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Background Parkinson's disease is a neurodegenerative disorder characterized pathologically by the loss of nigrostriatal dopamine neurons that project from the substantia nigra in the midbrain to the putamen and caudate nuclei, leading to the clinical features of bradykinesia, rigidity, and rest tremor. Oxidative stress from oxidized dopamine and related compounds may contribute to the degeneration characteristic of this disease. Results To investigate a possible role of the phospholipid hydroperoxidase glutathione peroxidase 4 (GPX4) in protection from oxidative stress, we investigated GPX4 expression in postmortem human brain tissue from individuals with and without Parkinson's disease. In both control and Parkinson's samples, GPX4 was found in dopaminergic nigral neurons colocalized with neuromelanin. Overall GPX4 was significantly reduced in substantia nigra in Parkinson's vs. control subjects, but was increased relative to the cell density of surviving nigral cells. In putamen, GPX4 was concentrated within dystrophic dopaminergic axons in Parkinson's subjects, although overall levels of GPX4 were not significantly different compared to control putamen. Conclusions This study demonstrates an up-regulation of GPX4 in neurons of substantia nigra and association of this protein with dystrophic axons in striatum of Parkinson's brain, indicating a possible neuroprotective role. Additionally, our findings suggest this enzyme may contribute to the production of neuromelanin.

Dopamine (DA) transmission plays a critical role in processing rewarding and pleasurable stimuli. Increased synaptic DA release in the nucleus accumbens (NAc) is a central component of the physiological effects of drugs of abuse. The essential trace element selenium mitigates methamphetamine-induced neurotoxicity. Selenium can also alter DA production and turnover. However, studies have not directly addressed the role of selenium in DA neurotransmission. Selenoprotein P (SELENOP1) requires selenium for synthesis and transports selenium to the brain, in addition to performing other functions. We investigated whether SELENOP1 directly impacts (1) DA signaling and (2) the dopaminergic response to methamphetamine. We used fast-scan cyclic voltammetry to investigate DA transmission and the response to methamphetamine in NAc slices from C57/BL6J SELENOP1 KO mice. Recordings from SELENOP1 KO mouse slices revealed reduced levels of evoked DA release and slower DA uptake rates. Methamphetamine caused a dramatic increase in vesicular DA release in SELENOP1 KO mice not observed in wild-type controls. This elevated response was attenuated by SELENOP1 application through a selenium-independent mechanism involving SELENOP1-apolipoprotein E receptor 2 (ApoER2) interaction to promote dopamine D2 receptor (D2R) function. In wild-type mice, increased vesicular DA release in response to methamphetamine was revealed by blocking D2R activation, indicating that the receptor suppresses the methamphetamine-induced vesicular increase. Our data provide evidence of a direct physiological role for SELENOP1 in the dopaminergic response to methamphetamine and suggest a signaling role for the protein in DA transmission.

There is probably not a black hole in the center of the Sun. Despite this detail, our goal in this work to convince the reader that this question is interesting and that work studying stars with central black holes is well motivated. If primordial black holes exist then they may exist in sufficiently large numbers to explain the dark matter in the universe. While primordial black holes may form at almost any mass, the asteroid-mass window between 10−16−10−10M⊙ remains a viable dark matter candidate and these black holes could be captured by stars upon formation. Such a star, partially powered by accretion luminosity from a microscopic black hole in its core, has been called a ‘Hawking star.’ Stellar evolution of Hawking stars is highly nontrivial and requires detailed stellar evolution models, which were developed in our recent work. We present here full evolutionary models of solar mass Hawking stars using two accretion schemes: one with a constant radiative efficiency, and one that is new in this work that uses an adaptive radiative efficiency to model the effects of photon trapping.

Methamphetamine (METH) is a drug with a high addictive potential that is widely abused across the world. Although it is known that METH dysregulates both dopamine transmission and dopamine reuptake, the specific mechanism of action remains obscure. One promising target of METH is the sigma receptor, a chaperone protein located on the membrane of the endoplasmic reticulum. Using fast-scan cyclic voltammetry, we show that METH-enhancement of evoked dopamine release and basal efflux is dependent on sigma receptor activation. METH-induced activation of sigma receptors results in oxidation of a cysteine residue on VMAT2, which decreases transporter function. Unilateral injections of the sigma receptor antagonist BD-1063 prior to METH administration increased dopamine-related ipsilateral circling behavior, indicating the involvement of sigma receptors. These findings suggest that interactions between METH and the sigma receptor lead to oxidative species (most likely superoxide) that in turn oxidize VMAT2. Altogether, these findings show that the sigma receptor has a key role in METH dysregulation of dopamine release and dopamine-related behaviors.

We present a machine learning method to estimate the physical parameters of classical pulsating stars such as RR Lyrae and Cepheid variables based on an automated comparison of their theoretical and observed light curve parameters at multiple wavelengths. We train artificial neural networks (ANNs) on theoretical pulsation models to predict the fundamental parameters (mass, radius, luminosity, and effective temperature) of Cepheid and RR Lyrae stars based on their period and light-curve parameters. The fundamental parameters of these stars can be estimated up to 60 percent more accurately when the light-curve parameters are taken into consideration. This method was applied to the observations of hundreds of Cepheids and thousands of RR Lyrae in the Magellanic Clouds to produce catalogs of estimated masses, radii, luminosities, and other parameters of these stars.

Background Selenoprotein W (Sepw1) is a selenium‐containing protein that is abundant in brain and muscle of vertebrate animals. Muscular expression of Sepw1 is reduced by dietary selenium (Se) deficiency in mammals, whereas brain expression is maintained. However, expression of Sepw1 depends on the Se transporter selenoprotein P (Sepp1). Methods We assessed the regional and cellular expression of Sepw1 in the mouse brain and neuronal cultures. Results We found that Sepw1 is widespread in neurons and neuropil of mouse brain and appears in both the soma and processes of neurons in culture. Pyramidal neurons of cortex and hippocampus express high levels of Sepw1. It is also abundant in Purkinje neurons and their dendritic arbors in the cerebellum. Analysis of synaptosome fractions prepared from mice brains indicated that Sepw1 is present at synapses, as were several proteins involved in selenoprotein synthesis. Synaptic expression of Sepw1 expression is reduced in mice lacking Sepp1 compared with control mice, although selenoprotein synthesis factors were similarly expressed in both genotypes. Lastly, Sepw1 mRNA coimmunoprecipitates with Staufen 2 protein in a human neuronal cell line. Conclusions Our results suggest that Sepw1 may be locally synthesized in distal compartments of neurons including synapses. In this report we assess the expression of Selenoprotein W (Sepw1) in the brains of mice and in cultured neurons, showing expression in neuronal processes and synapses. We also demonstrate association of Sepw1 mRNA with the mRNA‐binding protein, Staufen‐2, suggesting a potential role for Staufen‐2 in regulation of Sepw1 expression.

This paper discusses two aspects of current research on the Cepheid period-luminosity (P-L) relation: the derivation of mid-infrared (MIR) P-L relations and the investigation of multi-phase P-L relations. The MIR P-L relations for Cepheids are important in the James Webb Space Telescope era for the distance scale issue, as the relations have potential to derive the Hubble constant within ∼2% accuracy—a critical constraint in precision cosmology. Consequently, we have derived the MIR P-L relations for Cepheids in the Large and Small Magellanic Clouds, using archival data from Spitzer Space Telescope . We also compared currently empirical P-L relations for Cepheids in the Magellanic Clouds to the synthetic MIR P-L relations derived from pulsational models. For the study of multi-phase P-L relations, we present convincing evidence that the Cepheid P-L relations in the Magellanic Clouds are highly dynamic quantities that vary significantly when considered as a function of pulsational phase. We found that there is a difference in P-L relations as a function of phase between the Cepheids in each of the Clouds; the most likely cause for this is the metallicity difference between the two galaxies. We also investigated the dispersion of the multi-phase P-L relations, and found that the minimum dispersions do not differ significantly from the mean light P-L dispersion.

Selenoprotein P (SelP) plays a critical role in neuronal survival and is associated with Alzheimer's pathology. We sought to determine a potential neuroprotective role for SelP in Alzheimer's disease. We utilized RNAi to reduce SelP expression in neuronal N2A cells, and determined cell viability with flow cytometry. We subsequently measured neurotoxicity from exposure of aggregated amyloid beta (Abeta) peptides to SelP-knockdown and control N2A cells. We found that knockdown of SelP using siRNA in N2A cells reduced viability and increased apoptotic cell death. Additionally, knockdown of SelP using siRNA in N2A cells resulted in increased AB toxicity. Our findings demonstrate that SelP protects neuronal cells from Abeta-induced toxicity, suggesting a neuroprotective role for SelP in preventing neurodegenerative disorders.