Alpha-Synuclein Oligomers Interact with Metal Ions to Induce Oxidative Stress and Neuronal Death in Parkinson's Disease

Protein aggregation and oxidative stress are both key pathogenic processes in Parkinson's disease, although the mechanism by which misfolded proteins induce oxidative stress and neuronal death remains unknown. In this study, we describe how aggregation of alpha-synuclein (α-S) from its monomeric form to its soluble oligomeric state results in aberrant free radical production and neuronal toxicity

The Moon: Biogenic elements

The specific objectives of the organic chemical exploration of the Moon involve the search for molecules of possible biological or prebiological origin. Detailed knowledge of the amount, distribution, and exact structure of organic compounds present on the Moon is extremely important to our understanding of the origin and history of the Moon and to its relationship to the history of the Earth and solar system. Specifically, such knowledge is essential for determining whether life on the Moon exists, ever did exist, or could develop. In the absence of life or organic matter, it is still essential to determine the abundance, distribution, and origin of the biogenic elements (e.g., H, C, O, N, S, P) in order to understand how the planetary environment may have influenced the course of chemical evolution. The history and scope of this effort is presented

The invertebrate Caenorhabditis elegans biosynthesizes ascorbate.

l-Ascorbate, commonly known as vitamin C, serves as an antioxidant and cofactor essential for many biological processes. Distinct ascorbate biosynthetic pathways have been established for animals and plants, but little is known about the presence or synthesis of this molecule in invertebrate species. We have investigated ascorbate metabolism in the nematode Caenorhabditis elegans, where this molecule would be expected to play roles in oxidative stress resistance and as cofactor in collagen and neurotransmitter synthesis. Using high-performance liquid chromatography and gas-chromatography mass spectrometry, we determined that ascorbate is present at low amounts in the egg stage, L1 larvae, and mixed animal populations, with the egg stage containing the highest concentrations. Incubating C. elegans with precursor molecules necessary for ascorbate synthesis in plants and animals did not significantly alter ascorbate levels. Furthermore, bioinformatic analyses did not support the presence in C. elegans of either the plant or the animal biosynthetic pathway. However, we observed the complete (13)C-labeling of ascorbate when C. elegans was grown with (13)C-labeled Escherichia coli as a food source. These results support the hypothesis that ascorbate biosynthesis in invertebrates may proceed by a novel pathway and lay the foundation for a broader understanding of its biological role

Soy Products with Reduced Levels of Sulfite, Free Radicals and Methanethiol

Soy products or compositions are treated with a food grade iodate compound or a cystine compound to reduce levels of methanethiol, sulfites and sulfite free-radicals, sulfate free radicals and other free radicals generated from sulfite free radicals in the soy products or compositions by 1% to 95%

Radioanalytical Methods for Characterization of the Surface Modification of Nanoparticles

The use of iron oxide nanoparticles for a variety of applications has grown over the past few decades. Manipulation of surface chemistry of these materials is critical to customizing the properties of the particles for desired applications. Ligand exchange is a common and versatile tool for surface modification. There are many factors which affect ligand exchange including ligand chain length, number of binding groups, binding group chemistry, and particle aging and oxidation. Furthermore, ligand exchange may not always occur to completion. Therefore, it is important to characterize the surface of the particles to determine the extent of exchange. Current techniques to confirm and monitor ligand exchange can be limited in sensitivity and versatility, and often these techniques must be used in combination to thoroughly characterize the exchange. To address this issue, radioanalytical techniques were developed to quantify ligand exchange on iron oxide nanoparticles and investigate the factors which affect ligand exchange. Oleic acid coated iron oxide nanoparticles were synthesized via thermal decomposition with trace amounts of 14C-oleic acid on the surface. The particles were modified via ligand exchange with a variety of hydrophilic ligands. The modified particles were measured using liquid scintillation counting (LSC) to determine the activity and ultimately, the total number of 14C-oleic acid chains remaining after exchange. These techniques were used to determine effects of head group chemistry with polymeric ligands and effects of head group chemistry, number of binding groups, and ligand exchange reaction parameters with small molecule ligands. Results revealed catechols displace the most oleic acid during exchange. Furthermore, multidenticity, or multiple binding groups, increases the displacement of the oleic acid. Particle aging and oxidation was investigated using these techniques. Unlabeled, oleic acid coated particles which were aged in solution for 2, 7, and 30 days were mixed with 14C-oleic acid in exchange reactions. Results revealed that aging of the particles at 30 days effected an increase in the amount of 14C-oleic acid adsorbed on the particles after exchange. Kinetic analysis of these results indicated an increase in the desorption rate constant and a decrease in the adsorption rate constant with age but with no profound change in the overall reaction rates. A follow-up study with oxidized particles suggested that this behavior may be due to oxidation during aging. Overall, the results signify an increase in the number of available binding sites, possibly due to formation of a defective oxide shell during aging and/or oxidation

Labeling of mesenchymal stromal cells with iron oxide-poly(l-lactide) nanoparticles for magnetic resonance imaging: uptake, persistence, effects on cellular function and magnetic resonance imaging properties

Background aims. Mesenchymal stromal cells (MSC) are the focus of research in regenerative medicine aiming at the regulatory approval of these cells for specific indications. To cope with the regulatory requirements for somatic cell therapy, novel approaches that do not interfere with the natural behavior of the cells are necessary. In this context in vivo magnetic resonance imaging (MRI) of labeled MSC could be an appropriate tool. Cell labeling for MRI with a variety of different iron oxide preparations is frequently published. However, most publications lack a comprehensive assessment of the noninterference of the contrast agent with the functionality of the labeled MSC, which is a prerequisite for the validity of cell-tracking via MRI. Methods.We studied the effects of iron oxide-poly(L-lactide) nanoparticles in MSC with flow cytom-etry, transmission electron microscopy (TEM), confocal laser scanning microscopy (CLSM), Prussian blue staining, CyQuant® proliferation testing, colony-forming unit-fibroblast (CFU-F) assays, flow chamber adhesion testing, immuno-logic tests and differentiation tests. Furthermore iron-labeled MSC were studied by MRI in agarose phantoms and Wistar rats. Results. It could be demonstrated that MSC show rapid uptake of nanoparticles and long-lasting intracellular persistence in the endosomal compartment. Labeling of the MSC with these particles has no influence on viability, differentiation, clonogenicity, proliferation, adhesion, phenotype and immunosuppressive properties. They show excellent MRI properties in agarose phantoms and after subcutaneous implantation in rats over several weeks. Conclusions. These particles qualify for studying MSC homing and trafficking via MRI