PTEN negatively regulates the intracellular levels of PIP3 in cells and functions as a tumor suppressor by regulating Akt signaling pathway. Both PHLPP1 and PHLPP2 have been shown to directly dephosphorylate and therefore inactivate Akt isoforms at one of two critical phosphorylation sites required for their activation. PHLPP2 is able to dephosphorylate Akt1 at Ser473 whereas PHLPP1 preferentially dephosphorylates Akt2. Akt acts through a wide array of downstream protein substrates involved in apoptosis, mitogenesis, cell proliferation and survival. Conversely, JNK3, which is exclusively nuclear, is not expected to have direct access to the IRS proteins, and may only regulate them either at the transcriptional level or indirectly. The role of IRS2 in beta-cell growth and survival has been well studied in vitro using primary pancreatic islets, and in vivo. Mice with full deletion of Irs2 show peripheral insulin resistance and islet cell loss that progress to diabetes. Moreover, mice with deletion of the Irs2 gene specifically into pancreatic beta-cells develop glucose intolerance, and reduced beta-cell mass. Therefore, IRS2 which appears to regulate peripheral response to insulin action also controls pancreatic beta-cell mass. Conversely, Mogroside-III signal transduction via IRS1 is less critical for beta cell growth and survival as mice lacking Irs1 did not become diabetic because of an adequate expansion of beta cell mass in presence of IRS2. In our conditions, reducing JNK3 did not show a significant decrease of IRS1 protein which indicates specific regulation of IRS2 by the JNK3 isoform. One potential factor is diet. Dietary intake of carbohydrates can regulate the mRNA expression of disaccharidases and hexose transporters in mice and rats. Several studies suggest that ASD children exhibit feeding selectivity and aberrant nutrient consumption. Pyrosequencing analysis of mucoepithelial bacteria revealed significant multicomponent dysbiosis in AUTGI children, including decreased levels of Bacteroidetes, an increase in the Firmicute ratio, increased cumulative levels of Firmicutes and Proteobacteria, and increased levels of bacteria in the class Betaproteobacteria. A recent pyrosequencing study reported an increase in Bacteroidetes in fecal samples of ASD subjects. Although these findings may appear to be incongruent with those reported here, our data were obtained using biopsies rather than free fecal material. Others have reported differences in the composition of fecal versus mucosal microflora. Only about 50% of cells in feces are viable, with dead and injured cells making up the remaining fractions. The loss of Bacteroidetes from the mucoepithelium as a result of death, injury, or competition for binding in the mucosal space can result in increased wash out of Bacteroidete cells into the fecal stream. Thus, higher levels of Bacteroidetes in feces could be indicative of an inability to thrive in the mucosal Zoxazolamine microbiome rather than an indication that Bacteroidetes are found at higher levels in the microbiome. The trend toward increased Firmicutes was largely attributable to Clostridia with Ruminococcaceae and Lachnospiraceae as major contributors. Several Ruminococcaceae and Lachnospiraceae are known butyrate producers and may thus influence short-chain fatty acid levels. SCFA influence colonic pH, and some Bacteroides sp. are sensitive to acidic pH. Additionally, the study of the host immune response to M. ulcerans during RS may help advance the knowledge of immune-mediated mechanisms of protection operating in antibiotic-treated hosts.