CONSOLE Project - Deliverable 2.5 - "EIP-AGRI abstract on current experience and existing initiatives on collective, result-based and value chain solutions for AECPG provision"

To improve the provision of agri-environmental-climate public goods (AECPGs) from agriculture and forestry, new solutions, such as result-based payments or collective implementation, and new strategies along the value chain might help. The analysis of ca. 120 case studies in and outside EU showed that many real-life cases of implementation combine different contract types. Collective implementation can be a precondition for environmental effectiveness, particularly if AECPGs are addressed that can be hardly improved by measures on single plots, (e.g. water quality). Result-based contracts can target specific AECPGs and increase engagement of land-managers due to flexible management choices. Some recommendations for contract design and implementation are distilled: 1.) Targeting contracts to specific regions addresses regional criticalities and enhances the farmers’ and foresters’ interest and understanding of measures. 2.) Involving land-managers in target-setting and measure development leads to higher compatibility with their businesses and can create win-win situations. 3.) Involving control authorities in the design of indicators in result-based schemes can guarantee integrability into RDPs. 4.) Fostering bottom-up approaches and involving regional key actors as coordinating units enhances commitment and motivation in collective approaches. 5.) Guaranteeing good levels of equity and fairness enhances acceptance particularly in value-chain based solutions. It becomes clear that result-based and collective solutions don’t fit in each context situation, as they often demand high levels of knowledge and collaborative skills. Value chain approaches are often only suited if consumers’ awareness is high

CONSOLE Project - Deliverable 2.1 - "Catalogue of descriptive factsheets of all European case studies"

This document represents deliverable D2.1 “Catalogue of descriptive factsheets of all European case studies” within workpackage WP2 “Diagnostic of existing experiences on agri-environmantal-climate public goods (AECPGs)” of the EU Horizon 2020 project CONSOLE. The document describes the objectives and process of data collection and provides a catalogue of 60 factsheets. The factsheets illustrate 58 European (EU) case study examples of contract solutions for the improved provision of AECPGs. Also, the catalogue contains 2 examples beyond Europe, of which 1 comes from the USA and 1 from Guadaloupe (FR)

Exploring macro-environmental factors influencing adoption of result-based and collective agri-environmental measures: a PESTLE approach based on stakeholder statements

To promote more environmentally-friendly and cost-effective agri-environmental-climate measures in the EU, novel approaches such as result-based and collective schemes are advocated. This study explores macro-environmental factors facilitating or impeding the adoption of such schemes. By means of a PESTLE analysis and based on a survey of 85 stakeholders from Austria and Germany, we identify major adoption factors within the political, economic, social, technological, legal, and environmental domains. Our results indicate that economic, legal, and social factors are the most influential, with fair payment, clear contract design, and social relations being the most commonly mentioned. Moreover, the unpredictability of nature is a major impediment to the adoption of result-based schemes, while social dynamics and farmers' attitudes are key factors for a successful implementation of collective contracts. Overall, the study provides strategic and practical insights that can support the design and implementation of novel agri-environmental-climate measures under the Common Agricultural Policy

Report on research data management interviews conducted for HMC Hub Energy in 2022

The Energy Hub of the Helmholtz Metadata Collaboration (HMC) conducted interviews with various stakeholders from the Helmholtz Research Field Energy on the topic of research data management (RDM) in 2022. The intentions were to build and serve a metadata community in the energy research field and to extend the Helmholtz-wide survey conducted by HMC in 2021 Arndt et al., 2022). Besides the deeper insight into the current state of RDM and metadata handling at the Helmholtz sites relevant to the Energy Hub the interviews focused on the related needs and difficulties of researchers and their satisfaction with the current state. Furthermore, we tried to discover already existing workflows and software solutions, to establish contacts and to make HMC better known

Next generation 3D pharmacophore modeling

3D pharmacophore models are three‐dimensional ensembles of chemically defined interactions of a ligand in its bioactive conformation. They represent an elegant way to decipher chemically encoded ligand information and have therefore become a valuable tool in drug design. In this review, we provide an overview on the basic concept of this method and summarize key studies for applying 3D pharmacophore models in virtual screening and mechanistic studies for protein functionality. Moreover, we discuss recent developments in the field. The combination of 3D pharmacophore models with molecular dynamics simulations could be a quantum leap forward since these approaches consider macromolecule–ligand interactions as dynamic and therefore show a physiologically relevant interaction pattern. Other trends include the efficient usage of 3D pharmacophore information in machine learning and artificial intelligence applications or freely accessible web servers for 3D pharmacophore modeling. The recent developments show that 3D pharmacophore modeling is a vibrant field with various applications in drug discovery and beyond

The extracellular chaperone Clusterin enhances Tau aggregate seeding in a cellular model

Variants of the extracellular chaperone Clusterin are associated with Alzheimer's disease (AD) and Clusterin levels are elevated in AD patient brains. Here, the authors show that Clusterin binds to oligomeric Tau, which enhances the seeding capacity of Tau aggregates upon cellular uptake. They also demonstrate that Tau/Clusterin complexes enter cells via the endosomal pathway, resulting in damage to endolysosomes and entry into the cytosol, where they induce the aggregation of endogenous, soluble Tau. Spreading of aggregate pathology across brain regions acts as a driver of disease progression in Tau-related neurodegeneration, including Alzheimer's disease (AD) and frontotemporal dementia. Aggregate seeds released from affected cells are internalized by naive cells and induce the prion-like templating of soluble Tau into neurotoxic aggregates. Here we show in a cellular model system and in neurons that Clusterin, an abundant extracellular chaperone, strongly enhances Tau aggregate seeding. Upon interaction with Tau aggregates, Clusterin stabilizes highly potent, soluble seed species. Tau/Clusterin complexes enter recipient cells via endocytosis and compromise the endolysosomal compartment, allowing transfer to the cytosol where they propagate aggregation of endogenous Tau. Thus, upregulation of Clusterin, as observed in AD patients, may enhance Tau seeding and possibly accelerate the spreading of Tau pathology

The extracellular chaperone Clusterin enhances Tau aggregate seeding in a cellular model

Spreading of aggregate pathology across brain regions acts as a driver of disease progression in Tau-related neurodegeneration, including Alzheimer’s disease (AD) and frontotemporal dementia. Aggregate seeds released from affected cells are internalized by naïve cells and induce the prion-like templating of soluble Tau into neurotoxic aggregates. Here we show in a cellular model system and in neurons that Clusterin, an abundant extracellular chaperone, strongly enhances Tau aggregate seeding. Upon interaction with Tau aggregates, Clusterin stabilizes highly potent, soluble seed species. Tau/Clusterin complexes enter recipient cells via endocytosis and compromise the endolysosomal compartment, allowing transfer to the cytosol where they propagate aggregation of endogenous Tau. Thus, upregulation of Clusterin, as observed in AD patients, may enhance Tau seeding and possibly accelerate the spreading of Tau pathology

CONSOLE Project - Deliverable 2.2 - "Draft report on experiences from outside the EU"

The aim of task 2.3 is to collect the most promising and successful experiences outside the EU that could add new and interesting perspectives for application in EU and to feed into WP2 a wider range of opportunities for contract design. The task takes the form of a systematic literature review and this report provides a draft version of the outcomes of this review. The final version of the report will be provided in month 30. The review selected 79 documents, including both peer review papers and reports/grey literature having as a scope all countries outside those already represented by the CONSOLE partners. The main reasons for success identified for the reviewed cases are: a) reducing risks linked to results; b) reduced costs for monitoring results; c) farmers’ interest and social revenue; d) resources availability; e) additionality; f) relying on existing collectives; g) communication; payment setting; h)appropriate intermediaries. To a large extent the success factors listed above confirm insights from cases in the CONSOLE partner countries. However, they allow the consideration of a broader variety of solutions. On the other hand, this also depends on the specific institutional context where they are located, which means that potential for replication should be taken carefully. The fact that a large part of the experiences and certainly of the evidence is rather recent encourages the continuation of this task providing updates during the whole project life

CONSOLE Project - Deliverable 1.1 - "Preliminary framework"

The objective of this document is to provide an initial conceptual framework for the project CONSOLE. The initial framework aims at providing a basis for interpretation of the project activities, hence connecting project objectives, approach and the state of the art about the topic. In order to achieve this objective, this initial version of the framework takes mainly the approach of an organized broad literature review in support of the project expected activities. It also aims at identifying the relevant definitions and scope for the project. Finally and foremost, it investigates the tentative logic of a preliminary conceptual framework to be further developed into an operational framework in the following tasks of WP1 (and of the project as a whole). In order to meet these tasks, the literature considered is not restricted to the specific contract types addressed by the project (see below), but rather attempts to contextualise these contract types in the wider literature on agri- environmental-climate public goods (AECPGs) provision by agriculture and forestry. In doing so, we acknowledge the wide variety of hybrid and mixed solutions that may be relevant in practice. In addition, we have tried to review specifically the most recent scientific literature, including the most debated issues; some classical concepts that are well established in the literature may be neglected or under-represented here

Reactive oxygen species produced by myeloid cells in psoriasis as a potential biofactor contributing to the development of vascular inflammation.

Psoriasis is an immune-mediated inflammatory skin disease driven by interleukin-17A (IL-17A) and associated with cardiovascular dysfunction. We used a severe psoriasis mouse model of keratinocyte IL-17A overexpression (K14-IL-17Aind/+ , IL-17Aind/+ control mice) to investigate the activity of neutrophils and a potential cellular interconnection between skin and vasculature. Levels of dermal reactive oxygen species (ROS) and their release by neutrophils were measured by lucigenin-/luminol-based assays, respectively. Quantitative RT-PCR determined neutrophilic activity and inflammation-related markers in skin and aorta. To track skin-derived immune cells, we used PhAM-K14-IL-17Aind/+ mice allowing us to mark all cells in the skin by photoconversion of a fluorescent protein to analyze their migration into spleen, aorta, and lymph nodes by flow cytometry. Compared to controls, K14-IL-17Aind/+ mice exhibited elevated ROS levels in the skin and a higher neutrophilic oxidative burst accompanied by the upregulation of several activation markers. In line with these results psoriatic mice displayed elevated expression of genes involved in neutrophil migration (e.g., Cxcl2 and S100a9) in skin and aorta. However, no direct immune cell migration from the psoriatic skin into the aortic vessel wall was observed. Neutrophils of psoriatic mice showed an activated phenotype, but no direct cellular migration from the skin to the vasculature was observed. This suggests that highly active vasculature-invading neutrophils must originate directly from the bone marrow. Hence, the skin-vasculature crosstalk in psoriasis is most likely based on the systemic effects of the autoimmune skin disease, emphasizing the importance of a systemic therapeutic approach for psoriasis patients