Transcriptional toxicity of imidazolium- and cholinium-based ionic liquids
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA659001 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12508261_1.fastq.gz | Fastqsanger.gz | |||
| SRR12508261_2.fastq.gz | Fastqsanger.gz | |||
| SRR12508262_1.fastq.gz | Fastqsanger.gz | |||
| SRR12508262_2.fastq.gz | Fastqsanger.gz | |||
| SRR12508263_1.fastq.gz | Fastqsanger.gz |
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Project description:Ionic Liquids are a broad group of salts with low melting points that can be specifically tuned for a broad range of applications. Despite being initially considered “green” solvents, their better environmental friendliness compared to traditional solvents has been increasingly challenged. In this study, we aimed to investigate the molecular effects of ILs exposure by using RNA-sequencing to study differential gene expression patterns. Thus, we exposed Daphnia magna to 1-ethyl-3-methylimidazolium chloride ([C2mim]Cl), 1-dodecyl chloride-3-methylimidazolium ([C12mim]Cl) and cholinium chloride ([Chol]Cl). Results suggest that the three ILs share several mechanisms of toxicity, including cellular membrane and cytoskeleton damage, oxidative stress, inhibition of antioxidant enzymes, mitochondrial affectation, changes in protein biosynthesis and energy production, DNA damage, and ultimately, programmed cell death and disease initiation. Overall, the dataset revealed that [C2mim]Cl and [C12mim]Cl were, respectively, the least and the most toxic ILs at the transcriptional level. Also, it is reinforced that [Chol]Cl is not devoid of environmental hazardous potential. Unique gene expression signatures could also be identified for each IL.
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Project description:The study aims essentially in the analysis of the transcriptomic and metabolomic profiles induced by the presence of the tested ionic liquids in the metabolism of Aspergillus nidulans. Focusing specially on the secondary metabolism, which genes are clustered.
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Project description:Changes in the Gut Microbiota of Mice Orally Exposed to Methylimidazolium Ionic Liquids: an Observational Study
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Project description:Fungal secondary metabolites constitute a rich source of yet undiscovered bioactive compounds. Their production is often silent under standard laboratory conditions, but the production of some compounds can be triggered simply by altering the cultivation conditions. The usage of an organic salt - ionic liquid – as growth medium supplement can greatly impact the biosynthesis of secondary metabolites, leading to higher diversity of compounds accumulating extracellularly. This study examines if such supplements, specifically cholinium-based ionic liquids, can support the discovery of bioactive secondary metabolites across three model species: Neurospora crassa, Aspergillus nidulans and Aspergillus fumigatus. Enriched organic extracts obtained from medium supernatant revealed high diversity in metabolites. The supplementation led apparently to increased levels of either 1-aminocyclopropane-1-carboxylate or α-aminoisobutyric acid. The extracts where bioactive against two major foodborne bacterial strains: Staphylococcus aureus and Escherichia coli. In particular, those retrieved from N. crassa cultures showed greater bactericidal potential compared to control extracts derived from non-supplemented cultures. An untargeted mass spectrometry analysis using the Global Natural Product Social Molecular Networking tool enabled to capture the chemical diversity driven by the ionic liquid stimuli. Diverse macrolides, among other compounds, were putatively associated with A. fumigatus; whereas an unexpected richness of cyclic (depsi)peptides with N. crassa. Further studies are required to understand if the identified peptides are the major players of the bioactivity of N. crassa extracts, and to decode their biosynthesis pathways as well.
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Project description:Transcriptional network analysis of osmotic and ionic responses in Arabidopsis
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Project description:Despite investment in toxicogenomics, nonclinical safety studies are still used to predict clinical liabilities for new drug candidates. Network-based approaches for genomic analysis help overcome challenges with whole-genome transcriptional profiling using limited numbers of treatments for phenotypes of interest. Herein, we apply co-expression network analysis to safety assessment using rat liver gene expression data to define 415 modules, exhibiting unique transcriptional control, organized in a visual representation of the transcriptome (the ‘TXG-MAP’). Accounting for the overall transcriptional activity resulting from treatment, we explain mechanisms of toxicity and predict distinct toxicity phenotypes using module associations. We demonstrate that early network responses compliment traditional histology-based assessment in predicting outcomes for longer studies and identify a novel mechanism of hepatotoxicity involving endoplasmic reticulum stress and Nrf2 activation. Module-based molecular subtypes of cholestatic injury derived using rat translate to human. Moreover, compared to gene-level analysis alone, combining module and gene-level analysis performed in sequence identifies significantly more phenotype-gene associations, including established and novel biomarkers of liver injury.
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Project description:Nanowires (NWs), high-aspect-ratio nanomaterials, are increasingly used in technological materials and consumer products and may have toxicological characteristics distinct from nanoparticles. We carried out a comprehensive evaluation of the physicochemical stability of four silver nanowires (AgNWs) of two sizes and coatings and their toxicity to Daphnia magna. Inorganic aluminum-doped silica coatings were less effective than organic poly(vinyl pyrrolidone) coatings at preventing silver oxidation or Ag+ release and underwent a significant morphological transformation within 1 h following addition to low ionic strength Daphnia growth media. All AgNWs were highly toxic to D. magna but less toxic than ionic silver. Toxicity varied as a function of AgNW dimension, coating, and solution chemistry. Ag+ release in the media could not account for observed AgNW toxicity. Single-particle inductively coupled plasma mass spectrometry distinguished and quantified dissolved and nanoparticulate silver in microliter-scale volumes of Daphnia magna hemolymph with a limit of detection of approximately 10 ppb. The silver levels within the hemolymph of Daphnia exposed to both Ag+ and AgNW met or exceeded the initial concentration in the growth medium, indicating effective accumulation during filter feeding. Silver-rich particles were the predominant form of silver in hemolymph following exposure to both AgNWs and Ag+. Scanning electron microscopy imaging of dried hemolymph found both AgNWs and silver precipitates that were not present in the AgNW stock or the growth medium. Both organic and inorganic coatings on the AgNW were transformed during ingestion or absorption. Pathway, gene ontology, and clustering analyses of gene expression response indicated effects of AgNWs distinct from ionic silver on Daphnia magna. Four replicates each of five toxicant exposure groups of ~20 animals and four replicates of control, unexposed animals. Each control was compared to each exposed data set for a total of 16 comparisons per chemical condition.
2013-12-31 | E-GEOD-47064 | biostudies-arrayexpress
Project description:Bacteria respond to osmotic stress by a substantial increase in the intracellular osmolality, adjusting their cell turgor for altered growth conditions. Using E. coli as a model organism we demonstrate here that bacterial responses to hyperosmotic stress specifically depend on the nature of osmoticum used. We show that increasing acute hyperosmotic NaCl stress above ~1.0 Os kg-1 causes a dose-dependent K+ leak from the cell, resulting in a substantial decrease in cytosolic K+ content and a concurrent accumulation of Na+ in the cell. At the same time, isotonic sucrose or mannitol treatment (non-ionic osmotica) results in a gradual increase of the net K+ uptake. Ion flux data is consistent with growth experiments showing that bacterial growth is impaired by NaCl at the concentration resulting in a switch from net K+ uptake to efflux. Microarray experiments reveal that about 40% of up-regulated genes shared no similarity in their responses to NaCl and sucrose treatment, further suggesting specificity of osmotic adjustment in E. coli to ionic- and non-ionic osmotica The observed differences are explained by the specificity of the stress-induced changes in the membrane potential of bacterial cells highlighting the importance of voltage-gated K+ transporters for bacterial adaptation to hyperosmotic stress. Experiment Overall Design: Two biological replicates per treatment with microarray analysis using the Affymetrix GeneChip E. coli Genome array. Treatments used included: Experiment Overall Design: Control - E. coli Frag1, grown to early stationary growth phase in a mineral salts medium with 0.1% glucose at 25 C Experiment Overall Design: Sucrose hyperosmotic treatment - 1.25 M sucrose added to control culture Experiment Overall Design: for 10 min. Experiment Overall Design: NaCl hyperosmotic treatment - 1.37 M NaCl added to control culture Experiment Overall Design: For microarray data comparisons the sucrose and NaCl hyperosmotic treatment data was compared to the no treatment control data separately. The sucrose to control and NaCL to control comparison data tables are linked below.
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Project description:Few works have addressed the effects provoked by the exposure to cadmium containing nanoparticles (NPs) on adult zebrafish (Danio rerio). We studied the effects of CdS NPs (5 nm) or ionic cadmium (10 µg Cd/L) after 3 and 21 d of exposure and at 6 months post-exposure (mpe). Acute toxicity was recorded after exposure to both forms of cadmium. Significant cadmium accumulation was measured in the whole fish after both treatments and autometallography showed a higher accumulation of metal in the intestine than that in the liver. Histopathological alterations, such as inflammation in gills and vacuolization in the liver, were detected after the exposure to both cadmium forms and, in a lower extent, at 6 mpe. X-ray analysis proved the presence of CdS NPs in these organs. The hepatic transcriptome analysis revealed that gene ontology terms such as “immune response” or “actin binding” were over-represented after 21 d of exposure to ionic cadmium respect to CdS NPs treatment. Exposure to CdS NPs caused a significant effect on pathways involved in the immune response and oxidative stress, while the exposure to ionic cadmium affected significantly pathways involved in DNA damage and repair and in the energetic metabolism. Oxidative damage to liver proteins was detected after the exposure to ionic cadmium, while a stronger destabilization of the hepatocyte lysosomal membrane was recorded under exposure to CdS NPs. In summary, although ionic cadmium provoked stronger effects than CdS NPs, both cadmium forms exerted an array of lethal and sublethal effects to zebrafish.
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Project description:Despite investment in toxicogenomics, nonclinical safety studies are still used to predict clinical liabilities for new drug candidates. Network-based approaches for genomic analysis help overcome challenges with whole-genome transcriptional profiling using limited numbers of treatments for phenotypes of interest. Herein, we apply co-expression network analysis to safety assessment using rat liver gene expression data to define 415 modules, exhibiting unique transcriptional control, organized in a visual representation of the transcriptome (the ‘TXG-MAP’). Accounting for the overall transcriptional activity resulting from treatment, we explain mechanisms of toxicity and predict distinct toxicity phenotypes using module associations. We demonstrate that early network responses compliment traditional histology-based assessment in predicting outcomes for longer studies and identify a novel mechanism of hepatotoxicity involving endoplasmic reticulum stress and Nrf2 activation. Module-based molecular subtypes of cholestatic injury derived using rat translate to human. Moreover, compared to gene-level analysis alone, combining module and gene-level analysis performed in sequence identifies significantly more phenotype-gene associations, including established and novel biomarkers of liver injury.
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