional locations, chiefly from eastern North America but also 1 site each from western North America and from western Europe. Ten microsatellite loci were also investigated in all 320 clams. Nuclear markers showed reduced levels of variation in certain European samples. The same common COX1 haplotypes and microsatellite alleles were present throughout the range of M. arenaria, although significant differences were identified in haplotypic and allelic composition between many samples, particularly those from the 2 continents (Europe and North America). These findings support the hypothesis of post-Pleistocene colonisation of European shores from eastern North America (and the recorded human transfer of clams from the east to the west coast of North America in the 19th century)

Yield of binary- and multi-species swards relative to single-species swards in intensive silage systems

peer reviewedBinary- and multi-species sown mixtures may increase herbage yield and/or reduce inorganicnitrogen (N) requirement compared to perennial ryegrass (PRG) (Lolium perenne L.)swards. A split-plot design was used to compare yields of binary- and multi-speciesmixtures to single-species swards of three grasses and red clover managed for intensivesilage production under varying N application rates. Perennial and Italian (Loliummultiflorum Lam.) ryegrasses had greater annual yields when grown as single speciesreceiving 360 kg N/ha per year than in binary mixtures with red clover (Trifoliumpratense L.) receiving 0 kg N/ha per year, whereas timothy (Phleum pratense L.) producedequally high yields in both situations. When no inorganic N was applied, the annualdry matter yield of Mix 1 (10,738 kg/ha; PRG, timothy, red clover and white clover(Trifolium repens L.) and Mix 2 (11,679 kg/ha; PRG, timothy, red clover, ribwort plantain(Plantago lanceolata L.) and chicory (Cichorium intybus L.)) was greater than thatof a PRG sward (PRG/0N; 5,885 kg/ha) and derived more from the contribution of legumesthan herbs. This yield advantage of mixtures declined as inorganic N input increased,as did the legume and herb proportions in the multi-species swards. When averagedacross rates of inorganic N input, Mix 2 had a greater annual yield than Mix 1 (12,464vs. 11,893 kg/ha). Mix 2 receiving no inorganic fertiliser N and both Mix 1 and Mix2 receiving 120 kg N/ha per year matched the annual yield achieved by PRG receiving360 kg N/ha per year. Our results indicate that the yield performance of binary- andmulti-species grassland swards should be measured in situ rather than predicted fromsingle-species swards of constituent species

Beef production from feedstuffs conserved using new technologies to reduce negative environmental impacts

End of project reportMost (ca. 86%) Irish farms make some silage. Besides directly providing feed for livestock, the provision of grass silage within integrated grassland systems makes an important positive contribution to effective grazing management and improved forage utilisation by grazing animals, and to effective feed budgeting by farmers. It can also contribute to maintaining the content of desirable species in pastures, and to livestock not succumbing to parasites at sensitive times of the year. Furthermore, the optimal recycling of nutrients collected from housed livestock can often be best achieved by spreading the manures on the land used for producing the conserved feed. On most Irish farms, grass silage will remain the main conserved forage for feeding to livestock during winter for the foreseeable future. However, on some farms high yields of whole-crop (i.e. grain + straw) cereals such as wheat, barley and triticale, and of forage maize, will be an alternative option provided that losses during harvesting, storage and feedout are minimised and that input costs are restrained. These alternative forages have the potential to reliably support high levels of animal performance while avoiding the production of effluent. Their production and use however will need to advantageously integrate into ruminant production systems. A range of technologies can be employed for crop production and conservation, and for beef production, and the optimal options need to be identified. Beef cattle being finished indoors are offered concentrate feedstuffs at rates that range from modest inputs through to ad libitum access. Such concentrates frequently contain high levels of cereals such as barley or wheat. These cereals are generally between 14% to 18% moisture content and tend to be rolled shortly before being included in coarse rations or are more finely processed prior to pelleting. Farmers thinking of using ‘high-moisture grain’ techniques for preserving and processing cereal grains destined for feeding to beef cattle need to know how the yield, conservation efficiency and feeding value of such grains compares with grains conserved using more conventional techniques. European Union policy strongly encourages a sustainable and multifunctional agriculture. Therefore, in addition to providing European consumers with quality food produced within approved systems, agriculture must also contribute positively to the conservation of natural resources and the upkeep of the rural landscape. Plastics are widely used in agriculture and their post-use fate on farms must not harm the environment - they must be managed to support the enduring sustainability of farming systems. There is an absence of information on the efficacy of some new options for covering and sealing silage with plastic sheeting and tyres, and an absence of an inventory of the use, re-use and post-use fate of plastic film on farms. Irish cattle farmers operate a large number of beef production systems, half of which use dairy bred calves. In the current, continuously changing production and market conditions, new beef systems must be considered. A computer package is required that will allow the rapid, repeatable simulation and assessment of alternate beef production systems using appropriate, standardised procedures. There is thus a need to construct, evaluate and utilise computer models of components of beef production systems and to develop mathematical relationships to link system components into a network that would support their integration into an optimal system model. This will provide a framework to integrate physical and financial on-farm conditions with models for estimating feed supply and animal growth patterns. Cash flow and profit/loss results will be developed. This will help identify optimal systems, indicate the cause of failure of imperfect systems and identify areas where applied research data are currently lacking, or more basic research is required