Selenium and the Methionine Sulfoxide Reductase System

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution licenseSelenium is a chemical element participating in the synthesis of selenocysteine residues that play a pivotal role in the enzymatic activity efficiency of selenoproteines. The methionine sulfoxide reductase (Msr) system that reduces methionine sulfoxide (MetO) to methionine comprises the selenoprotein MsrB (MsrB1) and the non-selenoprotein MsrA, which reduce the R- and the S- forms of MetO, respectively. The effects of a selenium deficient (SD) diet, which was administrated to wild type (WT) and MsrA knockout mice (MsrA-/-), on the expression and function of Msr-related proteins are examined and discussed. Additionally, new data about the levels of selenium in brain, liver, and kidneys of WT and MsrA-/- mice are presented and discussed

Decreased Phosphorylation and Increased Methionine Oxidation of α-Synuclein in the Methionine Sulfoxide Reductase A Knockout Mouse

Previously, we have showed that overexpression of methionine-oxidized α-synuclein in methionine sulfoxide reductase A (MsrA) null mutant yeast cells inhibits α-synuclein phosphorylation and increases protein fibrillation. The current studies show that ablation of mouse MsrA gene caused enhanced methionine oxidation of α-synuclein while reducing its own phophorylation levels, especially in the hydrophobic cell-extracted fraction. These data provide supportive evidence that a compromised MsrA function in mammalian brain may cause enhanced pathologies associated with altered α-synuclein oxidation and phosphorylation levels

Clearance and Phosphorylation of Alpha-Synuclein Are Inhibited in Methionine Sulfoxide Reductase A Null Yeast Cells

Aggregated α-synuclein and the point mutations Ala30Pro and Ala53Thr of α-synuclein are associated with Parkinson’s disease. The physiological roles of α-synuclein and methionine oxidation of the α-synuclein protein structure and function are not fully understood. Methionine sulfoxide reductase A (MsrA) reduces methionine sulfoxide residues and functions as an antioxidant. To monitor the effect of methionine oxidation to α-synuclein on basic cellular processes, α-synucleins were expressed in msrA null mutant and wild-type yeast cells. Protein degradation was inhibited in the α-synuclein-expressing msrA null mutant cells compared to α-synuclein-expressing wild-type cells. Increased inhibition of degradation and elevated accumulations of fibrillated proteins were observed in SynA30P-expressing msrA null mutant cells. Additionally, methionine oxidation inhibited α-synuclein phosphorylation in yeast cells and in vitro by casein kinase 2. Thus, a compromised MsrA function combined with α-synuclein overexpression may promote processes leading to synucleinopathies

Quantification of Reserve Pool Dopamine in Methionine Sulfoxide Reductase A Null Mice

Methionine sulfoxide reductase A knockout (MsrA−/−) mice, which serve as a potential model for neurodegeneration, suffer from increased oxidative stress and have previously been found to have chronically elevated brain dopamine content levels relative to control mice. Additionally, these high levels parallel increased presynaptic dopamine release. In this work, fast-scan cyclic voltammetry at carbon-fiber microelectrodes was used to quantify striatal reserve pool dopamine in knockout mice and wild-type control mice. Reserve pool dopamine efflux, induced by amphetamine, was measured in brain slices from knockout and wild type mice in the presence of α-methyl-p-tyrosine, a dopamine synthesis inhibitor. Additionally, the stimulated release of reserve pool dopamine, mobilized by cocaine, was measured. Both efflux and stimulated release measurements were enhanced in slices from knockout mice, suggesting that these mice have greater reserve pool dopamine stores than wild-type and that these stores are effectively mobilized. Moreover, dopamine transporter labeling data indicate that the difference in measured dopamine efflux was likely not caused by altered dopamine transporter protein expression. Additionally, slices from MsrA−/− and wild-type mice were equally responsive to increasing extracellular calcium concentrations, suggesting that potential differences in either calcium entry or intracellular calcium handling are not responsible for increased reserve pool dopamine release. Collectively, these results demonstrate that MsrA−/− knockout mice maintain a larger dopamine reserve pool than wild-type control mice, and that this pool is readily mobilized

The astorb database at Lowell Observatory

The astorb database at Lowell Observatory is an actively curated catalog of all known asteroids in the Solar System. astorb has heritage dating back to the 1970s and has been publicly accessible since the 1990s. Work began in 2015 to modernize the underlying database infrastructure, operational software, and associated web applications. That effort involved the expansion of astorb to incorporate new data such as physical properties (e.g. albedo, colors, spectral types) from a variety of sources. The data in astorb are used to support a number of research tools hosted at https://asteroid.lowell.edu. Here we present a full description of the software tools, computational foundation, and data products upon which the astorb ecosystem has been built. (c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Peer reviewe

Caloric restriction alleviates abnormal locomotor activity and dopamine levels in the brain of the methionine sulfoxide reductase A knockout mouse

Oxidative stress is associated with the aging process, a risk factor for neurodegenerative diseases, and decreased by reduced energy intake. Oxidative modifications can affect protein function; the sulfur-containing amino acids, including methionine, are particularly susceptible to oxidation. A methionine sulfoxide can be enzymatically reduced by the methionine sulfoxide reductase (Msr) system. Previously, we have shown that MsrA−/− mice exhibit altered locomotor activity and brain dopamine levels as function of age. Previous studies have demonstrated that a caloric restriction enhances antioxidant defense and reduces the action of reactive oxygen species. Here we examine locomotor behavior and dopamine levels of MsrA−/− mice after caloric restriction starting at 8 months of age and ending at 17 months. The MsrA−/− mice did not have any significant difference in spontaneous distance traveled when compared to controls at 17 months of age. In contrast, our previous report showed decreased locomotor activity in the MsrA−/− mice at 12 months of age and older when fed ad-libitum. After completion of the caloric restriction diet, dopamine levels were comparable to control mice. This differs from the abnormal dopamine levels previously observed in MsrA−/− mice fed ad-libitum. Thus, caloric restriction had a neutralization effect on MsrA ablation. In summary, it is suggested that caloric restriction alleviates abnormal locomotor activity and dopamine levels in the brain of the methionine sulfoxide reductase A knockout mouse

The Near-Earth Encounter of Asteroid 308635 (2005 YU55): Thermal IR Observations

The near-Earth approach (0.00217 AU, or 0.845 lunar distances) of the C-type asteroid 308635 (2005 YU55) in November 2011 presented a rare opportunity for detailed observations of a low-albedo NEA in this size range. As part of a multi-telescope campaign to measure visible and infrared spectra and photometry, we obtained mid-infrared (approx. 8 to 22 micron) photometry and spectroscopy of 2005 YU55 using Michelle on the Gemini North telescope on UT November 9 and 10,2011. An extensive radar campaign together with optical light-curves established the rotation state of YU55. In addition, the radar imaging resulted in a shape model for the asteroid, detection of numerous boulders on its surface, and a preliminary estimate of its equatorial diameter at 380 +/- 20 m. In a preliminary analysis, applying the radar and lightcurve-derived parameters to a rough-surface thermophysical model fit to the Gemini/Michelle thermal emission photometry results in a thermal inertia range of approximately 500 to 1500 J/sq m/0.5s/K, with the low-thermal-inertia solution corresponding to the small end of the radar size range and vice versa. Updates to these results will be presented and modeling of the thermal contribution to the measured near-infrared spectra from Palomar/Triplespec and IRTF/SpeX will also be discussed