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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.
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.
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.
We applied coarse spectral analysis to more than 2 decades of daily near-surface water temperature (WT) measurements from Muggelsee, a shallow polymictic lake in Germany, to systematically characterize patterns in WT variability from daily to yearly temporal scales. Comparison of WT with local air temperature indicates that the WT variability patterns are likely attributable to both meteorological forcing and internal lake dynamics. We identified seasonal patterns of WT variability and showed that WT variability increases with increasing Schmidt stability, decreasing Lake number and decreasing ice cover duration, and is higher near the shore than in open water. We introduced the slope of WT spectra as an indicator for the degree of lake mixing to help explain the identified temporal and spatial scales of WT variability. The explanatory power of this indicator in other lakes with different mixing regimes remains to be established.
State variables in lake ecosystems are subject to processes that act on different time scales. The relative importance of each of these processes changes over time, e.g., due to varying constraints of physical, biological, and biogeochemical processes. Correspondingly, continuous automatic measurements at high temporal resolution often reveal intriguing patterns that can rarely be directly ascribed to single processes. In light of the rather complex interplay of such processes, disentangling them requires more powerful methods than researchers have applied up to this point. For this reason, we tested the potential of wavelet coherence, based on the assumption that different processes result in correlations between different variables, on different time scales and during different time windows across the seasons. The approach was tested on a set of multivariate hourly data measured between the onset of an ice cover and a cyanobacterial summer bloom in the year 2009 in the Muggelsee, a polymictic eutrophic lake. We found that processes such as photosynthesis and respiration, the growth and decay of phytoplankton biomass, dynamics in the CO2-carbonate system, wind-induced resuspension of particles, and vertical mixing all occasionally served as dominant drivers of the variability in our data. We therefore conclude that high-resolution data and a method capable of analyzing time series in both the time and the frequency domain can help to enhance our understanding of the time scales and processes responsible for the high variability in driver variables and response variables, which in turn can lay the ground for mechanistic analyses.
Phytoplankton biomass and production regulates key aspects of freshwater ecosystems yet its variability and subsequent predictability is poorly understood. We estimated within-lake variation in biomass using high-frequency chlorophyll fluorescence data from 18 globally distributed lakes. We tested how variation in fluorescence at monthly, daily, and hourly scales was related to high-frequency variability of wind, water temperature, and radiation within lakes as well as productivity and physical attributes among lakes. Within lakes, monthly variation dominated, but combined daily and hourly variation were equivalent to that expressed monthly. Among lakes, biomass variability increased with trophic status while, within-lake biomass variation increased with increasing variability in wind speed. Our results highlight the benefits of high-frequency chlorophyll monitoring and suggest that predicted changes associated with climate, as well as ongoing cultural eutrophication, are likely to substantially increase the temporal variability of algal biomass and thus the predictability of the services it provides.
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.
Bericht über die Arbeit des Menschenrechtsausschusses der Vereinten Nationen im Jahr 2004 - Teil 1 • Die Förderung sozialer Menschenrechte durch nicht-staatliche Organisationen • Die Afrikanische Union und der Afrikanische Menschenrechtsgerichtshof • Der Aristoteles des schiitischen Islam Eindrücke von einem Kant-Seminar in Teheran
The central aim of this thesis is to demonstrate the benefits of innovative frequency-based methods to better explain the variability observed in lake ecosystems. Freshwater ecosystems may be the most threatened part of the hydrosphere. Lake ecosystems are particularly sensitive to changes in climate and land use because they integrate disturbances across their entire catchment. This makes understanding the dynamics of lake ecosystems an intriguing and important research priority. This thesis adds new findings to the baseline knowledge regarding variability in lake ecosystems. It provides a literature-based, data-driven and methodological framework for the investigation of variability and patterns in environmental parameters in the time frequency domain.
Observational data often show considerable variability in the environmental parameters of lake ecosystems. This variability is mostly driven by a plethora of periodic and stochastic processes inside and outside the ecosystems. These run in parallel and may operate at vastly different time scales, ranging from seconds to decades. In measured data, all of these signals are superimposed, and dominant processes may obscure the signals of other processes, particularly when analyzing mean values over long time scales. Dominant signals are often caused by phenomena at long time scales like seasonal cycles, and most of these are well understood in the limnological literature. The variability injected by biological, chemical and physical processes operating at smaller time scales is less well understood. However, variability affects the state and health of lake ecosystems at all time scales. Besides measuring time series at sufficiently high temporal resolution, the investigation of the full spectrum of variability requires innovative methods of analysis.
Analyzing observational data in the time frequency domain allows to identify variability at different time scales and facilitates their attribution to specific processes. The merit of this approach is subsequently demonstrated in three case studies. The first study uses a conceptual analysis to demonstrate the importance of time scales for the detection of ecosystem responses to climate change. These responses often occur during critical time windows in the year, may exhibit a time lag and can be driven by the exceedance of thresholds in their drivers. This can only be detected if the temporal resolution of the data is high enough. The second study applies Fast Fourier Transform spectral analysis to two decades of daily water temperature measurements to show how temporal and spatial scales of water temperature variability can serve as an indicator for mixing in a shallow, polymictic lake. The final study uses wavelet coherence as a diagnostic tool for limnology on a multivariate high-frequency data set recorded between the onset of ice cover and a cyanobacteria summer bloom in the year 2009 in a polymictic lake. Synchronicities among limnological and meteorological time series in narrow frequency bands were used to identify and disentangle prevailing limnological processes.
Beyond the novel empirical findings reported in the three case studies, this thesis aims to more generally be of interest to researchers dealing with now increasingly available time series data at high temporal resolution. A set of innovative methods to attribute patterns to processes, their drivers and constraints is provided to help make more efficient use of this kind of data.
Portal Transfer
(2023)
Liebe Leserinnen und Leser, kein Nachrichtentag vergeht, an dem nicht die Expertise aus der Wissenschaft gefragt ist: Ob zum russischen Angriffskrieg in der Ukraine, zur UNKlimakonferenz in Ägypten, zur Flutkatastrophe in Pakistan, zum Dürresommer, zur Energiekrise, selbst zur umstrittenen Fußballweltmeisterschaft in Katar standen und stehen Expertinnen und Experten in den Medien Rede und Antwort. Auch aus der Universität Potsdam. Wir haben sie gefragt, wie sie damit umgehen, wie es ihnen gelingt, aus der laufenden Forschung heraus aktuelle Probleme zu bewerten. Und was davon bleibt, wenn das öffentliche Interesse abebbt. Für die Potsdamer Politik- und Verwaltungswissenschaftlerin Sabine Kuhlmann besteht die Kunst darin, „außerhalb der Krise Ideen und Lösungsansätze zu verstetigen und sie tatsächlich in die Praxis umzusetzen“.
In unserem Alumni- und Transfermagazin berichten wir davon, was und wie die Universität Potsdam dazu beiträgt. Wir erzählen, wie Erfindungen zu Innovationen in der Wirtschaft werden und sich Start-ups auf den Weg machen, ihr Produkt selbst zu vermarkten. Das Spektrum reicht von Meeresfrüchten auf Pflanzenbasis bis zu einer App, mit der sich Frühformen der Demenz erkennen lassen. Neben neuen Technologien kommt es aber vor allem darauf an, das an der Universität erzeugte Wissen in die Praxis zu transferieren. Deshalb stellen wir ein Programm zur Bekämpfung von Hassrede in der Schule vor oder auch eine Klettertherapie zur Behandlung von Skoliose. Und wir zeigen, wie eine Studie zur sportlichen Leistungskraft von Kindern helfen kann, den Sportunterricht zu verbessern.
Den größten Teil des an der Universität produzierten Wissens tragen die Studierenden in die Welt, wenn sie nach ihrem Abschluss als Musiklehrerin in einer Schule arbeiten oder als Software-Ingenieur im eigenen Unternehmen, als Geologin nach Seltenen Erden schürfen, als Ökologe ausgelaugte Böden wieder fruchtbar machen oder als Politikerin ein Ministerium leiten. Sie alle kommen in diesem Magazin zu Wort. Oder in unserem neuen Podcast „Listen.UP“, in dem Studierende, Forschende und Alumni von ihren Transferprojekten erzählen. Von der Gründerin Ulrike Böttcher erfährt man dort zum Beispiel, wie sie mit Schnallen, Ösen und Knöpfen aus Bio- Materialien die Modeindustrie in diesem Bereich nachhaltig verändern will. Nachzulesen ist das auch in diesem Heft. Immer dort, wo das „Listen. UP“-Logo erscheint, lohnt es, zusätzlich in den Podcast hineinzuhören.
Many lakes exhibit seasonal stratification, during which they develop strong thermal and chemical gradients. An expansion of depth-integrated monitoring programs has provided insight into the importance of organic carbon processing that occurs below the upper mixed layer. However, the chemical and physical drivers of metabolism and metabolic coupling remain unresolved, especially in the metalimnion. In this depth zone, sharp gradients in key resources such as light and temperature co-occur with dynamic physical conditions that influence metabolic processes directly and simultaneously hamper the accurate tracing of biological activity. We evaluated the drivers of metalimnetic metabolism and its associated uncertainty across 10 stratified lakes in Europe and North America. We hypothesized that the metalimnion would contribute highly to whole-lake functioning in clear oligotrophic lakes, and that metabolic rates would be highly variable in unstable polymictic lakes. Depth-integrated rates of gross primary production (GPP) and ecosystem respiration (ER) were modelled from diel dissolved oxygen curves using a Bayesian approach. Metabolic estimates were more uncertain below the epilimnion, but uncertainty was not consistently related to lake morphology or mixing regime. Metalimnetic rates exhibited high day-to-day variability in all trophic states, with the metalimnetic contribution to daily whole-lake GPP and ER ranging from 0% to 87% and < 1% to 92%, respectively. Nonetheless, the metalimnion of low-nutrient lakes contributed strongly to whole-lake metabolism on average, driven by a collinear combination of highlight, low surface-water phosphorous concentration and high metalimnetic volume. Consequently, a single-sensor approach does not necessarily reflect whole-ecosystem carbon dynamics in stratified lakes.