Polybrominated diphenyl ethers (PBDEs) have become widely distributed as environmental contaminants due to their use as flame retardants. Their structural similarity to other halogenated aromatic pollutants has led to speculation that they might share toxicological properties such as hepatic enzyme induction. In this work we synthesized a number of PBDE congeners, studied their affinity for rat hepatic Ah receptor through competitive binding assays, and determined their ability to induce hepatic cytochrome P-450 enzymes by means of EROD (ethoxyresorufin-O-deethylase) assays in human, rat, chick, and rainbow trout cells. Both pure PBDE congeners and commercial PBDE mixtures had Ah receptor binding affinities 10(-2)-10(-5) times that of 2,3,7,8-tetrachlorodibenzo-p-dioxin. In contrast with polychlorinated biphenyls, Ah receptor binding affinities of PBDEs could not be related to the planarity of the molecule, possibly because the large size of the bromine atoms expands the Ah receptor's binding site. EROD activities of the PBDE congeners followed a similar rank order in all cells. Some congeners, notably PBDE 85, did not follow the usual trend in which strength of Ah receptor binding affinity paralleled P-450 induction potency. Use of the gel retardation assay with a synthetic oligonucleotide indicated that in these cases the liganded Ah receptor failed to bind to the DNA recognition sequence.
At the initiation of drug treatment, attitudes toward medication and insight appear more relevant to medication adherence than side effects. Adherence appears to reflect a complex interaction of influences, which may change over time.
Unraveling the origins of Malesia's once vast, hyperdiverse rainforests is a perennial challenge. Major contributions to rainforest assembly came from floristic elements carried on the Indian Plate and montane elementsfrom the Australian Plate (Sahul). The Sahul component is now understood to include substantial two-way exchanges with Sunda inclusive of lowland taxa. Evidence for the relative contributions of the great Asiatic floristic interchanges (GAFIs) with India and Sahul, respectively, to the flora of Malesia comes from contemporary lineage distributions, the fossil record, time-calibrated phylogenies, functional traits, and the spatial structure of genetic diversity. Functional-trait and biome conservatism are noted features of montane austral lineages from Sahul (e.g., diverse Podocarpaceae), whereas the abundance and diversity of lowland lineages, including Syzygium (Myrtaceae) and the Asian dipterocarps (Dipterocarpoideae), reflect a less well understood combination of dispersal, ecology, and adaptive radiations. Thus, Malesian rainforest assembly has been shaped by sharply contrasting evolutionary origins and biogeographic histories.
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