Shelter seeking behaviour of donkeys and horses in a temperate climate

Domestic donkeys descended from wild asses, adapted to the semi-arid climates of Africa, whereas domestic horses originate from more temperate areas of Eurasia. Despite this difference in evolutionary history, modern domestic equids can be found throughout the world, in a wide range of conditions, many of which are very different from their natural environments. To explore the protection from the elements that different equid species may require in the temperate climate of the UK, the shelter seeking behaviour of 135 donkeys and 73 horses was assessed across a period of 16 months, providing a total of 13513 observations. The location of each animal (inside a constructed shelter, outside unprotected or using natural shelter) was recorded alongside measures of environmental conditions including temperature, wind speed, lux, precipitation and level of insect challenge. Statistical models revealed clear differences in the constructed-shelter-seeking behaviour of donkeys and horses. Donkeys sought shelter significantly more often at lower temperatures whereas horses tended to move inside when the temperature rose above 20°C. Donkeys were more affected by precipitation, with the majority of them moving indoors when it rained. Donkeys also showed a higher rate of shelter use when wind speed increased to moderate, while horses remained outside. Horses appeared to be more affected by insect challenge, moving inside as insect harassment outside increased. There were also significant differences in the use of natural shelter by the two species, with donkeys using natural shelter relatively more often to shelter from rain and wind and horses seeking natural shelter relatively more frequently when sunny. These results reflect donkeys’ and horses’ adaptation to different climates and suggest that the shelter requirements of these two equid species differ, with donkeys seeking additional protection from the elements in temperate climates

Weathering the weather: effects of the environment on donkey, mule and horse welfare

It is widely believed that donkeys are less adapted to wet, temperate climates than horses. To date there has been no scientific study assessing the shelter needs of donkeys. Our research addressed this important welfare area through three studies conducted in Devon, UK: (1) a comparison of hair coat properties between horses, mules and donkeys over the four seasons, (2) a behavioural study of shelter use (man-made and natural), and (3) a study of heat loss using infrared thermography. In study 1 hair samples were taken from 42 animals, 18 donkeys, 16 horses and eight mules, in March, June, September and December. The weight, length and width of hair were measured as indicators of the hair coat insulation properties. The donkeys’ coats properties did not differ much across the seasons, unlike the horses’, indicating that donkeys do not grow a winter coat. The donkeys’ coats were significantly lighter, shorter and thinner than that of horses and mules in winter. In study 2 the shelter seeking behaviour of 75 donkeys and 65 horses was observed over a period of 18 months. Results showed that donkeys’ and horses’ behaviour was differentially affected by environmental factors. When it rained there was a 54% increase in the number of donkeys in shelters and only a 14% increase in horses seeking shelter. Most donkeys stayed inside when the temperature was below 10°C and they came outside as temperatures increased. Horses preferred to be outside in temperatures up to 20°C, above which they started to seek shelter. In study 3 we used a thermoimaging camera to take photos of donkeys and horses at different temperatures. In addition to the rate of overall heat loss, the amount of heat lost from specific body areas was assessed (ears, neck, torso, rear and legs). In concordance with the findings of study 1 we found that in cold temperatures donkeys lose more heat than mules and horses, and also that their heat loss is higher through their ears and their rear. These findings provide valuable scientific evidence that can inform future guidelines on the welfare and shelter needs of equines and support the idea that donkeys are less well adapted to temperate climates and may require additional protection from the elements (in the form of man-made shelters) when compared to many horses

A case study investigating the impact of the London 2012 Olympic and Paralympic Games on participation in two non-traditional English sports, Judo and Fencing.

The hosting of the London 2012 Olympic and Paralympic Games (LOPG) brought with it detailed legacy plans aiming to ‘Inspire a Generation’. The idea that hosting a sports mega-event will encourage the host population to engage in more physical activity is commonly used by governments to justify the large investments they make. The aim of this research paper was to investigate the impact that hosting the 2012 Games had on grass-root sports participation within the host nation. This paper focuses on two non-traditional English sports, Fencing and Judo and investigated the changes in mass sports participation. The membership rate analysis of our sample highlighted an overall increase in participation between 2007 and 2013, in both Judo and Fencing. The data gathered from the interviews with the head office staff at the National Governing Bodies (NGBs) and local club coaches suggested that the grass-root participation programmes were the most effective way of increasing participation, rather than the reliance, solely on the inspiration effect from hosting the LOPG itself. The study highlighted the importance of strengthening communication between local voluntary clubs and the NGB, to ensure sports could promote themselves and capitalise on this global sporting phenomenon, which provided unprecedented media coverage and opportunities for these non-traditional sports. This case study provides initial results relating to the effect that a major international multi-sport event can have in the development of non-traditional sports in the host population, in terms of membership variations, participation programmes and organisational dynamics

αEβ7 Integrin Identifies Subsets of Pro-Inflammatory Colonic CD4+ T Lymphocytes in Ulcerative Colitis.

Background and Aims The αEβ7 integrin is crucial for retention of T lymphocytes at mucosal surfaces through its interaction with E-cadherin. Pathogenic or protective functions of these cells during human intestinal inflammation, such as ulcerative colitis [UC], have not previously been defined, with understanding largely derived from animal model data. Defining this phenotype in human samples is important for understanding UC pathogenesis and is of translational importance for therapeutic targeting of αEβ7-E-cadherin interactions. Methods αEβ7+ and αEβ7- colonic T cell localization, inflammatory cytokine production and expression of regulatory T cell-associated markers were evaluated in cohorts of control subjects and patients with active UC by immunohistochemistry, flow cytometry and real-time PCR of FACS-purified cell populations. Results CD4+αEβ7+ T lymphocytes from both healthy controls and UC patients had lower expression of regulatory T cell-associated genes, including FOXP3, IL-10, CTLA-4 and ICOS in comparison with CD4+αEβ7- T lymphocytes. In UC, CD4+αEβ7+ lymphocytes expressed higher levels of IFNγ and TNFα in comparison with CD4+αEβ7- lymphocytes. Additionally the CD4+αEβ7+ subset was enriched for Th17 cells and the recently described Th17/Th1 subset co-expressing both IL-17A and IFNγ, both of which were found at higher frequencies in UC compared to control. Conclusion αEβ7 integrin expression on human colonic CD4+ T cells was associated with increased production of pro-inflammatory Th1, Th17 and Th17/Th1 cytokines, with reduced expression of regulatory T cell-associated markers. These data suggest colonic CD4+αEβ7+ T cells are pro-inflammatory and may play a role in UC pathobiology

Human neutrophil clearance of bacterial pathogens triggers anti-microbial gamma delta T cell responses in early infection

Human blood Vc9/Vd2 T cells, monocytes and neutrophils share a responsiveness toward inflammatory chemokines and are rapidly recruited to sites of infection. Studying their interaction in vitro and relating these findings to in vivo observations in patients may therefore provide crucial insight into inflammatory events. Our present data demonstrate that Vc9/Vd2 T cells provide potent survival signals resulting in neutrophil activation and the release of the neutrophil chemoattractant CXCL8 (IL-8). In turn, Vc9/Vd2 T cells readily respond to neutrophils harboring phagocytosed bacteria, as evidenced by expression of CD69, interferon (IFN)-c and tumor necrosis factor (TNF)-a. This response is dependent on the ability of these bacteria to produce the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), requires cell-cell contact of Vc9/Vd2 T cells with accessory monocytes through lymphocyte function-associated antigen-1 (LFA-1), and results in a TNF-a dependent proliferation of Vc9/Vd2 T cells. The antibiotic fosmidomycin, which targets the HMB-PP biosynthesis pathway, not only has a direct antibacterial effect on most HMB-PP producing bacteria but also possesses rapid anti-inflammatory properties by inhibiting cd T cell responses in vitro. Patients with acute peritoneal-dialysis (PD)-associated bacterial peritonitis – characterized by an excessive influx of neutrophils and monocytes into the peritoneal cavity – show a selective activation of local Vc9/Vd2 T cells by HMB-PP producing but not by HMB-PP deficient bacterial pathogens. The cd T celldriven perpetuation of inflammatory responses during acute peritonitis is associated with elevated peritoneal levels of cd T cells and TNF-a and detrimental clinical outcomes in infections caused by HMB-PP positive microorganisms. Taken together, our findings indicate a direct link between invading pathogens, neutrophils, monocytes and microbe-responsive cd T cells in early infection and suggest novel diagnostic and therapeutic approaches.Martin S. Davey, Chan-Yu Lin, Gareth W. Roberts, Sinéad Heuston, Amanda C. Brown, James A. Chess, Mark A. Toleman, Cormac G.M. Gahan, Colin Hill, Tanya Parish, John D. Williams, Simon J. Davies, David W. Johnson, Nicholas Topley, Bernhard Moser and Matthias Eber

Acute immune signatures and their legacies in severe acute respiratory syndrome coronavirus-2 infected cancer patients

Given the immune system’s importance for cancer surveillance and treatment, we have investigated how it may be affected by SARS-CoV-2 infection of cancer patients. Across some heterogeneity in tumor type, stage, and treatment, virus-exposed solid cancer patients display a dominant impact of SARS-CoV-2, apparent from the resemblance of their immune signatures to those for COVID-19+ non-cancer patients. This is not the case for hematological malignancies, with virus-exposed patients collectively displaying heterogeneous humoral responses, an exhausted T cell phenotype and a high prevalence of prolonged virus shedding. Furthermore, while recovered solid cancer patients’ immunophenotypes resemble those of nonvirus-exposed cancer patients, recovered hematological cancer patients display distinct, lingering immunological legacies. Thus, while solid cancer patients, including those with advanced disease, seem no more at risk of SARS-CoV-2-associated immune dysregulation than the general population, hematological cancer patients show complex immunological consequences of SARS-CoV-2 exposure that might usefully inform their care

Regulator of G-protein signaling 1 critically supports CD8+ TRM cell-mediated intestinal immunity.

Members of the Regulator of G-protein signaling (Rgs) family regulate the extent and timing of G protein signaling by increasing the GTPase activity of Gα protein subunits. The Rgs family member Rgs1 is one of the most up-regulated genes in tissue-resident memory (TRM) T cells when compared to their circulating T cell counterparts. Functionally, Rgs1 preferentially deactivates Gαq, and Gαi protein subunits and can therefore also attenuate chemokine receptor-mediated immune cell trafficking. The impact of Rgs1 expression on tissue-resident T cell generation, their maintenance, and the immunosurveillance of barrier tissues, however, is only incompletely understood. Here we report that Rgs1 expression is readily induced in naïve OT-I T cells in vivo following intestinal infection with Listeria monocytogenes-OVA. In bone marrow chimeras, Rgs1 -/- and Rgs1 +/+ T cells were generally present in comparable frequencies in distinct T cell subsets of the intestinal mucosa, mesenteric lymph nodes, and spleen. After intestinal infection with Listeria monocytogenes-OVA, however, OT-I Rgs1 +/+ T cells outnumbered the co-transferred OT-I Rgs1- /- T cells in the small intestinal mucosa already early after infection. The underrepresentation of the OT-I Rgs1 -/- T cells persisted to become even more pronounced during the memory phase (d30 post-infection). Remarkably, upon intestinal reinfection, mice with intestinal OT-I Rgs1 +/+ TRM cells were able to prevent the systemic dissemination of the pathogen more efficiently than those with OT-I Rgs1 -/- TRM cells. While the underlying mechanisms are not fully elucidated yet, these data thus identify Rgs1 as a critical regulator for the generation and maintenance of tissue-resident CD8+ T cells as a prerequisite for efficient local immunosurveillance in barrier tissues in case of reinfections with potential pathogens

Leveraging the sport participation legacy of the London 2012 Olympics: Senior managers’ perceptions

The purpose of this study was to understand how a sports mega event (SME) was leveraged to try and increase participation, through the investigation of national governing bodies (NGBs) opinions and atti- tudes. Critical realism (CR) was used as a tool to aid understanding of leveraging and legacy conceptualisation, through an empirical investiga- tion. An extensive, mixed method online survey was conducted post London 2012 with senior staff members of NGBs, the main delivery agent chosen to support the participation initiatives associated with the London 2012 Olympics. This research provides valuable findings surrounding the use of CR as a tool to investigate legacy creation, whilst at the same time offering insights to enhance the policy implementation process within the sports development sector. The importance of com- munication, competitive nature of sports system, media, club engage- ment, organisational capacity and monitoring and evaluation were highlighted, which provided useful insights into the multidimensional constructs that can aid future leveraging strategies prior to hosting SMEs

Peripheral blood T-cell signatures from high-resolution immune phenotyping of γδ and αβ T-cells in younger and older subjects in the Berlin Aging Study II

Background Aging and latent infection with Cytomegalovirus (CMV) are thought to be major factors driving the immune system towards immunosenescence, primarily characterized by reduced amounts of naïve T-cells and increased memory T-cells, potentially associated with higher morbidity and mortality. The composition of both major compartments, γδ as well as αβ T-cells, is altered by age and CMV, but detailed knowledge of changes to the γδ subset is currently limited. Results Here, we have surveyed a population of 73 younger (23–35 years) and 144 older (62–85 years) individuals drawn from the Berlin Aging Study II, investigating the distribution of detailed differentiation phenotypes of both γδ and αβ T-cells. Correlation of frequencies and absolute counts of the identified phenotypes with age and the presence of CMV revealed a lower abundance of Vδ2-positive and a higher amount of Vδ1-positive cells. We found higher frequencies of late-differentiated and lower frequencies of early-differentiated cells in the Vδ1+ and Vδ1-Vδ2-, but not in the Vδ2+ populations in elderly CMV-seropositive individuals confirming the association of these Vδ2-negative cells with CMV-immunosurveillance. We identified the highest Vδ1:Vδ2 ratios in the CMV-seropositive elderly. The observed increased CD4:CD8 ratios in the elderly were significantly lower in CMV-seropositive individuals, who also possessed a lower naïve and a larger late-differentiated compartment of CD8+ αβ T-cells, reflecting the consensus in the literature. Conclusions Our findings illustrate in detail the strong influence of CMV on the abundance and differentiation pattern of γδ T-cells as well as αβ T-cells in older and younger people. Mechanisms responsible for the phenotypic alterations in the γδ T-cell compartment, associated both with the presence of CMV and with age require further clarification

NK Cells Promote Th-17 Mediated Corneal Barrier Disruption in Dry Eye

The conjunctiva contains a specialized population of lymphocytes that reside in the epithelium, named intraepithelial lymphocytes (IEL).Here we characterized the IEL population prior to and after experimental desiccating stress (DS) for 5 or 10 days (DS5, DS10) and evaluated the effect of NK depletion on DS. The frequency of IELs in normal murine conjunctiva was CD3(+)CD103(+) (~22%), CD3(+)γδ(+) (~9.6%), CD3(+)NK(+) (2%), CD3(-)NK(+) (~4.4%), CD3(+)CD8α (~0.9%), and CD4 (~0.6%). Systemic depletion of NK cells prior and during DS led to a decrease in the frequency of total and activated DCs, a decrease in T helper-17(+) cells in the cervical lymph nodes and generation of less pathogenic CD4(+)T cells. B6.nude recipient mice of adoptively transferred CD4(+)T cells isolated from NK-depleted DS5 donor mice showed significantly less corneal barrier disruption, lower levels of IL-17A, CCL20 and MMP-3 in the cornea epithelia compared to recipients of control CD4(+)T cells.Taken together, these results show that the NK IELs are involved in the acute immune response to desiccation-induced dry eye by activating DC, which in turn coordinate generation of the pathogenic Th-17 response