211 research outputs found

    Rechtsvinding en taalrelativisme

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    Geïntegreerd bosbeheer: de discussie woedt voort

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    Kritiek van bosdeskundigen op het boek 'Geïntegreerd bosbeheer. Praktijk, voorbeelden en achtergronden' (J.L. van der Jagt et al., 2000, EC-LNV nr. 50). Geïntegreerd bosbeheer (het streven naar multifunctionele bossen) wordt geheel beschreven in de polariteit van natuur en houtproductie, terwijl een bredere invalshoek gerechtvaardigd is. Het concept wordt aardig neergezet, maar er zijn onvoldoende praktische aanknopingspunten voor de professionele bosbeheerders door het ontbreken van gedetailleerde proceskenni

    Functional tests to guide management in an adult with loss of function of type-1 angiotensin II receptor

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    BACKGROUND: Genetic loss of function of AGT (angiotensinogen), REN (renin), ACE (angiotensin-converting enzyme), or AGTR1 (type-1 angiotensin II receptor) leads to renal tubular dysgenesis (RTD). This syndrome is almost invariably lethal. Most surviving patients reach stage 5 chronic kidney disease at a young age. METHODS: Here, we report a 28-year-old male with a homozygous truncating mutation in AGTR1 (p.Arg216*), who survived the perinatal period with a mildly impaired kidney function. In contrast to classic RTD, kidney biopsy showed proximal tubules that were mostly normal. During the subsequent three decades, we observed evidence of both tubular dysfunction (hyperkalemia, metabolic acidosis, salt-wasting and a urinary concentrating defect) and glomerular dysfunction (reduced glomerular filtration rate, currently ~30 mL/min/1.73 m(2), accompanied by proteinuria). To investigate the recurrent and severe hyperkalemia, we performed a patient-tailored functional test and showed that high doses of fludrocortisone induced renal potassium excretion by 155%. Furthermore, fludrocortisone lowered renal sodium excretion by 39%, which would have a mitigating effect on salt-wasting. In addition, urinary pH decreased in response to fludrocortisone. Opposite effects on urinary potassium and pH occurred with administration of amiloride, further supporting the notion that a collecting duct is present and able to react to fludrocortisone. CONCLUSIONS: This report provides living proof that even truncating loss-of-function mutations in AGTR1 are compatible with life and relatively good GFR and provides evidence for the prescription of fludrocortisone to treat hyperkalemia and salt-wasting in such patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00467-021-05018-7

    Dietary Mg2+ Intake and the Na+/Mg2+ Exchanger SLC41A1 Influence Components of Mitochondrial Energetics in Murine Cardiomyocytes

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    Cardiomyocytes are among the most energy-intensive cell types. Interplay between the components of cellular magnesium (Mg) homeostasis and energy metabolism in cardiomyocytes is poorly understood. We have investigated the effects of dietary Mg content and presence/functionality of the Na+/Mg2+ exchanger SLC41A1 on enzymatic functions of selected constituents of the Krebs cycle and complexes of the electron transport chain (ETC). The activities of aconitate hydratase (ACON), isocitrate dehydrogenase (ICDH), α-ketoglutarate dehydrogenase (KGDH), and ETC complexes CI–CV have been determined in vitro in mitochondria isolated from hearts of wild-type (WT) and Slc41a1−/− mice fed a diet with either normal or low Mg content. Our data demonstrate that both, the type of Mg diet and the Slc41a1 genotype largely impact on the activities of enzymes of the Krebs cycle and ETC. Moreover, a compensatory effect of Slc41a1−/− genotype on the effect of low Mg diet on activities of the tested Krebs cycle enzymes has been identified. A machine-learning analysis identified activities of ICDH, CI, CIV, and CV as common predictors of the type of Mg diet and of CII as suitable predictor of Slc41a1 genotype. Thus, our data delineate the effect of dietary Mg content and of SLC41A1 functionality on the energy-production in cardiac mitochondria

    Bridging the GUI gap with reactive values and relations

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    There are at present two ways to write GUIs for functional code. One is to use standard GUI toolkits, with all the benefits they bring in terms of feature completeness, choice of platform, conformance to platform-specific look-and-feel, long-term viability, etc. However, such GUI APIs mandate an imperative programming style for the GUI and related parts of the application. Alternatively, we can use a functional GUI toolkit. The GUI can then be written in a functional style, but at the cost of foregoing many advantages of standard toolkits that often will be of critical importance. This paper introduces a light-weight framework structured around the notions of reactive values and reactive relations . It allows standard toolkits to be used from functional code written in a functional style. We thus bridge the gap between the two worlds, bringing the advantages of both to the developer. Our framework is available on Hackage and has been been validated through the development of non-trivial applications in a commercial context, and with different standard GUI toolkits
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