Proteome analysis of human substantia nigra in Parkinson's disease

Protein expression has been compared in human substantia nigra specimens from Parkinson's disease (PD) patients and from controls, and 44 proteins expressed in this midbrain region were identified by peptide mass fingerprinting. Among them, nine showed changes in their abundance. L and M neurofilament chains are less abundant in PD specimens, whereas peroxiredoxin II, mitochondrial complex III, ATP synthase D chain, complexin I, profilin, L-type calcium channel delta-subunit, and fatty-acid binding protein are significantly more present in PD samples than in controls. Besides the consolidated view of oxidative stress involvement in PD pathogenesis, suggested by overexpression of mitochondrial and reactive oxygen species (ROS)-scavenging proteins, these results indicate a possible potentiation mechanism of afferent signals to substantia nigra following degeneration of dopaminergic neurons

Proteomic Modeling for HIV-1 Infected Microglia-Astrocyte Crosstalk

Background: HIV-1-infected and immune competent brain mononuclear phagocytes (MP; macrophages and microglia) secrete cellular and viral toxins that affect neuronal damage during advanced disease. In contrast, astrocytes can affect disease by modulating the nervous system’s microenvironment. Interestingly, little is known how astrocytes communicate with MP to influence disease. Methods and Findings: MP-astrocyte crosstalk was investigated by a proteomic platform analysis using vesicular stomatitis virus pseudotyped HIV infected murine microglia. The microglial-astrocyte dialogue was significant and affected microglial cytoskeleton by modulation of cell death and migratory pathways. These were mediated, in part, through F-actin polymerization and filament formation. Astrocyte secretions attenuated HIV-1 infected microglia neurotoxicity and viral growth linked to the regulation of reactive oxygen species. Conclusions: These observations provide unique insights into glial crosstalk during disease by supporting astrocytemediated regulation of microglial function and its influence on the onset and progression of neuroAIDS. The results open new insights into previously undisclosed pathogenic mechanisms and open the potential for biomarker discovery an

Linear and non-linear response to parameter variations in a mesoscale model

The article of record as published may be located at http://dx.doi.org/10.1111/j.1600-0870.2010.00505.xParameter uncertainty in atmospheric model forcing and closure schemes has motivated both parameter estimation with data assimilation and use of pre-specified distributions to simulate model uncertainty in short-range ensemble prediction. This work assesses the potential for parameter estimation and ensemble prediction by analysing 2 months of mesoscale ensemble predictions in which each member uses distinct, and fixed, settings for four model parameters. A space-filling parameter selection design leads to a unique parameter set for each ensemble member. An experiment to test linear scaling between parameter distribution width and ensemble spread shows the lack of a general linear response to parameters. Individual member near-surface spatial means, spatial variances and skill show that perturbed models are typically indistinguishable. Parameter–state rank correlation fields are not statistically significant, although the presence of other sources of noise may mask true correlations. Results suggest that ensemble prediction using perturbed parameters may be a simple complement to more complex model-error simulation methods, but that parameter estimation may prove difficult or costly for real mesoscale numerical weather prediction applications.This work was funded by the U.S.Air Force Weather Agency

Interim report on the Southeast Queensland Cloud Seeding Research Program

Water stresses are occurring in Southeast Queensland. In order to assess the feasibility of any future precipitation enhancement potential in clouds in the Southeast Queensland region, it is extremely important to obtain observations in a well-designed measurement program. Aerosol and microphysical measurements, in particular, can help determine if seeding could be beneficial and also help determine what the optimal seeding method would be with regards to potential for enhancing precipitation in local clouds. The potential for such manmade increases is strongly dependent on the natural microphysics and dynamics of the clouds that are being seeded (in this case microphysics means the size and concentration of water droplets and ice inside clouds). These factors can differ significantly from one geographical region to another, as well as during and between seasons in the same region. In some instances, clouds may not be suitable for seeding, or the frequency of occurrence of suitable clouds may be too low to warrant the investment in a cloud seeding program. Both factors need to be evaluated from a climatological perspective. It is therefore important to conduct preliminary studies on the microphysics and dynamics of the naturally forming clouds prior to commencing a larger, operational experiment. It is also important to conduct hydrological studies relating rainfall with river flows and reservoir levels, and to determine hydrological regions where reservoir catchments are most efficient. Seeding could then be optimized by preferentially targeting the most efficient watersheds. The following is a summary of key preliminary results derived from the analysis of data collected during the 2007-2008 season in Southeast Queensland