Global cropland could be almost halved: Assessment of land saving potentials under different strategies and implications for agricultural markets

The pressure on land resources continuously increases not only with the rising demand for agricultural commodities, but also with the growing need for action on global challenges, such as biodiversity loss or climate change, where land plays a crucial role. Land saving as a strategy, where agricultural productivity is increased to allow a reduction of required cropland while sustaining production volumes and meeting demand, could address this trade-off. With our interdisciplinary model-based study, we globally assess regional potentials of land saving and analyze resulting effects on agricultural production, prices and trade. Thereby, different land saving strategies are investigated that (1) minimize required cropland (2) minimize spatial marginalization induced by land saving and (3) maximize the attainable profit. We find that current cropland requirements could be reduced between 37% and 48%, depending on the applied land saving strategy. The generally more efficient use of land would cause crop prices to fall in all regions, but also trigger an increase in global agricultural production of 2.8%. While largest land saving potentials occur in regions with high yield gaps, the impacts on prices and production are strongest in highly populated regions with already high pressure on land. Global crop prices and trade affect regional impacts of land saving on agricultural markets and can displace effects to spatially distant regions. Our results point out the importance of investigating the potentials and effects of land saving in the context of global markets within an integrative, global framework. The resulting land saving potentials can moreover reframe debates on global potentials for afforestation and carbon sequestration, as well as on how to reconcile agricultural production and biodiversity conservation and thus contribute to approaching central goals of the 21st century, addressed for example in the Sustainable Development Goals, the Paris Agreement or the post-2020 global biodiversity framework

Scenarios for an impact assessment of global bioeconomy strategies: Results from a co-design process

The replacement of fossil resources with renewable biomass in a bioeconomy is seen as a major contribution to climate change mitigation. This transformation will affect all members of society, making it crucial to consider the views of different stakeholders to ensure a socially acceptable transition towards a sustainable bioeconomy. To explore potential outcomes of bioeconomy strategies assuming different future pathways, a scenario analysis is a tool to inform decision-makers about policy impacts and trade-offs. The inter- and transdisciplinary research project "BioNex - The future of the biomass nexus" is the first project to develop bioeconomy scenarios together with stakeholders from politics, industry, and civil society in an iterative co-design process. As a result, three storylines describing diverging potential global futures are developed and quantified: Towards sustainability, business as usual, and towards resource depletion. The futures are driven by different assumptions on climate policy, cropland expansion, productivity growth in agriculture, prices of fossil energy, and consumption behaviour. Additionally, in the co-design process, three bioeconomy policies are developed: policy as usual, stronger development of the bioeconomy, and no policies. Besides presenting the results of the stakeholder workshops, this paper evaluates the strengths and shortcomings of a stakeholder approach in terms of policy-oriented research. According to the experience made within this study, it provides valuable insights for researchers and funding authorities they can use to optimise the employment of stakeholder-based research approaches

Preclinical development of a vaccine against oligomeric alpha-synuclein based on virus-like particles

Parkinson's disease (PD) is a progressive and currently incurable neurological disorder characterised by the loss of midbrain dopaminergic neurons and the accumulation of aggregated alpha-synuclein (a-syn). Oligomeric a-syn is proposed to play a central role in spreading protein aggregation in the brain with associated cellular toxicity contributing to a progressive neurological decline. For this reason, a-syn oligomers have attracted interest as therapeutic targets for neurodegenerative conditions such as PD and other alpha-synucleinopathies. In addition to strategies using small molecules, neutralisation of the toxic oligomers by antibodies represents an attractive and highly specific strategy for reducing disease progression. Emerging active immunisation approaches using vaccines are already being trialled to induce such antibodies. Here we propose a novel vaccine based on the RNA bacteriophage (Qbeta) virus-like particle conjugated with short peptides of human a-syn. High titres of antibodies were successfully and safely generated in wild-type and human a-syn over-expressing (SNCA-OVX) transgenic mice following vaccination. Antibodies from vaccine candidates targeting the C-terminal regions of a-syn were able to recognise Lewy bodies, the hallmark aggregates in human PD brains. Furthermore, antibodies specifically targeted oligomeric and aggregated a-syn as they exhibited 100 times greater affinity for oligomeric species over monomer a-syn proteins in solution. In the SNCA-OVX transgenic mice used, vaccination was, however, unable to confer significant changes to oligomeric a-syn bioburden. Similarly, there was no discernible effect of vaccine treatment on behavioural phenotype as compared to control groups. Thus, antibodies specific for oligomeric a-syn induced by vaccination were unable to treat symptoms of PD in this particular mouse model.</p

The antiviral protein viperin regulates chondrogenic differentiation via CXCL10 protein secretion.

Viperin (also known as radical SAM domain-containing 2, RSAD2) is an interferon-inducible and evolutionary conserved protein that participates in the cell's innate immune response against a number of viruses. Viperin mRNA is a substrate for endoribonucleolytic cleavage by RNase mitochondrial RNA processing (MRP) and mutations in the RMRP small nucleolar RNA (snoRNA) subunit of the RNase MRP complex cause cartilage-hair hypoplasia (CHH), a human developmental condition characterized by metaphyseal chondrodysplasia and severe dwarfism. It is unknown how CHH-pathogenic mutations in RMRP snoRNA interfere with skeletal development and aberrant processing of RNase MRP substrate RNAs is thought to be involved. We hypothesized that viperin plays a role in chondrogenic differentiation. Using immunohistochemistry, RT-qPCR, immunoblotting, ELISA, siRNA-mediated gene silencing, plasmid-mediated gene overexpression, label-free mass-spectrometry proteomics and promoter reporter bioluminescence assays, we discovered here that viperin is expressed in differentiating chondrocytic cells and regulates their protein secretion and the outcome of chondrogenic differentiation by influencing transforming growth factor β (TGF-β)/SMAD family 2/3 (SMAD2/3) activity via C-X-C motif chemokine ligand 10 (CXCL10). Of note, we observed disturbances in this viperin-CXCL10-TGF-β/SMAD2/3 axis in CHH chondrocytic cells. Our results indicate that the anti-viral protein viperin controls chondrogenic differentiation by influencing secretion of soluble proteins and identify a molecular route that may explain impaired chondrogenic differentiation of cells from individuals with CHH

A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world

Primäre B Zell- und B Zell-Gedächtnisantworten auf Qβ-VLP in Mäusen

Extensive studies have been undertaken to describe naïve B cells differentiating into memory B cells at a cellular and molecular level. However, relatively little is known about the fate of memory B cells upon antigen re-encounter. We have previously established a system based on virus-like particles (VLPs) which allows to track VLP-specific B cells by flow cytometry as well as histology. Using allotype markers, it is possible to adoptively transfer memory B cells into a naïve mouse and track responses of naïve and memory B cells as well as antibody responses in the same mouse under physiological conditions.In contrast to previous reports using proteins, we have observed that VLP-specific memory B cells did not efficiently proliferate but quickly differentiated into plasma cells upon cognate antigen challenge. This was paralleled by an early onset of a strong humoral IgG response. Also upon tracking of distinct memory B cell populations, neither IgM+ nor IgG+ memory B cells proliferated extensively or entered germinal centers. Remarkably, plasma cells derived from memory B cells preferentially homed to the bone marrow early and produced superior amounts of antibody compared to plasma cells generated during the primary B cell response. Indeed, secondary plasma cells produced about 5 times more antibody than the corresponding primary plasma cells residing in the bone marrow. Hence, viral like particles provided a sufficient strong stimulus to drive terminal differentiation of memory B cells into highly effective secondary plasma cells preferentially homing the bone marrow. From a physiological point of view this may be explained by the immediate need for protective IgG antibodies in the presence of systemic viral particles.Interestingly, memory B cells failed to respond after multiple rounds of stimulation by cognate antigen, as the majority of Abs was only produced by memory derived secondary plasma cells after the first boost. In contrast, after second boost the humoral response was dominated by plasma cells derived from first-round memory B cells of the host. Under these conditions, the memory B cell pool was replaced by a new wave of memory B cells derived from primary B cells. Thus, memory B cells generated during a secondary response were largely derived from naïve B cells and may therefore harbor slightly different specificities than the concomitantly produced antibodies. As a consequence, the B cell response may remain dynamic and antigenic sub-specificities encountered during the primary response are not endlessly carried forward preventing adaptation of the B cell responses to newly emerging variants.We further investigated the role of CD4+ T helper cells during memory B cell responses. Here, we observed a graded T helper cell dependence. Proliferation of class-switched memory B cell followed by rapid generation of plasma cells and early IgG responses were generally highly T cell dependent. In contrast, late plasma cell generation as well as late IgG responses were mostly T helper cell independent. From a physiological point of view, this may reflect the goal of the immune system to rid pathogens that are present for extended time periods even at the risk of raising T cell independent memory IgG responses.All observations and conclusions made in this study may be representative for many VLPs and viral particles, as we assessed the majority of experiments with two different VLPs.These insights are important for our general understanding of B cell responses and may be of value for improving vaccination regimens to optimize generation of long-lived plasma cells

Semi-permeable coatings fabricated from comb-polymers efficiently protect proteins in vivo

In comparison to neutral linear polymers, functional and architecturally complex (that is, non-linear) polymers offer distinct opportunities for enhancing the properties and performance of therapeutic proteins. However, understanding how to harness these parameters is challenging, and studies that capitalize on them in vivo are scarce. Here we present an in vivo demonstration that modification of a protein with a polymer of appropriate architecture can impart low immunogenicity, with a commensurably low loss of therapeutic activity. These combined properties are inaccessible by conventional strategies using linear polymers. For the model protein L-asparaginase, a comb-polymer bio-conjugate significantly outperformed the linear polymer control in terms of lower immune response and more sustained bioactivity. The semi-permeability characteristics of the coatings are consistent with the phase diagram of the polymer, which will facilitate the application of this strategy to other proteins and with other therapeutic models

Semi-permeable coatings fabricated from comb-polymers efficiently protect proteins in vivo

ISSN:2041-172

Distinct T helper cell dependence of memory B-cell proliferation versus plasma cell differentiation

Several memory B-cell subclasses with distinct functions have been described, of which the most effective is the class-switched (CS) memory B-cell population. We have previously shown, using virus-like particles (VLPs), that the proliferative potential of these CS memory B cells is limited and they fail to re-enter germinal centres (GCs). However, VLP-specific memory B cells quickly differentiated into secondary plasma cells (PCs) with the virtue of elevated antibody production compared with primary PCs. Whereas the induction of VLP+ memory B cells was strongly dependent on T helper cells, we were wondering whether re-stimulation of VLP+ memory B cells and their differentiation into secondary PCs would also require T helper cells. Global absence of T helper cells led to strongly impaired memory B cell proliferation and PC differentiation. In contrast, lack of interleukin-21 receptor-dependent follicular T helper cells or CD40 ligand signalling strongly affected proliferation of memory B cells, but differentiation into mature secondary PCs exhibiting increased antibody production was essentially normal. This contrasts with primary B-cell responses, where a strong dependence on CD40 ligand but limited importance of interleukin-21 receptor was seen. Hence, T helper cell dependence differs between primary and secondary B-cell responses as well as between memory B-cell proliferation and PC differentiation