The sedative drug thalidomide ([+]-alpha-phthalimidoglutarimide), once abandoned for causing birth defects in humans, has found new therapeutic license in leprosy and other diseases, with renewed teratological consequences. Although the mechanism of teratogenesis and determinants of risk remain unclear, related teratogenic xenobiotics are bioactivated by embryonic prostaglandin H synthase (PHS) to a free-radical intermediates that produce reactive oxygen species (ROS), which cause oxidative damage to DNA and other cellular macromolecules. Similarly, thalidomide is bioactivated by horseradish peroxidase, and oxidizes DNA and glutathione, indicating free radical-mediated oxidative stress. Furthermore, thalidomide teratogenicity in rabbits is reduced by the PHS inhibitor acetylsalicylic acid, indicating PHS-catalyzed bioactivation. Here, we show in rabbits that thalidomide initiates embryonic DNA oxidation and teratogenicity, both of which are abolished by pre-treatment with the free radical spin trapping agent alpha-phenyl-N-t-butylnitrone (PBN). In contrast, in mice, a species resistant to thalidomide teratogenicity, thalidomide does not enhance DNA oxidation, even at a dose 300% higher than that used in rabbits, providing insight into an embryonic determinant of species-dependent susceptibility. In addition to their therapeutic implications, these results constitute direct evidence that the teratogenicity of thalidomide may involve free radical-mediated oxidative damage to embryonic cellular macromolecules.

We found a significant and positive relationship between fish species richness and four measures of stream size (drainage area, stream order, link magnitude, and downstream link) in three Illinois drainage basins. Downstream link (incorporating both stream size and size of stream at the next downstream confluence) explained the greatest portion of the variance. This suggests that downstream processes significantly influence the structure of fish communities inhabiting warmwater streams. Significantly higher numbers of fish species were collected from tributary streams (< 259 km2 drainage area) located lower in a drainage network and connected to a main channel system than from similarly sized streams located in the headwaters of a drainage network. The difference in species richness among station treatments was not due to a difference in the number of individuals collected among treatments. We were unable to accept or reject the hypothesis that differences in fish species richness were due to differences in physical habitat. The immigration–extinction hypothesis appears to provide a plausible explanation for the observed pattern in fish community structure within a drainage. The location of a stream channel within a network may provide a general template for fish community structure in warmwater drainages by regulating potential species richness.

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We analyzed data from 79 watersheds in an undegraded U.S. ecoregion to identify key environmental factors that explained stream fish assemblage patterns and to evaluate the relative influence of environmental factors operating at different spatial scales. A few key factors from the watershed, reach, and riparian scale explained a significant amount of the variance in fish attributes. Three environment–fish associations were evident. Top carnivores and intolerant cold-water fishes were associated with relatively narrow, deep, high-gradient, cold streams with strong groundwater inputs. Tolerant cyprinids occurred in small streams with low groundwater input, low dissolved oxygen, and abundant macrophytes. A diverse assemblage (Cyprinidae, Catostomidae, Centrarchidae, Percidae) existed in warm, wide streams in watersheds dominated by lacustrine sand and gravel geology and abundant wetlands and lakes. Overall, reach-scale variables directly explained the most, watershed-scale variables less, and riparian-scale variables the least variation in fish attributes. Watershed and riparian variables had indirect connections with fishes through their direct influence on reach variables. In conjunction with findings from more degraded regions, we conclude that the relative influence of reach-scale variables on fishes are greatest in undegraded areas and that direct effects of watershed-scale variables are increasingly important as human modifications of the landscape increase.

In the developing embryo and fetus, endogenous or xenobiotic-enhanced formation of reactive oxygen species (ROS) like hydroxyl radicals may adversely alter development by oxidatively damaging cellular lipids, proteins and DNA, and/or by altering signal transduction. The postnatal consequences may include an array of birth defects (teratogenesis), postnatal functional deficits, and diseases. In animal models, the adverse developmental consequences of in utero exposure to agents like thalidomide, methamphetamine, phenytoin, benzo[a]pyrene, and ionizing radiation can be modulated by altering pathways that control the embryonic ROS balance, including enzymes that bioactivate endogenous substrates and xenobiotics to free radical intermediates, antioxidative enzymes that detoxify ROS, and enzymes that repair oxidative DNA damage. ROS-mediated signaling via Ras, nuclear factor kappa B and related transducers also may contribute to altered development. Embryopathies can be reduced by free radical spin trapping agents and antioxidants, and enhanced by glutathione depletion. Further modulatory approaches to evaluate such mechanisms in vivo and/or in embryo culture have included the use of knockout mice, transgenic knock-ins and mutant deficient mice with altered enzyme activities, as well as antisense oligonucleotides, protein therapy with antioxidative enzymes, dietary depletion of essential cofactors and chemical enzyme inhibitors. In a few cases, measures anticipated to be protective have conversely enhanced the risk of adverse developmental outcomes, indicating the complexity of development and need for caution in testing therapeutic strategies in humans. A better understanding of the developmental effects of ROS may provide insights for risk assessment and the reduction of adverse postnatal consequences.

The largescale structure of an agriculturally developed prairie river system in central Illinois was examined and compared with predictions from current stream ecosystem theory. High rates of primary productivity (> 15 g carbon∙m−2∙d−1) were characteristic of the watershed, although longitudinal patterns in riparian vegetation, stream temperature, and primary productivity were inverted relative to typical streams in forested uplands. Empirical models of gross primary production and community respiration were developed. Light availability, mediated by both channel shading and turbidity, appeared to be the principal factor limiting primary productivity. Both nitrate and orthophosphorus were found in high concentrations throughout the watershed. Largescale patterns in nutrient availability suggest that landuse patterns, and particularly urbanization, strongly affected spatial and temporal distributions of both nutrients. Differences between prairie river systems and "prototype" structures envisioned by the River Continuum Concept (RCC) derive from the descriptive nature of the RCC, and its inability to incorporate nonstandard distributions of key driving variables. The use of empirical modelling in stream ecosystem studies is discussed.

1. Rapidly advancing geographical information systems (GIS) technologies are forcing a careful evaluation of the roles and biases of landscape and traditional site‐based perspectives on assessments of aquatic communities. Viewing the world at very different scales can lead to seeming contradictions about the nature of specific ecological systems. In the case of Michigan trout streams, landscape analyses suggest a predictable community shaped by large‐scale patterns in hydrology and geology. Most site‐based studies, however, suggest these communities are highly variable in structure over time, and are strongly shaped by site‐specific physical and biological dynamics. As the real world is comprised of processes operating both at local and landscape scales, an analytical framework for integrating these paradigms is desirable. 2. Decomposition of variances by factorial ANOVA into time, space and time–space interaction terms can provide a conceptual and analytical model for integrating processes operating at landscape and local scales. Using this approach, long‐term data sets were examined for three insects and two fishes common in Michigan trout streams. Each taxon had a unique variance structure, and the observed variance structure was highly dependent upon sample size. 3. Both spatially extensive designs with little sampling over time (typical of many GIS studies) and temporally extensive designs with little or no spatial sampling (typical of population and community studies), are biased in terms of their view of the relative importance of local and landscape factors. The necessary, but in many cases costly, solution is to develop and analyse data sets that are both spatially and temporally extensive.

Although the importance of water temperature to the ecology of stream fishes is well documented, relatively little information is available on the extent of regional variation in thermal regime and its influence on stream fish distribution and abundance patterns. In streams draining the heterogeneous glacial landscape of Michigan's Lower Peninsula, regional variation in summer mean temperature and temperature fluctuation is among the highest reported in the literature. We developed a habitat classification to simplify the description of thermal regimes and to describe the relationships between available thermal regimes and distribution patterns of stream fishes. Changes in community composition, species richness, and standing stocks of key fish species occurred across gradients in mean temperature and temperature fluctuation. These changes were used to identify three mean temperature categories (cold, <19°C; cool, 19–<22°C; and warm, ≥22°C) and three temperature fluctuation categories (stable, <5°C; moderate, 5–<10°C; and extreme, ≥10°C). The combination of these categories resulted in a 3 × 3 matrix with nine discrete thermal regimes. The classification developed in this study provides a framework for descriptions of the realized thermal niche of stream fishes, and can be used as a baseline for measurement of changes in distribution patterns associated with future climate warming. Our results suggest that observed differences in community structure among sites are largely attributable to spatial variation in mean temperature and temperature fluctuation. Thus, accounting for the linkage between regional variation in thermal regime and fish community structure should improve our ability to effectively assess and manage stream resources.