Increased lytic efficiency of bovine macrophages trained with killed mycobacteria

Innate immunity is evolutionarily conserved in multicellular organisms and was considered to lack memory until very recently. One of its more characteristic mechanisms is phagocytosis, the ability of cells to engulf, process and eventually destroy any injuring agent. We report the results of an ex vivo experiment in bovine macrophages in which improved clearance of Mycobacterium bovis (M. bovis) was induced by pre-exposure to a heat killed M. bovis preparation. The effects were independent of humoral and cellular adaptive immune responses and lasted up to six months. Specifically, our results demonstrate the existence of a training effect in the lytic phase of phagocytosis that can be activated by killed mycobacteria, thus suggesting a new mechanism of vaccine protection. These findings are compatible with the recently proposed concept of trained immunity, which was developed to explain the observation that innate immune responses provide unspecific protection against pathogens including other than those that originally triggered the immune response.Funding for these studies was provided by the EU project WildTBVac (Contract #613799) and by grants from the Instituto Nacional de Investigación y Tecnología Agraria y alimentaria (INIA, RTA2011-00049) and the Ministry of Science (MINECO, AGL2014-56305) and European Funds Regional Development (FEDER).Peer Reviewe

A Pair of Dopamine Neurons Target the D1-Like Dopamine Receptor DopR in the Central Complex to Promote Ethanol-Stimulated Locomotion in Drosophila

Dopamine is a mediator of the stimulant properties of drugs of abuse, including ethanol, in mammals and in the fruit fly Drosophila. The neural substrates for the stimulant actions of ethanol in flies are not known. We show that a subset of dopamine neurons and their targets, through the action of the D1-like dopamine receptor DopR, promote locomotor activation in response to acute ethanol exposure. A bilateral pair of dopaminergic neurons in the fly brain mediates the enhanced locomotor activity induced by ethanol exposure, and promotes locomotion when directly activated. These neurons project to the central complex ellipsoid body, a structure implicated in regulating motor behaviors. Ellipsoid body neurons are required for ethanol-induced locomotor activity and they express DopR. Elimination of DopR blunts the locomotor activating effects of ethanol, and this behavior can be restored by selective expression of DopR in the ellipsoid body. These data tie the activity of defined dopamine neurons to D1-like DopR-expressing neurons to form a neural circuit that governs acute responding to ethanol

Gendered performances in sport: an embodied approach

Despite significant advances in recent years, gender inequalities remain apparent within the context of sport participation and engagement. One of the problems, however, when addressing gender issues in sport is the continued assumption by many sport practitioners that the experiences of women and men will always be different because of perceived physiological characteristics. Adopting a focus based solely upon perceived gendered differences often overlooks the importance of recognising individual experience and the prevailing social influences that impact upon participation, such as age, class, race and ability. An embodied approach, as well as seeking to move beyond mind/body dualisms, incorporates the physiological with the social and psychological. Therefore, it is suggested that while considerations of gender remain important, they need to be interpreted alongside other interconnecting and influential (at varying times and occasions) social and physical factors. It is argued that taking the body as a starting point opens up more possibilities to manoeuvre through the mine field that is gender and sport participation. The appeal of an embodied approach to the study of gender and sport is in its accommodation of a wider multi-disciplinary lens. Particularly, by acknowledging the subjective, corporeal, lived experiences of sport engagement, an embodied approach offers a more flexible starting point to negotiate the theoretical and methodological challenges created by restrictive discourses of difference

Natural Regulatory T Cells in Malaria: Host or Parasite Allies?

Plasmodium falciparum malaria causes 500 million clinical cases with approximately one million deaths each year. After many years of exposure, individuals living in endemic areas develop a form of clinical immunity to disease known as premunition, which is characterised by low parasite burdens rather than sterilising immunity. The reason why malaria parasites persist under a state of premunition is unknown but it has been suggested that suppression of protective immunity might be a mechanism leading to parasite persistence. Although acquired immunity limits the clinical impact of infection and provides protection against parasite replication, experimental evidence indicates that cell-mediated immune responses also result in detrimental inflammation and contribute to the aetiology of severe disease. Thus, an appropriate regulatory balance between protective immune responses and immune-mediated pathology is required for a favourable outcome of infection. As natural regulatory T (Treg) cells are identified as an immunosuppressive lineage able to modulate the magnitude of effector responses, several studies have investigated whether this cell population plays a role in balancing protective immunity and pathogenesis during malaria. The main findings to date are summarised in this review and the implication for the induction of pathogenesis and immunity to malaria is discussed

The developmental impact of prenatal stress, prenatal dexamethasone and postnatal social stress on physiology, behaviour and neuroanatomy of primate offspring: studies in rhesus macaque and common marmoset

RATIONALE: Exposure of the immature mammalian brain to stress factors, including stress levels of glucocorticoids, either prenatally or postnatally, is regarded as a major regulatory factor in short- and long-term brain function and, in human, as a major aetiological factor in neuropsychiatric disorders. Experimental human studies are not feasible and animal studies are required to demonstrate causality and elucidate mechanisms. A number of studies have been conducted and reviewed in rodents but there are relatively few studies in primates. OBJECTIVES: Here we present an overview of our published studies and some original data on the effects of: (1) prenatal stress on hypothalamic-pituitary-adrenal (HPA) re/activity and hippocampus neuroanatomy in juvenile-adolescent rhesus macaques; (2) prenatal dexamethasone (DEX) on HPA activity, behaviour and prefrontal cortex neuroanatomy in infant-adolescent common marmosets; (3) postnatal daily parental separation stress on HPA re/activity, behaviour, sleep and hippocampus and prefrontal cortex neuroanatomy in infant-adolescent common marmoset. RESULTS: Prenatal stress increased basal cortisol levels and reduced neurogenesis in macaque. Prenatal DEX was without effect on HPA activity and reduced social play and skilled motor behaviour in marmoset. Postnatal social stress increased basal cortisol levels, reduced social play, increased awakening and reduced hippocampal glucocorticoid and mineralocorticoid receptor expression in marmoset. CONCLUSIONS: Perinatal stress-related environmental events exert short- and long-term effects on HPA function, behaviour and brain status in rhesus macaque and common marmoset. The mechanisms mediating the enduring effects remain to be elucidated, with candidates including increased basal HPA function and epigenetic programming

Buffering and the evolution of chromosome-wide gene regulation

Copy number variation (CNV) in terms of aneuploidies of both entire chromosomes and chromosomal segments is an important evolutionary driving force, but it is inevitably accompanied by potentially problematic variations in gene doses and genomic instability. Thus, a delicate balance must be maintained between mechanisms that compensate for variations in gene doses (and thus allow such genomic variability) and selection against destabilizing CNVs. In Drosophila, three known compensatory mechanisms have evolved: a general segmental aneuploidy-buffering system and two chromosome-specific systems. The two chromosome-specific systems are the male-specific lethal complex, which is important for dosage compensation of the male X chromosome, and Painting of fourth, which stimulates expression of the fourth chromosome. In this review, we discuss the origin and function of buffering and compensation using Drosophila as a model

Associations between social support, mental wellbeing, self-efficacy and technology use in first-time antenatal women: data from the BaBBLeS cohort study

Background: Information and communication technologies are used increasingly to facilitate social networks and support women during the perinatal period. This paper presents data on how technology use affects the association between women’s social support and, (i) mental wellbeing and, (ii) self-efficacy in the antenatal period. Methods: Data were collected as part of an ongoing study - the BaBBLeS study - exploring the effect of a pregnancy and maternity software application (app) on maternal wellbeing and self-efficacy. Between September 2016 and February 2017, we aimed to recruit first-time pregnant women at 12–16 gestation weeks in five maternity sites across England and asked them to complete questionnaires. Outcomes included maternal mental wellbeing (Warwick-Edinburgh Mental Wellbeing Scale), and antenatal self-efficacy (antenatal version of the Tool to Measure Parenting Self-Efficacy). Other variables assessed were perceived social support (Multidimensional Scale of Perceived Social Support), general technology use (adapted from Media and Technology Usage and Attitudes Scale). Potential confounders were age, ethnicity, education, socioeconomic deprivation, employment, relationship status and recruitment site. Linear regression models were developed to analyse the relationship between social support and the outcomes. Results: Participants (n = 492, median age = 28 years) were predominantly white British (64.6%). Half of them had a degree or higher degree (49.3%), most were married/living with a partner (83.6%) and employed (86.2%). Median (LQ-UQ) overall scores were 81.0 (74.0–84.0) for social support (range 12–84), 5.1 (4.7–5.4) for technology use (range 1–6), 54.0 (48.0–60.0) for mental well-being (range 14–70), and 319.0 (295.5–340) for self-efficacy (range 0–360). Social support was significantly associated with antenatal mental well-being adjusting for confounders [adj R2 = 0.13, p < .001]. The addition of technology use did not alter this model [adj R2 = 0.13, p < .001]. Social support was also significantly associated with self-efficacy after adjustment [adj R2 = 0.14, p < .001]; technology had limited impact on this association [adj R2 = 0.13, p < .001]. Conclusions: Social support is associated with mental well-being and self-efficacy in antenatal first-time mothers. This association was not significantly affected by general technology use as measured in our survey. Future work should investigate whether pregnancy-specific technologies yield greater potential to enhance the perceived social support, wellbeing and self-efficacy of antenatal women

Diving into the vertical dimension of elasmobranch movement ecology

This is the final version. Available on open access from the American Association for the Advancement of Science via the DOI in this recordData and materials availability: Processed data and code used in the analysis are accessible from the Zenodo Repository: 10.5281/zenodo.6885455Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements.Bertarelli FoundationResearch EnglandMoore FoundationPackard FoundationInstituto Politecnico NacionalDarwin InitiativeGeorgia AquariumRolex Awards for EnterpriseWhitley Fund for Natur