Genetic variation among lambs in peripheral IgE activity against the larval stages of <i>Teladorsagia circumcincta</i>

IgA and IgE activity against Teladorsagia circumcincta was investigated in a flock of Texel lambs following natural, mixed nematode infection among lambs. The distribution of IgA activity was similar to a gamma distribution whereas IgE activity was different. Box-Cox analysis demonstrated that X0.25 was a suitable transformation to normalise IgE responses. The transformed IgE activity was under moderate to strong genetic control. Nine different allergens were identified by proteomic analysis. Tropomyosin was selected for further analysis. IgE activity against tropomyosin was moderately heritable and associated with decreased egg counts and with reduced body weight at the time of sampling

Clouds, shadows, or twilight? Mayfly nymphs recognise the difference

1. We examined the relative changes in light intensity that initiate night-time locomotor activity changes in nymphs of the mayfly, Stenonema modestum (Heptageniidae). Tests were carried out in a laboratory stream to examine the hypothesis that nymphs increase their locomotion in response to the large and sustained reductions in relative light intensity that take place during twilight but not to short-term daytime light fluctuations or a minimum light intensity threshold. Ambient light intensity was reduced over a range of values representative of evening twilight. Light was reduced over the same range of intensities either continuously or in discrete intervals while at the same time nymph activity on unglazed tile substrata was video recorded. 2. Nymphs increased their locomotor activity during darkness in response to large, sustained relative light decreases, but not in response to short-term, interrupted periods of light decrease. Nymphs did not recognise darkness unless an adequate light stimulus, such as large and sustained relative decrease in light intensity, had taken place. 3. We show that nymphs perceive light change over time and respond only after a lengthy period of accumulation of light stimulus. The response is much lengthier than reported for other aquatic organisms and is highly adaptive to heterogeneous stream environments

Development and external validation study of a melanoma risk prediction model incorporating clinically assessed naevi and solar lentigines

Background: Melanoma risk prediction models could be useful for matching preventive interventions to patients’ risk. Objectives: To develop and validate a model for incident first‐primary cutaneous melanoma using clinically assessed risk factors. Methods: We used unconditional logistic regression with backward selection from the Australian Melanoma Family Study (461 cases and 329 controls) in which age, sex and city of recruitment were kept in each step, and we externally validated it using the Leeds Melanoma Case–Control Study (960 cases and 513 controls). Candidate predictors included clinically assessed whole‐body naevi and solar lentigines, and self‐assessed pigmentation phenotype, sun exposure, family history and history of keratinocyte cancer. We evaluated the predictive strength and discrimination of the model risk factors using odds per age‐ and sex‐adjusted SD (OPERA) and the area under curve (AUC), and calibration using the Hosmer–Lemeshow test. Results: The final model included the number of naevi ≥ 2 mm in diameter on the whole body, solar lentigines on the upper back (a six‐level scale), hair colour at age 18 years and personal history of keratinocyte cancer. Naevi was the strongest risk factor; the OPERA was 3·51 [95% confidence interval (CI) 2·71–4·54] in the Australian study and 2·56 (95% CI 2·23–2·95) in the Leeds study. The AUC was 0·79 (95% CI 0·76–0·83) in the Australian study and 0·73 (95% CI 0·70–0·75) in the Leeds study. The Hosmer–Lemeshow test P‐value was 0·30 in the Australian study and < 0·001 in the Leeds study. Conclusions: This model had good discrimination and could be used by clinicians to stratify patients by melanoma risk for the targeting of preventive interventions. What's already known about this topic? Melanoma risk prediction models may be useful in prevention by tailoring interventions to personalized risk levels. For reasons of feasibility, time and cost many melanoma prediction models use self‐assessed risk factors. However, individuals tend to underestimate their naevus numbers. What does this study add? We present a melanoma risk prediction model, which includes clinically‐assessed whole‐body naevi and solar lentigines, and self‐assessed risk factors including pigmentation phenotype and history of keratinocyte cancer. This model performs well on discrimination, the model's ability to distinguish between individuals with and without melanoma, and may assist clinicians to stratify patients by melanoma risk for targeted preventive interventions

Predictive ability of logistic regression, auto-logistic regression and neural network models in empirical land-use change modeling: a case study

The objective of this study is to compare the abilities of logistic, auto-logistic and artificial neural network (ANN) models for quantifying the relationships between land uses and their drivers. In addition, the application of the results obtained by the three techniques is tested in a dynamic land-use change model (CLUE-s) for the Paochiao watershed region in Taiwan. Relative operating characteristic curves (ROCs), kappa statistics, multiple resolution validation and landscape metrics were used to assess the ability of the three techniques in estimating the relationship between driving factors and land use and its subsequent application in land-use change models. The validation results illustrate that for this case study ANNs constitute a powerful alternative for the use of logistic regression in empirical modeling of spatial land-use change processes. ANNs provide in this case a better fit between driving factors and land-use pattern. In addition, auto-logistic regression performs better than logistic regression and nearly as well as ANNs. Auto-logistic regression and ANNs are considered especially useful when the performance of more conventional models is not satisfactory or the underlying data relationships are unknown. The results indicate that an evaluation of alternative techniques to specify relationships between driving factors and land use can improve the performance of land-use change models

Hydrodynamics of Spatially Ordered Superfluids

We derive the hydrodynamic equations for the supersolid and superhexatic phases of a neutral two-dimensional Bose fluid. We find, assuming that the normal part of the fluid is clamped to an underlying substrate, that both phases can sustain third-sound modes and that in the supersolid phase there are additional modes due to the superfluid motion of point defects (vacancies and interstitials).Comment: 24 pages of ReVTeX and 7 uuencoded figures. Submitted for publication in Phys. Rev.

Self-consistent calculation of total energies of the electron gas using many-body perturbation theory

The performance of many-body perturbation theory for calculating ground-state properties is investigated. We present fully numerical results for the electron gas in three and two dimensions in the framework of the GW approximation. The overall agreement with very accurate Monte Carlo data is excellent, even for those ranges of densities for which the GW approach is often supposed to be unsuitable. The latter seems to be due to the fulfillment of general conservation rules. These results open further prospects for accurate calculations of ground-state properties circumventing the limitations of standard density-functional theory

Evidence for a narrow dip structure at 1.9 GeV/c2^2 in 3π+3π−3\pi^+ 3\pi^- diffractive photoproduction

A narrow dip structure has been observed at 1.9 GeV/c$^2$ in a study of diffractive photoproduction of the $~3\pi^+3\pi^-$ final state performed by the Fermilab experiment E687.Comment: The data of Figure 6 can be obtained by downloading the raw data file e687_6pi.txt. v5 (2nov2018): added Fig. 7, the 6 pion energy distribution as requested by a reade

Density functional theories and self-energy approaches

A purpose-designed microarray platform (Stressgenes, Phase 1) was utilised to investigate the changes in gene expression within the liver of rainbow trout during exposure to a prolonged period of confinement. Tissue and blood samples were collected from trout at intervals up to 648 h after transfer to a standardised confinement stressor, together with matched samples from undisturbed control fish. Plasma ACTH, cortisol, glucose and lactate were analysed to confirm that the neuroendocrine response to confinement was consistent with previous findings and to provide a phenotypic context to assist interpretation of gene expression data. Liver samples for suppression subtractive hybridisation (SSH) library construction were selected from within the experimental groups comprising “early” stress (2–48 h) and “late” stress (96–504 h). In order to reduce redundancy within the four SSH libraries and yield a higher number of unique clones an additional subtraction was carried out. After printing of the arrays a series of 55 hybridisations were executed to cover 6 time points. At 2 h, 6 h, 24 h, 168 h and 504 h 5 individual confined fish and 5 individual control fish were used with control fish only at 0 h. A preliminary list of 314 clones considered differentially regulated over the complete time course was generated by a combination of data analysis approaches and the most significant gene expression changes were found to occur during the 24 h to 168 h time period with a general approach to control levels by 504 h. Few changes in expression were apparent over the first 6 h. The list of genes whose expression was significantly altered comprised predominantly genes belonging to the biological process category (response to stimulus) and one cellular component category (extracellular region) and were dominated by so-called acute phase proteins. Analysis of the gene expression profile in liver tissue during confinement revealed a number of significant clusters. The major patterns comprised genes that were up-regulated at 24 h and beyond, the primary examples being haptoglobin, β-fibrinogen and EST10729. Two representative genes from each of the six k-means clusters were validated by qPCR. Correlations between microarray and qPCR expression patterns were significant for most of the genes tested. qPCR analysis revealed that haptoglobin expression was up-regulated approximately 8-fold at 24 h and over 13-fold by 168 h.This project was part funded by the European Commission (Q5RS-2001-02211), Enterprise Ireland and the Natural Environment Research Council of the United Kingdom

Compound heterozygous variants in NBAS as a cause of atypical osteogenesis imperfecta

Background Osteogenesis imperfecta (OI), the commonest inherited bone fragility disorder, affects 1 in 15,000 live births resulting in frequent fractures and reduced mobility, with significant impact on quality of life. Early diagnosis is important, as therapeutic advances can lead to improved clinical outcome and patient benefit. Report Whole exome sequencing in patients with OI identified, in two patients with a multi-system phenotype, compound heterozygous variants in NBAS (neuroblastoma amplified sequence). Patient 1: NBAS c.5741G > A p.(Arg1914His); c.3010C > T p.(Arg1004*) in a 10-year old boy with significant short stature, bone fragility requiring treatment with bisphosphonates, developmental delay and immunodeficiency. Patient 2: NBAS c.5741G > A p.(Arg1914His); c.2032C > T p.(Gln678*) in a 5-year old boy with similar presenting features, bone fragility, mild developmental delay, abnormal liver function tests and immunodeficiency. Discussion Homozygous missense NBAS variants cause SOPH syndrome (short stature; optic atrophy; Pelger-Huet anomaly), the same missense variant was found in our patients on one allele and a nonsense variant in the other allele. Recent literature suggests a multi-system phenotype. In this study, patient fibroblasts have shown reduced collagen expression, compared to control cells and RNAseq studies, in bone cells show that NBAS is expressed in osteoblasts and osteocytes of rodents and primates. These findings provide proof-of-concept that NBAS mutations have mechanistic effects in bone, and that NBAS variants are a novel cause of bone fragility, which is distinguishable from ‘Classical’ OI. Conclusions Here we report on variants in NBAS, as a cause of bone fragility in humans, and expand the phenotypic spectrum associated with NBAS. We explore the mechanism underlying NBAS and the striking skeletal phenotype in our patients