Organic vs. Conventional Grassland Management: Do 15N and 13C Isotopic Signatures of Hay and Soil Samples Differ?

Distinguishing organic and conventional products is a major issue of food security and authenticity. Previous studies successfully used stable isotopes to separate organic and conventional products, but up to now, this approach was not tested for organic grassland hay and soil. Moreover, isotopic abundances could be a powerful tool to elucidate differences in ecosystem functioning and driving mechanisms of element cycling in organic and conventional management systems. Here, we studied the δ15N and δ13C isotopic composition of soil and hay samples of 21 organic and 34 conventional grasslands in two German regions. We also used Δδ15N (δ15N plant - δ15N soil) to characterize nitrogen dynamics. In order to detect temporal trends, isotopic abundances in organic grasslands were related to the time since certification. Furthermore, discriminant analysis was used to test whether the respective management type can be deduced from observed isotopic abundances. Isotopic analyses revealed no significant differences in δ13C in hay and δ15N in both soil and hay between management types, but showed that δ13C abundances were significantly lower in soil of organic compared to conventional grasslands. Δδ15N values implied that management types did not substantially differ in nitrogen cycling. Only δ13C in soil and hay showed significant negative relationships with the time since certification. Thus, our result suggest that organic grasslands suffered less from drought stress compared to conventional grasslands most likely due to a benefit of higher plant species richness, as previously shown by manipulative biodiversity experiments. Finally, it was possible to correctly classify about two third of the samples according to their management using isotopic abundances in soil and hay. However, as more than half of the organic samples were incorrectly classified, we infer that more research is needed to improve this approach before it can be efficiently used in practice

C‐reactive protein flare‐response predicts long‐term efficacy to first‐line anti‐PD‐1‐based combination therapy in metastatic renal cell carcinoma

Objectives Immune checkpoint blockade (IO) has revolutionised the treatment of metastatic renal cell carcinoma (mRCC). Early C-reactive protein (CRP) kinetics, especially the recently introduced CRP flare-response phenomenon, has shown promising results to predict IO efficacy in mRCC, but has only been studied in second line or later. Here, we aimed to validate the predictive value of early CRP kinetics for 1st-line treatment of mRCC with αPD-1 plus either αCTLA-4 (IO+IO) or tyrosine kinase inhibitor (IO+TKI). Methods In this multicentre retrospective study, we investigated the predictive potential of early CRP kinetics during 1st-line IO therapy. Ninety-five patients with mRCC from six tertiary referral centres with either IO+IO (N = 59) or IO+TKI (N = 36) were included. Patients were classified as CRP flare-responders, CRP responders or non-CRP responders as previously described, and their oncological outcome was compared. Results Our data validate the predictive potential of early CRP kinetics in 1st-line immunotherapy in mRCC. CRP responders, especially CRP flare-responders, had significantly prolonged progression-free survival (PFS) compared with non-CRP responders (median PFS: CRP flare-responder: 19.2 months vs. responders: 16.2 vs. non-CRP responders: 5.6, P < 0.001). In both the IO+IO and IO+TKI subgroups, early CRP kinetics remained significantly associated with improved PFS. CRP flare-response was also associated with long-term response ≥ 12 months. Conclusions Early CRP kinetics appears to be a low-cost and easy-to-implement on-treatment biomarker to predict response to 1st-line IO combination therapy. It has potential to optimise therapy monitoring and might represent a new standard of care biomarker for immunotherapy in mRCC

Direct and plant community mediated effects of management intensity on annual nutrient leaching risk in temperate grasslands

Grassland management intensity influences nutrient cycling both directly, by changing nutrient inputs and outputs from the ecosystem, and indirectly, by altering the nutrient content, and the diversity and functional composition of plant and microbial communities. However, the relative importance of these direct and indirect processes for the leaching of multiple nutrients is poorly studied. We measured the annual leaching of nitrate, ammonium, phosphate and sulphate at a depth of 10 cm in 150 temperate managed grasslands using a resin method. Using Structural Equation Modeling, we distinguished between various direct and indirect effects of management intensity (i.e. grazing and fertilization) on nutrient leaching. We found that management intensity was positively associated with nitrate, ammonium and phosphate leaching risk both directly (i.e. via increased nutrient inputs) and indirectly, by changing the stoichiometry of soils, plants and microbes. In contrast, sulphate leaching risk was negatively associated with management intensity, presumably due to increased outputs with mowing and grazing. In addition, management intensification shifted plant communities towards an exploitative functional composition (characterized by high tissue turnover rates) and, thus, further promoted the leaching risk of inorganic nitrogen. Plant species richness was associated with lower inorganic nitrogen leaching risk, but most of its effects were mediated by stoichiometry and plant community functional traits. Maintaining and restoring diverse plant communities may therefore mitigate the increased leaching risk that management intensity imposes upon grasslands

The Evolution of Ecological Diversity in Acidobacteria

Acidobacteria occur in a large variety of ecosystems worldwide and are particularly abundant and highly diverse in soils. In spite of their diversity, only few species have been characterized to date which makes Acidobacteria one of the most poorly understood phyla among the domain Bacteria. We used a culture-independent niche modeling approach to elucidate ecological adaptations and their evolution for 4,154 operational taxonomic units (OTUs) of Acidobacteria across 150 different, comprehensively characterized grassland soils in Germany. Using the relative abundances of their 16S rRNA gene transcripts, the responses of active OTUs along gradients of 41 environmental variables were modeled using hierarchical logistic regression (HOF), which allowed to determine values for optimum activity for each variable (niche optima). By linking 16S rRNA transcripts to the phylogeny of full 16S rRNA gene sequences, we could trace the evolution of the different ecological adaptations during the diversification of Acidobacteria. This approach revealed a pronounced ecological diversification even among acidobacterial sister clades. Although the evolution of habitat adaptation was mainly cladogenic, it was disrupted by recurrent events of convergent evolution that resulted in frequent habitat switching within individual clades. Our findings indicate that the high diversity of soil acidobacterial communities is largely sustained by differential habitat adaptation even at the level of closely related species. A comparison of niche optima of individual OTUs with the phenotypic properties of their cultivated representatives showed that our niche modeling approach (1) correctly predicts those physiological properties that have been determined for cultivated species of Acidobacteria but (2) also provides ample information on ecological adaptations that cannot be inferred from standard taxonomic descriptions of bacterial isolates. These novel information on specific adaptations of not-yet-cultivated Acidobacteria can therefore guide future cultivation trials and likely will increase their cultivation success

Field-induced phase transition in Bi1/2Na1/2TiO3-based lead-free piezoelectric ceramics

The origin of the electric field-induced strain in the polycrystalline ceramic 0.92Bi(1/2)Na(1/2)TiO(3)-0.06BaTiO(3)-0.02K(1/2)Na(1/2)NbO(3) was investigated using in situ high-resolution X-ray and neutron diffraction techniques. The initially existing tetragonal phase with pseudocubic lattice undergoes a reversible phase transition to a significantly distorted rhombohedral phase under electric field, accompanied by a change in the oxygen octahedral tilting from a 0 a 0 c + to a - a - a - and in the tilting angle. The polarization values for the tetragonal and rhombohedral phases were calculated based on the structural information from Rietveld refinements. The large recoverable electric field-induced strain is a consequence of a reversible electric field-induced phase transition from an almost nonpolar tetragonal phase to a ferroelectrically active rhombohedral phase.open686

Nutrient stoichiometry and land use rather than species richness determine plant functional diversity

Ajuts: Deutsche Forschungsgemeinschaft. Grant Numbers: FI 1246/6-1, HO 3830/2-1, KL 2265/5-1 - TRY initiative on plant traits DIVERSITAS/Future Earth and the German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig - Open Access Publication Fund of University of Muenster.Plant functional traits reflect individual and community ecological strategies. They allow the detection of directional changes in community dynamics and ecosystemic processes, being an additional tool to assess biodiversity than species richness. Analysis of functional patterns in plant communities provides mechanistic insight into biodiversity alterations due to anthropogenic activity. Although studies have consi-dered of either anthropogenic management or nutrient availability on functional traits in temperate grasslands, studies combining effects of both drivers are scarce. Here, we assessed the impacts of management intensity (fertilization, mowing, grazing), nutrient stoichiometry (C, N, P, K), and vegetation composition on community-weighted means (CWMs) and functional diversity (Rao's Q) from seven plant traits in 150 grasslands in three regions in Germany, using data of 6 years. Land use and nutrient stoichiometry accounted for larger proportions of model variance of CWM and Rao's Q than species richness and productivity. Grazing affected all analyzed trait groups; fertilization and mowing only impacted generative traits. Grazing was clearly associated with nutrient retention strategies, that is, investing in durable structures and production of fewer, less variable seed. Phenological variability was increased. Fertilization and mowing decreased seed number/mass variability, indicating competition-related effects. Impacts of nutrient stoichiometry on trait syndromes varied. Nutrient limitation (large N:P, C:N ratios) promoted species with conservative strategies, that is, investment in durable plant structures rather than fast growth, fewer seed, and delayed flowering onset. In contrast to seed mass, leaf-economics variability was reduced under P shortage. Species diversity was positively associated with the variability of generative traits. Synthesis. Here, land use, nutrient availability, species richness, and plant functional strategies have been shown to interact complexly, driving community composition, and vegetation responses to management intensity. We suggest that deeper understanding of underlying mechanisms shaping community assembly and biodiversity will require analyzing all these parameters

Above- and belowground biodiversity jointly tighten the P cycle in agricultural grasslands

Experiments showed that biodiversity increases grassland productivity and nutrient exploitation, potentially reducing fertiliser needs. Enhancing biodiversity could improve P-use efficiency of grasslands, which is beneficial given that rock-derived P fertilisers are expected to become scarce in the future. Here, we show in a biodiversity experiment that more diverse plant communities were able to exploit P resources more completely than less diverse ones. In the agricultural grasslands that we studied, management effects either overruled or modified the driving role of plant diversity observed in the biodiversity experiment. Nevertheless, we show that greater above- (plants) and belowground (mycorrhizal fungi) biodiversity contributed to tightening the P cycle in agricultural grasslands, as reduced management intensity and the associated increased biodiversity fostered the exploitation of P resources. Our results demonstrate that promoting a high above- and belowground biodiversity has ecological (biodiversity protection) and economical (fertiliser savings) benefits. Such win-win situations for farmers and biodiversity are crucial to convince farmers of the benefits of biodiversity and thus counteract global biodiversity loss

Immune signatures predict development of autoimmune toxicity in patients with cancer treated with immune checkpoint inhibitors.

BACKGROUND Immune checkpoint inhibitors (ICIs) are among the most promising treatment options for melanoma and non-small cell lung cancer (NSCLC). While ICIs can induce effective anti-tumor responses, they may also drive serious immune-related adverse events (irAEs). Identifying biomarkers to predict which patients will suffer from irAEs would enable more accurate clinical risk-benefit analysis for ICI treatment and may also shed light on common or distinct mechanisms underpinning treatment success and irAEs. METHODS In this prospective multi-center study, we combined a multi-omics approach including unbiased single-cell profiling of over 300 peripheral blood mononuclear cell (PBMC) samples and high-throughput proteomics analysis of over 500 serum samples to characterize the systemic immune compartment of patients with melanoma or NSCLC before and during treatment with ICIs. FINDINGS When we combined the parameters obtained from the multi-omics profiling of patient blood and serum, we identified potential predictive biomarkers for ICI-induced irAEs. Specifically, an early increase in CXCL9/CXCL10/CXCL11 and interferon-γ (IFN-γ) 1 to 2 weeks after the start of therapy are likely indicators of heightened risk of developing irAEs. In addition, an early expansion of Ki-67+ regulatory T cells (Tregs) and Ki-67+ CD8+ T cells is also likely to be associated with increased risk of irAEs. CONCLUSIONS We suggest that the combination of these cellular and proteomic biomarkers may help to predict which patients are likely to benefit most from ICI therapy and those requiring intensive monitoring for irAEs. FUNDING This work was primarily funded by the European Research Council, the Swiss National Science Foundation, the Swiss Cancer League, and the Forschungsförderung of the Kantonsspital St. Gallen

Struktur und Gitterdynamik wasserstoffbeladener austenitischer Edelstähle

Austenitische Edelstähle finden einen sehr weitverbreiteten Einsatz. Ihre Anwendungen reichen von Haushaltsgegenständen über Druckkessel zu Schiffspropellern und Turbinen. Für zahlreiche Anwendungen austenitischer Edelstähle stellt die Verschlechterung mechanischer Eigenschaften durch Aufnahme von Wasserstoff aus der Umgebung ein großes Problem dar. Trotz intensiver Forschungsarbeiten in den letzten Jahrzehnten sind die Mechanismen der Wasserstoffversprödung in Stählen noch immer nicht vollständig verstanden. Unter den postulierten Mechanismen der Wasserstoffversprödung in austenitischen Edelstählen ist die wasserstoffinduzierte Bildung versprödender Hydrid- und Martensitphasen in der Diskussion. Zur Untersuchung des Phasenumwandlungsverhaltens infolge von Wasserstoffbeladungen wurden in der vorliegenden Arbeit Stahlproben untersucht, welche unter hohen Drücken hydriert worden waren. Die Ergebnisse wurden mit aus der Literatur bekannten Ergebnissen an elektrolytisch beladenen Proben verglichen. Hochdruck-Hydrierungen führen zu einer weitgehend homogenen Wasserstoffverteilung im Volumen, während elektrolytische Beladungen eine Wasserstoffabscheidung an der Oberfläche mit starken Konzentrationsgradienten ins Probeninnere bewirken. Mittels elastischer und inelastischer Neutronenstreuung sowie Röntgenbeugung wurde der Einfluss von Wasserstoff auf Struktur und Gitterdynamik der austenitischen Edelstähle Fe/Cr18/Ni10 und Fe/Cr25/Ni20 untersucht. Die Inelastische Neutronenstreuung liefert aufgrund ihrer hohen Sensitivität bzgl. Wasserstoff u.a. auch Informationen zur Bildung von Hydriden komplementär zur Beugung. Es wurde festgestellt, dass Wasserstoff- bzw. Deuteriumatome in beiden Stahlsorten ausschließlich die Oktaederlücken besetzen. Im Rahmen der Nachweisempfindlichkeit wurden keine wasserstoffinduzierten Phasenumwandlungen im Stahl Fe/Cr25/Ni20 über den gesamten Konzentrationsbereich bis zu H/Me = 1 beobachtet. Im Falle von Fe/Cr18/Ni10 trat die Bildung von Epsilon-Martensit bei Hydrierungen unter 3.0 und 7.0 GPa bei Wasserstoffgehalten von H/Me = 0.56 bzw. H/Me = 1.03 auf, sowie bei Beaufschlagung von 4.0 GPa ohne Wasserstoff. Weder die elastischen noch die inelastischen Neutronenstreuexperimente gaben Hinweise auf Hydride. In den Schwingungsspektren wurde eine kontinuierliche Abnahme der Schwingungsenergien der optischen Moden mit zunehmendem Me-H - Atomabstand deutlich. Die optischen Moden in den Proben beider Stahlsorten mit den höchsten Wasserstoffgehalten (H/Me = 1) zeigten jeweils eine Aufspaltung, welche durch longitudinale und transversale Schwingungsmoden beschrieben werden konnte. In allen Proben wiesen die optischen Moden eine deutliche Verbreiterung auf, die wohl hauptsächlich aus der Modifikation der Schwingungsenergie mit Anordnungen der Nachbaratome in den vorliegenden ungeordneten Legierungen resultierte. Die Hochdruck-hydrierten Proben zeigten selbst bei maximalen Wasserstoffgehalten eine deutlich geringere Tendenz zur Bildung von Epsilon-Martensit als im Falle der elektrolytischen Hydrierung. Die Ergebnisse weisen darauf hin, dass für die Bildung von Epsilon-Martensit infolge von Wasserstoffbeladungen weniger die Wasserstoffkonzentration entscheidend ist, als vielmehr die aus der Wasserstoffverteilung resultierenden Spannungszustände. Diese Arbeit brachte einige Ergebnisse hervor, welche eindeutig gegen die These der wasserstoffinduzierten Hydrid- und Martensitbildung zur Beschreibung der Wasserstoffversprödung in austenitischen Edelstählen sprechen: In den Stahlsorten Fe/Cr25/Ni20 und Fe/Cr18/Ni10 wurden keine Hinweise für für die Ausscheidung einer Hydridphase gefunden; im Stahl Fe/Cr25/Ni20 erfolgte über den kompletten Konzentrationsbereich bis H/Me = 1 keine Phasenumwandlung; im Stahl Fe/Cr18/Ni10 konnten auch ohne die Anwesenheit von Wasserstoff Martensitumwandlungen durch hohe Drücke erzeugt werden