The embryonic thermal environment has positive but weak effects on thermal tolerance later in life in the aquatic invertebrate Gammarus chevreuxi.

Recent evidence suggests that the adult phenotype is influenced by temperatures experienced in early life. However, our understanding of the extent to which the embryonic environment can modulate thermal tolerance later in life is limited, owing to the paucity of studies with appropriate experimental designs to test for this form of developmental plasticity. We investigated whether the thermal environment experienced during embryonic development affects thermal limits in later life. Embryos of the estuarine amphipod Gammarus chevreuxi were incubated until hatching to 15 °C, 20 °C and 25 °C, then reared under a common temperature. Using thermal ramping assays, we determined upper thermal limits in juveniles, four weeks post-hatch. Individuals exposed to higher temperatures during embryonic development displayed greater thermal tolerance as juveniles (acclimation response ratio ≈ 0.10-0.25 for upper lethal temperature). However, we suggest that the degree of developmental plasticity observed is limited, and will provide little benefit under future climate change scenarios.

Structure Activity Relationships of αv Integrin Antagonists for Pulmonary Fibrosis by Variation in Aryl Substituents.

Antagonism of αvß6 is emerging as a potential treatment of idiopathic pulmonary fibrosis based on strong target validation. Starting from an αvß3 antagonist lead and through simple variation in the nature and position of the aryl substituent, the discovery of compounds with improved αvß6 activity is described. The compounds also have physicochemical properties commensurate with oral bioavailability and are high quality starting points for a drug discovery program. Compounds 33S and 43E1 are pan αv antagonists having ca. 100 nM potency against αvß3, αvß5, αvß6, and αvß8 in cell adhesion assays. Detailed structure activity relationships with these integrins are described which also reveal substituents providing partial selectivity (defined as at least a 0.7 log difference in pIC50 values between the integrins in question) for αvß3 and αvß5.