57 research outputs found

    Activation of immune defences against parasitoid wasps does not underlie the cost of infection

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    Parasites reduce the fitness of their hosts, and different causes of this damage have fundamentally different consequences for the evolution of immune defences. Damage to the host may result from the parasite directly harming its host, often due to the production of virulence factors that manipulate host physiology. Alternatively, the host may be harmed by the activation of its own immune defences, as these can be energetically demanding or cause self-harm. A well-studied model of the cost of infection is Drosophila melanogaster and its common natural enemy, parasitoid wasps. Infected Drosophila larvae rely on humoral and cellular immune mechanisms to form a capsule around the parasitoid egg and kill it. Infection results in a developmental delay and reduced adult body size. To disentangle the effects of virulence factors and immune defences on these costs, we artificially activated anti-parasitoid immune defences in the absence of virulence factors. Despite immune activation triggering extensive differentiation and proliferation of immune cells together with hyperglycaemia, it did not result in a developmental delay or reduced body size. We conclude that the costs of infection do not result from these aspects of the immune response and may instead result from the parasite directly damaging the host

    Treatment preferences towards thrombopoietin-receptor agonists for immune thrombocytopenia and experience of disease (TRAPeze): Italy cohort

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    Objective: Identify patient preference towards thrombopoietin-receptor agonists (TPO-RAs) and determine the clinical and social impact of immune thrombocytopenia (ITP) in Italy.Methods: The Thrombopoietin-Receptor Agonist Patient experience (TRAPeze) survey collected responses from Italian residents from 17th January to 28th February 2022. TRAPeze utilized a discrete choice experiment (DCE) to elicit patient preferences towards TPO-RA attributes and a patient burden survey (PBS) to determine ITP disease characteristics and social impact.Results: Seventy-six respondents completed the DCE, of which 69 completed both the DCE and PBS (mean [range] age 45 [18.0-73.0] years, 80% female). TPO-RA attributes with the greatest influence over respondent choice were method of administration (odds ratio [OR] 2.96; 95% confidence interval [CI] 2.16-4.06), drug-food interactions (OR 1.48; 95% CI 1.17-1.86) and frequency of dosing (OR 1.32; 95% CI 1.15-1.52). Respondents were more likely to prefer therapies administered orally over subcutaneous injection (OR 3.76; 95% CI 2.51-5.63), once weekly over once daily (OR 1.83; 95% CI 1.26-2.65), and therapies without food restrictions over with restrictions (OR 1.58; 95% CI 1.17-2.14).The most frequently reported symptoms were bruising (82%), petechiae (65%) and fatigue (64%). Most respondents (84%) felt ITP impacted familial relationships and 71% of employed respondents reported fatigue influencing their ability to work, with 31% reducing working hours.The most frequently reported symptoms were bruising (82%), petechiae (65%) and fatigue (64%). Most respondents (84%) felt ITP impacted familial relationships and 71% of employed respondents reported fatigue influencing their ability to work, with 31% reducing working hours.Conclusion: Although responses indicated a moderate perception of general health, ITP clearly impacted respondent work and social life. Our findings demonstrate respondents preferred TPO-RAs delivered orally, with less frequent dosing and without food restrictions

    The extent and distribution of joint conservation-development funding in the tropics

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    Despite ongoing debates about the viability of sustaining economic growth while maintaining environmental integrity, international sustainability agendas increasingly propose reconciling socio-economic development and global environmental goals. Achieving these goals is impeded by limited funding and a lack of information on where financial flows to integrate environment and development are targeted. We analyze World Bank and Global Environment Facility data to investigate the extent and distribution of such funding across the tropics. We find a misalignment between funding flows and need with highly biodiverse, low development (HBLD) countries receiving no more funding than non-HBLD countries. Countries with low biodiversity receive more funding than highly biodiverse countries and there was no statistical association between a country's development status and funds received. Rather than environment-development need, funding appears to be driven by governance and political-economic factors. Future research should investigate how such factors and funding flows are associated with conservation and development outcomes. This study analyzes 381 projects of the World Bank and the Global Environment Facility (GEF) concluded between 1995 and 2013 to show how much money is spent on joint conservation and development in the tropics, where the money is directed, whether it is directed to areas of greatest environmental and development need, and finally what factors drive funding allocation decisions. The total extent of funding was US16.5billionacross75countries,representingapproximatelyUS16.5 billion across 75 countries, representing approximately US870 million per year. Countries with high biodiversity and low human development receive no more funding for integrated conservation and development than other countries. Notably, countries with a low biodiversity status receive relatively more funding than highly biodiverse countries and there was no association between development need and funds received. Therefore, we find that neither biodiversity nor human development status explain funding allocation, but rather that governance and political-economic factors are most likely more influential. This study analyzes the extent and distribution of World Bank and GEF funding for joint conservation and development in the tropics, whether it is directed to areas of greatest environmental and development need, and finally what factors drive funding allocation decisions. Total spending was US$16.5 billion across 75 countries. We find that neither biodiversity nor HDI status are driving funding allocation, but rather that governance and political-economic factors are most likely more influential

    Miklat Laila

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    Metaphysical reflection 27

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    Role of PTP-alpha in integrated c-Kit and Fc-epsilon R1 mast cell activation

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    Mast cells (MCs) play a crucial role in the induction of allergic asthma by secreting inflammatory mediators in response to allergens. In addition to MC activation via the antigen/IgE receptor FcεR1, MC tissue recruitment and responsiveness is greatly enhanced by co-stimulation with the stem cell factor (SCF). Levels of SCF are elevated in the asthmatic lung, where it stimulates the c-Kit receptor on MCs. Sufficient signaling through c-Kit and FcεR1 requires the activation of Src family kinases, which can be regulated by protein tyrosine phosphatase alpha (PTPα). Our lab has previously demonstrated that PTPα exerts positive regulatory effects on SCF-stimulated c-Kit phosphorylation and MC migration. In contrast, PTPα negatively regulates antigen-induced mast cell activation and the release of inflammatory mediators. To determine the role of PTPα in the integrated c-Kit and FcεR1 signaling that is believed to facilitate allergic inflammation, mouse bone marrow-derived WT and PTPα-KO MCs were treated with combinations of antigen and SCF, and analyzed for secretory and migratory responses as well as for the activation of key signaling proteins. However, the expected MC hyper-responsiveness due to the lack of PTPα was not observed, which may have arisen from intrinsic changes in the cultured mast cells and not from testing methodologies. Co-treatment with antigen and SCF produced synergistic degranulation and cytokine release that was similar between WT and PTPα-KO MCs. Yet, PTPα was required for the full phosphorylation of Akt and p38 after 15 min co-treatment with antigen and SCF. PTPα itself was found to be dephosphorylated at tyrosine 789, especially upon treatment with antigen. During fibronectin-aided Transwell migration towards SCF, the addition of antigen significantly reduced the number of PTPα-KO but not WT MCs that remained attached to fibronectin. Interestingly, in the presence of fibronectin, the SCF-mediated migration of WT and PTPα-KO MCs was not significantly affected by the addition of antigen, whereas fibronectin-independent MC migration was synergistically enhanced by antigen and SCF. Taken together, despite effects on the FcεRI/c-Kit integrated activation of downstream signaling proteins, the overall SCF-enhanced mediator release and migration of mast cells were found to be independent of PTPα.Medicine, Faculty ofMedicine, Department ofExperimental Medicine, Division ofGraduat

    Fiscus bonsai

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