1,020 research outputs found

    Genome-wide association studies of parasite resistance, productivity and immunology traits in meat in Scottish Blackface sheep

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    Gastrointestinal parasitism represents a global problem for grazing ruminants, which can be addressed sustainably by breeding animals to be more resistant against infection by parasites. The aim of this study was to assess the genetic architecture underlying traits associated with gastrointestinal parasite resistance, immunological profile and production in meat sheep, and identify and characterise candidate genes affecting these traits. Data on gastrointestinal parasite infection (faecal egg counts for Strongyles (FECS) and Nematodirus (FECN) and faecal oocyst counts for Coccidia, along with faecal soiling scores (DAG), characterised by the accumulation of faeces around the perineum) and production (live weight (LWT)) were gathered from a flock Scottish Blackface lambs at three and four months of age. Data on the immune profile were also collected from a subset of these lambs at two and five months of age. Immune traits included the production of Interferon-γ (IFN-γ), Interleukin (IL)-4 and IL-10 following stimulation of whole blood with pokeweed mitogen (PWM) or antigen from the gastric parasite Teladorsagia circumcincta (T-ci), and serum levels of T. circumcincta-specific immunoglobulin A (IgA). Animals were genotyped with genome-wide DNA arrays, and a total of 1 766 animals and 45 827 Single Nucleotide Polymorphisms (SNPs) were retained following quality control and imputation. Genome-wide association studies were performed for 24 traits. The effects of individual markers with significant effects were estimated, and the genotypic effect solutions were used to estimate additive and dominance effects, and the proportion of additive genetic variance attributed to each SNP locus. A total of 15 SNPs were associated at least at a suggestive level with FECS, FECN, DAG, IgA, PWM-induced IFN-γ and IL-4, and T-ci-induced IL-10. This study uncovered 52 genes closely related to immune function in proximity to these SNPs. A number of genes encoding C-type lectins and killer cell lectin-like family members were close to a SNP associated with FECN while several genes encoding IL-1 cytokine family members were found to be associated with IgA. Potential candidate genes belonging to or in close proximity with the Major Histocompatibility Complex (MHC) were revealed, including Homeostatic Iron Regulator and butyrophilin coding genes associated with IFN-γ(PWM), and IL-17 coding genes associated with IgA. Due to the importance of the MHC in the control of immune responses, these genes may play an important role in resistance to parasitic infections. Our results reveal a largely complex and polygenic genetic profile of the studied traits in this Scottish Blackface sheep population.</p

    Vaccination with viral vectors expressing NP, M1 and chimeric hemagglutinin induces broad protection against influenza virus challenge in mice

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    Seasonal influenza virus infections cause up to half a million deaths each year, the majority of which are older adults. Annual influenza virus vaccination protects against disease, but in the event of a mismatch between the circulating strain and vaccine strain, vaccine effectiveness is severely impacted. Therefore, there is an urgent need for a vaccine that induces broad protection against drifted seasonal and emerging pandemic influenza viruses. One approach in designing such a universal influenza virus vaccine is based on targeting conserved regions of the influenza virus hemagglutinin (HA), the major glycoprotein on the surface of the virus. Using chimeric hemagglutinin constructs (cHA), the immune system can be primed to produce antibody responses against the conserved immunosubdominant stalk region rather than the variable immunodominant head region. Furthermore, replication deficient viral vectors based on Chimpanzee Adenovirus (ChAdOx1) and Modified Vaccinia Ankara (MVA) virus expressing the influenza virus internal antigens, such as the nucleoprotein (NP) and the matrix protein 1 (M1), are capable of inducing strong influenza specific T cell responses in vaccinated individuals. This is another approach towards a broadly cross-protective influenza vaccine given the degree of conservation of NP and M1 across different influenza virus strains. Here, we combine these two platforms to evaluate the efficacy of a viral vector-based group 2 cHA intramuscular vaccination regime in mice to confer protection against influenza virus challenge of matched and mismatched group 2 strains. We show that vectored vaccines expressing both cHA and an NP-M1 fusion protein, in a prime-boost regimen (with different cHAs given at each vaccination), provide enhanced protection against H3N2 and H10N8 virus challenge when compared to vaccination with cHA alone or NP-M1 alone. The vaccine induced antibody responses against divergent HAs, NP, M1, and whole virus correlated with nature of administered vaccine and extent of protection seen across vaccinated groups. Influenza specific T cell responses were also increased in the vectored vaccines expressing both the cHA and the NP-M1 fusion protein. For further characterization, we are interested in looking at an optimal vaccination regimen, the possibility of an additional boost to induce cross-reactive antibodies, and the nature of the induced antibodies. Overall, these results improve our understanding of vaccination platforms capable of harnessing cellular and humoral immunity with the ultimate goal of designing a universal influenza vaccine

    Bridge distress caused by approach embankment settlement

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    Surtees Bridge, which carries the A66(T) over the River Tees near Thornaby-on-Tees in the UK, has been showing signs of distress that predate its opening in 1981. Subsequent investigations have shown that the bridge distress is related to unexpectedly large settlement of the eastern approach embankment. Recent ground investigations prompted by a proposed widening of the river crossing have produced many new data on the alluvial deposits underlying the site, and explain why embankment settlement was so much larger than originally anticipated. Comparison of the geotechnical parameters obtained from the original and more recent ground investigations suggests that the original investigation significantly underestimated the thickness of an alluvial clay layer underlying the site, and that its coefficient of consolidation was overestimated. Settlement analyses using geotechnical data from the original ground investigations predict moderate embankment settlements occurring principally during construction. Settlement analyses based on all the available data predict far larger embankment settlements occurring over extended time periods. The latter analyses predict an embankment settlement similar to that observed and of sufficient magnitude to cause the observed lateral displacement of the bridge due to lateral loading of its piled foundation

    Association of invasion-promoting tenascin-C additional domains with breast cancers in young women

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    Introduction: Tenascin-C (TNC) is a large extracellular matrix glycoprotein that shows prominent stromal expression in many solid tumours. The profile of isoforms expressed differs between cancers and normal breast, with the two additional domains AD1 and AD2 considered to be tumour associated. The aim of the present study was to investigate expression of AD1 and AD2 in normal, benign and malignant breast tissue to determine their relationship with tumour characteristics and to perform in vitro functional assays to investigate the role of AD1 in tumour cell invasion and growth. Methods: Expression of AD1 and AD2 was related to hypoxanthine phosphoribosyltransferase 1 as a housekeeping gene in breast tissue using quantitative RT-PCR, and the results were related to clinicopathological features of the tumours. Constructs overexpressing an AD1-containing isoform (TNC-14/AD1/16) were transiently transfected into breast carcinoma cell lines (MCF-7, T-47 D, ZR-75-1, MDA-MB-231 and GI-101) to assess the effect in vitro on invasion and growth. Statistical analysis was performed using a nonparametric Mann-Whitney test for comparison of clinicopathological features with levels of TNC expression and using Jonckheere-Terpstra trend analysis for association of expression with tumour grade. Results: Quantitative RT-PCR detected AD1 and AD2 mRNA expression in 34.9% and 23.1% of 134 invasive breast carcinomas, respectively. AD1 mRNA was localised by in situ hybridisation to tumour epithelial cells, and more predominantly to myoepithelium around associated normal breast ducts. Although not tumour specific, AD1 and AD2 expression was significantly more frequent in carcinomas in younger women (age ≤40 years; P < 0.001) and AD1 expression was also associated with oestrogen receptor-negative and grade 3 tumours (P < 0.05). AD1 was found to be incorporated into a tumour-specific isoform, not detected in normal tissues. Overexpression of the TNC-14/AD1/16 isoform significantly enhanced tumour cell invasion (P < 0.01) and growth (P < 0.01) over base levels. Conclusions: Together these data suggest a highly significant association between AD-containing TNC isoforms and breast cancers in younger women (age ≤40 years), which may have important functional significance in vivo

    The Pure Virtual Braid Group Is Quadratic

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    If an augmented algebra K over Q is filtered by powers of its augmentation ideal I, the associated graded algebra grK need not in general be quadratic: although it is generated in degree 1, its relations may not be generated by homogeneous relations of degree 2. In this paper we give a sufficient criterion (called the PVH Criterion) for grK to be quadratic. When K is the group algebra of a group G, quadraticity is known to be equivalent to the existence of a (not necessarily homomorphic) universal finite type invariant for G. Thus the PVH Criterion also implies the existence of such a universal finite type invariant for the group G. We apply the PVH Criterion to the group algebra of the pure virtual braid group (also known as the quasi-triangular group), and show that the corresponding associated graded algebra is quadratic, and hence that these groups have a (not necessarily homomorphic) universal finite type invariant.Comment: 53 pages, 15 figures. Some clarifications added and inaccuracies corrected, reflecting suggestions made by the referee of the published version of the pape

    Comparison of Winter Strawberry Production in a Commercial Heated High Tunnel versus a University Greenhouse

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    For the past 4 years, the University of Nebraska strawberry team has worked to develop low cost, sustainable methods for farmers and growers to produce strawberries in a double polyethylene greenhouse during the winter. This past year, this growing system was adapted to become a commercial grower’s heated high tunnel for the winter/spring of 2013-14. The idea was to scale up to a farm-size demonstration and compare it to the university greenhouse production system with a goal to expand marketing opportunities for strawberries into the winter season

    Factors affecting ewe longevity on sheep farms in three European countries

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    peer-reviewedThe ability to identify ewes that can outperform their contemporaries, in terms of how long they remain productive in the flock, will help towards improving flock efficiency and profitability. The main objectives of this study were to: (1) identify the main reasons for mortality or culling within diverse sheep production systems in Ireland, Norway and UK; (2) investigate the influence of early life factors on ewe longevity within each of these systems; and (3) determine whether common approaches or recommendations could be employed to improve ewe longevity. The main reasons for mortality or culling were, in addition to old age, mastitis (Irish and Norwegian sheep) and tooth loss (UK hill sheep). In each country, there were significant differences in age at last lambing due to the year the ewe was born (but in no consistent pattern), and due to her flock of birth (P < 0.05). From the Norwegian data, there was some indication ewes from younger dams lambed for the last time at a younger age, however, this trend was not seen in the Irish or UK data. Ewes born as singletons, in the Irish data, lambed for the last time at an older age than those that had been born in larger litters, although this was not observed in the other data sets. Age at first lambing and some breed proportions (proportion of Texel and Suffolk particularly) of the animal (both not fitted in the Norwegian or UK analyses) were found to have a highly significant (P < 0.0001) effect on age at last lambing in the Irish analyses. The results suggest that longevity is influenced by a range of different factors and the early life predictors investigated could not be used to provide consistent recommendations across countries, production systems and breeds that would influence ewe longevity. One common definition or solution to select ewes for longer productive life in divergent sheep flocks may not be appropriate.Department for Environment, Food and Rural Affairs, UK Governmen

    Mesoscopic Capacitors: A Statistical Analysis

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    The capacitance of mesoscopic samples depends on their geometry and physical properties, described in terms of characteristic times scales. The resulting ac admittance shows sample to sample fluctuations. Their distribution is studied here -through a random-matrix model- for a chaotic cavity capacitively coupled to a backgate: it is observed from the distribution of scattering time delays for the cavity, which is found analytically for the orthogonal, unitary, and symplectic universality classes, one mode in the lead connecting the cavity to the reservoir and no direct scattering. The results agree with numerical simulations.Comment: 4 pages (Revtex), 4 PS figures. Minor corrections. New e-mail address: [email protected] [email protected] e-mail address: [email protected]
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