The course of development of glucose intolerance in the monkey (Macaca mulatta).

Longitudinal studies of the rhesus monkey reveal a syndrome of diabetes mellitus in those that become middle-aged and obese. The sequence of events in the development of the disease progresses from normoinsulinemia with normoglycemia through stages of hyperinsulinemia followed by below normal insulin levels with hyperglycemia and glycosuria. We believe the rhesus to be an excellent nonhuman primate model for maturity-onset diabetes in humans.     

Separate Intramolecular Targets for Protein Kinase A Control N-Methyl-d-aspartate Receptor Gating and Ca2+ Permeability

Protein kinase A (PKA) enhances synaptic plasticity in the central nervous system by increasing NMDA receptor current amplitude and Ca²⁺ flux in an isoform-dependent yet poorly understood manner. PKA phosphorylates multiple residues on GluN1, GluN2A, and GluN2B subunits in vivo, but the functional significance of this multiplicity is unknown. We examined gating and permeation properties of recombinant NMDA receptor isoforms and of receptors with altered C-terminal domain (CTDs) prior to and after pharmacological inhibition of PKA. We found that PKA inhibition decreased GluN1/GluN2B but not GluN1/GluN2A gating; this effect was due to slower rates for receptor activation and resensitization and was mediated exclusively by the GluN2B CTD. In contrast, PKA inhibition reduced NMDA receptor-relative Ca²⁺ permeability (P_Ca/P_Na) regardless of the GluN2 isoform and required the GluN1 CTD; this effect was due primarily to decreased unitary Ca²⁺ conductance, because neither Na⁺ conductance nor Ca²⁺-dependent block was altered substantially. Finally, we show that both the gating and permeation effects can be reproduced by changing the phosphorylation state of a single residue: GluN2B Ser-1166 and GluN1 Ser-897, respectively. We conclude that PKA effects on NMDA receptor gating and Ca²⁺ permeability rely on distinct phosphorylation sites located on the CTD of GluN2B and GluN1 subunits. This separate control of NMDA receptor properties by PKA may account for the specific effects of PKA on plasticity during synaptic development and may lead to drugs targeted to alter NMDA receptor gating or Ca²⁺ permeability.     

Some comparisons of cellulases from two different strains of aspergillus fumigatus

Michaelis-Menten kinetics for exoglucanase, endoglucanase and β-glucosidase activities from two different strains of Aspergillus fumigatus were compared in the absence and the presence of ammonium ions. Inhibitory effects, evident in only one strain, were quantified, suggesting non-competitive inhibition for endoglucanase and β-glucosidase, but competitive inhibition of exocellulase. Possible reasons are discussed.