The turbidity maximum zone of the Yenisei River (Siberia) and its impact on organic and inorganic proxies

A general overview of the processes taking place in the summer mixing zone of the fresh Yenisei River water with the marine waters of the Kara Sea is given in this study, with special emphasis on the interaction between bulk (total suspended matter), inorganic (Fe, Mn) and organic (suspended organic carbon, suspended nitrogen) proxies. Within the mixing zone, a zone of enhanced turbidity (maximum turbidity zone) was observed comparable to studies in other rivers. Flocculation of particles due to changes in salinity and hydrography cause this maximum turbidity zone, and resuspension additionally enhances the turbidity in the near-bottom layers. Organic matter behaves conservatively in the mixing zone in terms of its percentage of suspended matter. It, however, undergoes degradation as revealed by amino acid data. Inorganic, redox- and salinity-sensitive, proxies (Mn, Fe) behave non-conservatively. Dissolved iron is removed at low salinities (<2) due to precipitation of iron oxyhydroxides and adsorption of manganese on suspended particles, enhancing the Mn/Al ratio of the suspended matter in the same zone. At higher salinities within the mixing zone, Fe/Al and Mn/Al ratios of the suspended particles are depleted due to resuspension of sediment with lower Fe/Al and Mn/Al ratios. Dissolved manganese concentrations are significantly higher in the near-bottom layers of the mixing zone due to release from the anoxic sediment. All things considered, the Yenisei River mixing zone shows patterns similar to other world's rivers

A metabolomics approach to reveal the mechanism of developmental toxicity in zebrafish embryos exposed to 6-propyl-2-thiouracil

A crucial component of a substance registration and regulation is the evaluation of human prenatal developmental toxicity. Current toxicological tests are based on mammalian models, but these are costly, time consuming and may pose ethical concerns. The zebrafish embryo has evolved as a promising alternative model to study developmental toxicity. However, the implementation of the zebrafish embryotoxicity test is challenged by lacking information on the relevance of observed morphological alterations in fish for human developmental toxicity. Elucidating the mechanism of toxicity could help to overcome this limitation. Through LC-MS/MS and GC-MS metabolomics, we investigated whether changes to the endogenous metabolites can indicate pathways associated with developmental toxicity. To this aim, zebrafish embryos were exposed to different concentrations of 6-propyl-2-thiouracil (PTU), a compound known to induce developmental toxicity. The reproducibility and the concentration-dependence of the metabolome response and its association with morphological alterations were studied. Major morphological findings were reduced eye size, and other craniofacial anomalies; major metabolic changes included increased tyrosine, pipecolic acid and lysophosphatidylcholine levels, decreased methionine levels, and disturbance of the ‘Phenylalanine, tyrosine and tryptophan biosynthesis’ pathway. This pathway, and the changes in tyrosine and pipecolic acid levels could be linked to the mode of action of PTU, i.e., inhibition of thyroid peroxidase (TPO). The other findings suggested neurodevelopmental impairments. This proof-of-concept study demonstrated that metabolite changes in zebrafish embryos are robust and provide mechanistic information associated with the mode of action of PTU

Application of high throughput in vitro metabolomics for hepatotoxicity mode of action characterization and mechanistic-anchored point of departure derivation: a case study with nitrofurantoin

Omics techniques have been increasingly recognized as promising tools for Next Generation Risk Assessment. Targeted metabolomics offer the advantage of providing readily interpretable mechanistic information about perturbed biological pathways. In this study, a high-throughput LC–MS/MS-based broad targeted metabolomics system was applied to study nitrofurantoin metabolic dynamics over time and concentration and to provide a mechanistic-anchored approach for point of departure (PoD) derivation. Upon nitrofurantoin exposure at five concentrations (7.5 µM, 15 µM, 20 µM, 30 µM and 120 µM) and four time points (3, 6, 24 and 48 h), the intracellular metabolome of HepG2 cells was evaluated. In total, 256 uniquely identified metabolites were measured, annotated, and allocated in 13 different metabolite classes. Principal component analysis (PCA) and univariate statistical analysis showed clear metabolome-based time and concentration effects. Mechanistic information evidenced the differential activation of cellular pathways indicative of early adaptive and hepatotoxic response. At low concentrations, effects were seen mainly in the energy and lipid metabolism, in the mid concentration range, the activation of the antioxidant cellular response was evidenced by increased levels of glutathione (GSH) and metabolites from the de novo GSH synthesis pathway. At the highest concentrations, the depletion of GSH, together with alternations reflective of mitochondrial impairments, were indicative of a hepatotoxic response. Finally, a metabolomics-based PoD was derived by multivariate PCA using the whole set of measured metabolites. This approach allows using the entire dataset and derive PoD that can be mechanistically anchored to established key events. Our results show the suitability of high throughput targeted metabolomics to investigate mechanisms of hepatoxicity and derive point of departures that can be linked to existing adverse outcome pathways and contribute to the development of new ones

Atlas der Stadt- und Regionalentwicklung 2022: Unter besonderer Berücksichtigung der räumlichen Auswirkungen von COVID-19

Der Ausbruch der COVID-19-Pandemie im Jahr 2020 hat massive Einschnitte für Gesellschaft und Wirtschaft nach sich gezogen. Kontaktbeschränkungen, Schulschließungen, Homeoffice und Maskenpflicht veränderten den Alltag aller Menschen. Die Pandemie hat Gewissheiten in Frage gestellt, aber auch den Blick auf Herausforderungen in Gesellschaft, Wirtschaft und Verwaltung geschärft. Sie hat den Weg geöffnet für neue Formen der mobilen Arbeit. Sie hat Debatten um soziale Ungleichheit und unterschiedliche Bildungschancen befeuert. Die Pandemie hat gezeigt, wie staatliche Instrumente wie das Kurzarbeitergeld die Arbeitsmärkte wirksam gestützt haben. Sie hat den Blick auf die Zukunft der Innenstädte gelenkt und Impulse für die Verkehrswende gesetzt. Und sie hat deutlich gemacht, dass die Digitalisierung in allen Bereichen noch schneller vorangehen muss als bisher. Der vorliegende Atlas umreißt in Karten und Abbildungen die Entwicklungen in den Teilräumen Deutschlands und über Daten erfassbare Veränderungen zwischen 2020, dem ersten Pandemiejahr, und 2019. In Teilbereichen liegen auch schon kleinräumige Informationen für das zweite Pandemiejahr 2021 vor. Welche Veränderungen sind bereits kurzfristig zur "vorpandemischen Normalität" beobachtbar? Lassen sich die vermuteten Veränderungen überhaupt in den Kennzahlen und Entwicklungsverläufen der Regionen ablesen? Wie groß sind die regionalen Unterschiede hinsichtlich u.a. der demografischen, sozialen, Siedlungsstruktur; welche werden durch die Pandemie verstärkt? Die datengestützten Einschätzungen zum COVID-19-Effekt auf die regionalen Entwicklungen wird über Forschungsergebnisse und Literatur untermauert. In vielen Fällen wirkt sich die Pandemie beschleunigend auf Entwicklungen, die sich bereits vor der Pandemie abzeichneten

DNA methylome analysis in Burkitt and follicular lymphomas identifies differentially methylated regions linked to somatic mutation and transcriptional control

Although Burkitt lymphomas and follicular lymphomas both have features of germinal center B cells, they are biologically and clinically quite distinct. Here we performed whole-genome bisulfite, genome and transcriptome sequencing in 13 IG-MYC translocation-positive Burkitt lymphoma, nine BCL2 translocation-positive follicular lymphoma and four normal germinal center B cell samples. Comparison of Burkitt and follicular lymphoma samples showed differential methylation of intragenic regions that strongly correlated with expression of associated genes, for example, genes active in germinal center dark-zone and light-zone B cells. Integrative pathway analyses of regions differentially methylated in Burkitt and follicular lymphomas implicated DNA methylation as cooperating with somatic mutation of sphingosine phosphate signaling, as well as the TCF3-ID3 and SWI/SNF complexes, in a large fraction of Burkitt lymphomas. Taken together, our results demonstrate a tight connection between somatic mutation, DNA methylation and transcriptional control in key B cell pathways deregulated differentially in Burkitt lymphoma and other germinal center B cell lymphomas

Identification of Disparities in Personalized Cancer Care—A Joint Approach of the German WERA Consortium

(1) Background: molecular tumor boards (MTBs) are crucial instruments for discussing and allocating targeted therapies to suitable cancer patients based on genetic findings. Currently, limited evidence is available regarding the regional impact and the outreach component of MTBs; (2) Methods: we analyzed MTB patient data from four neighboring Bavarian tertiary care oncology centers in Würzburg, Erlangen, Regensburg, and Augsburg, together constituting the WERA Alliance. Absolute patient numbers and regional distribution across the WERA-wide catchment area were weighted with local population densities; (3) Results: the highest MTB patient numbers were found close to the four cancer centers. However, peaks in absolute patient numbers were also detected in more distant and rural areas. Moreover, weighting absolute numbers with local population density allowed for identifying so-called white spots—regions within our catchment that were relatively underrepresented in WERA MTBs; (4) Conclusions: investigating patient data from four neighboring cancer centers, we comprehensively assessed the regional impact of our MTBs. The results confirmed the success of existing collaborative structures with our regional partners. Additionally, our results help identifying potential white spots in providing precision oncology and help establishing a joint WERA-wide outreach strategy

Azimuthal anisotropy of charged jet production in root s(NN)=2.76 TeV Pb-Pb collisions

We present measurements of the azimuthal dependence of charged jet production in central and semi-central root s(NN) = 2.76 TeV Pb-Pb collisions with respect to the second harmonic event plane, quantified as nu(ch)(2) (jet). Jet finding is performed employing the anti-k(T) algorithm with a resolution parameter R = 0.2 using charged tracks from the ALICE tracking system. The contribution of the azimuthal anisotropy of the underlying event is taken into account event-by-event. The remaining (statistical) region-to-region fluctuations are removed on an ensemble basis by unfolding the jet spectra for different event plane orientations independently. Significant non-zero nu(ch)(2) (jet) is observed in semi-central collisions (30-50% centrality) for 20 <p(T)(ch) (jet) <90 GeV/c. The azimuthal dependence of the charged jet production is similar to the dependence observed for jets comprising both charged and neutral fragments, and compatible with measurements of the nu(2) of single charged particles at high p(T). Good agreement between the data and predictions from JEWEL, an event generator simulating parton shower evolution in the presence of a dense QCD medium, is found in semi-central collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe

Forward-central two-particle correlations in p-Pb collisions at root s(NN)=5.02 TeV

Two-particle angular correlations between trigger particles in the forward pseudorapidity range (2.5 2GeV/c. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B. V.Peer reviewe