The Peculiar Facets of Nitric Oxide as a Cellular Messenger: From Disease-Associated Signaling to the Regulation of Brain Bioenergetics and Neurovascular Coupling

In this review, we address the regulatory and toxic role of ^·NO along several pathways, from the gut to the brain. Initially, we address the role on ^·NO in the regulation of mitochondrial respiration with emphasis on the possible contribution to Parkinson’s disease via mechanisms that involve its interaction with a major dopamine metabolite, DOPAC. In parallel with initial discoveries of the inhibition of mitochondrial respiration by ^·NO, it became clear the potential for toxic ^·NO-mediated mechanisms involving the production of more reactive species and the post-translational modification of mitochondrial proteins. Accordingly, we have proposed a novel mechanism potentially leading to dopaminergic cell death, providing evidence that NO synergistically interact with DOPAC in promoting cell death via mechanisms that involve GSH depletion. The modulatory role of NO will be then briefly discussed as a master regulator on brain energy metabolism. The energy metabolism in the brain is central to the understanding of brain function and disease. The core role of ^·NO in the regulation of brain metabolism and vascular responses is further substantiated by discussing its role as a mediator of neurovascular coupling, the increase in local microvessels blood flow in response to spatially restricted increase of neuronal activity. The many facets of NO as intracellular and intercellular messenger, conveying information associated with its spatial and temporal concentration dynamics, involve not only the discussion of its reactions and potential targets on a defined biological environment but also the regulation of its synthesis by the family of nitric oxide synthases. More recently, a novel pathway, out of control of NOS, has been the subject of a great deal of controversy, the nitrate:nitrite:NO pathway, adding new perspectives to ^·NO biology. Thus, finally, this novel pathway will be addressed in connection with nitrate consumption in the diet and the beneficial effects of protein nitration by reactive nitrogen species.

     

Intraspecific genetic variation of a Fagus sylvatica population in a temperate forest derived from airborne imaging spectroscopy time series

1. The growing pace of environmental change has increased the need for large‐scale monitoring of biodiversity. Declining intraspecific genetic variation is likely a critical factor in biodiversity loss, but is especially difficult to monitor: assessments of genetic variation are commonly based on measuring allele pools, which requires sampling of individuals and extensive sample processing, limiting spatial coverage. Alternatively, imaging spectroscopy data from remote platforms may hold the potential to reveal genetic structure of populations. In this study, we investigated how differences detected in an airborne imaging spectroscopy time series correspond to genetic variation within a population of Fagus sylvatica under natural conditions.
2. We used multi‐annual APEX (Airborne Prism Experiment) imaging spectrometer data from a temperate forest located in the Swiss midlands (Laegern, 47°28'N, 8°21'E), along with microsatellite data from F. sylvatica individuals collected at the site. We identified variation in foliar reflectance independent of annual and seasonal changes which we hypothesize is more likely to correspond to stable genetic differences. We established a direct connection between the spectroscopy and genetics data by using partial least squares (PLS) regression to predict the probability of belonging to a genetic cluster from spectral data.
3. We achieved the best genetic structure prediction by using derivatives of reflectance and a subset of wavebands rather than full‐analyzed spectra. Our model indicates that spectral regions related to leaf water content, phenols, pigments, and wax composition contribute most to the ability of this approach to predict genetic structure of F. sylvatica population in natural conditions.
4. This study advances the use of airborne imaging spectroscopy to assess tree genetic diversity at canopy level under natural conditions, which could overcome current spatiotemporal limitations on monitoring, understanding, and preventing genetic biodiversity loss imposed by requirements for extensive in situ sampling.

     

Cyclo(His-Pro) up-regulates heme oxygenase 1 via activation of Nrf2-ARE signalling

Paraquat (1,1'-dimethyl-4,4'-bipyridinium), a widely used non-selective herbicide, is a redox cycling agent with adverse effects on dopamine systems. Epidemiological data have shown that exposure to paraquat is one of the several risk factors for Parkinson's disease. We have already shown that cyclo(His-Pro), an endogenous cyclic dipeptide produced by the cleavage of the thyrotropin releasing hormone, has a cytoprotective effect through a mechanism involving Nrf2 activation that decreases production of reactive oxygen species and increases glutathione synthesis. Using primary neuronal cultures and PC12 cells as targets of paraquat neurotoxicity, we addressed whether and how cyclo(His-Pro) causes cellular protective response against paraquat-mediated cell death. We found that cyclo(His-Pro) attenuated reactive oxygen species production, and prevented glutathione depletion by up-regulating Nrf2 gene expression, triggering its nuclear accumulation and activating the expression of heme oxygenase1. These protective effects were abolished by RNA interference-mediated Nrf2 knock down whereas were unaffected by RNA interference-mediated Keap1 knock down. Inhibition of heme oxygenase activity decreased cyclo(His-Pro)-induced neuroprotection. These results suggest that cyclo(His-Pro), acting as a selective activator of the brain modulable Nrf2 pathway, may be a promising candidate as neuroprotective agent that act through induction of phase II genes.     

A split-pot experiment with sorghum to test a root water uptake partitioning model

Correct modeling of root water uptake partitioning over depth is an important issue in hydrological and crop growth models. Recently a physically based model to describe root water uptake was developed at single root scale and upscaled to the root system scale considering a homogeneous distribution of roots per soil layer. Root water uptake partitioning is calculated over soil layers or compartments as a function of respective soil hydraulic conditions, specifically the soil matric flux potential, root characteristics and a root system efficiency factor to compensate for within-layer root system heterogeneities. The performance of this model was tested in an experiment performed in two-compartment split-pot lysimeters with sorghum plants. The compartments were submitted to different irrigation cycles resulting in contrasting water contents over time. The root system efficiency factor was determined to be about 0.05. Release of water from roots to soil was predicted and observed on several occasions during the experiment; however, model predictions suggested root water release to occur more often and at a higher rate than observed. This may be due to not considering internal root system resistances, thus overestimating the ease with which roots can act as conductors of water. Excluding these erroneous predictions from the dataset, statistical indices show model performance to be of good quality.