It is notable that the strongest inconsistency in our data from the hyperbolic expectation comes from the dominance properties of beneficial mutations. Note that the inclusion of beneficial mutations in our collection was possible only because we initiated the study with a relatively low fitness wildtype phage. Thus, our observation of recessive beneficial mutations highlights two important weaknesses of most previous studies. Most examined mutations with only a small subset of selection coefficients – generally either lethal or slightly deleterious mutations and none have examined the GW2974 impact of variation in wildtype fitness. More work is needed to determine whether our observations are unique to the gene and the system that we examined, or whether dominance patterns often deviate from the hyperbolic curves common to enzymes. Supplementation with the amino acid leucine and its metabolite a-ketoisocaproate has been at the focus of investigations into skeletal muscle disorders for some 35 years, that is, since they were discovered to be potent anti-catabolic compounds. b-Hydroxy b-methylbutyrate, another metabolite of leucine, has also been an interesting target for studies since Nissen et al. demonstrated its efficacy as a potent therapeutical supplement for the treatment of muscle disorders. Following studies showed that HMB might attenuate the muscle mass loss caused by AIDS, endotoxemia, and aging, and that this effect is achieved by the inhibition of protein degradation and/or stimulated protein synthesis. In addition, recent studies have demonstrated that HMB supplementation in Proguanil hydrochloride cachexia dampens skeletal muscle degradation and promotes protein synthesis. Furthermore, some authors have suggested that MAP kinase and the PI3K /Akt signaling pathways are involved in these beneficial effects of HMB on skeletal muscle. However, the molecular mechanisms involved have not been determined and the effects of HMB not fully investigated. Glucocorticoids are used as therapeutic agents due to their potent anti-inflammatory and immunosuppressive functions. Despite of its advantage usage, high doses or the sustained usage of glucocorticoids by cortisol producing adrenal tumors or treatment with steroids for inflammatory conditions are associated with muscle wasting and weakness. Dexamethasone- induced muscle atrophy is caused by catabolic conditions and the roles of glucocorticoids during muscle wasting are complex and reflect regulation at the molecular level of multiple mechanisms influencing both the synthesis and degradation of muscle proteins.