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Povzetek: Potato (Solanum tuberosum) is highly water and space efficient but susceptible to abiotic stresses such as heat, drought, and flooding, which are severely exacerbated by climate change. Our understanding of crop acclimation to abiotic stress, however, remains limited. Here, we present a comprehensive molecular and physiological high-throughput profiling of potato (Solanum tuberosum, cv. Désirée) under heat, drought, and waterlogging applied as single stresses or in combinations designed to mimic realistic future scenarios. Stress responses were monitored via daily phenotyping and multi-omics analyses of leaf samples comprising proteomics, targeted transcriptomics, metabolomics, and hormonomics at several timepoints during and after stress treatments. Additionally, critical metabolites of tuber samples were analyzed at the end of the stress period. We performed integrative multi-omics data analysis using a bioinformatic pipeline that we established based on machine learning and knowledge networks. Waterlogging produced the most immediate and dramatic effects on potato plants, interestingly activating ABA responses similar to drought stress. In addition, we observed distinct stress signatures at multiple molecular levels in response to heat or drought and to a combination of both. In response to all treatments, we found a downregulation of photosynthesis at different molecular levels, an accumulation of minor amino acids, and diverse stress-induced hormones. Our integrative multi-omics analysis provides global insights into plant stress responses, facilitating improved breeding strategies toward climate-adapted potato varieties.
Ključne besede: potato, Solanum tuberosum, abiotic stress responses, heat, drought, waterlogging, multi-omics, integrative omics, adaptomics, panomics
Objavljeno v DiRROS: 14.04.2025; Ogledov: 160; Prenosov: 126
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Povzetek: Given the need to reduce animal testing for environmental risk assessment, we aim to develop a fish invitrome, an alternative fish modular framework capable of predicting chemical toxicity in fish without the use of animals. The central module of the framework is the validated RTgill-W1 cell line assay that predicts fish acute toxicity of chemicals (Organization for Economic Cooperation and Development Test Guideline (OECD TG) 249). Expanding towards prediction of chronic toxicity, the fish invitrome includes two other well-advanced modules for chemical bioaccumulation/biotransformation and inhibition of fish growth. This framework is expected to continuously evolve with the development of modules that predict, for instance, neurotoxicity and reproductive toxicity. We envisage the fish invitrome framework to become part of the broader academic field of New Approach Methodologies (NAMs), where it will remain flexible and open to integration of new developments from research groups around the world. To accelerate the development and uptake of this framework, we strive for transdisciplinarity, integrating both natural and social sciences, along with broader stakeholder interactions. A stepwise socio-technical approach has been chosen, where mainstreaming the fish invitrome involves progressive adoption across various ecotoxicological contexts. The framework will be co-designed with stakeholders from academia, industry, and regulatory bodies. Rather than aiming for immediate regulatory acceptance, this approach aims to build trust and familiarity with fish cell line-based testing among stakeholders. By doing so, it encourages broader use of the framework in practical applications while gradually overcoming institutional, cultural, and technical barriers. Additionally, establishing a clear roadmap for mainstreaming the fish invitrome will help identify and address challenges to its uptake, ensuring a smoother transition to non-organismal testing methodologies.
Ključne besede: new approach methodologies (NAMs), rainbow trout cell lines, toxicity testing, socio-technical approach, co-design with stakeholders, ekotoksikologija
Objavljeno v DiRROS: 03.02.2025; Ogledov: 299; Prenosov: 132
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Povzetek: An important goal in toxicology is the development of new ways to increase the speed, accuracy, and applicability of chemical hazard and risk assessment approaches. A promising route is the integration of in vitro assays with biological pathway information. We examined how the adverse outcome pathway (AOP) framework can be used to develop pathway-based quantitative models useful for regulatory chemical safety assessment. By using AOPs as initial conceptual models and the AOP knowledge base as a source of data on key event relationships, different methods can be applied to develop computational quantitative AOP models (qAOPs) relevant for decision making. A qAOP model may not necessarily have the same structure as the AOP it is based on. Useful AOP modeling methods range from statistical, Bayesian networks, regression, and ordinary differential equations to individual-based models and should be chosen according to the questions being asked and the data available. We discuss the need for toxicokinetic models to provide linkages between exposure and qAOPs, to extrapolate from in vitro to in vivo, and to extrapolate across species. Finally, we identify best practices for modeling and model building and the necessity for transparent and comprehensive documentation to gain confidence in the use of qAOP models and ultimately their use in regulatory applications. Environ Toxicol Chem 2019;38:1850–1865. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.
Ključne besede: Quantitative Adverse Outcome pathways, TKTD modelling, alternatives to animal testing, predictive toxicology, species extrapolation, prioritization of chemicals
Objavljeno v DiRROS: 06.08.2024; Ogledov: 468; Prenosov: 279
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Povzetek: Toxicology has been an active research field for many decades, with academic, industrial and government involvement. Modern omics and computational approaches are changing the field, from merely disease-specific observational models into target-specific predictive models. Traditionally, toxicology has strong links with other fields such as biology, chemistry, pharmacology, and medicine. With the rise of synthetic and new engineered materials, alongside ongoing prioritisation needs in chemical risk assessment for existing chemicals, early predictive evaluations are becoming of utmost importance to both scientific and regulatory purposes. ELIXIR is an intergovernmental organisation that brings together life science resources from across Europe. To coordinate the linkage of various life science efforts around modern predictive toxicology, the establishment of a new ELIXIR Community is seen as instrumental. In the past few years, joint efforts, building on incidental overlap, have been piloted in the context of ELIXIR. For example, the EU-ToxRisk, diXa, HeCaToS, transQST, and the nanotoxicology community have worked with the ELIXIR TeSS, Bioschemas, and Compute Platforms and activities. In 2018, a core group of interested parties wrote a proposal, outlining a sketch of what this new ELIXIR Toxicology Community would look like. A recent workshop (held September 30th to October 1st, 2020) extended this into an ELIXIR Toxicology roadmap and a shortlist of limited investment-high gain collaborations to give body to this new community. This Whitepaper outlines the results of these efforts and defines our vision of the ELIXIR Toxicology Community and how it complements other ELIXIR activities.
Ključne besede: toxicology, ELIXIR, interoperability, FAIR
Objavljeno v DiRROS: 05.08.2024; Ogledov: 523; Prenosov: 303
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Povzetek: Adverse outcomes that result from chemical toxicity are rarely caused by dysregulation of individual proteins; rather, they are often caused by system-level perturbations in networks of molecular events. To fully understand the mechanisms of toxicity, it is necessary to recognize the interactions of molecules, pathways, and biological processes within these networks. The developing brain is a prime example of an extremely complex network, which makes developmental neurotoxicity one of the most challenging areas in toxicology. We have developed a systems toxicology method that uses a computable biological network to represent molecular interactions in the developing brain of zebrafish larvae. The network is curated from scientific literature and describes interactions between biological processes, signaling pathways, and adverse outcomes associated with neurotoxicity. This allows us to identify important signaling hubs, pathway interactions, and emergent adverse outcomes, providing a more complete understanding of neurotoxicity. Here, we describe the construction of a zebrafish developmental neurotoxicity network and its validation by integration with publicly available neurotoxicity-related transcriptomic datasets. Our network analysis identified consistent regulation of tumor suppressors p53 and retinoblastoma 1 (Rb1) as well as the oncogene Krüppel-like factor (Klf8) in response to chemically induced developmental neurotoxicity. The developed network can be used to interpret transcriptomic data in a neurotoxicological context.
Objavljeno v DiRROS: 19.07.2024; Ogledov: 495; Prenosov: 297
Celotno besedilo (3,16 MB)
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