2,084 research outputs found

    ELIXIR and Toxicology: a community in development [version 2; peer review: 2 approved]

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    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

    Polystyrene Microplastics of Varying Sizes and Shapes Induce Distinct Redox and Mitochondrial Stress Responses in a Caco-2 Monolayer

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    Currently, we lack crucial knowledge on how the physicochemical properties of particles affect cellular health, resulting in an important gap in our understanding of the human toxicity of microplastics (MPs). Our aim was to evaluate the impact of the size and the shape of MPs on uptake and the intracellular effects in a human epithelial colorectal adenocarcinoma (Caco-2) cell line. Spherical (200 nm and 2 µm) and fibre-/fragment-shaped (8.9 ± 10.1 µm by 1.14 ± 0.97 µm) polystyrene microplastics (PS-MPs) were used to study their uptake and the potential to induce redox and mitochondrial stress responses after 24 h of exposure. We demonstrated the cellular uptake of both spherical and fibre-/fragment-shaped MPs in a size-dependent manner. In response to 2 µm spheres, we observed differential expressions of redox-related genes, including HMOX1, CAT, and GPX1. All PS-MPs decreased the intracellular H2O2 levels, which can be attributed to mitochondrial stress responses, such as increased mitochondrial DNA content, footprint, and morphology. Altogether, we demonstrated uptakes and changes in redox and mitochondrial parameters for all PS-MPs, with the 200 nm spheres showing the most profound effects. This suggests that the induction of defensive responses in Caco-2 cells mainly correlates with the number of particles taken up

    Association of indoor dust microbiota with cognitive function and behavior in preschool-aged children

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    BACKGROUND: Childhood cognitive development depends on neuroimmune interactions. Immunomodulation by early-life microbial exposure may influence neuropsychological function. In this study, we investigate the association between residential indoor microbiota and cognition and behavior among preschoolers. RESULTS: Indoor-settled dust bacterial and fungal characteristics were assessed using 16S and ITS amplicon sequencing (microbial diversity) and qPCR measurements (microbial loads). Child behavior was assessed using four scales: peer relationship, emotional, conduct, and hyperactivity was assessed by the Strengths and Difficulties Questionnaire (SDQ). Cognitive function was assessed using four tasks of the Cambridge Neuropsychological Test Automated Battery (CANTAB) software. The first two tasks were designed to assess attention and psychomotor speed (Motor Screening (MOT) and Big/Little Circle (BLC)) and the last two to evaluate the child’s visual recognition/working memory (Spatial Span (SSP) and Delayed Matching to Sample (DMS)). Among the 172 included children (age 4–6 years), we observed a 51% (95%CI;75%;9%) lower odds of children scoring not normal for hyperactivity and a decrease of 3.20% (95%CI, −6.01%; −0.30%) in BLC response time, for every IQR increase in fungal Shannon diversity. Contrarily, microbial loads were directly associated with SDQ scales and response time. For example, a 2-fold increase in Gram-positive bacterial load was associated with 70% (95%CI 18%; 156%) higher odds of scoring not normal for hyperactivity and an increase of 5.17% (95%CI 0.87%; 9.65%) in DMS response time. CONCLUSIONS: Our findings show that early-life exposure to diverse indoor fungal communities is associated with better behavioral and cognitive outcomes, whereas higher indoor microbial load was associated with worse outcomes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40168-022-01406-9

    Knowledge-Based Support for Adhesive Selection: Will it Stick?

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    As the popularity of adhesive joints in industry increases, so does the need for tools to support the process of selecting a suitable adhesive. While some such tools already exist, they are either too limited in scope, or offer too little flexibility in use. This work presents a more advanced tool, that was developed together with a team of adhesive experts. We first extract the experts' knowledge about this domain and formalize it in a Knowledge Base (KB). The IDP-Z3 reasoning system can then be used to derive the necessary functionality from this KB. Together with a user-friendly interactive interface, this creates an easy-to-use tool capable of assisting the adhesive experts. To validate our approach, we performed user testing in the form of qualitative interviews. The experts are very positive about the tool, stating that, among others, it will help save time and find more suitable adhesives. Under consideration in Theory and Practice of Logic Programming (TPLP).Comment: Under consideration in Theory and Practice of Logic Programming (TPLP

    Fetal MRI of the heart and brain in congenital heart disease

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    Antenatal assessment of congenital heart disease and associated anomalies by ultrasound has improved perinatal care. Fetal cardiovascular MRI and fetal brain MRI are rapidly evolving for fetal diagnostic testing of congenital heart disease. We give an overview on the use of fetal cardiovascular MRI and fetal brain MRI in congenital heart disease, focusing on the current applications and diagnostic yield of structural and functional imaging during pregnancy. Fetal cardiovascular MRI in congenital heart disease is a promising supplementary imaging method to echocardiography for the diagnosis of antenatal congenital heart disease in weeks 30–40 of pregnancy. Concomitant fetal brain MRI is superior to brain ultrasound to show the complex relationship between fetal haemodynamics in congenital heart disease and brain development.</p

    Incomplete reproductive barriers and genomic differentiation impact the spread of resistance mutations between green- and red-colour morphs of a cosmopolitan mite pest

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    Pesticide resistance represents a clear and trackable case of adaptive evolution with a strong societal impact. Understanding the factors associated with the evolution and spread of resistance is imperative to develop sustainable crop management strategies. The two-spotted spider mite Tetranychus urticae, a major crop pest with worldwide distribution and a polyphagous lifestyle, has evolved resistance to most classes of pesticides. Tetranychus urticae exists as either a green- or a red-coloured morph. However, the extent of genetic divergence and reproductive compatibility vary across populations of these colour morphs, complicating their taxonomic resolution at the species level. Here, we studied patterns of genetic differentiation and barriers to gene flow within and between morphs of T. urticae in order to understand the factors that influence the spread of resistance mutations across its populations. We derived multiple iso-female lines from Tetranychus populations collected from agricultural crops. We generated genomic and morphological data, characterized their bacterial communities and performed controlled crosses. Despite morphological similarities, we found large genomic differentiation between the morphs. This pattern was reflected in the incomplete, but strong postzygotic incompatibility in crosses between colour morphs, while crosses within morphs from different geographical locations were largely compatible. In addition, our results suggest recent/on-going gene flow between green-coloured T. urticae and T. turkestani. By screening the sequences of 10 resistance genes, we found evidence for multiple independent origins and for single evolutionary origins of target-site resistance mutations. Our results indicate that target-site mutations mostly evolve independently in populations on different geographical locations, and that these mutations can spread due to incomplete barriers to gene flow within and between populations

    Ascertaining the knowledge of the general public and stakeholders in the forestry sector to invasive alien species - a Pan-European study

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    Against the background of the phenomenon of globalisation, which has increasingly intensified in recent decades, invasive alien species (IAS) have led to biological invasions that have resulted in multiple negative effects on economies, human health, and especially on the environment. In order to control invasive alien species, preventive actions are considered the most effective methods. In this context, society can actively participate in the process of early detection and preventing the spread of these organisms, but there is a need to raise public awareness. In order for this process to take place in the most efficient way, it is necessary to initially evaluate the knowledge of the general public to IAS. Through a questionnaire that was circulated in ten European countries and had over two thousand respondents, this study aimed to investigate the level of knowledge of some stakeholders in the forestry sector regarding IAS. The results showed that a vast majority of respondents who participated in the study had heard about IAS and provided a correct definition of these organisms. Most of the respondents in this study heard for the first time about IAS from school, the Internet, or journal articles. Data analysis also showed that stakeholders in the forestry sector (foresters, forest owners, and members of environmental NGOs) were more likely than the other respondents to be aware of the impact of IAS. The results of this study offer an insight to researchers and decision makers assessing the differences of opinion regarding invasive alien species, and the necessary steps that could be adopted in the process of raising awareness in society

    Uptake and intracellular effects of different size-shape polystyrene microplastics in a Caco-2 monolayer

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    Our current understanding of the human toxicity of plastic particles constitutes a major knowledge gap. MPs can vary largely in their characteristics, and parameters such as size, shape, and chemical composition need to be included in risk assessment strategies. In the present study, we aimed to evaluate the impact of shape on uptake and intracellular effects of MPs comparing both spherical and irregularly shaped polystyrene particles in a human epithelial colorectal adenocarcinoma (Caco-2) cell line. Two sizes of carboxylated polystyrene spheres (200 nm and 2 μm) and self-synthesized irregularly shaped polystyrene particles (average length and diameter: 8.9 μm and 1.14 μm respectively) were used to study on one hand their ability to penetrate cells, and on the other hand their potential to induce changes in metabolic activity, membrane integrity, general reactive oxygen species levels, mitochondrial DNA content and expression of oxidative stress-related genes. Altogether, our study demonstrates that both spheres and irregularly-shaped MPs are internalized by Caco-2 cells in a size-dependent manner, i.e., smaller particles are more easily taken up after 24 h exposure. Intracellularly, a lowering in H2O2 levels was observed for all MPs. This was complemented with mitochondrial changes after exposure to the 200 nm spheres and irregularly-shaped particles, while differential expression of pro- and anti- oxidative genes, namely HMOX1, CAT and GPX1,was observed during exposure to the 2 μm spheres. These adverse (anti)-oxidative responses indicate that effects are related to the physicochemical and toxicokinetic characteristics of the particles, and highlight the importance of particle characterization to acquire fundamental insights vital for proper hazard profiling
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