Biological responses to a formerly fi shless lake in the Cascade Range, Oregon (USA) were assessed through monitoring of recent changes and paleolimnological techniques to assess earlier changes. We used un- published fi sheries reports, sediment cores, and available published and unpublished water quality data to evaluate changes to the lake. Diamond Lake has undergone four periods of fiintroductions in the 20 th century. Rainbow trout (Salmo gairdneri) were annually released from 1910-2006, except for 1949 and 1954. Tui chub (Gila bicolor), an omnivorous cyprinid, were introduced in the late 1930s and the late 1980s, presumably as discarded live bait. Diamond Lake was treated with rotenone in 1954 which successfully eradicated the tui chub. The introductions of trout caused relatively modest changes in water quality and lake biota, whereas the introductions of tui chub caused major increases in cyanobacteria, changes in diatom community composition, reduction in transparency, increases in the proportion of rotifers, major reduction in benthic standing crop, and virtual elimination of amphipods, gas- tropods, and other large-bodied invertebrates. The unintended biomanipulations demonstrate the importance of an omnivorous cyprinid in promoting a series of biological responses throughout the lake food web.

BACKGROUND:CC chemokine ligand 11 (CCL11) is the outstanding member of all described CC chemokine receptor 3 (CCR3) ligands and is shown to be selective for this receptor. However, it also activates CCR5 but only in the micromolar range. The in vivo activity of CCL11 is expected to be temporally restricted, as it is degraded by specific proteases such as the dipeptidyl-peptidase IV (DP4), also termed CD26. Based on the approach to inactivate chemokine receptors in allergic disease models as has been demonstrated for DP4-resistant n-nonanoyl (NNY)-CCL14 and for amino-oxypentane (AOP)-CCL5, it is tempting to study similar compounds derived from CCL11.METHODS:Synthesis of NNY-CCL11 was performed and it was characterized for biological functions in human and mouse eosinophils as well as in cell lines stably transfected either with human CCR3 or CCR5. Resistance to DP4 treatment was also investigated.RESULTS:The functional activities of NNY-CCL11 mediated via CCR3 show an almost identical pattern to CCL11 with respect to intracellular calcium mobilization and CCR3 internalization. N-terminal cleavage of CCL11 by preincubation with DP4 results in a reduced capacity to internalize CCR3, while preincubation of NNY-CCL11 shows no influence. In contrast to CCL11, NNY-CCL11 also activates CCR5+ cell lines and human monocytes in the nanomolar range, being about 100 times more potent than CCL11.CONCLUSIONS:n-Nonanoyl-CCL11 represents a compound with dual activity restricted to CCR3 and CCR5. Because of its receptor-inactivating capacity and stability against DP4 degradation, NNY-CCL11 is a suitable tool for the decoding of the pathophysiological mechanisms of allergic diseases.