Estimating the false discovery rate by the method of BAY 73-4506 VEGFR/PDGFR inhibitor Benjamini and Hochberg, tests would be 0.011, which implies that all significant associations, except for the combined genotype analyses in relation to obesity, would be false-positive. nherent to the individual’s physiology. How much does the heightened activity seen in the lean rats contribute to their daily energy expenditure, then? As expected, energy expenditure increased with activity throughout the day in rats, as illustrated in Figure 2D. Compared to the relatively subtle effects on the speed of retinal angiogenesis and endothelial cell proliferation, astrocyte VEGF deletion had more pronounced consequences on vessel stability. Although, the width of capillary free spaces was unchanged, the number of artery side branches was clearly reduced. It therefore appears that during normal development astrocyte-derived VEGF is only critical for endothelial cell survival within a defined zone around arteries, where high oxygen and low VEGF levels prevail. However, when animals were exposed to hyperoxia, this zone dramatically expanded, and animals that lacked astrocyte-derived VEGF were more affected. Most noticeably, radial arteries and veins became more susceptible to collapse in mutant animals. These large vessels have been considered to be resistant to hyperoxia due to their maturity and, in the case of arteries, due to their association with vascular smooth muscle cells. However, our results demonstrate that reducing the supply of VEGF can still affect these vessels within the first postnatal week of retinal vasculature development. Why in this instance other sources of VEGF in the retina do not rescue the dying vessels is not clear. Although we found no changes in VEGF isoform ratios in our mutant mice, it is likely that an additional layer of complexity is added by mechanisms that control distribution and bioavailability of VEGF protein. Since our study focuses only on Vegf mRNA production and distribution we cannot exclude that the distribution of astrocyte-derived VEGF protein might be different from neuron-derived VEGF protein. Moreover, when resting energy expenditure and energy expenditure of activity were calculated according to body weight for each rat, EEA was significantly higher in the high-endurance rats. In other words, the lean rats used more calories to move a given mass than the overweight, lowendurance rats. This does not take into account potential differences in fuel economy of activity that can also affect daily EEA and contribute to total daily energy expenditure. As a consequence, newly arising microbial strains or species with functionally important, but previously unobserved, genomic variants may prove difficult or impossible to detect and identify. Resting energy expenditure was also higher in lean compared to overweight rats.