76 research outputs found

    Activation of Nrf2 by electrophiles is largely independent of the selenium status of HepG2 cells

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    Selenoenzymes, whose activity depends on adequate selenium (Se) supply, and phase II enzymes, encoded by target genes of nuclear factor erythroid 2-related factor 2 (Nrf2), take part in governing cellular redox homeostasis. Their interplay is still not entirely understood. Here, we exposed HepG2 hepatoma cells cultured under Se-deficient, Se-adequate, or Se-supranutritional conditions to the Nrf2 activators sulforaphane, cardamonin, or diethyl maleate. Nrf2 protein levels and intracellular localization were determined by immunoblotting, and mRNA levels of Nrf2 target genes and selenoproteins were assessed by qRT-PCR. Exposure to electrophiles resulted in rapid induction of Nrf2 and its enrichment in the nucleus, independent of the cellular Se status. All three electrophilic compounds caused an enhanced expression of Nrf2 target genes, although with differences regarding extent and time course of their induction. Whereas Se status did not significantly affect mRNA levels of the Nrf2 target genes, gene expression of selenoproteins with a low position in the cellular “selenoprotein hierarchy”, such as glutathione peroxidase 1 (GPX1) or selenoprotein W (SELENOW), was elevated under Se-supplemented conditions, as compared to cells held in Se-deficient media. In conclusion, no major effect of Se status on Nrf2 signalling was observed in HepG2 cells

    Draft genome sequence of the marine Rhodobacteraceae strain O3.65, cultivated from oil-polluted seawater of the Deepwater Horizon oil spill

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    The marine alphaproteobacterium strain O3.65 was isolated from an enrichment culture of surface seawater contaminated with weathered oil (slicks) from the Deepwater Horizon (DWH) oil spill and belongs to the ubiquitous, diverse and ecological relevant Roseobacter group within the Rhodobacteraceae. Here, we present a preliminary set of physiological features of strain O3.65 and a description and annotation of its draft genome sequence. Based on our data we suggest potential ecological roles of the isolate in the degradation of crude oil within the network of the oil-enriched microbial community. The draft genome comprises 4,852,484 bp with 4,591 protein-coding genes and 63 RNA genes. Strain O3.65 utilizes pentoses, hexoses, disaccharides and amino acids as carbon and energy source and is able to grow on several hydroxylated and substituted aromatic compounds. Based on 16S rRNA gene comparison the closest described and validated strain is Phaeobacter inhibens DSM 17395, however, strain O3.65 is lacking several phenotypic and genomic characteristics specific for the genus Phaeobacter. Phylogenomic analyses based on the whole genome support extensive genetic exchange of strain O3.65 with members of the genus Ruegeria, potentially by using the secretion system type IV. Our physiological observations are consistent with the genomic and phylogenomic analyses and support that strain O3.65 is a novel species of a new genus within the Rhodobacteraceae

    Systemic availability of lipophilic organic UV filters through dermal sunscreen exposure

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    Background Chemical UV filters are common components in sunscreens and cosmetic products and used to protect the skin against harmful effects of sunlight like sunburn. However, the effectiveness of sunscreens in the prevention of skin cancer is in some parts still controversial. Meanwhile, questions about negative effects of the chemical UV filters on human health arise and request an effective risk assessment. Real-life exposure data in humans after application of these products are still rare. Thus, we explored whether and to what extent UV filters are absorbed through the skin into the human body. Material and methods Plasma and urine samples from 20 healthy volunteers were collected before, during and after a real-life exposure scenario (1st application: 2 mg/cm2; 2nd and 3rd (after 2 and 4 h): 1 mg/cm2 each) using a commercial sunscreen formulation for one day. These samples were analyzed for their content of the currently prominent UV filters octocrylene and avobenzone as well as 2-cyano-3,3-diphenylacrylic acid (CDAA) as the main octocrylene metabolite by using different liquid chromatography electrospray-ionization tandem mass spectrometric procedures. Results Following dermal sunscreen exposure, avobenzone, octocrylene and CDAA reached concentrations up to 11â€ŻÎŒg/L, 25â€ŻÎŒg/L and 1352â€ŻÎŒg/L in plasma. In urine detection rates of avobenzone and octocrylene were low while CDAA showed a high detection rate and reached up to 5207â€ŻÎŒg/g creatinine. Kinetic models could be fitted for octocrylene and CDAA in plasma and CDAA in urine. Concentration peaks were reached between 10 and 16 h after first application and half-life periods were in the range of 1.5 to 2 days. The lipophilic UV filter octocrylene and its metabolite CDAA showed a much slower elimination than other more hydrophilic UV filters. Concordantly, the metabolite CDAA in particular showed a markedly increased renal excretion over the whole sampling period and indicated high internal exposure to OC. Discussion Real-life sunscreen usage leads to considerable bioavailability of organic UV filters and their metabolites which is rarely seen for other environmental exposures. A combined monitoring of the parent compound and its metabolites is important to fully address internal exposure to the UV filter in humans. Considering the kinetic profiles a prolonged systemic release due to depot formation in skin and a potential accumulation through multi-day exposure is presumed. High in-vivo loads call for a critical toxicological assessment of the UV filters and their metabolites

    Forschungsdaten und Bibliometrie: Neue Services fĂŒr die Wissenschaft

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    Die gezielte UnterstĂŒtzung universitĂ€rer Forschung ist fĂŒr UniversitĂ€tsbibliotheken keine neue Herausforderung, denn die bedarfsgerechte Erwerbung und Erschließung relevanter Fachinformationen sowie die GewĂ€hrleistung des Zugangs zu den benötigten Medien sind ihre zentralen Aufgaben. Neu an dieser Herausforderung sind die schier unerschöpflichen Möglichkeiten der Informationsversorgung, die aus der digitalen Medienrevolution und der rasanten Entwicklung der Informationstechnologie erwachsen. Die Wissenschaftler/-innen erwarten einen umfassenden, schnellen, komfortablen und jederzeit störungsfreien Zugang zu den Informationsquellen. Der direkte Weg vom bibliographischen Nachweis aus Katalogen und Datenbanken zum elektronisch verfĂŒgbaren Volltext wird – mindestens bei den MINT-FĂ€chern (Mathematik, Informatik, Naturwissenschaften, Technik) – mittlerweile als Standard angesehen. Bibliothekarische Angebote wie Schulungen zur Förderung der Informations- und Medienkompetenz, Literaturverwaltung, Publikationsserver haben das bibliothekarische Portfolio in den letzten Jahren erweitert und zĂ€hlen inzwischen zum bibliothekarischen AlltagsgeschĂ€ft

    Genetic Regulation of Cytokine Response in Patients with Acute Community-Acquired Pneumonia

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    Background: Community-acquired pneumonia (CAP) is an acute disease condition with a high risk of rapid deteriorations. We analysed the influence of genetics on cytokine regulation to obtain a better understanding of patient’s heterogeneity. Methods: For up to N = 389 genotyped participants of the PROGRESS study of hospitalised CAP patients, we performed a genome-wide association study of ten cytokines IL-1ÎČ, IL-6, IL-8, IL-10, IL-12, MCP-1 (MCAF), MIP-1α (CCL3), VEGF, VCAM-1, and ICAM-1. Consecutive secondary analyses were performed to identify independent hits and corresponding causal variants. Results: 102 SNPs from 14 loci showed genome-wide significant associations with five of the cytokines. The most interesting associations were found at 6p21.1 for VEGF (p = 1.58 × 10−20), at 17q21.32 (p = 1.51 × 10−9) and at 10p12.1 (p = 2.76 × 10−9) for IL-1ÎČ, at 10p13 for MIP-1α (CCL3) (p = 2.28 × 10−9), and at 9q34.12 for IL-10 (p = 4.52 × 10−8). Functionally plausible genes could be assigned to the majority of loci including genes involved in cytokine secretion, granulocyte function, and cilial kinetics. Conclusion: This is the first context-specific genetic association study of blood cytokine concentrations in CAP patients revealing numerous biologically plausible candidate genes. Two of the loci were also associated with atherosclerosis with probable common or consecutive pathomechanisms

    Model-based analysis of an adaptive evolution experiment with Escherichia coli in a pyruvate limited continuous culture with glycerol

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    Bacterial strains that were genetically blocked in important metabolic pathways and grown under selective conditions underwent a process of adaptive evolution: certain pathways may have been deregulated and therefore allowed for the circumvention of the given block. A block of endogenous pyruvate synthesis from glycerol was realized by a knockout of pyruvate kinase and phosphoenolpyruvate carboxylase in E. coli. The resulting mutant strain was able to grow on a medium containing glycerol and lactate, which served as an exogenous pyruvate source. Heterologous expression of a pyruvate carboxylase gene from Corynebacterium glutamicum was used for anaplerosis of the TCA cycle. Selective conditions were controlled in a continuous culture with limited lactate feed and an excess of glycerol feed. After 200–300 generations pyruvate-prototrophic mutants were isolated. The genomic analysis of an evolved strain revealed that the genotypic basis for the regained pyruvate-prototrophy was not obvious. A constraint-based model of the metabolism was employed to compute all possible detours around the given metabolic block by solving a hierarchy of linear programming problems. The regulatory network was expected to be responsible for the adaptation process. Hence, a Boolean model of the transcription factor network was connected to the metabolic model. Our model analysis only showed a marginal impact of transcriptional control on the biomass yield on substrate which is a key variable in the selection process. In our experiment, microarray analysis confirmed that transcriptional control probably played a minor role in the deregulation of the alternative pathways for the circumvention of the block

    Cross-realm assessment of climate change impacts on species' abundance trends

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    Climate change, land-use change, pollution and exploitation are among the main drivers of species' population trends; however, their relative importance is much debated. We used a unique collection of over 1,000 local population time series in 22 communities across terrestrial, freshwater and marine realms within central Europe to compare the impacts of long-term temperature change and other environmental drivers from 1980 onwards. To disentangle different drivers, we related species' population trends to species- and driver-specific attributes, such as temperature and habitat preference or pollution tolerance. We found a consistent impact of temperature change on the local abundances of terrestrial species. Populations of warm-dwelling species increased more than those of cold-dwelling species. In contrast, impacts of temperature change on aquatic species' abundances were variable. Effects of temperature preference were more consistent in terrestrial communities than effects of habitat preference, suggesting that the impacts of temperature change have become widespread for recent changes in abundance within many terrestrial communities of central Europe.Additionally, we appreciate the open access marine data provided by the International Council for the Exploration of the Sea. We thank the following scientists for taxonomic or technical advice: C. Brendel, T. Caprano, R. Claus, K. Desender, A. Flakus, P. R. Flakus, S. Fritz, E.-M. Gerstner, J.-P. Maelfait, E.-L. Neuschulz, S. Pauls, C. Printzen, I. Schmitt and H. Turin, and I. Bartomeus for comments on a previous version of the manuscript. R.A. was supported by the EUproject LIMNOTIP funded under the seventh European Commission Framework Programme (FP7) ERA-Net Scheme (Biodiversa, 01LC1207A) and the long-term ecological research program at the Leibniz-Institute of Freshwater Ecology and Inland Fisheries (IGB). R.W.B. was supported by the Scottish Government Rural and Environment Science and Analytical Services Division (RESAS) through Theme 3 of their Strategic Research Programme. S.D. acknowledges support of the German Research Foundation DFG (grant DO 1880/1-1). S.S. acknowledges the support from the FP7 project EU BON (grant no. 308454). S.K., I.KĂŒ. and O.S. acknowledge funding thorough the Helmholtz Association’s Programme Oriented Funding, Topic ‘Land use, biodiversity, and ecosystem services: Sustaining human livelihoods’. O.S. also acknowledges the support from FP7 via the Integrated Project STEP (grant no. 244090). D.E.B. was funded by a Landes–Offensive zur Entwicklung Wissenschaftlich–ökonomischer Exzellenz (LOEWE) excellence initiative of the Hessian Ministry for Science and the Arts and the German Research Foundation (DFG: Grant no. BO 1221/23-1).Peer Reviewe

    Update on the diagnosis and treatment of neuromyelitis optica spectrum disorders (NMOSD) – revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part II: Attack therapy and long-term management

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    TRY plant trait database – enhanced coverage and open access

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    Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives
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