593 research outputs found
Comparative field study on bioassay responses and micropollutant uptake of POCIS, Speedisk and SorbiCell polar passive samplers
High resolution effect-directed analysis of steroid hormone (ant)agonists in surface and wastewater quality monitoring
Monitoring of chemical water quality is extremely challenging due to the large variety of compounds and the presence of biologically active compounds with unknown chemical identity. Previously, we developed a high resolution Effect-Directed Analysis (EDA) platform that combines liquid chromatography with high resolution mass spectrometry and parallel bioassay detection. In this study, the platform is combined with CALUX bioassays for (anti)androgenic, estrogenic and glucocorticoid activities, and the performance of the platform is evaluated. It appeared to render very repeatable results, with high recoveries of spiked compounds and high consistency between the mass spectrometric and bioassay results. Application of the platform to wastewater treatment plant effluent and surface water samples led to the identification of several compounds contributing to the measured activities. Eventually, a workflow is proposed for the application of the platform in a routine monitoring context. The workflow divides the platform into four phases, of which one to all can be performed depending on the research question and the results obtained. This allows one to make a balance between the effort put into the platform and the certainty and depth by which active compounds will be identified. The EDA platform is a valuable tool to identify unknown bioactive compounds, both in an academic setting as in the context of legislative, governmental or routine monitoring
Identifying adverse outcome pathways (AOP) for Amsterdam City Fish by integrated field monitoring
This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordThe European City Fish project aimed to develop a generic methodology for ecological risk assessment for urban rivers. Since traditional methods only consider a small fraction of substances present in the water cycle, biological effect monitoring is required for a more reliable assessment of the pollution status. A major challenge for environmental risk assessment (ERA) is the application of adverse outcome pathways (AOP), i.e. the linking of pollutant exposure via early molecular and biochemical changes to physiological effects and, ultimately, effects on populations and ecosystems.
We investigated the linkage between responses at these different levels. Many AOP aspects were investigated, from external and internal exposure to different classes of micropollutants, via molecular key events (MKE) the impacts on organs and organisms (fish physiology), to changes in the population dynamics of fish. Risk assessment procedures were evaluated by comparing environmental quality standards, bioassay responses, biomarkers in caged and feral fish, and the impact on fish populations. Although no complete AOP was observed, indirect relationships linking pollutant exposure via MKE to impaired locomotion were demonstrated at the most polluted site near a landfill for chemical waste. The pathway indicated that several upstream key events requiring energy for stress responses and toxic defence are likely to converge at a single common MKE: increased metabolic demands. Both fish biomarkers and the bioanalytical SIMONI strategy are valuable indicators for micropollutant risks to fish communities.City of AmsterdamEuropean UnionWaternet Institute for the Urban Water Cycle, Amsterda
Structural basis for CRISPR RNA-guided DNA recognition by Cascade
The CRISPR (clustered regularly interspaced short palindromic repeats) immune system in prokaryotes uses small guide RNAs to neutralize invading viruses and plasmids. In Escherichia coli, immunity depends on a ribonucleoprotein complex called Cascade. Here we present the composition and low-resolution structure of Cascade and show how it recognizes double-stranded DNA (dsDNA) targets in a sequence-specific manner. Cascade is a 405-kDa complex comprising five functionally essential CRISPR-associated (Cas) proteins (CasA1B2C6D1E1) and a 61-nucleotide CRISPR RNA (crRNA) with 5′-hydroxyl and 2′,3′-cyclic phosphate termini. The crRNA guides Cascade to dsDNA target sequences by forming base pairs with the complementary DNA strand while displacing the noncomplementary strand to form an R-loop. Cascade recognizes target DNA without consuming ATP, which suggests that continuous invader DNA surveillance takes place without energy investment. The structure of Cascade shows an unusual seahorse shape that undergoes conformational changes when it binds target DNA.
B cell immune profiles in dysbiotic vermiform appendixes of pancreatic cancer patients
Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid tumors and is resistant to immunotherapy. B cells play an essential role in PDAC progression and immune responses, both locally and systemically. Moreover, increasing evidence suggests that microbial compositions inside the tumor, as well as in the oral cavity and the gut, are important factors in shaping the PDAC immune landscape. However, the gut-associated lymphoid tissue (GALT) has not previously been explored in PDAC patients. In this study, we analyzed healthy vermiform appendix (VA) from 20 patients with PDAC and 32 patients with colon diseases by gene expression immune profiling, flow cytometry analysis, and microbiome sequencing. We show that the VA GALT of PDAC patients exhibits markers of increased inflammation and cytotoxic cell activity. In contrast, B cell function is decreased in PDAC VA GALT based on gene expression profiling; B cells express significantly fewer MHC class II surface receptors, whereas plasma cells express the immune checkpoint molecule HLA-G. Additionally, the vermiform appendix microbiome of PDAC patients is enriched with Klebsiella pneumoniae, Bifidobacterium animalis, and Adlercreutzia equolifaciens, while certain commensals are depleted. Our findings may suggest impaired B cell function within the GALT of PDAC patients, which could potentially be linked to microbial dysbiosis. Additional investigations are imperative to validate our observations and explore these potential targets of future therapies.</p
B cell immune profiles in dysbiotic vermiform appendixes of pancreatic cancer patients
Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid tumors and is resistant to immunotherapy. B cells play an essential role in PDAC progression and immune responses, both locally and systemically. Moreover, increasing evidence suggests that microbial compositions inside the tumor, as well as in the oral cavity and the gut, are important factors in shaping the PDAC immune landscape. However, the gut-associated lymphoid tissue (GALT) has not previously been explored in PDAC patients. In this study, we analyzed healthy vermiform appendix (VA) from 20 patients with PDAC and 32 patients with colon diseases by gene expression immune profiling, flow cytometry analysis, and microbiome sequencing. We show that the VA GALT of PDAC patients exhibits markers of increased inflammation and cytotoxic cell activity. In contrast, B cell function is decreased in PDAC VA GALT based on gene expression profiling; B cells express significantly fewer MHC class II surface receptors, whereas plasma cells express the immune checkpoint molecule HLA-G. Additionally, the vermiform appendix microbiome of PDAC patients is enriched with Klebsiella pneumoniae, Bifidobacterium animalis, and Adlercreutzia equolifaciens, while certain commensals are depleted. Our findings may suggest impaired B cell function within the GALT of PDAC patients, which could potentially be linked to microbial dysbiosis. Additional investigations are imperative to validate our observations and explore these potential targets of future therapies.</p
Catalase activity in Smicridea McLachlan, 1871 (Insecta, Trichoptera) collected from natural and altered/impacted streams
Induction of fish biomarkers by synthetic-based drilling muds
The study investigated the effects of chronic exposure of pink snapper (Pagrus auratus Forster), to synthetic based drilling muds (SBMs). Fish were exposed to three mud systems comprised of three different types of synthetic based fluids (SBFs): an ester (E), an isomerized olefin (IO) and linear alpha olefin (LAO). Condition factor (CF), liver somatic index (LSI), hepatic detoxification (EROD activity), biliary metabolites, DNA damage and stress proteins (HSP-70) were determined. Exposure to E caused biologically significant effects by increasing CF and LSI, and triggered biliary metabolite accumulation. While ester-based SBFs have a rapid biodegradation rate in the environment, they caused the most pronounced effects on fish health. IO induced EROD activity and biliary metabolites and LAO induced EROD activity and stress protein levels. The results demonstrate that while acute toxicity of SBMs is generally low, chronic exposure to weathering cutting piles has the potential to affect fish health. The study illustrates the advantages of the Western Australian government case-by-case approach to drilling fluid management, and highlights the importance of considering the receiving environment in the selection of SBMs
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