Differential expression of Dusp1 and immediate early response genes in the hippocampus of rats, subjected to forced swim test.

The forced swim test (FST) is widely used to screen for potential antidepressant drugs and treatments. Despite this, the nature of stillness during FST and whether it resembles "depressive-like behavior" are widely debated issues. Furthermore, despite being widely used as a behavioral assay, the effects of the FST on the brain transcriptome are rarely investigated. Therefore, in this study we have investigated changes in the transcriptome of the rat hippocampus 20 min and 24 h after FST exposure. RNA-Seq is performed on the hippocampus tissues of rats 20 min and 24 h after an FST. Differentially expressed genes (DEGs) were identified using limma and used to construct gene interaction networks. Fourteen differentially expressed genes (DEGs) were identified only in the 20-m group. No DEGs were identified 24 h after the FST. These genes were used for Gene Ontology term enrichment and gene-network construction. Based on the constructed gene-interaction networks, we identified a group of DEGs (Dusp1, Fos, Klf2, Ccn1, and Zfp36) that appeared significant based on multiple methods of downstream analysis. Dusp1 appears especially important, as its role in the pathogenesis of depression has been demonstrated both in various animal models of depression and in patients with depressive disorders.

Fraction of plasma exomeres and low-density lipoprotein cholesterol as a predictor of fatal outcome of COVID-19.

Transcriptomic analysis conducted by us previously revealed upregulation of genes involved in low-density lipoprotein particle receptor (LDLR) activity pathway in lethal COVID-19 caused by SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus 2). Last data suggested the possible role of extracellular vesicles in COVID-19 pathogenesis. The aim of the present study was to retrospectively evaluate parameters of cholesterol metabolism and newly identified EVs, exomeres, as possible predictors of fatal outcome of COVID-19 patients infected by the Alpha and the Delta variants of SARS-CoV-2 virus. Blood from 67 patients with severe COVID-19 were collected at the time of admission to the intensive care unit (ICU) and 7 days after admission to the ICU. After 30 days patients were divided into two subgroups according to outcome-34 non-survivors and 33 survivors. This study demonstrated that plasma low- and high-density lipoprotein cholesterol levels (LDL-C and HDL-C) were decreased in non-survivors compared to controls at the time of admission to the ICU. The conjoint fraction of exomeres and LDL particles measured by dynamic light scattering (DLS) was decreased in non-survivors infected by the Alpha and the Delta variants compared to survivors at the time of admission to the ICU. We first showed that reduction of exomeres fraction may be critical in fatal outcome of COVID-19.

Plasmon-Enhanced Ultraviolet Luminescence in Colloid Solutions and Nanostructures Based on Aluminum and ZnO Nanoparticles.

Aluminum nanoparticles attract scientific interest as a promising low-cost material with strong plasmon resonance in the ultraviolet region, which can be used in various fields of photonics. In this paper, for the first time, ultraviolet luminescence of zinc oxide nanoparticles in colloid solutions and nanostructure films in the presence of plasmonic aluminum nanoparticles 60 nm in size with a metal core and an aluminum oxide shell were studied. Mixture colloids of ZnO and Al nanoparticles in isopropyl alcohol solution with concentrations from 0.022 to 0.44 g/L and 0.057 to 0.00285 g/L, correspondingly, were investigated. The enhancement of up to 300% of ZnO emission at 377 nm in colloids mixtures with metal nanoparticles due to formation of Al-ZnO complex agglomerates was achieved. Plasmon nanostructures with different configurations of layers, such as Al on the surface of ZnO, ZnO on Al, sandwich-like structure and samples prepared from a colloidal mixture of ZnO and Al nanoparticles, were fabricated by microplotter printing. We demonstrated that photoluminescence can be boosted 2.4-fold in nanostructures prepared from a colloidal mixture of ZnO and Al nanoparticles, whereas the sandwich-like structure gave only 1.1 times the amplification of luminescence. Calculated theoretical models of photoluminescence enhancement of ideal and weak emitters near aluminum nanoparticles of different sizes showed comparable results with the obtained experimental data.

Transcriptome Profiling Reveals Differential Expression of Circadian Behavior Genes in Peripheral Blood of Monozygotic Twins Discordant for Parkinson's Disease.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Investigating individuals with the most identical genetic background is optimal for minimizing the genetic contribution to gene expression. These individuals include monozygotic twins discordant for PD. Monozygotic twins have the same genetic background, age, sex, and often similar environmental conditions. The aim of this study was to carry out a transcriptome analysis of the peripheral blood of three pairs of monozygotic twins discordant for PD. We identified the metabolic process "circadian behavior" as a priority process for further study. Different expression of genes included in the term "circadian behavior" confirms that this process is involved in PD pathogenesis. We found increased expression of three genes associated with circadian behavior, i.e., PTGDS, ADORA2A, and MTA1, in twins with PD. These genes can be considered as potential candidate genes for this disease.

Transcriptome Analysis of Induced Pluripotent Stem Cells and Neuronal Progenitor Cells, Derived from Discordant Monozygotic Twins with Parkinson's Disease.

Parkinson's Disease (PD) is a widespread severe neurodegenerative disease that is characterized by pronounced deficiency of the dopaminergic system and disruption of the function of other neuromodulator systems. Although heritable genetic factors contribute significantly to PD pathogenesis, only a small percentage of sporadic cases of PD can be explained using known genetic risk factors. Due to that, it could be inferred that changes in gene expression could be important for explaining a significant percentage of PD cases. One of the ways to investigate such changes, while minimizing the effect of genetic factors on experiment, are the study of PD discordant monozygotic twins. In the course of the analysis of transcriptome data obtained from IPSC and NPCs, 20 and 1906 differentially expressed genes were identified respectively. We have observed an overexpression of TNF in NPC cultures, derived from twin with PD. Through investigation of gene interactions and gene involvement in biological processes, we have arrived to a hypothesis that TNF could play a crucial role in PD-related changes occurring in NPC derived from twins with PD, and identified INHBA, WNT7A and DKK1 as possible downstream effectors of TNF.

Transcriptomic Profiles Reveal Downregulation of Low-Density Lipoprotein Particle Receptor Pathway Activity in Patients Surviving Severe COVID-19.

To assess the biology of the lethal endpoint in patients with SARS-CoV-2 infection, we compared the transcriptional response to the virus in patients who survived or died during severe COVID-19. We applied gene expression profiling to generate transcriptional signatures for peripheral blood mononuclear cells (PBMCs) from patients with SARS-CoV-2 infection at the time when they were placed in the Intensive Care Unit of the Pavlov First State Medical University of St. Petersburg (Russia). Three different bioinformatics approaches to RNA-seq analysis identified a downregulation of three common pathways in survivors compared with nonsurvivors among patients with severe COVID-19, namely, low-density lipoprotein (LDL) particle receptor activity (GO:0005041), important for maintaining cholesterol homeostasis, leukocyte differentiation (GO:0002521), and cargo receptor activity (GO:0038024). Specifically, PBMCs from surviving patients were characterized by reduced expression of PPARG, CD36, STAB1, ITGAV, and ANXA2. Taken together, our findings suggest that LDL particle receptor pathway activity in patients with COVID-19 infection is associated with poor disease prognosis.

Targeted exome analysis of Russian patients with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM), described as the presence of hypertrophy of left ventricular, is the most prevalent heritable cardiovascular disease with predominantly an autosomal dominant type of inheritance. However, pathogenic alleles are not identified in at least 25% of patients with HCM, and the spectrum of pathogenic variants that contribute to the development of HCM in Russia has not been fully described. Therefore, the goal of our study was to identify genetic variants associated with the etiopathogenesis of HCM in Russian patients. METHODS: The study cohort included 98 unrelated adult patients with HCM. We performed targeted exome sequencing, an analysis using various algorithms for prediction of the impact of variants on protein structure and the prediction of pathogenicity using ACMG Guidelines. RESULTS: The frequency of pathogenic and likely pathogenic variants in all HCM-related genes was 8% in our patients. We also identified 20 variants of uncertain significance in all HCM-related genes. CONCLUSIONS: The prevalence of individual pathogenic variants in HCM-related genes in Russian population appears to be lower than in general European population, which could be explained by ethnic features of Russian population, age characteristics of our sample, or unidentified pathogenic variants in genes previously not linked with HCM.

Microplotter printing of planar solid electrolytes in the CeO2-Y2O3 system.

The formation process for planar solid electrolytes in the CeO2-Y2O3 system has been studied using efficient, high-performance, high-resolution microplotter printing technology, using functional ink based on nanopowders (the average size of crystallites was 12-15 nm) of a similar composition obtained by programmed coprecipitation of metal hydroxides. The dependence of the microstructure of the oxide nanoparticles obtained and their crystal structure on yttrium concentration has been studied using a wide range of methods. According to X-ray diffraction (XRD), the nanopowders and coatings produced are single-phase, with a cubic crystal structure of the fluorite type, and the electronic state and content of cerium and yttrium in the printed coatings have been determined using X-ray photoelectron spectroscopy (XPS). The results of scanning electron (SEM) and atomic force microscopy (AFM) have shown that the coatings produced are homogeneous, they do not contain defects in the form of fractures and the height difference over an area of 1 µm2 is 30-45 nm. The local electrophysical characteristics of the oxide coatings produced (the work function of the coating surface, capacitance values, maps of the surface potential and capacitive contrast distribution over the surface) have been studied using Kelvin-probe force microscopy (KPFM) and scanning capacitive microscopy (SCM). Using impedance spectroscopy, the dependence of the electrophysical characteristics of printed planar solid electrolytes in the CeO2-Y2O3 system on yttrium content has been determined and the prospects of the technology developed for the manufacture of modern, intermediate-temperature, solid oxide fuel cells have been demonstrated.

Microplotter-Printed On-Chip Combinatorial Library of Ink-Derived Multiple Metal Oxides as an "Electronic Olfaction" Unit.

Information about the surrounding atmosphere at a real timescale significantly relies on available gas sensors to be efficiently combined into multisensor arrays as electronic olfaction units. However, the array's performance is challenged by the ability to provide orthogonal responses from the employed sensors at a reasonable cost. This issue becomes more demanded when the arrays are designed under an on-chip paradigm to meet a number of emerging calls either in the internet-of-things industry or in situ noninvasive diagnostics of human breath, to name a few, for small-sized low-powered detectors. The recent advances in additive manufacturing provide a solid top-down background to develop such chip-based gas-analytical systems under low-cost technology protocols. Here, we employ hydrolytically active heteroligand complexes of metals as ink components for microplotter patterning a multioxide combinatorial library of chemiresistive type at a single chip equipped with multiple electrodes. To primarily test the performance of such a multisensor array, various semiconducting oxides of the p- and n-conductance origins based on pristine and mixed nanocrystalline MnOx, TiO2, ZrO2, CeO2, ZnO, Cr2O3, Co3O4, and SnO2 thin films, of up to 70 nm thick, have been printed over hundred µm areas and their micronanostructure and fabrication conditions are thoroughly assessed. The developed multioxide library is shown to deliver at a range of operating temperatures, up to 400 °C, highly sensitive and highly selective vector signals to different, but chemically akin, alcohol vapors (methanol, ethanol, isopropanol, and n-butanol) as examples at low ppm concentrations when mixed with air. The suggested approach provides us a promising way to achieve cost-effective and well-performed electronic olfaction devices matured from the diverse chemiresistive responses of the printed nanocrystalline oxides.

Whole-Transcriptome Analysis of Dermal Fibroblasts, Derived from Three Pairs of Monozygotic Twins, Discordant for Parkinson's Disease.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. In most cases, the development of the disease is sporadic and is not associated with any currently known mutations associated with PD. It is believed that changes associated with the epigenetic regulation of gene expression may play an important role in the pathogenesis of this disease. The study of individuals with an almost identical genetic background, such as monozygotic twins, is one of the best approaches to the analysis of such changes. A whole-transcriptome analysis of dermal fibroblasts obtained from three pairs of monozygotic twins discordant for PD was carried out in this work. Twenty-nine differentially expressed genes were identified in the three pairs of twins. These genes were included in seven processes within two clusters, according to the results of an enrichment analysis. The cluster with the greatest statistical significance included processes associated with the regulation of the differentiation of fat cells, the action potential, and the regulation of glutamatergic synaptic transmission. The most significant genes, which occupied a central position in this cluster, were PTGS2, SCN9A, and GRIK2. These genes can be considered as potential candidate genes for PD.

Reducing Humidity Response of Gas Sensors for Medical Applications: Use of Spark Discharge Synthesis of Metal Oxide Nanoparticles.

The application of gas sensors in breath analysis is an important trend in the early diagnostics of different diseases including lung cancer, ulcers, and enteric infection. However, traditional methods of synthesis of metal oxide gas-sensing materials for semiconductor sensors based on wet sol-gel processes give relatively high sensitivity of the gas sensor to changing humidity. The sol-gel process leading to the formation of superficial hydroxyl groups on oxide particles is responsible for the strong response of the sensing material to this factor. In our work, we investigated the possibility to synthesize metal oxide materials with reduced sensitivity to water vapors. Dry synthesis of SnO2 nanoparticles was implemented in gas phase by spark discharge, enabling the reduction of the hydroxyl concentration on the surface and allowing the production of tin dioxide powder with specific surface area of about 40 m²/g after annealing at 610 °C. The drop in sensor resistance does not exceed 20% when air humidity increases from 40 to 100%, whereas the response to 100 ppm of hydrogen is a factor of 8 with very short response time of about 1 s. The sensor response was tested in mixtures of air with hydrogen, which is the marker of enteric infections and the marker of early stage fire, and in a mixture of air with lactate (marker of stomach cancer) and ammonia gas (marker of Helicobacter pylori, responsible for stomach ulcers).

Whole-Exome Sequencing in Searching for New Variants Associated With the Development of Parkinson's Disease.

Background: Parkinson's disease (PD) is a complex disease with its monogenic forms accounting for less than 10% of all cases. Whole-exome sequencing (WES) technology has been used successfully to find mutations in large families. However, because of the late onset of the disease, only small families and unrelated patients are usually available. WES conducted in such cases yields in a large number of candidate variants. There are currently a number of imperfect software tools that allow the pathogenicity of variants to be evaluated. Objectives: We analyzed 48 unrelated patients with an alleged autosomal dominant familial form of PD using WES and developed a strategy for selecting potential pathogenetically significant variants using almost all available bioinformatics resources for the analysis of exonic areas. Methods: DNA sequencing of 48 patients with excluded frequent mutations was performed using an Illumina HiSeq 2500 platform. The possible pathogenetic significance of identified variants and their involvement in the pathogenesis of PD was assessed using SNP and Variation Suite (SVS), Combined Annotation Dependent Depletion (CADD) and Rare Exome Variant Ensemble Learner (REVEL) software. Functional evaluation was performed using the Pathway Studio database. Results: A significant reduction in the search range from 7082 to 25 variants in 23 genes associated with PD or neuronal function was achieved. Eight (FXN, MFN2, MYOC, NPC1, PSEN1, RET, SCN3A and SPG7) were the most significant. Conclusions: The multistep approach developed made it possible to conduct an effective search for potential pathogenetically significant variants, presumably involved in the pathogenesis of PD. The data obtained need to be further verified experimentally.