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Many bacteria act pathogenic by the release of AB-type protein toxins that efficiently enter human or animal cells and act as enzymes in their cytosol. This leads to disturbed cell functions and the clinical symptoms characteristic for the individual toxin. Therefore, molecules that directly target and neutralize these toxins provide promising novel therapeutic options. Here, we found that the FDA-approved drug disulfiram (DSF), used for decades to treat alcohol abuse, protects cells from intoxication with diphtheria toxin (DT) from Corynebacterium diphtheria, the causative agent of diphtheria, lethal toxin (LT) from Bacillus anthracis, which contributes to anthrax, and C2 enterotoxin from Clostridium botulinum when applied in concentrations lower than those found in plasma of patients receiving standard DSF treatment for alcoholism (up to 20 µM). Moreover, this inhibitory effect is increased by copper, a known enhancer of DSF activity. LT and C2 are binary toxins, consisting of two non-linked proteins, an enzyme (A) and a separate binding/transport (B) subunit. To act cytotoxic, their proteolytically activated B subunits PA63 and C2IIa, respectively, form barrel-shaped heptamers that bind to their cellular receptors and form complexes with their respective A subunits LF and C2I. The toxin complexes are internalized via receptor-mediated endocytosis and in acidified endosomes, PA63 and C2IIa form pores in endosomal membranes, which facilitate translocation of LF and C2I into the cytosol, where they act cytotoxic. In DT, A and B subunits are located within one protein, but DT also forms pores in endosomes that facilitate translocation of the A subunit. If cell binding, membrane translocation, or substrate modification is inhibited, cells are protected from intoxication. Our results implicate that DSF neither affects cellular binding nor the catalytic activity of the investigated toxins to a relevant extend, but interferes with the toxin pore-mediated translocation of the A subunits of DT, LT and C2 toxin, as demonstrated by membrane-translocation assays and toxin pore conductivity experiments in the presence or absence of DSF. Since toxin translocation across intracellular membranes represents a central step during cellular uptake of many bacterial toxins, DSF might neutralize a broad spectrum of medically relevant toxins.

Mountainous grassland soils are considered one of the most unique biological hotspots, rich in organic carbon (OC). At the same time, they are exposed to great threats, as climate warming is more pronounced in mountainous regions than in lowland areas. In this study, we assessed the effect of simulated warming (+1K, +2K, and + 3 K) on OC stocks and soil structure in grassland soils of the Northern Limestone Alps in Germany by translocating plant-soil mesocosms from high- (1260 m a.s.l., Rendzic Phaeozem) and mid- (860 m a. s. l., Haplic Cambisol) to low-elevation (600 m a.s.l). Plant-soil mesocosms were exposed to both extensive and intensive grassland management practices. Four years after translocation, we observed a rapid decrease of topsoil SOC stocks under intensive (−1.0 t C ha yr−1) and extensive management (-2.2 t C ha yr−1), under the highest temperature increase. Intensive management with about 1 t C ha−1 yr−1 higher manure C return than extensive management (1.6 vs. 0.8 t C ha−1 yr−1 intensive and extensive, respectively) may explain the difference in SOC losses between different management treatments. Under both management practices, the loss of SOC was mainly associated with a decrease of large macroaggregates, at both management practices. In addition, different aggregate specific OC loss rates resulted in an altered distribution of OC among the aggregate size classes. Our study provides evidence that simulated climate change induced a rapid and substantial decline of SOC in mountainous, OC-rich grassland soils, which may be attributed to decreased physical OC protection within large macroaggregates. Optimized grassland management in form of increased application of organic fertilizers could only partially offset the SOC loss by improved formation of small macroaggregates.

Abstract Many phenomena of high relevance for economic development such as human capital, geography and climate vary considerably within countries as well as between them. Yet, global data sets of economic output are typically available at the national level only, thereby limiting the accuracy and precision of insights gained through empirical analyses. Recent work has used interpolation and downscaling to yield estimates of sub-national economic output at a global scale, but respective data sets based on official, reported values only are lacking. We here present DOSE — the MCC-PIK Database Of Sub-national Economic Output. DOSE contains harmonised data on reported economic output from 1,661 sub-national regions across 83 countries from 1960 to 2020. To avoid interpolation, values are assembled from numerous statistical agencies, yearbooks and the literature and harmonised for both aggregate and sectoral output. Moreover, we provide temporally- and spatially-consistent data for regional boundaries, enabling matching with geo-spatial data such as climate observations. DOSE provides the opportunity for detailed analyses of economic development at the subnational level, consistent with reported values.

In this review, we investigated published data on the occurrence of microplastic in Arctic fish, and the suitability of the data and species for risk assessment and monitoring. As of 11 November 2021, we found nine studies in the peer-reviewed literature, one thesis and one report, confirming the occurrence of microplastic in fishes from multiple Arctic regions. The studies varied in methodology, detection, and quantification limitations, reported categories of size, shape, and chemical identity. All these factors influence the numbers of microplastic reported, thus limiting comparability and hindering integrative analysis. The physiological impacts of the reported microplastic contamination cannot be determined, as all studies targeted stomach/intestine contents and did not use methods with limits of detection low enough to determine particle translocation from the intestine to other organs, tissues, or body fluids within the fish. Furthermore, there is a fundamental lack of understanding the transfer and the effects of plastic additives to Arctic fishes. In addition to discussing methodological challenges and knowledge gaps, we consider ecosystem needs, commercial interests, Indigenous people’s subsistence, food safety and food sovereignty concerns, and developed a framework to harmonize and facilitate pan-Arctic microplastic monitoring.

Carbon sequestration in Plaggic Anthrosols is most often investigated by bulk soil carbon inventories, without considering the form in which the carbon is stored (e.g., particulate or mineral-associated organic matter (OM), its capacity, or its chemical composition). Here, we focus on the unusual high organic carbon (OC) accumulation in sandy Plaggic Anthrosols and adjacent reference soils under agricultural use. In these soils, the mineral fraction ≤20 µm which is commonly assumed to be the major factor for OC stabilization, are very low in mass proportion. Soil organic matter (SOM) physical fractionation was done to evaluate the quantity and quality of OC in the topsoil (Ap horizon). For the fraction ≤20 µm (medium and fine silt-, and clay-sized particles), we measured the concentration of OC and calculated its OC storage capacity and contribution. The OC of the fraction ≤20 µm was radiocarbon-dated and analyzed for its chemical composition by solid-state 13C NMR spectroscopy. The highly sandy (∼90 % sand and coarse silt) soils showed an accumulation of OC much higher than the conventionally calculated saturation level controlled by the proportion of the fraction ≤20 µm. Unexpectedly, Plaggic Anthrosols and the respective reference soils showed similar fractional OC concentrations, radiocarbon ages, and OM composition. The isolated fraction ≤20 µm contained, on average, 81 % of the total soil OC in only 9 % of the corresponding soil mass. All soil fractions ≤20 µm are characterized by a high mean OC concentration in the topsoil (reference soils: 226 ± 66.5 mg OC g−1, Plaggic Anthrosols: 202 ± 59.0 mg OC g−1) with a C/N ratio of 15 on average for both soils. The OM composition of the fraction ≤20 µm was specifically rich in alkyl-C, with unusually low proportions of O-alkyl-C and low contents of aryl-C. The radiocarbon concentration (F14C) indicated that topsoil OM of the ≤20 µm fraction is stored for long time periods with high mean conventional radiocarbon ages (14C) not only for Plaggic Anthrosols (F14C: 0.92 ± 0.04; 14C: 639 yBP) but also for the reference soils (F14C: 0.93 ± 0.04; 14C: 575 yBP) and received low inputs of OC derived from recent photosynthesis. Our data indicate the existence of specific SOM accumulation processes in the investigated sandy agricultural soils, resulting particularly large SOM stocks which cannot be explained by mechanistic association of OM with mineral surfaces. It is not clear, if this inherited OM is stable under present-day soil and management conditions.