Cohort antler size signals environmental stress in a moderate climate.

Research in northern latitudes confirms that climate teleconnections exert important influences on ungulate fitness, but studies from regions with milder climates are lacking. We explored the influence of the Pacific Decadal Oscillation (PDO), Northern Atlantic Oscillation (NAO), and El Niño-Southern Oscillation (ENSO) on male, 2.5-year-old white-tailed deer (Odocoileus virginianus) antler and body mass in Mississippi, USA, a region with mild winters and warm, humid summers. Explanatory variables were seasonal averages of each climate index extending back to 3 years prior to account for possible maternal and lag effects. Seasonal climate indices from the period of gestation and the first year of life were correlated with deer morphometrics. Reduced antler mass was largely correlated (R2 = 0.52) with PDO values indicating dry conditions during parturition and neonatal development and NAO values indicating warmer than normal winters during gestation and the first year of life. Body mass was less correlated (R2 = 0.16) to climate indices, responding negatively to warmer winter weather during the first winter of life. Climate may promote variable fitness among cohorts through long-term effects on male competition for dominance and breeding access. Because broad-scale climate indices simplify complex weather systems, they may benefit management at larger scales. Although this study compared climate with morphological variables, it is likely that demographic characteristics can likewise be modeled using climate indices. As climate change in this region is projected to include greater variability in summer precipitation, we may see concomitantly greater variability in fitness among cohorts of white-tailed deer.

Stromal response to Hedgehog signaling restrains pancreatic cancer progression.

Pancreatic ductal adenocarcinoma (PDA) is the most lethal of common human malignancies, with no truly effective therapies for advanced disease. Preclinical studies have suggested a therapeutic benefit of targeting the Hedgehog (Hh) signaling pathway, which is activated throughout the course of PDA progression by expression of Hh ligands in the neoplastic epithelium and paracrine response in the stromal fibroblasts. Clinical trials to test this possibility, however, have yielded disappointing results. To further investigate the role of Hh signaling in the formation of PDA and its precursor lesion, pancreatic intraepithelial neoplasia (PanIN), we examined the effects of genetic or pharmacologic inhibition of Hh pathway activity in three distinct genetically engineered mouse models and found that Hh pathway inhibition accelerates rather than delays progression of oncogenic Kras-driven disease. Notably, pharmacologic inhibition of Hh pathway activity affected the balance between epithelial and stromal elements, suppressing stromal desmoplasia but also causing accelerated growth of the PanIN epithelium. In striking contrast, pathway activation using a small molecule agonist caused stromal hyperplasia and reduced epithelial proliferation. These results indicate that stromal response to Hh signaling is protective against PDA and that pharmacologic activation of pathway response can slow tumorigenesis. Our results provide evidence for a restraining role of stroma in PDA progression, suggesting an explanation for the failure of Hh inhibitors in clinical trials and pointing to the possibility of a novel type of therapeutic intervention.