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

Activation of a Translocated Human c-\u3ci\u3emyc\u3c/i\u3e Gene by an Enhancer in the Immunoglobulin Heavy-Chain Locus

A tissue-specific transcriptional enhancer element that is associated with the human immunoglobulin heavy-chain locus is defined. In a non-Hodgkin’s lymphoma that contains a translocated c-myc gene this enhancer is retained on the 14q+ chromosome and occurs within sequences shown to activate previously cryptic promoters of the c-myc gene

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

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

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

Human γδ T cells recognize CD1b by two distinct mechanisms

γδ T cells form an abundant part of the human cellular immune system, where they respond to tissue damage, infection, and cancer. The spectrum of known molecular targets recognized by Vδ1-expressing γδ T cells is becoming increasingly diverse. Here we describe human γδ T cells that recognize CD1b, a lipid antigen-presenting molecule, which is inducibly expressed on monocytes and dendritic cells. Using CD1b tetramers to study multiple donors, we found that many CD1b-specific γδ T cells use Vδ1. Despite their common use of Vδ1, three CD1b-specific γδ T cell receptors (TCRs) showed clear differences in the surface of CD1b recognized, the requirement for lipid antigens, and corecognition of butryophilin-like proteins. Several Vγ segments were present among the CD1b-specific TCRs, but chain swap experiments demonstrated that CD1b specificity was mediated by the Vδ1 chain. One of the CD1b-specific Vδ1+ TCRs paired with Vγ4 and shows dual reactivity to CD1b and butyrophilin-like proteins. αβ TCRs typically recognize the peptide display platform of MHC proteins. In contrast, our results demonstrate the use of rearranged receptors to mediate diverse modes of recognition across the surface of CD1b in ways that do and do not require carried lipids

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

β2 integrins differentially regulate γδ T cell subset thymic development and peripheral maintenance

The γδ T cells reside predominantly at barrier sites and play essential roles in immune protection against infection and cancer. Despite recent advances in the development of γδ T cell immunotherapy, our understanding of the basic biology of these cells, including how their numbers are regulated in vivo, remains poor. This is particularly true for tissue-resident γδ T cells. We have identified the β2 family of integrins as regulators of γδ T cells. β2-integrin–deficient mice displayed a striking increase in numbers of IL-17–producing Vγ6Vδ1+ γδ T cells in the lungs, uterus, and circulation. Thymic development of this population was normal. However, single-cell RNA sequencing revealed the enrichment of genes associated with T cell survival and proliferation specifically in β2-integrin–deficient IL-17+ cells compared to their wild-type counterparts. Indeed, β2-integrin–deficient Vγ6+ cells from the lungs showed reduced apoptosis ex vivo, suggesting that increased survival contributes to the accumulation of these cells in β2-integrin–deficient tissues. Furthermore, our data revealed an unexpected role for β2 integrins in promoting the thymic development of the IFNγ-producing CD27+ Vγ4+ γδ T cell subset. Together, our data reveal that β2 integrins are important regulators of γδ T cell homeostasis, inhibiting the survival of IL-17–producing Vγ6Vδ1+ cells and promoting the thymic development of the IFNγ-producing Vγ4+ subset. Our study introduces unprecedented mechanisms of control for γδ T cell subsets

Autoantibody Repertoire in APECED Patients Targets Two Distinct Subgroups of Protiens

High titer autoantibodies produced by B lymphocytes are clinically important features of many common autoimmune diseases. APECED patients with deficient autoimmune regulator (AIRE) gene collectively display a broad repertoire of high titer autoantibodies, including some which are pathognomonic for major autoimmune diseases. AIRE deficiency severely reduces thymic expression of gene-products ordinarily restricted to discrete peripheral tissues, and developing T cells reactive to those gene-products are not inactivated during their development. However, the extent of the autoantibody repertoire in APECED and its relation to thymic expression of self-antigens are unclear. We here undertook a broad protein array approach to assess autoantibody repertoire in APECED patients. Our results show that in addition to shared autoantigen reactivities, APECED patients display high inter-individual variation in their autoantigen profiles, which collectively are enriched in evolutionarily conserved, cytosolic and nuclear phosphoproteins. The APECED autoantigens have two major origins; proteins expressed in thymic medullary epithelial cells and proteins expressed in lymphoid cells. These findings support the hypothesis that specific protein properties strongly contribute to the etiology of B cell autoimmunity.Peer reviewe