The 69 types of non-kinase domain sequence variations we identified are currently undergoing confirmation. Nevertheless, the prevalence thus far of non-synonymous somatic mutations per megabase of tumor sequenced in this study was 4.1. There is considerable controversy concerning the evidence for the presence of C. pneumoniae in CSF either from MS patients or from patients with other neurological diseases. The initial report of the association of C. pneumoniae and MS included both isolation of this microorganism by blinded cell cultures as well as the presence of C. pneumoniae DNA in CSF by PCR. A number of other investigators subsequently have confirmed the presence of C. pneumoniae DNA in CSF from MS patients by PCR methods, although usually in a smaller percent of patients. For example, Lay-Schmitt initially was able to show the presence of C. pneumoniae DNA in 22% of MS patients; this number increased to over 50% when phenol/chloroform extraction techniques were used. The fact that not all tissue weights were proportionally decreased or increased relative to body weights in PLP and recuperated mice suggests that selective metabolic resource allocation is triggered to maintain the growth of more important tissues, such as brain. Among the tissues examined in PLP mice, brain, lung and thymus showed no reduction in weights as compared to control tissues. When adjusted by body weights brain and thymus in PLP mice were significantly heavier. This may suggest that enhanced functional capacity of brain and thymus is beneficial to health and longevity in mice. Decreased fasting glucose and insulin concentrations in PLP mice suggest that these animals had a better insulin sensitivity. Improved insulin sensitivity is a frequently observed feature in mouse models with increased lifespan such as those of caloric restriction and genetic mutations. It was observed that calorie restricted rats maintained decreased plasma glucose and insulin concentrations throughout life. Long lived dwarf mice that are deficient in or resistant to growth hormone are hypoinsulinemic and exhibit enhanced whole-animal insulin sensitivity. Moreover, the association between insulin sensitivity and longevity has also been observed in humans as healthy centenarians were found to have a preserved glucose tolerance and insulin action. Our long lived PLP mice therefore bear a common phenotypic characteristic to the long lived dwarf mice and CR MK-2206 2HCl clinical trial rodents and human centenarians. Similarly, we recently observed that PLP rats exhibited significant reduced fasting insulin concentrations at 21 days of age. The better whole body insulin sensitivity in PLP mice was reflected by the protein expression profiles of insulin signalling molecules. Skeletal muscle of PLP mice had significantly higher expression of IRS1 and PKCf compared to controls. IRS1 belongs to the IRS family of adaptor molecules and is tyrosine phosphorylated in response to the activation of insulin receptor by insulin binding.