The interaction of population dynamics and movement among two habitat types (toxic transgenic fields and nontoxic refuge fields) on the evolution of insecticide resistance was examined in two different simulation models. The two models were developed to test the hypothesis that increasing habitat grain from fine-grained to coarse-grained, and the resultant increase in nonrandom mating, would increase the rate of local adaptation, here the evolution of resistance. The first model, a complex, stochastic spatially explicit model, altered habitat grain by varying adult dispersal rates between habitat patches. In contrast to the expectation that increasing patch isolation and increasing the coarseness of the habitats would increase the rate of resistance evolution, intermediate levels of dispersal actually delayed resistance by as much as fivefold over the range of dispersal levels observed. Source-sink dynamics related to ovipositional patterns and the related population dynamics appear to explain the results. A simple deterministic model was developed to abstract out the separate impacts of mating and ovipositional behaviors. This model showed qualitatively the same results, although under similar assumptions it predicted much longer delays in resistance evolution. In this model, nonrandom mating alone always increased the rate at which insects adapted to transgenic crops, but nonrandom mating in combination with nonrandom oviposition could significantly delay resistance evolution. Differences between the two models may be due to the population regulation incorporated in the spatially explicit model. The models clearly suggest that resistance management programs using untreated refuges should not over-emphasize random mating at the cost of making the habitat too fine-grained.

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We discuss assay approaches for monitoring the sensitivity of Lepidoptera to Bacillus thuringiensis (Bt) insecticidal proteins and compare the relative sensitivity of larval feeding bioassays in which, respectively, mortality or growth inhibition were scored. Heliothis virescens (F.) and Helicoverpa zea (Boddie), major lepidopteran pests targeted for control by transgenic cotton, were used for assay comparison. Larval growth inhibition assays using sublethal CryIA(c) protein concentrations were considerably more sensitive than dose-response mortality assays. Growth inhibition assays were easy to set-up and read, and could readily deliver a diagnostic dose allowing for visual discrimination of resistant from susceptible phenotypes. The ability of a larval growth assay, combined with a diagnostic dose, to unambiguously separate resistant from susceptible insects was validated using a CryIA(c) protein resistant strain of H. virescens and F 1 hybrids derived by crossing the resistant strain to a susceptible H. virescens strain.

The TEL/PDGF␤R gene, which encodes a fusion protein containing the ETS-family member TEL fused to the protein-tyrosine kinase domain of the platelet-derived growth factor receptor-␤ (PDGF␤R), confers interleukin 3 (IL-3)-independent growth on Ba/F3 hematopoietic cells. TEL/ PDGF␤R mutants have been generated that contain tyrosine-to-phenylalanine (Tyr3Phe) substitutions at phosphorylation sites present in the native PDGF␤R to assess the role of these sites in cell transformation by TEL/PDGF␤R. Similar to previous findings in a murine bone marrow transplantation model, full transformation of Ba/F3 cells to IL-3-independent survival and proliferation required the TEL/PDGF␤R juxtamembrane and carboxy terminal phosphorylation sites. In contrast to previous reports concerning comparable mutants in the native PDGF␤R, each of the TEL/PDGF␤R mutants is fully active as a protein-tyrosine kinase. IntroductionChronic myelomonocytic leukemia (CMML) is characterized by clonal proliferation of myeloid cells and frequent progression to acute leukemia. A recurring cytogenetic abnormality in CMML is the t(5;12)(q33;p13) chromosomal translocation. The resulting gene rearrangement fuses the 5Ј region of TEL to the gene encoding the platelet-derived growth factor receptor-␤ (PDGF␤R). 1 TEL is a member of the ETS family of transcription factors, and it consists of an amino terminal Pointed domain (PNT) and a carboxy terminal DNA-binding domain that shares sequence homology with the winged helix-turn-helix motif. In the TEL/PDGF␤R fusion protein, the amino terminal region of TEL (which contains the PNT domain) is fused to the membrane-spanning segment and the entire cytoplasmic protein-tyrosine kinase domain of PDGF␤R. The PNT domain present in the TEL segment mediates homotypic oligomerization of the fusion protein. 2,3 Fusion of TEL sequences to PDGF␤R results in constitutive oligomerization and activation of protein-tyrosine kinase activity 2 ; numerous examples of receptor tyrosine kinase activation through homotypic oligomerization have been described (reviewed by Lemmon and Schlessinger 4 ).The Ba/F3 murine hematopoietic cell line, which requires interleukin-3 (IL-3) for survival, 5 can be transformed to IL-3 independence by the TEL/PDGF␤R fusion. 2 TEL/PDGF␤R is constitutively phosphorylated on tyrosine residues, and a point mutation corresponding to a kinase-inactivating mutation in the native PDGF␤R abrogates TEL/ PDGF␤R kinase activation and transformation of Ba/F3 cells. Moreover, the PDGF␤R tyrosine kinase inhibitor CGP 57148 6 inhibits TEL/PDGF␤R kinase activity in vitro, inhibits autophosphorylation in vivo, and abrogates proliferation of Ba/F3 cells transformed by TEL/ PDGF␤R. 7 Thus, hematopoietic transformation by TEL/PDGF␤R requires protein-tyrosine kinase activity.Similar structure-function relationships have been described for the HIP1/PDGF␤R fusion 8,9 associated with the t(5;7)(q33;q11.2) translocation, and the H4/PDGF␤R fusion that is expressed as a consequence of the t(5;10)(q33;q22) translocation. 10 Each of...