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A catalog of genetic loci associated with kidney function from analyses of a million individuals
(2019)
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
In the favoured core-accretion model of formation of planetary systems, solid planetesimals accumulate to build up planetary cores, which then accrete nebular gas if they are sufficiently massive. Around M-dwarf stars ( the most common stars in our Galaxy), this model favours the formation of Earth-mass (M+) to Neptune-mass planets with orbital radii of 1 to 10 astronomical units (AU), which is consistent with the small number of gas giant planets known to orbit M-dwarf host stars(1-4). More than 170 extrasolar planets have been discovered with a wide range of masses and orbital periods, but planets of Neptune's mass or less have not hitherto been detected at separations of more than 0.15 AU from normal stars. Here we report the discovery of a 5.5(-2.7)(+5.5)M(+) planetary companion at a separation of 2.6(- 0.6)(+1.5) AU from a 0.22(-0.11)(+0.21)M(.) M-dwarf star, where M-. refers to a solar mass. (We propose to name it OGLE- 2005-BLG-390Lb, indicating a planetary mass companion to the lens star of the microlensing event.) The mass is lower than that of GJ876d (ref. 5), although the error bars overlap. Our detection suggests that such cool, sub-Neptune-mass planets may be more common than gas giant planets, as predicted by the core accretion theory.
Die Tagung HDI 2014 in Freiburg zur Hochschuldidaktik der Informatik HDI wurde erneut vom Fachbereich Informatik und Ausbildung / Didaktik der Informatik (IAD) in der Gesellschaft für Informatik e. V. (GI) organisiert. Sie dient den Lehrenden der Informatik in Studiengängen an Hochschulen als Forum der Information und des Austauschs über neue didaktische Ansätze und bildungspolitische Themen im Bereich der Hochschulausbildung aus der fachlichen Perspektive der Informatik.
Die HDI 2014 ist nun bereits die sechste Ausgabe der HDI. Für sie wurde das spezielle Motto „Gestalten und Meistern von Übergängen“ gewählt. Damit soll ein besonderes Augenmerk auf die Übergänge von Schule zum Studium, vom Bachelor zum Master, vom Studium zur Promotion oder vom Studium zur Arbeitswelt gelegt werden.
GrassPlot is a collaborative vegetation-plot database organised by the Eurasian Dry Grassland Group (EDGG) and listed in the Global Index of Vegetation-Plot Databases (GIVD ID EU-00-003). GrassPlot collects plot records (releves) from grasslands and other open habitats of the Palaearctic biogeographic realm. It focuses on precisely delimited plots of eight standard grain sizes (0.0001; 0.001;... 1,000 m(2)) and on nested-plot series with at least four different grain sizes. The usage of GrassPlot is regulated through Bylaws that intend to balance the interests of data contributors and data users. The current version (v. 1.00) contains data for approximately 170,000 plots of different sizes and 2,800 nested-plot series. The key components are richness data and metadata. However, most included datasets also encompass compositional data. About 14,000 plots have near-complete records of terricolous bryophytes and lichens in addition to vascular plants. At present, GrassPlot contains data from 36 countries throughout the Palaearctic, spread across elevational gradients and major grassland types. GrassPlot with its multi-scale and multi-taxon focus complements the larger international vegetationplot databases, such as the European Vegetation Archive (EVA) and the global database " sPlot". Its main aim is to facilitate studies on the scale-and taxon-dependency of biodiversity patterns and drivers along macroecological gradients. GrassPlot is a dynamic database and will expand through new data collection coordinated by the elected Governing Board. We invite researchers with suitable data to join GrassPlot. Researchers with project ideas addressable with GrassPlot data are welcome to submit proposals to the Governing Board.
Moving in the Anthropocene
(2018)
Animal movement is fundamental for ecosystem functioning and species survival, yet the effects of the anthropogenic footprint on animal movements have not been estimated across species. Using a unique GPS-tracking database of 803 individuals across 57 species, we found that movements of mammals in areas with a comparatively high human footprint were on average one-half to one-third the extent of their movements in areas with a low human footprint. We attribute this reduction to behavioral changes of individual animals and to the exclusion of species with long-range movements from areas with higher human impact. Global loss of vagility alters a key ecological trait of animals that affects not only population persistence but also ecosystem processes such as predator-prey interactions, nutrient cycling, and disease transmission.
Major depression is a highly prevalent severe mood disorder that is treated with antidepressants. The molecular targets of antidepressants require definition. We investigated the role of the acid sphingomyelinase (Asm)-ceramide system as a target for antidepressants. Therapeutic concentrations of the antidepressants amitriptyline and fluoxetine reduced Asm activity and ceramide concentrations in the hippocampus, increased neuronal proliferation, maturation and survival and improved behavior in mouse models of stress-induced depression. Genetic Asm deficiency abrogated these effects. Mice overexpressing Asm, heterozygous for acid ceramidase, treated with blockers of ceramide metabolism or directly injected with C16 ceramide in the hippocampus had higher ceramide concentrations and lower rates of neuronal proliferation, maturation and survival compared with controls and showed depression-like behavior even in the absence of stress. The decrease of ceramide abundance achieved by antidepressant-mediated inhibition of Asm normalized these effects. Lowering ceramide abundance may thus be a central goal for the future development of antidepressants.
This review presents recommended nomenclature for the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs), a rapidly growing class of natural products. The current knowledge regarding the biosynthesis of the >20 distinct compound classes is also reviewed, and commonalities are discussed.
Was wird unter „nachhaltiger Prävention“ in der Präventionsforschung verstanden? Welche guten Beispiele für nachhaltige Prävention gibt es in der Praxis? Und v. a.: Wie lässt sich Prävention in den verschiedenen Bereichen wie Kriminalität, Gewalt und Rechtsextremismus nachhaltig gestalten? Diesen Fragen will der vorliegende Sammelband nachgehen und damit der Präventionsdebatte neue Impulse verleihen. Der Band will insbesondere die nationale sowie internationale Fachdebatte konstruktiv aufgreifen, Theorie und Praxis verbinden, „good practice“ Beispiele darstellen sowie Perspektiven nachhaltiger Prävention aufzeigen. Mit diesem Themenspektrum richtet er sich sowohl an die Wissenschaft als auch an die Praxis sowie insgesamt an eine interessierte Öffentlichkeit.
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.