In U.S. Pacific Northwest coho salmon (Oncorhynchus kisutch), stormwater exposure annually causes unexplained acute mortality when adult salmon migrate to urban creeks to reproduce. By investigating this phenomenon, we identified a highly toxic quinone transformation product of N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD), a globally ubiquitous tire rubber antioxidant. Retrospective analysis of representative roadway runoff and stormwater-affected creeks of the U.S. West Coast indicated widespread occurrence of 6PPD-quinone (<0.3 to 19 micrograms per liter) at toxic concentrations (median lethal concentration of 0.8 ± 0.16 micrograms per liter). These results reveal unanticipated risks of 6PPD antioxidants to an aquatic species and imply toxicological relevance for dissipated tire rubber residues.
Epithelial-mesenchymal transition (EMT) is known to play an important role in cancer progression, metastasis and drug resistance. Although there are controversies surrounding the causal relationship between EMT and cancer metastasis, the role of EMT in cancer drug resistance has been increasingly recognized. Numerous EMT-related signaling pathways are involved in drug resistance in cancer cells. Cells undergoing EMT show a feature similar to cancer stem cells (CSCs), such as an increase in drug efflux pumps and anti-apoptotic effects. Therefore, targeting EMT has been considered a novel opportunity to overcome cancer drug resistance. This review describes the mechanism by which EMT contributes to drug resistance in cancer cells and summarizes new advances in research in EMT-associated drug resistance.
Urban stormwater is a major threat to ecological health, causing a range of adverse, mostly sublethal effects. In western North America, urban runoff is acutely lethal to adult coho salmon ( Oncorhynchus kisutch) that spawn each fall in freshwater creeks. Although the mortality syndrome is correlated to urbanization and attributed to road runoff contaminant(s), the causal agent(s) remain unknown. We applied high-resolution mass spectrometry to isolate a coho mortality chemical signature: a list of nontarget and identified features that co-occurred in waters lethal to coho spawners (road runoff from controlled exposures and urban receiving waters from two field observations of symptomatic coho). Hierarchical cluster analysis indicated that tire wear particle (TWP) leachates were most chemically similar to the waters with observed toxicity, relative to other vehicle-derived sources. Prominent road runoff contaminants in the signature included two groups of nitrogen-containing compounds derived from TWP, polyethylene glycols, octylphenol ethoxylates, and polypropylene glycols. A (methoxymethyl)melamine compound family, previously unreported in North America, was detected in road runoff and urban creeks at concentrations up to ∼9 and ∼0.3 μg/L, respectively. The results indicate TWPs are an under-appreciated contaminant source in urban watersheds and should be prioritized for fate and toxicity assessment.
A variety of potentially inhibitory degradation products are produced during pretreatment of lignocellulosic biomass. Qualitative and quantitative interrogation of pretreatment hydrolysates is paramount to identifying potential correlations between pretreatment chemistries and microbial inhibition in downstream bioconversion processes. In the present study, corn stover, poplar, and pine feedstocks were pretreated under eight different chemical conditions, which are representative of leading pretreatment processes. Pretreatment processes included: 0.7% H(2)SO(4), 0.07% H(2)SO(4), liquid hot water, neutral buffer solution, aqueous ammonia, lime, lime with oxygen pressurization, and wet oxidation. Forty lignocellulosic degradation products resulting from pretreatment were analyzed using high performance liquid chromatography in combination with UV spectroscopy or tandem mass spectrometry detection (HPLC-PDA-MS/MS) and ion chromatography (IC). Of these compounds, several have been reported to be inhibitory, including furfural, hydroxymethyl furfural, ferulic acid, 3,4-dihydroxybenzaldehyde, syringic acid among others. Formation and accumulation of monitored compounds in hydrolysates is demonstrated to be a function of both the feedstock and pretreatment conditions utilized.
Though pharmaceuticals are increasingly observed in a variety of organisms from coastal and inland aquatic systems, trophic transfer of pharmaceuticals in aquatic food webs have not been reported. In this study, bioaccumulation of select pharmaceuticals was investigated in a lower order effluent-dependent stream in central Texas, USA, using isotope dilution liquid chromatography–tandem mass spectrometry (MS). A fish plasma model, initially developed from laboratory studies, was tested to examine observed versus predicted internal dose of select pharmaceuticals. Pharmaceuticals accumulated to higher concentrations in invertebrates relative to fish; elevated concentrations of the antidepressant sertraline and its primary metabolite desmethylsertraline were observed in the Asian clam, Corbicula fluminea , and two unionid mussel species. Trophic positions were determined from stable isotopes (δ 15 N and δ 13 C) collected by isotope ratio-MS; a Bayesian mixing model was then used to estimate diet contributions towards top fish predators. Because diphenhydramine and carbamazepine were the only target compounds detected in all species examined, trophic magnification factors (TMFs) were derived to evaluate potential trophic transfer of both compounds. TMFs for diphenhydramine (0.38) and carbamazepine (1.17) indicated neither compound experienced trophic magnification, which suggests that inhalational and not dietary exposure represented the primary route of uptake by fish in this effluent-dependent stream.
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