Postfledging Survival, Movements, and Dispersal of Ring Ouzels (Turdus torquatus)

We thank Invercauld Estate for cooperation with access to Glen Clunie. S. Redpath, J. Wilson, and S. Roos provided valuable comments on the manuscript. This study was funded by the Royal Society for the Protection of Birds, Scottish Natural Heritage, and the Cairngorms National Park Authority. J.L.L. was supported by the Natural Environment Research Council.Peer reviewedPublisher PD

T. brucei cathepsin-L increases arrhythmogenic sarcoplasmic reticulum-mediated calcium release in rat cardiomyocytes

Aims: African trypanosomiasis, caused by Trypanosoma brucei species, leads to both neurological and cardiac dysfunction and can be fatal if untreated. While the neurological-related pathogenesis is well studied, the cardiac pathogenesis remains unknown. The current study exposed isolated ventricular cardiomyocytes and adult rat hearts to T. brucei to test whether trypanosomes can alter cardiac function independent of a systemic inflammatory/immune response. Methods and results: Using confocal imaging, T. brucei and T. brucei culture media (supernatant) caused an increased frequency of arrhythmogenic spontaneous diastolic sarcoplasmic reticulum (SR)-mediated Ca2+ release (Ca2+ waves) in isolated adult rat ventricular cardiomyocytes. Studies utilising inhibitors, recombinant protein and RNAi all demonstrated that this altered SR function was due to T. brucei cathepsin-L (TbCatL). Separate experiments revealed that TbCatL induced a 10–15% increase of SERCA activity but reduced SR Ca2+ content, suggesting a concomitant increased SR-mediated Ca2+ leak. This conclusion was supported by data demonstrating that TbCatL increased Ca2+ wave frequency. These effects were abolished by autocamtide-2-related inhibitory peptide, highlighting a role for CaMKII in the TbCatL action on SR function. Isolated Langendorff perfused whole heart experiments confirmed that supernatant caused an increased number of arrhythmic events. Conclusion: These data demonstrate for the first time that African trypanosomes alter cardiac function independent of a systemic immune response, via a mechanism involving extracellular cathepsin-L-mediated changes in SR function

Gene therapy with Angiotensin-(1-9) preserves left ventricular systolic function after myocardial infarction

BACKGROUND: Angiotensin-(1-9) [Ang-(1-9)] is a novel peptide of the counter-regulatory axis of the renin angiotensin system previously demonstrated to have therapeutic potential in hypertensive cardiomyopathy when administered via osmotic minipump in mice. Here, we investigate whether gene transfer of Ang-(1-9) is cardioprotective in a murine model of myocardial infarction (MI). OBJECTIVES: To evaluate effects of Ang-(1-9) gene therapy on myocardial structural and functional remodeling post infarction. METHODS: C57BL/6 mice underwent permanent left anterior descending coronary artery ligation and cardiac function was assessed using echocardiography for 8 weeks followed by a terminal measurement of left ventricular (LV) pressure-volume loops. Ang-(1-9) was delivered by adeno-associated viral vector via single tail vein injection immediately following induction of MI. Direct effects of Ang-(1-9) on cardiomyocyte excitation–contraction coupling and cardiac contraction were evaluated in isolated mouse and human cardiomyocytes and in an ex vivo Langendorff perfused whole heart model. RESULTS: Gene delivery of Ang-(1-9) significantly reduced sudden cardiac death post-MI. Pressure–volume measurements revealed complete restoration of end systolic pressure, ejection fraction, end systolic volume and the end diastolic pressure–volume relationship by Ang-(1-9) treatment. Stroke volume and cardiac output were significantly increased versus sham. Histological analysis revealed only mild effects on cardiac hypertrophy and fibrosis, but a significant increase in scar thickness. Direct assessment of Ang-(1-9) on isolated cardiomyocytes demonstrated a positive inotropic effect via increasing calcium transient amplitude and increasing contractility. Ang-(1-9) increased contraction in the Langendorff model through a protein kinase A-dependent mechanism. CONCLUSIONS: Our novel findings show that Ang-(1-9) gene therapy preserves LV systolic function post-MI, restoring cardiac function. Furthermore, Ang-(1-9) has a direct effect on cardiomyocyte 3 calcium handling through a protein kinase A-dependent mechanism. These data highlight Ang-(1-9) gene therapy as a potential new strategy in the context of MI

A survey of farm management practices relating to the risk factors, prevalence, and causes of lamb mortality in Ireland

SIMPLE SUMMARY: A reduction in lamb mortality would benefit farmers both economically and ethically. The major causes of lamb mortality are similar worldwide. Targeting the specific causes can result in reduced lamb mortality. This involves identifying underlying factors associated with lamb mortality and subsequently recommending changes to management practices. The objective of this study was to investigate the risk factors associated with lamb mortality on Irish sheep farms to provide a greater understanding of the necessary management practices required to reduce lamb mortality. This was achieved by identifying relationships between on-farm practices and risk factors of lamb mortality associated with these practices. Predators, lamb birth weight, and diseases were perceived by farmers to be the main causes of lamb mortality. Individual lambing pens were used on most sheep farms but were not cleaned and/or disinfected on 26% of them. Lamb mortality tended to be lower on farms that used best-known practices. Full-time farmers that used hospital and individual pens had a higher gross margin (€18/ewe). Management systems affect both lamb mortality and flock gross margin. Every 1% decrease in average lamb mortality across Irish flocks is worth ~€3 million annually to the Irish sheep sector. ABSTRACT: Lamb mortality is a key factor influencing ewe productivity and profitability. The current study investigated risk factors associated with and management practices implemented on sheep farms to reduce lamb mortality. A survey consisting of 13 multiple-part questions (57 separate questions) was administered to all sheep farmers participating in the Teagasc National Farm Survey, representative of the Irish national population of sheep farms. A total of 60% of respondents identify mating or lambing date, and this practice tended to be associated with reduced lamb mortality (1.2%, p = 0.08). Individual lambing pens were used by 88% of farmers, but 26% did not clean or disinfect them. A total of 79% and 9.5% of farmers applied iodine to all lambs’ navels and administered antibiotics to all lambs to treat and/or prevent diseases, respectively. Most farmers vaccinated their ewes (86%) and lambs (79%) against clostridial diseases and/or pasteurellosis; 13% vaccinated against abortion agents. Lamb mortality tended to be lower (Kruskal–Wallis (KW) = 2.749; p = 0.09) on farms that used stomach tubing, heat box, iodine, hospital, and individual pens compared with farms that do not implement all those practices. Predators, lamb birth weight, and diseases were perceived by respondents to be the three main causes of live-born lamb mortality. The gross margin is significantly higher on lowland farms by €37 per ewe compared with hill farms (Kruskal–Wallis (KW) = 4.056; p < 0.001). The combination of full-time farming and the use of hospital and individual pens improved gross margin (€18/ewe, p = 0.028). It is concluded that on-farm management practices affect both lamb mortality and flock gross margin

X-linked Inhibitor of Apoptosis Complicated by Granulomatous Lymphocytic Interstitial Lung Disease (GLILD) and Granulomatous Hepatitis

The X-linked inhibitor of apoptosis (XIAP) deficiency is a primary immunodeficiency characterized by Epstein-Barr virus (EBV)-driven hemophagocytic lymphohistiocytosis (HLH), splenomegaly, and colitis. Here, we present, for the first time, granulomatous hepatitis and granulomatous and lymphocytic interstitial lung disease (GLILD) as manifestations of XIAP deficiency. We report successful treatment of GLILD in XIAP deficiency with rituximab and azathioprine and discuss the role of XIAP deficiency in immune dysregulation

Preclinical models of myocardial infarction: from mechanism to translation

Approximately 7 million people are affected by acute myocardial infarction (MI) each year, and despite significant therapeutic and diagnostic advancements, MI remains a leading cause of mortality worldwide. Pre-clinical animal models have significantly advanced our understanding of MI and enable the development of therapeutic strategies to combat this debilitating disease. Notably, some drugs currently used to treat MI and heart failure (HF) in patients had initially been studied in pre-clinical animal models. Despite this, pre-clinical models are limited in their ability to fully recapitulate the complexity of MI in humans. The pre-clinical model must be carefully selected to maximise the translational potential of experimental findings. This review describes current experimental models of MI and considers how they have been used to understand drug mechanisms of action (MOA) and support translational medicine development