We, however, could not observe such resistance in the DILP2-knock-down lines or the mNSC-ablated flies. The increased trehalose in the dilp2RNAi/ d2GAL flies correlated with a slight increase in resistance to starvation, indicating that these trehalose stores play, if any, only a minor part in starvation tolerance. Furthermore, this observation also indicates that the starvation resistance of the mNSC-ablated flies does not stem from the increased whole-body trehalose. These data are consistent with a recent finding that Drosophila ARC protein, which is expressed in the dilp-producing mNSCs, is a regulator of behavioural responses to starvation but is not a general regulator of insulin signalling. Mutants are starvation resistant likely due to their loss of normal starvation induced hyperlocomotion. It is therefore possible that the mNSC-ablated flies are starvation resistant predominantly because of a reduction in ARC, and the slight effect on starvation resistance following DILP2 knock down in the dilp2RNAi flies may be due to an alteration of metabolic rates and the consumption and distribution of energy sources, of which increased whole body trehalose may be a sign. Further investigation of putative specific roles of the individual DILPs, which awaits production of specific mutants or CP-358774 inquirer effective RNAi against dilps 3 and 5, may shed light on the links between the different aspects of fly physiology they control. However, our finding that DILP2 levels are not limiting for lifespan, fecundity and stress resistance ASP1517 HIF inhibitor clearly demonstrates that we need to change our thinking about how dilps regulate lifespan and other traits, and we need direct experimental manipulation to address this issue. Ribonucleotide reductases catalyze the reduction of the four ribonucleotides to the corresponding deoxyribonucleotides, providing the precursors for the DNA synthesis and repair in all living organisms. This step is an attractive target for drug design strategies against rapidly proliferating cells such as cancers and various pathogens, as it is the rate limiting step in the DNA synthesis. RNRs are grouped into three classes: I, II and III, based on differences in cofactor biosynthesis, oxygen dependency, and quaternary structure. The most prevalent is class I RNR, which is found – with few exceptions – in all eukaryotes, some prokaryotes and viruses. Most class I RNRs are homodimeric complexes that assemble into enzymatically active tetramers or higher order oligomers. The R1/R1E subunit contains the active site for reduction of the ribonucleotides, while the R2/R2F subunit contains the di-metal-oxygen cofactor responsible for the formation of the oxygen dependent catalytic tyrosyl radical. The generated R2 radical is shuttled approximately 35 A �� to the active site of the R1 subunit where it forms a thiyl radical, through a proposed conserved network of hydrogen bonded amino acids. Division of class I RNR into subclasses Ia-Ic is based primarily on differences in operon structure and metal cofactor.