684 research outputs found

    Genetic profile of adaptive immune traits and relationships with parasite resistance and productivity in Scottish Blackface sheep

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    Gastrointestinal (GI) parasites cause significant production losses in grazing ruminants which can be mitigated by breeding animals resistant to disease. Lymphocyte cytokine production and parasite-specific Immunoglobulin A (IgA) are adaptive immune traits associated with immunity to GI parasites. To explore the utility of these traits for selective breeding purposes, this study estimated the genetic parameters of the immune traits in sheep and assessed their relationship with disease and productivity traits. Whole blood stimulation assays were performed on 1 040 Scottish Blackface lambs at two months of age in 2016–2017. Blood was stimulated with either pokeweed mitogen (PWM), a non-specific activator of lymphocytes, and Teladorsagia circumcincta (T-ci) larval antigen to activate parasite-specific T lymphocytes. The type of adaptive immune response was determined by quantifying production of cytokines interferon-gamma (IFN-γ), interleukin (IL)-4, and IL-10, which relate to T-helper type (Th) 1, Th2 and regulatory T cell responses, respectively. Serum T-ci specific IgA was also quantified. Heritabilities were estimated for each immune trait by univariate analyses. Genetic and phenotypic correlations were estimated between different immune traits, and between immune traits vs. disease and productivity traits that were recorded at three months of age. Disease phenotypes were expressed as faecal egg counts (FEC) of nematode parasites (Strongyles and Nematodirus), faecal oocyst counts (FOC) of coccidian parasites, and faecal soiling score; production was measured as lamb live weight. Significant genetic variation was observed in all immune response traits. Heritabilities of cytokine production varied from low (0.14 ± 0.06) to very high (0.77 ± 0.09) and were always significantly greater than zero (P < 0.05). IgA heritability was found to be moderate (0.41 ± 0.09). Negative associations previously identified between IFN-γ production and FOC, and IL-4 production and strongyle FEC, were not evident in this study, potentially due to the time-lag between immune and parasitology measures. Instead, a positive genetic correlation was found between FOC and PWM-induced IFN-γ production, while a negative genetic correlation was found between FOC and T-ci induced IL-10. Live weight was negatively genetically correlated with IFN-γ responses. Overall, IFN-γ and IL-4 responses were positively correlated, providing little evidence of cross-regulation of Th1 and Th2 immunity within individual sheep. Furthermore, T-ci specific IgA was highly positively correlated with PWM-induced IL-10, indicating a possible role for this cytokine in IgA production. Our results suggest that while genetic selection for adaptive immune response traits is possible and may be beneficial for parasite control, selection of high IFN-γ responsiveness may negatively affect productivity

    Silicon accumulation suppresses arbuscular mycorrhizal fungal colonisation in the model grass Brachypodium distachyon

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    Purpose Silicon (Si) accumulation by grasses alleviates diverse biotic and abiotic stresses. Despite this important functional role, we have limited understanding of how root microbial symbionts, such as arbuscular mycorrhizal (AM) fungi, affect Si uptake and even less about how Si supply and accumulation affect AM fungal colonisation. Our objective was to determine the nature of this two–way interaction in the model grass, Brachypodium distachyon. Methods We grew B. distachyon with five levels of Si supplementation using wild-type plants and a mutant (Bdlsi1-1) that has little capacity for Si uptake. Half of the plants were colonised by AM fungi; half were free of AM fungi. We measured Si accumulation, AM fungal colonisation, leaf carbon (C), nitrogen (N) and phosphorus (P) concentrations. Results AM fungi did not affect Si accumulation, although small increases occurred when root mass was included as a covariate. Si supplemented soil promoted plant growth and P uptake. Si accumulation suppressed colonisation by AM fungi and C concentrations in wild type but not in Bdlsi1-1 plants. Si concentrations were negatively correlated with C and N concentrations, with correlations being stronger in wild-type plants than Bdlsi1-1 plants. Conclusions Our results indicate that Si accumulation in the plant, rather than Si availability in the soil, underpinned reduced AMF colonisation. We propose that Si accumulation is unlikely to be impacted by AM fungi in plants with inherently high Si accumulation, but Si accumulation may suppress AM fungal colonisation in such plants

    Measuring Health and Broader Well-Being Benefits in the Context of Opiate Dependence: The Psychometric Performance of the ICECAP-A and the EQ-5D-5L

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    BACKGROUND: Measuring outcomes in economic evaluations of social care interventions is challenging because both health and well-being benefits are evident. The ICEpop CAPability instrument for adults (ICECAP-A) and the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) are measures potentially suitable for the economic evaluation of treatments for substance use disorders. Evidence for their validity in this context is, however, lacking. OBJECTIVES: To assess the construct validity of the ICECAP-A and the EQ-5D-5L in terms of convergent and discriminative validity and sensitivity to change on the basis of standard clinical measures (Clinical Outcomes in Routine Evaluation-Outcome Measure, Treatment Outcomes Profile, Interpersonal Support Evaluation List, Leeds Dependence Questionnaire, and Social Satisfaction Questionnaire). METHODS: A secondary analysis of pilot trial data for heroin users in opiate substitution treatment was conducted. Baseline convergence with clinical measures was assessed using the Pearson correlation coefficient. Discriminative validity was assessed using one-way analysis of variance and stepwise regressions. Sensitivity to changes in clinical indicators was assessed at 3 and 12 months using the standardized response mean statistic and parametric and nonparametric testing. RESULTS: Both measures had the same level of construct validity, except for clinical indicators of well-being, for which the ICECAP-A performed better. The ICECAP-A was sensitive to changes in both health and well-being indicators. The EQ-5D-5L had lower levels of sensitivity to change, and a ceiling effect (27%), particularly evident in the dimensions of self-care (89%), mobility (75%), and usual activities (72%). CONCLUSIONS: The findings support the construct validity of both measures, but the ICECAP-A gives more attention to broader impacts and is more sensitive to change. The ICECAP-A shows promise in evaluating treatments for substance use disorders for which recovery is the desired outcome

    Light echoes reveal an unexpectedly cool Eta Carinae during its 19th-century Great Eruption

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    Eta Carinae (Eta Car) is one of the most massive binary stars in the Milky Way. It became the second-brightest star in the sky during its mid-19th century "Great Eruption," but then faded from view (with only naked-eye estimates of brightness). Its eruption is unique among known astronomical transients in that it exceeded the Eddington luminosity limit for 10 years. Because it is only 2.3 kpc away, spatially resolved studies of the nebula have constrained the ejected mass and velocity, indicating that in its 19th century eruption, Eta Car ejected more than 10 M_solar in an event that had 10% of the energy of a typical core-collapse supernova without destroying the star. Here we report the discovery of light echoes of Eta Carinae which appear to be from the 1838-1858 Great Eruption. Spectra of these light echoes show only absorption lines, which are blueshifted by -210 km/s, in good agreement with predicted expansion speeds. The light-echo spectra correlate best with those of G2-G5 supergiant spectra, which have effective temperatures of ~5000 K. In contrast to the class of extragalactic outbursts assumed to be analogs of Eta Car's Great Eruption, the effective temperature of its outburst is significantly cooler than allowed by standard opaque wind models. This indicates that other physical mechanisms like an energetic blast wave may have triggered and influenced the eruption.Comment: Accepted for publication by Nature; 4 pages, 4 figures, SI: 6 pages, 3 figures, 5 table

    The effect of Psoroptes ovis infestation on ovine epidermal barrier function

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    Sheep scab is an intensively pruritic, exudative and allergic dermatitis of sheep caused by the ectoparasitic mite Psoroptes ovis. The purpose of the present study was to investigate the effect of P. ovis infestation on different components of the ovine epidermal barrier within the first 24 hours post-infestation (hpi). To achieve this, the expression of epidermal differentiation complex (EDC) genes and epidermal barrier proteins, the nature and severity of epidermal pathology and transepidermal water loss (TEWL) were evaluated. By 1 hpi a significant dermal polymorphonuclear infiltrate and a significant increase in TEWL with maximal mean TEWL (598.67 g/m(2)h) were observed. Epidermal pathology involving intra-epidermal pustulation, loss of epidermal architecture and damage to the basement membrane was seen by 3 hpi. Filaggrin and loricrin protein levels in the stratum corneum declined significantly in the first 24 hpi and qPCR validation confirmed the decrease in expression of the key EDC genes involucrin, filaggrin and loricrin observed by microarray analysis, with 5.8-fold, 4.5-fold and 80-fold decreases, respectively by 24 hpi. The present study has demonstrated that early P. ovis infestation disrupts the ovine epidermal barrier causing significant alterations in the expression of critical barrier components, epidermal pathology, and TEWL. Many of these features have also been documented in human and canine atopic dermatitis suggesting that sheep scab may provide a model for the elucidation of events occurring in the early phases of atopic sensitisation

    Long-Term Optical Monitoring of Eta Carinae. Multiband light curves for a complete orbital period

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    The periodicity of 5.5 years for some observational events occurring in Eta Carinae manifests itself across a large wavelength range and has been associated with its binary nature. These events are supposed to occur when the binary components are close to periastron. To detect the previous periastron passage of Eta Car in 2003, we started an intensive, ground-based, optical, photometric observing campaign. We continued observing the object to monitor its photometric behavior and variability across the entire orbital cycle. Our observation program consisted of daily differential photometry from CCD images, which were acquired using a 0.8 m telescope and a standard BVRI filter set at La Plata Observatory. The photometry includes the central object and the surrounding Homunculus nebula. We present up-to-date results of our observing program, including homogeneous photometric data collected between 2003 and 2008. Our observations demonstrated that Eta Car has continued increasing in brightness at a constant rate since 1998. In 2006, it reached its brightest magnitude (V ~ 4.7) since about 1860s. The object then suddenly reverted its brightening trend, fading to V = 5.0 at the beginning of 2007, and has maintained a quite steady state since then. We continue the photometric monitoring of Eta Car in anticipation of the next "periastron passage", predicted to occur at the beginning of 2009.Comment: Accepted by A&A. The paper contains 3 figures and 2 table

    Designed switch from covalent to non-covalent inhibitors of carboxylesterase Notum activity

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    N-Acyl indolines 4 are potent, non-covalent Notum inhibitors developed from a covalent virtual screening hit 2a. The lead compounds were simple to synthesise, achieved excellent potency in a biochemical Notum-OPTS assay and restored Wnt signalling in a cell-based TCF/LEF reporter assay. Multiple high resolution X-ray structures established a common binding mode of these inhibitors with the indoline bound centred in the palmiteolate pocket with key interactions being aromatic stacking and a water mediated hydrogen bond to the oxyanion hole. These N-acyl indolines 4 will be useful tools for use in vitro studies to investigate the role of Notum in disease models, especially when paired with a structurally related covalent inhibitor (e.g. 4w and 2a). Overall, this study highlights the designed switch from covalent to non-covalent Notum inhibitors and so illustrates a complementary approach for hit generation and target inhibition

    The Chandra X-ray Survey of Planetary Nebulae (ChanPlaNS): Probing Binarity, Magnetic Fields, and Wind Collisions

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    We present an overview of the initial results from the Chandra Planetary Nebula Survey (ChanPlaNS), the first systematic (volume-limited) Chandra X-ray Observatory survey of planetary nebulae (PNe) in the solar neighborhood. The first phase of ChanPlaNS targeted 21 mostly high-excitation PNe within ~1.5 kpc of Earth, yielding 4 detections of diffuse X-ray emission and 9 detections of X-ray-luminous point sources at the central stars (CSPNe) of these objects. Combining these results with those obtained from Chandra archival data for all (14) other PNe within ~1.5 kpc that have been observed to date, we find an overall X-ray detection rate of ~70%. Roughly 50% of the PNe observed by Chandra harbor X-ray-luminous CSPNe, while soft, diffuse X-ray emission tracing shocks formed by energetic wind collisions is detected in ~30%; five objects display both diffuse and point-like emission components. The presence of X-ray sources appears correlated with PN density structure, in that molecule-poor, elliptical nebulae are more likely to display X-ray emission (either point-like or diffuse) than molecule-rich, bipolar or Ring-like nebulae. All but one of the X-ray point sources detected at CSPNe display X-ray spectra that are harder than expected from hot (~100 kK) central star photospheres, possibly indicating a high frequency of binary companions to CSPNe. Other potential explanations include self-shocking winds or PN mass fallback. Most PNe detected as diffuse X-ray sources are elliptical nebulae that display a nested shell/halo structure and bright ansae; the diffuse X-ray emission regions are confined within inner, sharp-rimmed shells. All sample PNe that display diffuse X-ray emission have inner shell dynamical ages <~5x10^3 yr, placing firm constraints on the timescale for strong shocks due to wind interactions in PNe.Comment: 41 pages, 6 figures; submitted to the Astronomical Journa
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