Alterations in Metal Homeostasis Occur Prior to Canonical Markers in Huntington Disease

Objective: The importance of metal biology in neurodegenerative diseases such as Huntingtin Disease is well documented with evidence of direct interactions between metals such as copper, zinc, iron and manganese and mutant Huntingtin pathobiology. To date, it is unclear whether these interactions are observed in humans, how this impacts other metals, and how mutant Huntington alters homeostatic mechanisms governing levels of copper, zinc, iron and manganese in cerebrospinal fluid and blood in HD patients.Methods: Plasma and cerebrospinal fluid from control, pre-manifest, manifest and late manifest HD participants were collected as part of HD-Clarity. Levels of cerebrospinal fluid and plasma copper, zinc, iron and manganese were measured as well as levels of mutant Huntingtin and neurofilament in a sub-set of cerebrospinal fluid samples.Results: We find that elevations in cerebrospinal fluid copper, manganese and zinc levels are altered early in disease prior to alterations in canonical biomarkers of HD although these changes are not present in plasma. We also evidence that CSF iron is elevated in manifest patients. The relationships between plasma and cerebrospinal fluid metal are altered based on disease stage.Interpretation: These findings demonstrate that there are alterations in metal biology selectively in the CSF which occur prior to changes in known canonical biomarkers of disease. Our work indicates that there are pathological changes related to alterations in metal biology in individuals without elevations in neurofilament and mutant Huntingtin.

Influence of an Inclined Cooling Plate on the Production of A356/CNF and A356/SiC MMC by Compocasting

The influence of an inclined cooling plate utilized as a modification in the compocasting process of aluminum alloy is studied in this paper. Based on the crystal separation theory, molten A356 is poured on the inclined copper plate in order to produce solidification nuclei inside the fluid metal, which is, then, mechanically stirred while reinforcement is added through its surface. Carbon nano fibers (CNF) and particulate SiC were utilized as reinforcement, in quantities varying from 0.5 to 15vol%. Dispersion of the reinforcements was observed by macro and microstructure analysis. For CNF, addition of quantities up to 1vol% resulted in homogeneous dispersion through the matrix, although SEM analysis showed the presence of clusters of up to 50μm in some points of the samples. SiC was properly mixed into matrix until 10vol%. Globular crystals were obtained, but some coarsening occurred, especially for small quantities of reinforcement. Utilization of the inclined cooling plate produced good inclusion and homogenization for two different reinforcements through an A356 matrix. The best results were obtained for a 180mm cooling plate, with inclination of 60o. The pouring temperature utilized was 10oC over the melting point of the alloy, and temperature of the tundish was kept around 598oC during stirring.