Project description:Coal-fired power plant is a major method of electricity generation worldwide with serious concerns relating to air pollution. In recent years, fly ash from coal-fired power plants has become a major target of pollution control by worldwide regulatory agencies. In this present study, fly ash particulate matter (PM) obtained from the electrostatic precipitator of Mae Moh Coal-fired Power Plant (Lampang, Thailand) was selected as a model for determination of physicochemical characteristics and toxicological profiles in mice. The average size of the fly ash PM was 4.29 ± 1.85 µm as determined by electron microscopy. Major heavy metal was iron at 101,067.31 ± 8,246.12 mg/kg as detected by ICPMS. Acenaphthene was the most abundant polyaromatic hydrocarbon at 40.77 ± 0.003 mg/kg as analyzed by GCMS. The toxicological profiles of the characterized fly ash PM were conducted in Balb/c mice by intratracheal instillation at 1 and 10 mg/kg/day for 7 days, compared to vehicle as negative control and standard PM 2.5 as positive control. The fly ash PM and the standard PM induced significant pulmonary inflammation in mice lungs compared to vehicle control. In addition, molecular toxicology of mice lungs investigated by proteomics demonstrated 3 inflammation associated pathways, which include leukocyte transendothelial migration, phagosome, and neutrophil extracellular trap formation. Furthermore, only high dose (10 mg/kg/day) standard PM and high dose fly ash PM showed high expression of NCF2, which potentially promotes cancer in the long run. This study is the first to report on the physicochemical characterization, histopathology, and proteomic-associated toxicological profiles of the fly ash PM obtained from the largest coal-fired power plant in Thailand. Information obtained from this study is useful for academic researchers, electricity enterprises, and policymakers to develop appropriate strategies to manage air pollution from coal-fired power plants worldwide.
Project description:Ecological risk assessments have traditionally relied on simplified models that expose single species to individual chemicals under controlled laboratory conditions. However, real-world ecosystems are subject to multiple, interacting stressors, particularly from anthropogenic sources, that challenge the predictive power of these conventional approaches. To address this gap, we investigated the effects of coal ash, a complex mixture of heavy metals, on the freshwater invertebrate Daphnia magna. We quantified both suborganismal (transcriptomic) and individual-level (survival, growth, reproduction) responses to coal ash exposure. These data were integrated into a Dynamic Energy Budget (DEB) model to simulate physiological modes of action (pMoAs). Using machine learning, we identified gene sets predictive of DEB state variables and prioritized differentially expressed genes to determine the most plausible bioenergetic disruption. This study demonstrates a scalable framework for linking molecular perturbations to organismal outcomes, offering a mechanistic basis for assessing the ecological impact of complex chemical mixtures. Our approach advances predictive ecotoxicology by moving beyond chemical-specific assays toward integrative, systems-level models that better reflect environmental realities.
Project description:The goal of our study was to determine the effect the TRPV1 I585V SNP has on lung cells. NHBE cells, obtained from 4 different donor (Lonza), were genotyped to identify the presence of the TRPV1 SNP I585V. Of the 4 patient samples, 2 were heterozygous for the I585V SNP and 2 expressed WT TRPV1. These cells were plated in 12 well plates and treated with Coal Fly Ash (CFA) at multiple concentrations and capsasian. Differences between the patient samples were assessed.
Project description:In order to investigate the underlying mechanisms of methylmecury (MeHg)-mediated toxicity to Atlantic cod (Gadus morhua), we analyzed the liver proteome of fish exposed in vivo to MeHg (0, 0.5, 2 mg/kg body weight) for 2 weeks. Label-free quantitative mass spectrometry enabled quantification of 1143 proteins, and 125 were differentially regulated between MeHg-treated samples and controls. Six proteins among the top differentially regulated (T23O, GLNA EPS8L2, APOA4, RAP1B, CZTZ) were analyzed using selected reaction monitoring (SRM). Supported by bioinformatics analyses, we conclude that MeHg disrupts mainly redox homeostasis and energy generating metabolic pathways in cod liver, the latter potentially modulated through MeHg-induced oxidative stress.
Project description:Exposure to indoor air pollution generated from the combustion of solid fuels is a major risk factor for a spectrum of cardiovascular and respiratory diseases, including lung cancer. In Chinaâs rural counties of Xuanwei and Fuyuan, lung cancer rates are among the highest in the country. While the elevated disease risk in this population has been linked to the widespread usage of bituminous (smoky) coal as compared to anthracite (smokeless) coal, the underlying physiologic mechanism that smoky coal induces in comparison to other fuel types is unclear. As we have previously used airway gene-expression profiling to gain molecular insights into the physiologic effects of cigarette smoke, here we profiled the buccal epithelium of residents exposed to the burning of smoky and smokeless coal in order to understand the physiologic effects of solid fuels. Buccal mucosa scrapings were collected from healthy, non-smoking female residents of Xuanwei and Fuyuan counties who burn coal indoors. RNA was isolated and hybridized onto Affymetrix Human gene 1.0 ST GeneChips, capturing the gene-expression response of (n=26) smoky coal users and (n=9) smokeless coal users. 24-hour indoor personal exposure levels (PM2.5, Polycyclic Aromatic Hydrocarbons) were also captured during this sampling period.
Project description:Methylmercury (MeHg) is a highly toxic environmental pollutant. To understand the mechanisms of toxicity of the compound and possibly to discover new biomarkers for environmental monitoring, we have conducted toxicogenomics studies. We designed 126k-cod-oligonucleotide arrays and performed genome-wide gene expression assays in liver samples from juvenile cod treated with MeHg (0.5 and 2 mg/kg body weight). Microarray analysis showed MeHg differentially regulated hundreds of genes. Gene Ontology and pathway analyses of differentially regulated genes revealed that MeHg modulated mainly genes involved in immune response, oxidative stress response, tissue remodelling, and energy pathways such as lipid, carbohydrate and amino acid metabolism. The results provide insights into the mechanisms of toxicity of MeHg and provide candidate biomarkers of exposure to MeHg for further evaluation. Analyzed 5 samples from each of 3 groups: control, 0.5 mg/BW MeHg treated, and 2 mg/BW MeHg treated. Liver total RNA was reverse transcribed, Cy3-labeled, and hybridized (one-color hybridzation).
Project description:Methylmercury (MeHg) is an environmental pollutant of global public health concern. MeHg is associated with immune dysfunction but the underlying mechanisms are unclear. The most common route of MeHg exposure is through consumption of fatty fish that contain beneficial n-3 polyunsaturated fatty acids (PUFA) that may protect against MeHg toxicity. To better inform individual costs and benefits of fish consumption, we aimed to identify candidate epigenetic biomarkers of biological responses that reflect MeHg toxicity and PUFA protection.
Project description:Coal is a major energy source that generates diverse environmental impacts through its production, primarily by the release of coal dust particles. An aqueous coal dust extract was obtained from a mineral sample taken from one of the largest coal mines in Colombia (La Loma, Cesar), trace elements by ICP/MS were measured, and its toxicity evaluated using the zebrafish (Danio rerio) vertebrate model. In this study, zebrafish embryos were exposed to different concentrations of aqueous coal extract (0, 0.1, 1, 10, 100 and 1000 parts per million (ppm; μg/mL) to establish acute toxicity, as well as morphological and transcriptome alterations. Trace elements within the coal extract yielding the highest concentrations included Sr, Zn, Ba, As, Cu, Se, Li, Ni, Sb, Rb, Co, and Cr. In addition, Cd and Pb were found in lower concentrations. No significant difference in mortality was observed with survival near 90% in all treatments. A significant decrease in rate of hatching was observed in the 0.1 and 1000 ppm treatment groups at 72 hpf. Furthermore, no significant differences in total body length, head length, or head diameter was observed in any of the treatment groups. Transcriptomic results of zebrafish larvae revealed alterations in 77, 61, and 1,376 genes in the 1, 10, and 100 ppm treatments, respectively. Gene ontology analysis revealed gene alterations associated with hematological system development and function, tissue morphology and development, connective tissue development and function, and embryonic development. Overall, these findings are the first to identify gene expression alterations in response to a developmental aqueous coal dust residue from coal mining.
Project description:ASH-1 orthologs are H3K36-specific methyltransferases that are conserved from fungi to humans but are poorly understood, in part because they are typically essential for viability. Here we examine the H3K36 methylation pathway of Neurospora crassa, which we find has just two H3K36 methyltransferases, ASH-1 and RNA polymerase II-associated SET-2. Our investigation of the interplay between SET-2 and ASH-1 uncovered a regulatory mechanism connecting ASH-1-catalyzed H3K36 methylation to repression of poorly transcribed genes. Our findings provide new insight into ASH-1 function, H3K27me2/3 establishment, and repression at facultative heterochromatin.
Project description:Methylmercury (MeHg) is a highly toxic environmental pollutant. To understand the mechanisms of toxicity of the compound and possibly to discover new biomarkers for environmental monitoring, we have conducted toxicogenomics studies. We designed 126k-cod-oligonucleotide arrays and performed genome-wide gene expression assays in liver samples from juvenile cod treated with MeHg (0.5 and 2 mg/kg body weight). Microarray analysis showed MeHg differentially regulated hundreds of genes. Gene Ontology and pathway analyses of differentially regulated genes revealed that MeHg modulated mainly genes involved in immune response, oxidative stress response, tissue remodelling, and energy pathways such as lipid, carbohydrate and amino acid metabolism. The results provide insights into the mechanisms of toxicity of MeHg and provide candidate biomarkers of exposure to MeHg for further evaluation.