Recurrent climate winter regimes in reconstructed and modelled 500hPa geopotential height fields over the North Atlantic/European sector 1659-1990

Recurrent climate winter regimes are examined from statistically reconstructed and modelled 500hPa geopotential height fields over the North Atlantic/European sector for the period 1659-1990. We investigate the probability density function of the state space spanned by the first two empirical orthogonal functions of combined winter data. Regimes are detected as patterns that correspond to areas of the state space with an unexpected high recurrence probability using a Monte Carlo approach. The reconstruction and the model reveal four recurrent climate regimes. They correspond to the two phases of the North Atlantic Oscillation and two opposite blocking patterns. Complemented by the investigation of the temporal evolution of the climate regimes this leads to the conclusion that the reconstructed and the modelled data for this geographic sector reproduce low-frequency atmospheric variability in the form of regime-like behaviour. The overall evidence for recurrent climate regimes is higher for the model than for the reconstruction. However, comparisons with independent data sources for the period 1659-1990 revealed a more realistic temporal evolution of the regimes for the reconstructed dat

SARS-CoV-2-mediated dysregulation of metabolism and autophagy uncovers host-targeting antivirals

Viruses manipulate cellular metabolism and macromolecule recycling processes like autophagy. Dysregulated metabolism might lead to excessive inflammatory and autoimmune responses as observed in severe and long COVID-19 patients. Here we show that SARS-CoV-2 modulates cellular metabolism and reduces autophagy. Accordingly, compound-driven induction of autophagy limits SARS-CoV-2 propagation. In detail, SARS-CoV-2-infected cells show accumulation of key metabolites, activation of autophagy inhibitors (AKT1, SKP2) and reduction of proteins responsible for autophagy initiation (AMPK, TSC2, ULK1), membrane nucleation, and phagophore formation (BECN1, VPS34, ATG14), as well as autophagosome-lysosome fusion (BECN1, ATG14 oligomers). Consequently, phagophore-incorporated autophagy markers LC3B-II and P62 accumulate, which we confirm in a hamster model and lung samples of COVID-19 patients. Single-nucleus and single-cell sequencing of patient-derived lung and mucosal samples show differential transcriptional regulation of autophagy and immune genes depending on cell type, disease duration, and SARS-CoV-2 replication levels. Targeting of autophagic pathways by exogenous administration of the polyamines spermidine and spermine, the selective AKT1 inhibitor MK-2206, and the BECN1-stabilizing anthelmintic drug niclosamide inhibit SARS-CoV-2 propagation in vitro with IC(50) values of 136.7, 7.67, 0.11, and 0.13 μM, respectively. Autophagy-inducing compounds reduce SARS-CoV-2 propagation in primary human lung cells and intestinal organoids emphasizing their potential as treatment options against COVID-19

Overview of the MOSAiC expedition—Atmosphere

With the Arctic rapidly changing, the needs to observe, understand, and model the changes are essential. To support these needs, an annual cycle of observations of atmospheric properties, processes, and interactions were made while drifting with the sea ice across the central Arctic during the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) expedition from October 2019 to September 2020. An international team designed and implemented the comprehensive program to document and characterize all aspects of the Arctic atmospheric system in unprecedented detail, using a variety of approaches, and across multiple scales. These measurements were coordinated with other observational teams to explore cross-cutting and coupled interactions with the Arctic Ocean, sea ice, and ecosystem through a variety of physical and biogeochemical processes. This overview outlines the breadth and complexity of the atmospheric research program, which was organized into 4 subgroups: atmospheric state, clouds and precipitation, gases and aerosols, and energy budgets. Atmospheric variability over the annual cycle revealed important influences from a persistent large-scale winter circulation pattern, leading to some storms with pressure and winds that were outside the interquartile range of past conditions suggested by long-term reanalysis. Similarly, the MOSAiC location was warmer and wetter in summer than the reanalysis climatology, in part due to its close proximity to the sea ice edge. The comprehensiveness of the observational program for characterizing and analyzing atmospheric phenomena is demonstrated via a winter case study examining air mass transitions and a summer case study examining vertical atmospheric evolution. Overall, the MOSAiC atmospheric program successfully met its objectives and was the most comprehensive atmospheric measurement program to date conducted over the Arctic sea ice. The obtained data will support a broad range of coupled-system scientific research and provide an important foundation for advancing multiscale modeling capabilities in the Arctic

Atmospheric and Surface Processes, and Feedback Mechanisms Determining Arctic Amplification: A Review of First Results and Prospects of the (AC)3 Project

Mechanisms behind the phenomenon of Arctic amplification are widely discussed. To contribute to this debate, the (AC)3 project has been established in 2016. It comprises modeling and data analysis efforts as well as observational elements. The project has assembled a wealth of ground-based, airborne, ship-borne, and satellite data of physical, chemical, and meteorological properties of the Arctic atmosphere, cryosphere, and upper ocean that are available for the Arctic climate research community. Short-term changes and indications of long-term trends in Arctic climate parameters have been detected using existing and new data

Partially ¹³C-labeled mouse tissue as reference for LC-MS based untargeted metabolomics

The inclusion of stable isotope-labeled reference standards in the sample is an established method for the detection and relative quantification of metabolic features in untargeted metabolomics. In order to quantify as many metabolites as possible, the reference should ideally include the same metabolites in their stable isotope-labeled form as the sample under investigation. We present here an attempt to use partially C-13-labeled mouse material as internal standard for relative metabolite quantification of mouse and human samples in untargeted metabolomics. We fed mice for 14 days with a C-13-labeled Ralstonia eutropha based diet. Tissue and blood amino acids from these mice showed C-13 enrichment levels that ranged from 6% to 75%. We used MetExtract II software to automatically detect native and labeled peak pairs in an untargeted manner. In a dilution series and with the implementation of a correction factor, partially C-13-labeled mouse plasma resulted in accurate relative quantification of human plasma amino acids using liquid chromatography coupled to mass spectrometry, The coefficient of variation for the relative quantification is reduced from 27% without internal standard to 10% with inclusion of partially C-13-labeled internal standard. We anticipate the method to be of general use for the relative metabolite quantification of human specimens

Effects of Dissolved Copper on Select Hematological, Biochemical, and Immunological Parameters of Wild Rainbow Trout (Oncorhynchus Mykiss)

Rainbow trout (Oncorhynchus mykiss) were sampled from a creek in the western Sierra Nevada, Plumas County, CA, that receives run-off from a 40-ha copper (Cu) tailings pile. Reference sites included a site upstream of the Cu input and another site located on a nearby creek. Hepatic Cu concentrations were significantly elevated in trout from sites with elevated dissolved Cu concentrations compared with concentrations in trout from reference sites. Trout at the Cu-contaminated sites also exhibited decreased hematocrit (Hct), leukocrit (Lct), and percentage of lymphocytes in blood compared to trout from reference sites. The percentage of monocytes in blood and respiratory burst activity were affected by gender and age, respectively. Condition factor, percentage of neutrophils in blood, muscle glycogen and protein, and plasma acetylcholinesterase were not affected by dissolved Cu concentration or gender. Age also did not appear to be a factor. The data from this study support the use of immune system parameters to assess alterations in salmonids experiencing prolonged exposure to low-level Cu contamination and illustrate the variability in physiological responses of wild fish caused by demographic features. Overall, of the parameters measured, Hct, Lct, and percentage of lymphocytes in blood appeared to offer robust measures for assessing effects of metals on wild fish and did not appear affected by select demographic features