Does Divergence in Habitat Breadth Associate with Species Differences in Decision Making in Drosophila Sechellia and Drosophila Simulans?

Decision making is involved in many behaviors contributing to fitness, such as habitat choice, mate selection, and foraging. Because of this, high decision-making accuracy (i.e., selecting the option most beneficial for fitness) should be under strong selection. However, decision making is energetically costly, often involving substantial time and energy to survey the environment to obtain high-quality information. Thus, for high decision making accuracy to evolve, its benefits should outweigh its costs. Inconsistency in the net benefits of decision making across environments is hypothesized to be an important means for maintaining variation in this trait. However, very little is known about how environmental factors influence the evolution of decision making to produce variation among individuals, genotypes, and species. Here, we compared two recently diverged species of Drosophila differing substantially in habitat breadth and degree of environmental predictability and variability: Drosophilasechellia and Drosophilasimulans. We found that the species evolving under higher environmental unpredictability and variability showed higher decision-making accuracy, but not higher environmental sampling.

Oncogenic KRAS-Driven Metabolic Reprogramming in Pancreatic Cancer Cells Utilizes Cytokines from the Tumor Microenvironment.

A hallmark of pancreatic ductal adenocarcinoma (PDAC) is an exuberant stroma comprised of diverse cell types that enable or suppress tumor progression. Here, we explored the role of oncogenic KRAS in protumorigenic signaling interactions between cancer cells and host cells. We show that KRAS mutation (KRAS*) drives cell-autonomous expression of type I cytokine receptor complexes (IL2rγ-IL4rα and IL2rγ-IL13rα1) in cancer cells that in turn are capable of receiving cytokine growth signals (IL4 or IL13) provided by invading Th2 cells in the microenvironment. Early neoplastic lesions show close proximity of cancer cells harboring KRAS* and Th2 cells producing IL4 and IL13. Activated IL2rγ-IL4rα and IL2rγ-IL13rα1 receptors signal primarily via JAK1-STAT6. Integrated transcriptomic, chromatin occupancy, and metabolomic studies identified MYC as a direct target of activated STAT6 and that MYC drives glycolysis. Thus, paracrine signaling in the tumor microenvironment plays a key role in the KRAS*-driven metabolic reprogramming of PDAC. SIGNIFICANCE: Type II cytokines, secreted by Th2 cells in the tumor microenvironment, can stimulate cancer cell-intrinsic MYC transcriptional upregulation to drive glycolysis. This KRAS*-driven heterotypic signaling circuit in the early and advanced tumor microenvironment enables cooperative protumorigenic interactions, providing candidate therapeutic targets in the KRAS* pathway for this intractable disease.