IRS-2 Deficiency Impairs NMDA Receptor-Dependent Long-term Potentiation

The beneficial effects of insulin and insulin-like growth factor I on cognition have been documented in humans and animal models. Conversely, obesity, hyperinsulinemia, and diabetes increase the risk for neurodegenerative disorders including Alzheimer's disease (AD). However, the mechanisms by which insulin regulates synaptic plasticity are not well understood. Here, we report that complete disruption of insulin receptor substrate 2 (Irs2) in mice impairs long-term potentiation (LTP) of synaptic transmission in the hippocampus. Basal synaptic transmission and paired-pulse facilitation were similar between the 2 groups of mice. Induction of LTP by high-frequency conditioning tetanus did not activate postsynaptic N-methyl-D-aspartate (NMDA) receptors in hippocampus slices from Irs2−/− mice, although the expression of NR2A, NR2B, and PSD95 was equivalent to wild-type controls. Activation of Fyn, AKT, and MAPK in response to tetanus stimulation was defective in Irs2−/− mice. Interestingly, IRS2 was phosphorylated during induction of LTP in control mice, revealing a potential new component of the signaling machinery which modulates synaptic plasticity. Given that IRS2 expression is diminished in Type 2 diabetics as well as in AD patients, these data may reveal an explanation for the prevalence of cognitive decline in humans with metabolic disorders by providing a mechanistic link between insulin resistance and impaired synaptic transmission

Development of disease symptoms and fungal pathogens on shoot bases in continuous winter wheat, and effects of fungicides

Field plots in three consecutive crops of winter wheat were sampled at approximately 2-week intervals from April to July in 1989, 1990 and 1991. Culm and stem bases were examined for symptoms of eyespot, sharp eyespot and brown foot rot. The W-type and R-type of Pseudocercosporella herpotrichoides, P. anguioides, Fusarium culmorum, F. avenaceum and Microdochium nivale grown from this plant material on agar were identified. Eyespot was most severe in 1991, when plant development was least rapid following cool weather in late winter and the summer was relatively cool and wet. Sharp eyespot was most severe in 1990, which had a warm summer with moderate rainfall. The other warm summer, 1989, was drier and these conditions favoured late development of brown foot rot, associated mainly with F. culmorum which was scarce at other times. Sharp eyespot sometimes increased where prochloraz, which decreased eyespot, was applied. Distinct symptoms of more than one disease occurred less frequently on the same stem than expected from the individual total occurrences, but co-occurrences of different fungi were often more frequent than expected. In July 1990, Fusarium spp. co-occurred with R-type, but not W-type, P. herpotrichoides more frequently than expected, and in July 1990 and 1991 M. nivale and both W-type and R-type co-occurred more frequently than expected. Fusarium spp. and M. nivale were more frequent, especially in the earlier samples, on nodes than on internodes, whilst P. herpotrichoides normally infected at the internodes. The results suggest that stems weakened or altered by a primary colonizer are often a suitable substrate for a secondary colonizer, often a Fusarium sp., which may begin infection at a distance from the original lesion and often not cause distinct symptoms itself