lts in GH resistance downstream of JAK2 signaling and that the relative expression of FGF21 in AL vs. CR mice exhibits a characteristic circadian pattern. We have also shown that FGF21 is not necessary for the reductions in IGF-1 or cell proliferation rates in response to moderate CR. Finally, in the context of AL feeding, our data indirectly suggest that FGF21 may have antianabolic/anti-mitotic effects. While FGF21 does not appear to be necessary for the reduction in circulating IGF-1 in response to moderate CR in adult mice, there is evidence that FGF21 is sufficient to reduce circulating IGF-1 levels in mice when exogenously administered and when overexpressed. Given these observations in conjunction with its glucose-lowering and insulin-sensitizing effects, FGF21 appears to mimic several of the beneficial effects of CR, underscoring its therapeutic potential. PPR is generally considered a more serious disease in goats than sheep, however, increased susceptibility of sheep, goat and outbreaks involving both sheep and goats have been equally reported. Goats appear not to be affected in some outbreaks, while sheep suffer with high rates of mortality and morbidity. Strain specific virulence of PPRV has been reported when the same breed of goats were experimentally infected, and different breeds of goat have been shown to respond differently to infection with the same virus. Speciesspecific disease occurrence has been observed with foot and mouth disease, where cattle were highly affected while sheep had less severe infection with the virus. Epizootic haemorrhagic disease virus affects cattle but sheep do not suffer from this disease. It is well recognised that ducks were generally resistant to avian influenza virus whereas chickens suffer from severe disease with rapid death following infection with highly pathogenic AIV. The reason for this species specificity is unclear at present. The natural susceptibility to PPRV in goats could be attributed to several host-derived or virus-derived factors. One such hostderived factor could be the differential presence or distribution of specific viral receptors in these species, such as the signalling lymphocyte activation molecule that has previously been observed to be associated with PPRV and other morbilli viruses such as measles virus and canine distemper virus. Host Cabozantinib msds immune mechanisms could also account for this differential susceptibility, although this has not been explored in detail in ruminant species or breeds. Toll like receptors are type 1 transmembrane proteins expressed in almost all cell types and activate the innate immune system upon sensing pathogen associated molecular patterns. Intracellular TLR that sense viral nucleic acids include TLR3, TLR7 and TLR8 and TLR9. Imiquimod and poly I:C are standard agonists used to induce TLR7 and TLR3 respectively leading to the production of inflammatory cytokines including type I interferons and immune cell maturation.