Refine
Year of publication
Document Type
- Article (21)
- Postprint (5)
- Review (2)
- Part of Periodical (1)
- Working Paper (1)
Is part of the Bibliography
- yes (30)
Keywords
- Antarctica (2)
- Carlini Station (2)
- Chytridiomycota (2)
- Illumina amplicon sequencing (2)
- Russia’s invasion of Ukraine (2)
- acute kidney injury (2)
- aquatic fungi (2)
- end-stage kidney disease (2)
- genome-wide association (2)
- phytoplankton host (2)
Institute
- Institut für Biochemie und Biologie (16)
- Hasso-Plattner-Institut für Digital Engineering GmbH (3)
- Fachgruppe Volkswirtschaftslehre (2)
- Institut für Chemie (2)
- Institut für Umweltwissenschaften und Geographie (2)
- Department Sport- und Gesundheitswissenschaften (1)
- Dezernat 2: Studienangelegenheiten (1)
- Fakultät für Gesundheitswissenschaften (1)
- Mathematisch-Naturwissenschaftliche Fakultät (1)
Specialized glial subtypes provide support to developing and functioning neural networks. Astrocytes modulate information processing by neurotransmitter recycling and release of neuromodulatory substances, whereas ensheathing glial cells have not been associated with neuromodulatory functions yet. To decipher a possible role of ensheathing glia in neuronal information processing, we screened for glial genes required in the Drosophila central nervous system for normal locomotor behavior. Shopper encodes a mitochondrial sulfite oxidase that is specifically required in ensheathing glia to regulate head bending and peristalsis. shopper mutants show elevated sulfite levels affecting the glutamate homeostasis which then act on neuronal network function. Interestingly, human patients lacking the Shopper homolog SUOX develop neurological symptoms, including seizures. Given an enhanced expression of SUOX by oligodendrocytes, our findings might indicate that in both invertebrates and vertebrates more than one glial cell type may be involved in modulating neuronal activity.
Specialized glial subtypes provide support to developing and functioning neural networks. Astrocytes modulate information processing by neurotransmitter recycling and release of neuromodulatory substances, whereas ensheathing glial cells have not been associated with neuromodulatory functions yet. To decipher a possible role of ensheathing glia in neuronal information processing, we screened for glial genes required in the Drosophila central nervous system for normal locomotor behavior. Shopper encodes a mitochondrial sulfite oxidase that is specifically required in ensheathing glia to regulate head bending and peristalsis. shopper mutants show elevated sulfite levels affecting the glutamate homeostasis which then act on neuronal network function. Interestingly, human patients lacking the Shopper homolog SUOX develop neurological symptoms, including seizures. Given an enhanced expression of SUOX by oligodendrocytes, our findings might indicate that in both invertebrates and vertebrates more than one glial cell type may be involved in modulating neuronal activity.
The homodinuclear ruthenium(II) complex [{Ru(l-N4Me2)}(2)(-tape)](PF6)(4) {[1](PF6)(4)} (l-N4Me2=N,N-dimethyl-2,11-diaza[3.3](2,6)-pyridinophane, tape=1,6,7,12-tetraazaperylene) can store one or two electrons in the energetically low-lying * orbital of the bridging ligand tape. The corresponding singly and doubly reduced complexes [{Ru(l-N4Me2)}(2)(-tape(.-))](PF6)(3) {[2](PF6)(3)} and [{Ru(l-N4Me2)}(2)(-tape(2-))](PF6)(2) {[3](PF6)(2)}, respectively, were electrochemically generated, successfully isolated and fully characterized by single-crystal X-ray crystallography, spectroscopic methods and magnetic susceptibility measurements. The singly reduced complex [2](PF6)(3) contains the -radical tape(.-) and the doubly reduced [3](PF6)(2) the diamagnetic dianion tape(2-) as bridging ligand, respectively. Nucleophilic aromatic substitution at the bridging tape in [1](4+) by two sulfite units gave the complex [{Ru(l-N4Me2)}(2){-tape-(SO3)(2)}](2+) ([4](2+)). Complex dication [4](2+) was exploited as a redox mediator between an anaerobic homogenous reaction solution of an enzyme system (sulfite/sulfite oxidase) and the electrode via participation of the low-energy *-orbital of the disulfonato-substituted bridging ligand tape-(SO3)(2)(2-) (E-red1=-0.1V versus Ag/AgCl/1m KCl in water).
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.
Iron-sulfur (Fe-S) clusters are essential protein cofactors. In enzymes, they are present either in the rhombic [2Fe-2S] or the cubic [4Fe-4S] form, where they are involved in catalysis and electron transfer and in the biosynthesis of metal-containing prosthetic groups like the molybdenum cofactor (Moco). Here, we give an overview of the assembly of Fe-S clusters in bacteria and humans and present their connection to the Moco biosynthesis pathway. In all organisms, Fe-S cluster assembly starts with the abstraction of sulfur froml-cysteine and its transfer to a scaffold protein. After formation, Fe-S clusters are transferred to carrier proteins that insert them into recipient apo-proteins. In eukaryotes like humans and plants, Fe-S cluster assembly takes place both in mitochondria and in the cytosol. Both Moco biosynthesis and Fe-S cluster assembly are highly conserved among all kingdoms of life. Moco is a tricyclic pterin compound with molybdenum coordinated through its unique dithiolene group. Moco biosynthesis begins in the mitochondria in a Fe-S cluster dependent step involving radical/S-adenosylmethionine (SAM) chemistry. An intermediate is transferred to the cytosol where the dithiolene group is formed, to which molybdenum is finally added. Further connections between Fe-S cluster assembly and Moco biosynthesis are discussed in detail.
Das prolongierte Weaning von Patienten mit neurologischen oder neurochirurgischen Erkrankungen weist Besonderheiten auf, denen die Deutsche Gesellschaft für Neurorehabilitation e. V. in einer eigenen Leitlinie Rechnung trägt.
Im Hinblick auf Definitionen (z. B. Weaningerfolg und -versagen), Weaningkategorien, Pathophysiologie des Weaningversagens und allgemeine Weaningstrategien wird ausdrücklich auf die aktuelle S2k-Leitlinie der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e. V. verwiesen.
In der neurologisch-neurochirurgischen Frührehabilitation werden Patienten mit zentralen Störungen der Atmungsregulation (z. B. Hirnstammläsionen), des Schluckaktes (neurogene Dysphagien), mit neuromuskulären Problemen (z. B. Critical-illness-Polyneuropathie, Guillain-Barre-Syndrom, Querschnittlähmungen, Myasthenia gravis) und/oder kognitiven Störungen (z. B. Bewusstseins- und Vigilanzstörungen, schwere Kommunikationsstörungen) versorgt, deren Betreuung bei der Entwöhnung von der Beatmung neben intensivmedizinischer Kompetenz auch neurologische bzw. neurochirurgische und neurorehabilitative Expertise erfordert. In Deutschland wird diese Kompetenz in Zentren der neurologisch-neurochirurgischen Frührehabilitation vorgehalten, und zwar als Krankenhausbehandlung.
Der Leitlinie liegt eine systematische Recherche von Leitliniendatenbanken und Medline zugrunde. Unter Moderation durch die Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) erfolgte die Konsensfindung mittels nominalen Gruppenprozesses und Delphi-Verfahren.
In der vorliegenden Leitlinie der DGNR wird auf die strukturellen und inhaltlichen Besonderheiten der neurologisch-neurochirurgischen Frührehabilitation sowie vorhandene Studien zum Weaning in Frührehabilitationseinrichtungen eingegangen.
Adressaten der Leitlinie sind Neurologen, Neurochirurgen, Anästhesisten, Palliativmediziner, Logopäden, Intensivpflegekräfte, Ergotherapeuten, Physiotherapeuten und Neuropsychologen. Ferner richtet sich diese Leitlinie zur Information an Fachärzte für Physikalische Medizin und Rehabilitation (PMR), Pneumologen, Internisten, Atmungstherapeuten, den Medizinischen Dienst der Krankenkassen (MDK) und des Spitzenverbands Bund der Krankenkassen e. V. (MDS). Das wesentliche Ziel dieser Leitlinie ist es, den aktuellen Wissensstand zum Thema „Prolongiertes Weaning in der neurologisch-neurochirurgischen Frührehabilitation“ zu vermitteln.
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.