Environmental risk factors for canine atopic dermatitis: a retrospective large‐scale study in Labrador and golden retrievers

Background - canine atopic dermatitis (cAD) is one the most common and distressing skin disorders seen in dogs. It is characterised by dysfunction in the skin barrier, with a complex pathogenesis combining both genetic and environmental factors.Objectives - to evaluate associations between environmental factors and case-control status in two closely related, at-risk breeds, the Labrador and Golden retriever.Animals - 2,445 pet dogs, of which 793 were classed as cases (575 Labradors and218 Golden retrievers) and 1,652 as controls (1,120 Labradors and 532 Golden retrievers). Methods – case-control status was assigned based upon owner response to a standardised validated questionnaire. Retrospective data on rearing environment was collected via additional questions. Univariate and multivariate logistic regressions were utilised to evaluate associations between environmental factors and case-control status.Results - risk factors included being reared in an urban environment (not living currently in an urban environment), being male, being neutered, receiving flea control, and being allowed on upholstered furniture. Protective factors included living with other dogs (not cats) and walking in woodlands, fields or beaches. Additionally, amongst Labradors, chocolate coated dogs were at greater risk of having cAD than black or yellow coated dogs.Conclusions and clinical importance - This study is the largest of its kind to date to investigate the role of the environment in canine atopic dermatitis. Although precise triggers are unclear, this study contributes to those of earlier studies to highlight the protective role of a rural environment and highlights some novel associations with disease development

"She's a dog at the end of the day": guide dog owners' perspectives on the behaviour of their guide dog

A guide dog is a domestic dog (Canis familiaris) that is specifically educated to provide mobility support to a blind or visually impaired owner. Current dog suitability assessments focus on behavioural traits, including: trainability, reactivity or attention to environmental stimuli, low aggressiveness, fearfulness and stress behaviour, energy levels, and attachment behaviour. The aim of this study was to find out which aspects of guide dog behaviour are of key importance to guide dog owners themselves. Sixty-three semi-structured interview surveys were carried out with guide dog owners. Topics included the behaviour of their guide dog both within and outside their working role, and also focused on examples of behaviour which might be considered outside a guide dog owner’s typical expectations. Both positive and negative examples and situations were covered. This allowed for the discovery of new perspectives and emerging themes on living and working with a guide dog. Thematic analysis of the results reveals that a dog’s safe behaviour in the face of traffic was the most important positive aspect of a guide dog’s behaviour and pulling or high tension on the lead and /or harness was the most discussed negative aspect. Other aspects of guide dog behaviour were highlighted as particularly pleasing or disappointing by owners including attentiveness to the task, work, environment and owner; confidence in work and decision making (with confident dogs resulting in confident owners) obedience and control; calmness and locating objectives. The results reveal important areas of behaviour that are not currently considered priorities in guide dog assessments; these key areas were consistency of behaviour, the dog’s maturity and the dog’s behaviour in relation to children. The survey revealed a large range in what owners considered problematic or pleasing behaviours and this highlights the heterogeneity in guide dog owners and the potential multifarious roles of the guide dog. This study contributes to the literature on which behaviour is considered appropriate or inappropriate in dogs and on the nature of human-animal interactions

Behavioural Differences in Dogs with Atopic Dermatitis Suggest Stress Could Be a Significant Problem Associated with Chronic Pruritus

Canine atopic dermatitis (cAD) is a common allergic skin condition in dogs that causes chronic pruritus. The overall quality of life in dogs with cAD is known to be reduced, and human patients with pruritic conditions report significant psychological burdens from pruritus-induced stress, and atopic dermatitis is associated with significant psychopathological morbidities. We tested the hypothesis that dogs with cAD would display more problem behaviours that could be indicative of stress than would healthy controls. Behavioural data were gathered directly from owners using a validated dog behaviour questionnaire for 343 dogs with a diagnosis of cAD and 552 healthy controls, and scores were also provided for their dog’s pruritus severity. Regression modelling, controlling for potential confounding variables (age, sex, breed, neuter status or other health problem(s)) showed for the first time that pruritus severity in dogs with cAD was associated with increased frequency of behaviours often considered problematic, such as mounting, chewing, hyperactivity, coprophagia, begging for and stealing food, attention-seeking, excitability, excessive grooming, and reduced trainability. Whilst causality cannot be ascertained from this study, the behaviours that were associated with pruritus severity are redirected, self/environment-directed displacement behaviours, which are often considered indicative of stress. Further investigation is warranted, and stress reduction could be helpful when treating dogs with cAD

GPX-Macrophage Expression Atlas: A database for expression profiles of macrophages challenged with a variety of pro-inflammatory, anti-inflammatory, benign and pathogen insults

BACKGROUND: Macrophages play an integral role in the host immune system, bridging innate and adaptive immunity. As such, they are finely attuned to extracellular and intracellular stimuli and respond by rapidly initiating multiple signalling cascades with diverse effector functions. The macrophage cell is therefore an experimentally and clinically amenable biological system for the mapping of biological pathways. The goal of the macrophage expression atlas is to systematically investigate the pathway biology and interaction network of macrophages challenged with a variety of insults, in particular via infection and activation with key inflammatory mediators. As an important first step towards this we present a single searchable database resource containing high-throughput macrophage gene expression studies. DESCRIPTION: The GPX Macrophage Expression Atlas (GPX-MEA) is an online resource for gene expression based studies of a range of macrophage cell types following treatment with pathogens and immune modulators. GPX-MEA follows the MIAME standard and includes an objective quality score with each experiment. It places special emphasis on rigorously capturing the experimental design and enables the searching of expression data from different microarray experiments. Studies may be queried on the basis of experimental parameters, sample information and quality assessment score. The ability to compare the expression values of individual genes across multiple experiments is provided. In addition, the database offers access to experimental annotation and analysis files and includes experiments and raw data previously unavailable to the research community. CONCLUSION: GPX-MEA is the first example of a quality scored gene expression database focussed on a macrophage cellular system that allows efficient identification of transcriptional patterns. The resource will provide novel insights into the phenotypic response of macrophages to a variety of benign, inflammatory, and pathogen insults. GPX-MEA is available through the GPX website at

Whole blood gene expression profiling of neonates with confirmed bacterial sepsis

peer-reviewedNeonatal infection remains a primary cause of infant morbidity and mortality worldwide and yet our understanding of how human neonates respond to infection remains incomplete. Changes in host gene expression in response to infection may occur in any part of the body, with the continuous interaction between blood and tissues allowing blood cells to act as biosensors for the changes. In this study we have used whole blood transcriptome profiling to systematically identify signatures and the pathway biology underlying the pathogenesis of neonatal infection. Blood samples were collected from neonates at the first clinical signs of suspected sepsis alongside age matched healthy control subjects. Here we report a detailed description of the study design, including clinical data collected, experimental methods used and data analysis workflows and which correspond with data in Gene Expression Omnibus (GEO) data sets (GSE25504). Our data set has allowed identification of a patient invariant 52-gene classifier that predicts bacterial infection with high accuracy and lays the foundation for advancing diagnostic, prognostic and therapeutic strategies for neonatal sepsis

Molecular profiling of the human testis reveals stringent pathway-specific regulation of RNA expression following gonadotropin suppression and progestogen treatment

Gonadotropin withdrawal induces changes in gene expression in all 3 major cell types of the testis. Knowledge of the genes affected, in both the presence and absence of additional progestogen, will give insight into the regulation of human testicular function and aid development of novel contraceptive methods. We have undertaken a whole‐genome analysis of RNA expression in testicular biopsies from normal men and after 4 weeks of gonadotropin suppression induced by gonadotropin‐releasing hormone antagonist plus testosterone administration sufficient to cause marked suppression of spermatogenesis. Microarray analysis shows that interindividual variability is markedly low, and the response to treatment is focused on a small subset of genes particularly related to pathways in steroidogenesis and cholesterol biosynthesis or metabolism, the Leydig cell gene INSL3, and genes involved in early meiosis or Sertoli—germ cell junctions. These changes in expression were confirmed by quantitative reverse transcriptase polymerase chain reaction. No major changes in gene expression were identified in men additionally treated with a progestogen, although FLJ35767, an expressed sequence tag that is expressed in the germ cell compartment, did show a small but significant additional effect of progestogen. Overall, the results of this investigation disclose a remarkably stringent regulation of testicular gene expression, revealing the genes most sensitive to gonadotropin withdrawal, and might reflect the most labile pathways in the regulation of testicular functio

Implementing responsible innovation: the role of the meso-level(s) between project and organisation

Much of academic discussion of responsible innovation (RI) has focused on RI integration into research projects. In addition, significant attention has also been paid to RI structures and policies at the research policy and institutional level. This article reports experiences of RI implementation with a focus on the intermediate i.e. meso-level. The research described here included a series of interviews that aimed to clarify researchers' perspectives on RI as well as barriers to and benefits of RI implementation. Two cases of engagement with research projects, with the aim of promoting RI, were undertaken. The analysis of the data demonstrates the crucial contribution that the meso-level of a research programme can make in interpreting, implementing and perpetuating RI across related activities. The article provides strong evidence that the scholarly debate surrounding RI should pay more explicit attention to this meso-level, ultimately strengthening RI theory and practice

Assessing responsible innovation training

There is broad agreement that one important aspect of responsible innovation (RI) is to provide training on its principles and practices to current and future researchers and innovators, notably including doctoral students. Much less agreement can be observed concerning the question of what this training should consist of, how it should be delivered and how it could be assessed. The increasing institutional embedding of RI leads to calls for the alignment of RI training with training in other subjects. One can therefore observe a push towards the official assessment of RI training, for example in the recent call for proposals for centres for doctoral training by UK Research and Innovation. This editorial article takes its point of departure from the recognition that the RI community will need to react to the call for assessment of RI training. It provides an overview of the background and open questions around RI training and assessment as a background of examples of RI training assessment at doctoral level. There is unlikely to be one right way of assessing RI training across institutions and disciplines, but we expect that the examples provided in this article can help RI scholars and practitioners orient their training and its assessment in ways that are academically viable as well as supportive of the overall aims of RI

A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to identify HFs critical for disease progression and outcome

Social rearing environment influences dog behavioral development

Early life experiences are known to influence behavior later in life. In dogs, environmental influences of early home rearing could be exploited to improve the chances of developing adult behavior most suited to the adult environment. For working dog organizations, such as Guide Dogs, suitable adult behavior is important to ensure that dogs can fulfill their role as guides for people with visual impairment. Here, we test the hypothesis that dogs' home rearing environment will influence behavioral development. To investigate this hypothesis, carers of potential guide dogs (puppy walkers) completed a questionnaire, termed the Puppy Walker Questionnaire (PWQ), about the dog's behavior at 5, 8, and 12 months of age. An additional 11 questions were answered about the home environment at the last assessment. Because no questionnaire existed which measured behavior most relevant to Guide Dogs, questions from an existing questionnaire (Canine Behaviour and Research Questionnaire) were combined with additional questions. Thus, a subsidiary aim of the study was to test the reliability of the PWQ for measuring behavioral development of potential guide dogs. The PWQ, scored on a 100-mm visual analogue scale, grouped into 5 new scales: trainability, distractibility, general anxiety, body sensitivity, and stair anxiety, with 4 Canine Behaviour and Research Questionnaire scales: excitability, separation-related behavior, attachment and attention seeking, and energy level. For each reliable scale, multivariate linear regression identified significant predictors from the home environmental questions. The results suggest that home rearing environment is indeed important for behavioral development: 9 of 11 environmental variables were significant predictors of behavioral scores. Those environmental variables that appeared most important were social in nature. Dogs were scored as higher in energy level, excitability, and distractibility if they had been raised in a home with children, lower on energy level and distractibility the more experience of puppy walking their carer had, and lower on separation-related behavior the more they had been able to play with other dogs. These findings have implications for matching between dogs' early and later home environments. Follow-up of dogs in this study could help to elucidate effects on guiding suitability and matching between dog and guide dog owner