Electronic Supplementary Material from Oxidative stress mediates the impact of heat waves on survival, growth and immune status in a lizard

Climate change often includes increases in the occurrence of extreme environmental events. Among these, heat-waves affect the pace of life and performance of wildlife, particularly ectothermic animals, owing to their low thermoregulatory abilities. However, the underlying mechanisms by which this occurs remain unclear. Evidence shows that heat waves alter the redox balance of ectotherms, and oxidative stress is a major mediator of life-history trade-offs. Therefore, oxidative stress may mediate the effect of extreme thermal conditions on the life histories of ectotherms. To test this hypothesis, a 2 × 2 experiment was conducted to manipulate the redox balance (through a mitochondrial uncoupler that alleviates oxidative stress) of the desert toad-headed agama (Phrynocephalus przewalskii) exposed to heat wave conditions. We recorded lizard growth and survival rates and quantified their redox and immune statuses. In control lizards (unmanipulated redox balance), heat wave conditions decreased growth and survival and induced oxidative damage and immune responses. By contrast, lizards with alleviated oxidative stress showed close-to-normal growth, survival, and immune status when challenged with heat waves. These results provide mechanistic insight into the role of oxidative stress in mediating the effects of extreme temperatures on ectothermic vertebrates, which may have major eco-evolutionary implications

Discovery of Pyrrole−Indoline-2-ones as Aurora Kinase Inhibitors with a Different Inhibition Profile

A series of pyrrole−indolin-2-ones were synthesized, and their inhibition profile for Aurora kinases was studied. The potent compound 33 with phenylsulfonamido at the C-5 position and a carboxyethyl group at the C-3′ position selectively inhibited Aurora A over Aurora B with IC50 values of 12 and 156 nM, respectively. Replacement of the carboxyl group with an amino group led to compound 47, which retained the activity for Aurora B and lost activity for Aurora A (IC50 = 2.19 μM). Computation modeling was used to address the different inhibition profiles of 33 and 47. Compounds 47 and 36 (the ethyl ester analogue of 33) inhibited the proliferation of HCT-116 and HT-29 cells and suppressed levels of the phosphorylated substrates of Aurora A and Aurora B in the Western blots