The Mitochondrial Permeability Transition as a Target for Neuroprotection

Mitochondria serve as checkpoints and amplifiers on cell death pathways. In the central nervous system, mitochondrial involvement seems essential for normal expression of cell death phenotypes, and interference with these pathways thus seems a reasonable approach to neuroprotection. We have been involved in examining the potential involvement of the mitochondrial permeability transition (mPT) as one of several possible mechanisms by which mitochondria may be drawn into these death cascades. This possibility, though still controversial, is supported by evidence that factors that may stimulate mPT induction are associated with some forms of cell death (e.g., in stroke) and are modulated by diseases of the central nervous system (e.g., Huntington's). Evidence of neuroprotection seen with compounds such as N-Met-Val cyclosporine also support this possibility.     

Insulin feedback actions: complex effects involving isoforms of islet nitric oxide synthase

The present study examined the effects of exogenous insulin on C-peptide release in relation to islet activities of neural constitutive nitric oxide synthase (ncNOS) and inducible NOS (iNOS). The dose-response curves for glucose-stimulated insulin and C-peptide release from isolated islets were practically identical: 0.05-0.1 nmol/l insulin stimulated, 1-100 nmol/l had no effect, whereas concentrations >/=250 nmol/l ("high insulin"), inhibited C-peptide release. Both the stimulatory and inhibitory effects were abolished by the phosphatidylinositol 3'-kinase inhibitor wortmannin. Addition of a NOS inhibitor partially reversed the inhibitory action of high insulin, but had no effect on the stimulatory action of low insulin (0.1 nmol/l). Moreover, high insulin markedly increased islet ncNOS activity and induced a strong iNOS activity. As shown biochemically and with confocal microscopy, the stimulatory action of high insulin on NOS activities and the associated inhibition of C-peptide release were reversed by raising cyclic AMP through addition of either glucagon-like peptide 1 (GLP-1) or dibutyryl cyclic AMP (Bt(2)cAMP) to the incubated islets. We conclude that the positive feedback mechanisms of action of insulin are independent of islet NOS activities and remain unclear. The negative feedback action of insulin, however, can be explained by its ability to stimulate both islet ncNOS activity and the expression and activity of iNOS. The effects on iNOS are most likely transduced through phosphatidylinositol 3'-kinase and are counteracted by raising islet cyclic AMP levels.     

Recapture of male and female dragonflies in relation to parasitism by mites, time of season, wing length and wing cell symmetry

For aquatic mites parasitic on dragonflies, completion of their life cycle depends on their being returned to appropriate water bodies by their hosts, after completion of engorgement. We examined whether differences among hosts in timing of emergence or phenotypic attributes might affect their probability of return to an emergence pond, and hence success of mites. Parasitized males and females of the dragonfly Sympetrum obtrusum (Hagen) did not differ in overall recapture rates. Females that had wing cell symmetry and emerged early were more likely to be recaptured than females that emerged later or had wing cell asymmetry, but there were no consistent relations between these variables and parasitism by mites. No such relations between wing cell asymmetry, emergence date, and recapture likelihood were found for males. Using randomization tests, we found that mean intensities of Arrenurus planus (Marshall) mites at host emergence were the same for recaptured females and females not recaptured; however, males that were recaptured had lower mean intensities of mites at emergence than males not recaptured. Further, mature females carried more mites than mature males, and the latter had fewer mites than newlyemerged males not recaptured. Biases in detachment of engorging mites do not explain the differences in parasitism between mature males and females, nor the differences in mite numbers between mature males and newly emerged males that were not recaptured. Rather, heavily parasitized males appear to disperse or die and are not recaptured, which should have implications for dispersal of mites and fitness of male hosts.     

Conserving tropical nature: current challenges for ecologists

Tropical biodiversity continues to erode unabated, which calls for ecologists to address the problem directly, placing less reliance on indirect interventions, such as community-based development schemes. Ecologists must become more assertive in providing scientifically formulated and adaptively managed interventions, involving biodiversity payments, to serve local, regional and global interests in tropical nature. Priorities for tropical ecologists thus include the identification of key thresholds to ecological resilience, and the formulation of clear monitoring protocols and management strategies for implementation by local resource managers. A particular challenge is to demonstrate how nature reserves contribute to the adaptive capacity of regional land-use matrices and, hence, to the provision of sustainable benefits at multiple spatial and temporal scales.