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.

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Background: cytb 5 modulates catalysis performed by cytsP450, in vivo and in vitro. Results: The structure of full-length cytb 5 was solved by NMR, and the cytP450-binding site on cytb 5 was identified by mutagenesis and NMR. Conclusion: A model of the cytb 5 -cytP450 complex is presented. Addition of a substrate strengthens the cytb 5 -cytP450 interaction. Significance: The cytb 5 -cytP450 complex structure will help unravel the mechanism by which cytb 5 regulates catalysis by cytP450.

Self-association of human islet amyloid polypeptide (hIAPP) is correlated with the development of type II diabetes by the disruption of cellular homeostasis in islet cells through the formation of membrane-active oligomers. The toxic species of hIAPP responsible for membrane damage has not been identified. In this study, we show by pulsed field gradient NMR spectroscopy that the monomeric form of the toxic, amyloidogenic human variant of IAPP (hIAPP) adopts a temperature dependent compact folded conformation that is absent in both the nontoxic and nonamyloidogenic rat variant of IAPP and absent in hIAPP at low temperatures, suggesting this compact form of monomeric hIAPP may be linked to its later aggregation and cytotoxicity. In addition to the monomeric form of hIAPP, a large oligomeric species greater than 100 nm in diameter is also present but does not trigger the nucleation-dependent aggregation of IAPP at 4 degrees C, indicating the large oligomeric species may be an off-pathway intermediate that has been predicted by kinetic models of IAPP fiber formation. Furthermore, analysis of the polydispersity of the calculated diffusion values indicates small oligomeric species of hIAPP are absent in agreement with a recent ultracentrifugation study. The absence of small oligomeric species in solution suggests the formation of small, well-defined ion channels by hIAPP may proceed by aggregation of monomeric IAPP on the membrane, rather than by the insertion of preformed structured oligomers from the solution state as has been proposed for other amyloidogenic proteins.

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Comprehensive Multiphase NMR provides an overview as to all components (liquids, gels, solids) in a living organism.

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Nuclear magnetic resonance (NMR) is arguably the most powerful and versatile tool in modern science. It has the capability to solve complex structures and interactions in situ even in complex heterogeneous multiphase samples such as soil, plants, and tissues. NMR has vast potential in environmental research and can provide insight into a diverse range of environmental processes at the molecular level be it identifying the binding site in human blood for a specific contaminant or the compositional dynamics of soil with climate change. Modern NMR-based metabonomics is elucidating contaminant toxicity and toxic mode of action rapidly and at sub lethal concentrations. Combined modern NMR approaches provide a powerful framework to better understand carbon cycling and sustainable agriculture, as well as contaminant fate, bioavailability, toxicity, sequestration, and remediation.