Mannitol Reduces the Hydrostatic Pressure in the Proximal Tubule of the Isolated Blood-Perfused Rabbit Kidney during Hypoxic Stress and Improves Its Function

Background/Aims: Hypoxia may play a role in the development of renal failure in donated kidneys. In the present study, the effects of hypoxia on isolated blood-perfused rabbit kidneys were investigated and the effects of mannitol were explored, giving special attention to intratubular pressure. Methods: Kidneys were perfused with their autologous blood during four 30-min periods (P1–P4). P1 was considered baseline function. In P2, hypoxia was induced either alone or with an infusion of mannitol (15 mg/min) during P2–P4. Reoxygenation was applied after P2. Proximal intratubular pressure was measured in all conditions. Results: During hypoxia, renal blood flow doubled and restored immediately in P3. Urine flow stopped in P2, except in the series with mannitol, but gradually resumed in P3 and P4. Likewise, creatinine clearance recovered slightly (50% of P1. Proximal intratubular pressure (mean ± SD) increased from 12 ± 5 in P1 to 24 ± 11 mm Hg during hypoxia and returned to 10 ± 6 mm Hg in P3. This increase was not observed with mannitol. Conclusion: Cellular swelling might be responsible for the suppressed filtration during hypoxia and can be prevented by mannitol

Building Social Media Observatories for Monitoring Online Opinion Dynamics

Social media house a trove of relevant information for the study of online opinion dynamics. However, harvesting and analyzing the sheer overload of data that is produced by these media poses immense challenges to journalists, researchers, activists, policy makers, and concerned citizens. To mitigate this situation, this article discusses the creation of (social) media observatories: platforms that enable users to capture the complexities of social behavior, in particular the alignment and misalignment of opinions, through computational analyses of digital media data. The article positions the concept of "observatories" for social media monitoring among ongoing methodological developments in the computational social sciences and humanities and proceeds to discuss the technological innovations and design choices behind social media observatories currently under development for the study of opinions related to cultural and societal issues in European spaces. Notable attention is devoted to the construction of Penelope: an open, web-services-based infrastructure that allows different user groups to consult and contribute digital tools and observatories that suit their analytical needs. The potential and the limitations of this approach are discussed on the basis of a climate change opinion observatory that implements text analysis tools to study opinion dynamics concerning themes such as global warming. Throughout, the article explicitly acknowledges and addresses potential risks of the machine-guided and human-incentivized study of opinion dynamics. Concluding remarks are devoted to a synthesis of the ethical and epistemological implications of the exercise of positioning observatories in contemporary information spaces and to an examination of future pathways for the development of social media observatories

A new single nephron model of focal and segmental glomerulosclerosis in the Munich-Wistar rat

A new single nephron model of focal and segmental glomerulosclerosis in the Munich-Wistar rat. The hypothesis that damage to the visceral epithelial cell plays a central role in the pathogenesis of focal and segmental glomerulosclerosis was tested by injecting saponin solutions of increasing concentration (0.1, 0.3, 0.6 and 1.0 mg/ml) in Bowman's space of superficial glomeruli in the Munich-Wistar rat. The microinjections were performed both with and without intermittent clamping of the renal vessels during two minutes. After 8 to 14 days the injected glomeruli were examined by light microscopy. The injected glomeruli were classified as, normal (NL), showing visceral epithelial cell damage (VECD), showing focal and segmental glomerulosclerosis (FSGS) or showing global sclerosis (GS). Swelling and intracellular vacuolation of the visceral epithelial cells (VEC) were considered as VECD. FSGS-lesions were seen most frequently in the glomeruli injected with 10 nl of a saponin solution with a concentration higher than 0.3 mg/ml. In view of the light microscopic lesions four glomeruli in a 0 mg/ml, the 0.1 mg/ml and the 0.6 mg/ml saponin groups were examined after 40 minutes with transmission electron microscopy (TEM) to evaluate the selectivity of the lesions. In the 0 and 0.1 mg/ml group only occasional limited fusion of the foot processes of the podocytes was seen. In the 0.6 mg/ml group segmental lysis of the VEC without ultrastructural damage to the capillary basement membrane or the endothelial and mesangial cells was seen. It is concluded that it is possible to induce direct segmental lysis of the visceral epithelial cells in a single glomerulus, and that this damage to the visceral epithelial cells is related to the development of focal and segmental glomerulosclerosis

Glycine and Glycine Receptor Signalling in Non-Neuronal Cells

Glycine is an inhibitory neurotransmitter acting mainly in the caudal part of the central nervous system. Besides this neurotransmitter function, glycine has cytoprotective and modulatory effects in different non-neuronal cell types. Modulatory effects were mainly described in immune cells, endothelial cells and macroglial cells, where glycine modulates proliferation, differentiation, migration and cytokine production. Activation of glycine receptors (GlyRs) causes membrane potential changes that in turn modulate calcium flux and downstream effects in these cells. Cytoprotective effects were mainly described in renal cells, hepatocytes and endothelial cells, where glycine protects cells from ischemic cell death. In these cell types, glycine has been suggested to stabilize porous defects that develop in the plasma membranes of ischemic cells, leading to leakage of macromolecules and subsequent cell death. Although there is some evidence linking these effects to the activation of GlyRs, they seem to operate in an entirely different mode from classical neuronal subtypes

Informaticawetenschappen in het leerplichtonderwijs

Dit standpunt bepleit en beargumenteert de noodzaak om elke jongere een opleiding informaticawetenschappen aan te bieden die toelaat om ’informaticavaardig’ te worden. Informaticavaardigheid gaat verder dan louter ‘digitale geletterdheid’, en houdt ook in dat de jongere in staat moet zijn ‘computationeel’ te denken. Computers zijn onmisbaar geworden, zowel in het professionele leven als in de privésfeer. Om de technologische evolutie te kunnen volgen is het van groot belang dat alle jongeren niet alleen de bestaande technologie leren gebruiken, maar ook de onderliggende werking leren begrijpen. Om de technologische evolutie te kunnen sturen, is het nodig dat voldoende jongeren in staat en gemotiveerd zijn om nieuwe technologie te creëren. Om deze doelstellingen te realiseren, dient het onderwijs van de informatica in het leerplichtonderwijs grondig hervormd te worden. In het basis- en secundair onderwijs dient een basisopleiding informaticawetenschappen opgenomen te worden, waarop in specifieke STEM richtingen voortgebouwd wordt. Een nieuw leerprogramma, goed opgeleide leraars en een goede informatica-infrastructuur zijn broodnodig. Ons leerplichtonderwijs is de belangrijkste actor om volgende generaties voor te bereiden op het leven, zowel professioneel als privé. De digitalisering van onze maatschappij kan haar voordelen alleen waarmaken als het onderwijs aangepast is aan deze digitale realiteit. Informatica- wetenschappen is een autonome wetenschap geworden met haar eigen manier van denken, en haar eigen basisbegrippen, te vergelijken met wiskunde, natuurkunde, en andere wetenschap- pen, die haar plaats in het onderwijs verdient. Het moet duidelijk zijn dat het hier niet gaat over het onderwijs van de traditionele vakken met de steun van informaticahulpmiddelen maar wel over de informaticawetenschappen zelf als vormend vak. Dit standpunt kwam tot stand binnen een werkgroep, opgericht door de KVAB en de Jonge Academie en samengesteld met leden uit diverse academische disciplines, onderwijsdeskundi- gen en actoren uit de bedrijfswereld

Phenotypic heterogeneity in fungi: importance and methodology

Phenotypic heterogeneity describes the variation that exists between individual cells, spores or other biological entities within genetically-uniform populations of fungi or other organisms. Studies over the last 10-15 years have successfully used laboratory- and modelling-based approaches to demonstrate the prevalence of phenotypic heterogeneity and characterise the molecular bases of the phenomenon (primarily centred around heterogeneous gene expression). In contrast to progress in these areas, the relevance of phenotypic heterogeneity for the competitive success of organisms in different natural scenarios, although widely speculated upon, has only recently begun to be investigated. This focus review addresses this latter question as tackled in recent studies with yeasts and filamentous fungi. We concentrate on the relevance to fungal activities such as survival against environmental stressors, pathogenesis, and spoilage. We also discuss methodologies for interrogating phenotypic heterogeneity in fungi. The emerging prevalence and apparent importance of fungal phenotypic heterogeneity provides a timely reminder that certain, potentially core aspects of fungal biology still remain widely under-explored