811 research outputs found

    The Philanthropy As One Big Impact Investment: A Framework For Evaluating A Foundation’s Blended Performance

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    While some foundations have put their entire focus on impact investing, philanthropy still lacks the tools that enable such investments to be made with the same rigor as the best financial investments and philanthropic grants. This reveals a more fundamental problem: We do not currently manage foundations as the integrated portfolios that they are. This article proposes a framework for evaluating a foundation’s blended performance that enables both grantmaking and endowment investing to be evaluated jointly, and thus also allows a complete evaluation of how impact investments could improve — or fail to improve — overall performance. The article demonstrates the framework’s utility by using it to evaluate a set of actual impact investments in the field of the environment. Using this framework to assess foundations’ performance would not only improve fundamental performance, but also potentially unlock vast new areas of social entrepreneurship

    Interfering polysialyltransferase ST8SiaII/STX mRNA inhibits neurite growth during early hippocampal development

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    AbstractPolysialic acid (PSA) attached to NCAM is involved in cell–cell interactions participating in structural and functional plasticity of neuronal circuits. Two polysialyltransferases, ST8SiaII/STX and ST8SiaIV/PST, polysialylate NCAM. We previously suggested that ST8SiaII/STX is the key enzyme for polysialylation in hippocampus. Here, polysialyltransferase mRNA interference experiments showed that, knock down of ST8SiaIV/PST transcripts did not affect PSA expression, but PSA was almost absent from neuronal surfaces when ST8SiaII/STX mRNA was interfered. Non-polysialylated neurons bore a similar number of neurites per cell than polysialylated neurons. However, non-polysialylated processes were shorter and a lower density of synaptophysin clusters accompanied this reduced neuritic growth. Therefore, ST8SiaII/STX expression is essential to allow a correct neuritic development at initial stages of hippocampus ontogeny

    Impact of Chronic Fetal Hypoxia and Inflammation on Cardiac Pacemaker Cell Development.

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    Chronic fetal hypoxia and infection are examples of adverse conditions during complicated pregnancy, which impact cardiac myogenesis and increase the lifetime risk of heart disease. However, the effects that chronic hypoxic or inflammatory environments exert on cardiac pacemaker cells are poorly understood. Here, we review the current evidence and novel avenues of bench-to-bed research in this field of perinatal cardiogenesis as well as its translational significance for early detection of future risk for cardiovascular disease

    First evidence that intrinsic fetal heart rate variability exists and is affected by hypoxic pregnancy.

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    KEY POINTS: We introduce a technique to test whether intrinsic fetal heart rate variability (iFHRV) exists and we show the utility of the technique by testing the hypothesis that iFHRV is affected by chronic fetal hypoxia, one of the most common adverse outcomes of human pregnancy complicated by fetal growth restriction. Using an established late gestation ovine model of fetal development under chronic hypoxic conditions, we identify iFHRV in isolated fetal hearts and show that it is markedly affected by hypoxic pregnancy. Therefore, the isolated fetal heart has intrinsic variability and carries a memory of adverse intrauterine conditions experienced during the last third of pregnancy. ABSTRACT: Fetal heart rate variability (FHRV) emerges from influences of the autonomic nervous system, fetal body and breathing movements, and from baroreflex and circadian processes. We tested whether intrinsic heart rate variability (iHRV), devoid of any external influences, exists in the fetal period and whether it is affected by chronic fetal hypoxia. Chronically catheterized ewes carrying male singleton fetuses were exposed to normoxia (n = 6) or hypoxia (10% inspired O2 , n = 9) for the last third of gestation (105-138 days of gestation (dG); term ∌145 dG) in isobaric chambers. At 138 dG, isolated hearts were studied using a Langendorff preparation. We calculated basal intrinsic FHRV (iFHRV) indices reflecting iFHRV's variability, predictability, temporal symmetry, fractality and chaotic behaviour, from the systolic peaks within 15 min segments in each heart. Significance was assumed at P < 0.05. Hearts of fetuses isolated from hypoxic pregnancy showed approximately 4-fold increases in the Grid transformation as well as the AND similarity index (sgridAND) and a 4-fold reduction in the scale-dependent Lyapunov exponent slope. We also detected a 2-fold reduction in the Recurrence quantification analysis, percentage of laminarity (pL) and recurrences, maximum and average diagonal line (dlmax, dlmean) and the Multiscale time irreversibility asymmetry index. The iHRV measures dlmax, dlmean, pL and sgridAND correlated with left ventricular end-diastolic pressure across both groups (average R2  = 0.38 ± 0.03). This is the first evidence that iHRV originates in fetal life and that chronic fetal hypoxia significantly alters it. Isolated fetal hearts from hypoxic pregnancy exhibit a time scale-dependent higher complexity in iFHRV.British Heart Foundatio

    Homeotic Genes Autonomously Specify the Anteroposterior Subdivision of the Drosophila Dorsal Vessel into Aorta and Heart

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    AbstractThe embryonic dorsal vessel in Drosophila possesses anteroposterior polarity and is subdivided into two chamber-like portions, the aorta in the anterior and the heart in the posterior. The heart portion features a wider bore as compared with the aorta and develops inflow valves (ostia) that allow the pumping of hemolymph from posterior toward the anterior. Here, we demonstrate that homeotic selector genes provide positional information that determines the anteroposterior subdivision of the dorsal vessel. Antennapedia (Antp), Ultrabithorax (Ubx), abdominal-A (abd-A), and Abdominal-B (Abd-B) are expressed in distinct domains along the anteroposterior axis within the dorsal vessel, and, in particular, the domain of abd-A expression in cardioblasts and pericardial cells coincides with the heart portion. We provide evidence that loss of abd-A function causes a transformation of the heart into aorta, whereas ectopic expression of abd-A in more anterior cardioblasts causes the aorta to assume heart-like features. These observations suggest that the spatially restricted expression and activity of abd-A determine heart identities in cells of the posterior portion of the dorsal vessel. We also show that Abd-B, which at earlier stages is expressed posteriorly to the cardiogenic mesoderm, represses cardiogenesis. In light of the developmental and morphological similarities between the Drosophila dorsal vessel and the primitive heart tube in early vertebrate embryos, these data suggest that Hox genes may also provide important anteroposterior cues during chamber specification in the developing vertebrate heart

    O FUTURO DO DIREITO ANIMAL: INDO ALÉM DE "ENSINAR O PAI NOSSO AO VIGÁRIO"

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    O artigo analisa o futuro do direito animal, oferecendo umavisĂŁo geral do sucesso alcançado pelo direito animal nas faculdadesde direito dos EUA. Em seguida, a partir de uma anĂĄlise comparativacom o direito ambiental, as autoras demonstram a importĂąncia de seacionar algumas “alavancas” que podem promover o avanço jurĂ­dicona proteção animal: o interesse humano, os depoimentos de pessoascredibilizadas, a adesĂŁo de nĂŁo-ativistas e a pressĂŁo polĂ­tica. Finalmente,sugere açÔes concretas que podem desenvolver ainda mais odireito animal, com vista a expandir o cĂ­rculo de compaixĂŁo para alĂ©mdos animalistas
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