Project description:Effective toxicological testing of the vast number of new and existing chemicals currently in use will require efficient and cost effective methods. We evaluated the utility of a simple, low cost toxicity testing system employing the nematode Caenorhabditis elegans to identify toxicologically relevant changes in gene expression. The objective of this research is to determine genomic and proteomic responses in the model nematode C. elegans to exposures to representatives of several classes of toxic industrial chemicals/materials (TICs/TIMs). A total of 3 chemicals (acrylamide, cadmium chloride, and mercuric chloride) were used in these experiments. Affymetrix GeneChip for C. elegans was used to examine genome-wide responses in the 19,000+ genes of this model organism.
Project description:Effective toxicological testing of the vast number of new and existing chemicals currently in use will require efficient and cost effective methods. We evaluated the utility of a simple, low cost toxicity testing system employing the nematode Caenorhabditis elegans to identify toxicologically relevant changes in gene expression. The objective of this research is to determine genomic and proteomic responses in the model nematode C. elegans to exposures to representatives of several classes of toxic industrial chemicals/materials (TICs/TIMs). A total of 3 chemicals (acrylamide, cadmium chloride, and mercuric chloride) were used in these experiments. Affymetrix GeneChip for C. elegans was used to examine genome-wide responses in the 19,000+ genes of this model organism. Mid-vulval L4 worms were exposed to one of four concentrations of acrylamide, cadmium or mercury for 4h and 8h. Exposures were performed in triplicate.
Project description:BackgroundCooling towers (CTs) are crucial to myriad industrial processes, supporting thermal exchange between fluids in heat exchangers using water from lakes and rivers as coolant. However, CT water can sometimes introduce microbial contaminants that adhere to and colonize various surfaces within the CT system. These microorganisms can form biofilms, significantly hindering the system's thermal exchange efficiency. Current treatment strategies employ oxidizing biocides to prevent microbial growth. However, despite their affordability, they do not eliminate biofilms effectively and can lead to corrosive damage within the system. Herein, we aim to devise an anti-biofilm strategy utilizing hydrolytic enzymes (such as α-amylase, glucoamylase, pectin-lyase, cellulase, protease, and DNase) alongside antibiotics (including meropenem, ciprofloxacin, gentamicin, erythromycin, chloramphenicol, and ceftriaxone) to combat microbial growth and biofilm formation in cooling systems.ResultsAll enzymes reduced the development of the biofilms significantly compared to controls (p < 0.05). The polysaccharidases exhibited biomass reduction of 90%, except for pectin-lyase (80%), followed by DNAse and protease at 43% and 49%, respectively. The antibiotics reduced the biofilms of 70% of isolates in concentration of > 2 mg/mL. The minimal biofilm eradication concentration (MBEC) lower than 1 mg/mL was detected for some 7-day-old sessile isolates. The enzymes and antibiotics were also used in combination against biofilms using the modified Chequerboard method. We found six synergistic combinations, with Fractional inhibitory concentrations (FIC) < 0.5, out of the ten tested. In the presence of the enzymatic mixture, MBECs presented a significant decrease (p < 0.05), at least 4-fold for antibiotics and 32-fold for enzymes. Moreover, we characterized high molecular weight (> 12 kDa) exopolysaccharides (EPS) from biofilms of ten isolates, and glycosyl composition analysis indicated a high frequency of glucose, mannose, erythrose, arabinose, and idose across isolates EPS contrasting with rhamnose, allose, and those carbohydrates, which were detected in only one isolate.ConclusionThe synergistic approach of combining enzymes with antibiotics emerges as a highly effective and innovative strategy for anti-biofilm intervention, highlighting its potential to enhance biofilm management practices.
Project description:Exposure to environmental chemicals can impair neurodevelopment, and oligodendrocytes may be particularly vulnerable as their development extends from gestation into adulthood. However, few environmental chemicals have been assessed for potential risks to oligodendrocytes. Here, using a high-throughput developmental screen in cultured cells, we identified environmental chemicals in two classes that disrupt oligodendrocyte development through distinct mechanisms. Quaternary compounds, ubiquitous in disinfecting agents and personal care products, were potently and selectively cytotoxic to developing oligodendrocytes, whereas organophosphate flame retardants, commonly found in household items such as furniture and electronics, prematurely arrested oligodendrocyte maturation. Chemicals from each class impaired oligodendrocyte development postnatally in mice and in a human 3D organoid model of prenatal cortical development. Analysis of epidemiological data showed that adverse neurodevelopmental outcomes were associated with childhood exposure to the top organophosphate flame retardant identified by our screen. This work identifies toxicological vulnerabilities for oligodendrocyte development and highlights the need for deeper scrutiny of these compounds’ impacts on human health.
Project description:Exposure to environmental chemicals can impair neurodevelopment. Oligodendrocytes that wrap around axons to boost neurotransmission may be particularly vulnerable to chemical toxicity as they develop throughout fetal development and into adulthood. However, few environmental chemicals have been assessed for potential risks to oligodendrocyte development. Here, we utilized a high-throughput developmental screen and human cortical brain organoids, which revealed environmental chemicals in two classes that disrupt oligodendrocyte development. Quaternary compounds, ubiquitous in disinfecting agents, hair conditioners, and fabric softeners, were potently and selectively cytotoxic to developing oligodendrocytes through activation of the integrated stress response. Organophosphate flame retardants, commonly found in household items such as furniture and electronics, were non-cytotoxic but prematurely arrested oligodendrocyte maturation. Chemicals from each of the two classes impaired human oligodendrocyte development in a 3D organoid model of prenatal cortical development. In analysis of epidemiological data from the CDC’s National Health and Nutrition Examination Survey, adverse neurodevelopmental outcomes were associated with childhood exposure to the top organophosphate flame retardant identified in our oligodendrocyte toxicity platform. Collectively, our work identifies toxicological vulnerabilities specific to oligodendrocyte development and highlights common household chemicals with high exposure risk to children that warrant deeper scrutiny for their impact on human health.