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The influence of Light Induced Atomic Desorption (LIAD) on the potassium D2 line magneto-optical resonances in uncoated buffer-gas optical cell is investigated. LIAD effect reduces the drawbacks of conventional heating for achieving high atomic density that is essential for many spectroscopy-based applications. Another feature of LIAD is the impact on the dwelling time of the atoms when colliding with the surface of the cell. In this work we investigate LIAD from point of view to distinguish the influence of LIAD on the atomic density from the dwelling time as well as to control and improve the parameters of magneto-optical resonances in potassium vapor. The results are interesting for development of new precise optical sensors and devices for various applications.

Autophagy is an intracellular turnover pathway. It has special relevance for neurodegenerative proteinopathies, such as Alzheimer disease, Parkinson disease, and Huntington disease (HD), which are characterized by the accumulation of misfolded proteins. Although induction of autophagy enhances clearance of misfolded protein and has therefore been suggested as a therapy for proteinopathies, neurons appear to be less responsive to classic autophagy inducers than nonneuronal cells. Searching for improved inducers of neuronal autophagy, we discovered an N¹⁰-substituted phenoxazine that, at proper doses, potently and safely up-regulated autophagy in neurons in an Akt- and mTOR-independent fashion. In a neuron model of HD, this compound was neuroprotective and decreased the accumulation of diffuse and aggregated misfolded protein. A structure/activity analysis with structurally similar compounds approved by the US Food and Drug Administration revealed a defined pharmacophore for inducing neuronal autophagy. This pharmacophore should prove useful in studying autophagy in neurons and in developing therapies for neurodegenerative proteinopathies.

Monitoring the half-life of mutant huntingtin protein reveals how specific neurons are more susceptible to its toxic effects and to Huntington's disease. In polyglutamine (polyQ) diseases, only certain neurons die, despite widespread expression of the offending protein. PolyQ expansion may induce neurodegeneration by impairing proteostasis, but protein aggregation and toxicity tend to confound conventional measurements of protein stability. Here, we used optical pulse labeling to measure effects of polyQ expansions on the mean lifetime of a fragment of huntingtin, the protein that causes Huntington's disease, in living neurons. We show that polyQ expansion reduced the mean lifetime of mutant huntingtin within a given neuron and that the mean lifetime varied among neurons, indicating differences in their capacity to clear the polypeptide. We found that neuronal longevity is predicted by the mean lifetime of huntingtin, as cortical neurons cleared mutant huntingtin faster and lived longer than striatal neurons. Thus, cell type–specific differences in turnover capacity may contribute to cellular susceptibility to toxic proteins, and efforts to bolster proteostasis in Huntington's disease, such as protein clearance, could be neuroprotective.

Hypoxia is a major pathogenetic factor in many cancers. Individual resistance to suboptimal oxygen availability is subject to broad variation and its possible role in tumorigenesis remains underexplored. This study aimed at specific characterization of glioblastoma progression in male tolerant and susceptible to hypoxia Wistar rats. Hypoxia resistance was assessed by gasping time measurement in an 11,500 m altitude-equivalent hypobaric decompression chamber. Based on the outcome, the animals were assigned to three groups termed ‘tolerant to hypoxia’ (n = 13), ‘normal’, and ‘susceptible to hypoxia’ (n = 24). The ‘normal’ group was excluded from subsequent experiments. One month later, the animals underwent inoculation with rat glioblastoma 101.8 followed by monitoring of survival, body weight dynamics and neurological symptoms. The animals were sacrificed on post-inoculation days 11 (subgroup 1) and 15 (subgroup 2). Relative vessels number, necrosis areas and Ki-67 index were assessed microscopically; tumor volumes were determined by 3D reconstruction from histological images; serum levels of HIF-1α, IL-1β, and TNFα were determined by ELISA. None of the tolerant to hypoxia animals died of the disease during observation period, cf. 85% survival on day 11 and 55% survival on day 15 in the susceptible group. On day 11, proliferative activity of the tumors in the tolerant animals was higher compared with the susceptible group. On day 15, proliferative activity, necrosis area and volume of the tumors in the tolerant to hypoxia animals were higher compared with the susceptible group. ELISA revealed no dynamics in TNFα levels, elevated levels of IL-1β in the susceptible animals on day 15 in comparison with day 11 and tolerant ones. Moreover, there were elevated levels of HIF-1α in the tolerant animals on day 15 in comparison with day 11. Thus, the proliferative activity of glioblastoma cells and the content of HIF-1α were higher in tolerant to hypoxia rats, but the mortality associated with the tumor process and IL-1β level in them were lower than in susceptible animals. Specific features of glioblastoma 101.8 progression in tolerant and susceptible to hypoxia rats, including survival, tumor growth rates and IL-1β level, can become the basis of new personalized approaches for cancer diseases treatment in accordance to individual hypoxia resistance.

Guanine-rich DNA sequences can fold into four-stranded G-quadruplex (G4-DNA) structures. G4-DNA regulates replication and transcription, at least in cancer cells. Here, we demonstrate that, in neurons, pharmacologically stabilizing G4-DNA with G4 ligands strongly downregulates the Atg7 gene. Atg7 is a critical gene for the initiation of autophagy that exhibits decreased transcription with aging. Using an in vitro assay, we show that a putative G-quadruplex-forming sequence (PQFS) in the first intron of the Atg7 gene folds into a G4. An antibody specific to G4-DNA and the G4-DNA-binding protein PC4 bind to the Atg7 PQFS. Mice treated with a G4 stabilizer develop memory deficits. Brain samples from aged mice contain G4-DNA structures that are absent in brain samples from young mice. Overexpressing the G4-DNA helicase Pif1 in neurons exposed to the G4 stabilizer improves phenotypes associated with G4-DNA stabilization. Our findings indicate that G4-DNA is a novel pathway for regulating autophagy in neurons.

Peroxisomes exist in most cells, where they participate in lipid metabolism, as well as scavenging the reactive oxygen species (ROS) that are produced as by-products of their metabolic functions. In certain tissues such as the liver and kidneys, peroxisomes have more specific roles, such as bile acid synthesis in the liver and steroidogenesis in the adrenal glands. In the brain, peroxisomes are critically involved in creating and maintaining the lipid content of cell membranes and the myelin sheath, highlighting their importance in the central nervous system (CNS). This review summarizes the peroxisomal lifecycle, then examines the literature that establishes a link between peroxisomal dysfunction, cellular aging, and age-related disorders that affect the CNS. This review also discusses the gap of knowledge in research on peroxisomes in the CNS.

The coherent magneto-optical resonances on the potassium D 2 line are investigated from the point of view of magnetometry applications. The measurements are performed in Hanle configuration with potassium excited by circularly polarized laser beam in cell with dimensions 8 mm and buffer gas 30 Torr Ne. The parameters of the resonances registered in fluorescence and transmission are compared. The capability of the laser system to work with magnetically unshielded cell is demonstrated. The registration of bright and dark magneto-optical resonances detected in fluorescence by controlling the optical thickness of potassium vapor is discussed. The influence of the laser power and transverse magnetic field are considered. The experimental results show the potential of the system for magnetic field sensing and calibration.

Chemical compatibility and cation interdiffusion between the double perovskite cobaltites RBaCo2O6−δ (R = Gd, Pr) and proton-conducting electrolyte BaZr0.8Y0.2O3−δ were studied. Chemical interaction was found to occur already at 1100 °C as a result of the partial dissolution of RBaCo2O6−δ (R = Gd, Pr) in BaZr0.8Y0.2O3−δ. Analysis of the element distribution along the cross sections of diffusion couples RBaCo2O6−δ(R = Gd, Pr)|BaZr0.8Y0.2O3−δ showed strong interdiffusion of cations, with cobalt being the most mobile one. Its diffusion depth in the electrolyte reaches up to several hundreds of micrometers. The addition of NiO as a sintering aid to BaZr0.8Y0.2O3−δ promotes cation diffusion especially through the grain boundary mechanism, increasing the diffusion depth of Co. The possible implications of cation interdiffusion on the performance of proton-conducting SOFCs are discussed based on the results obtained.

Autophagy is an important homeostatic mechanism that eliminates long-lived proteins, protein aggregates and damaged organelles. Its dysregulation is involved in many neurodegenerative disorders. Autophagy is therefore a promising target for blunting neurodegeneration. We searched for novel autophagic pathways in primary neurons and identified the cytosolic sphingosine-1-phosphate (S1P) pathway as a regulator of neuronal autophagy. S1P, a bioactive lipid generated by sphingosine kinase 1 (SK1) in the cytoplasm, is implicated in cell survival. We found that SK1 enhances flux through autophagy and that S1P-metabolizing enzymes decrease this flux. When autophagy is stimulated, SK1 relocalizes to endosomes/autophagosomes in neurons. Expression of a dominant-negative form of SK1 inhibits autophagosome synthesis. In a neuron model of Huntington’s disease, pharmacologically inhibiting S1P-lyase protected neurons from mutant huntingtin-induced neurotoxicity. These results identify the S1P pathway as a novel regulator of neuronal autophagy and provide a new target for developing therapies for neurodegenerative disorders.

Coronavirus disease (COVID-19), caused by SARS-CoV-2, leads to symptoms ranging from asymptomatic disease to death. Although males are more susceptible to severe symptoms and higher mortality due to COVID-19, patient sex has rarely been examined. Sex-associated metabolic changes may implicate novel biomarkers and therapeutic targets to treat COVID-19. Here, using serum samples, we performed global metabolomic analyses of uninfected and SARS-CoV-2-positive male and female patients with severe COVID-19. Key metabolic pathways that demonstrated robust sex differences in COVID-19 groups, but not in controls, involved lipid metabolism, pentose pathway, bile acid metabolism, and microbiome-related metabolism of aromatic amino acids, including tryptophan and tyrosine. Unsupervised statistical analysis showed a profound sexual dimorphism in correlations between patient-specific clinical parameters and their global metabolic profiles. Identification of sex-specific metabolic changes in severe COVID-19 patients is an important knowledge source for researchers striving for development of potential sex-associated biomarkers and druggable targets for COVID-19 patients.