Microbial Signatures in COVID-19: Distinguishing Mild and Severe Disease via Gut Microbiota.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has significantly impacted global healthcare, underscoring the importance of exploring the virus's effects on infected individuals beyond treatments and vaccines. Notably, recent findings suggest that SARS-CoV-2 can infect the gut, thereby altering the gut microbiota. This study aimed to analyze the gut microbiota composition differences between COVID-19 patients experiencing mild and severe symptoms. We conducted 16S rRNA metagenomic sequencing on fecal samples from 49 mild and 43 severe COVID-19 cases upon hospital admission. Our analysis identified a differential abundance of specific bacterial species associated with the severity of the disease. Severely affected patients showed an association with Enterococcus faecium, Akkermansia muciniphila, and others, while milder cases were linked to Faecalibacterium prausnitzii, Alistipes putredinis, Blautia faecis, and additional species. Furthermore, a network analysis using SPIEC-EASI indicated keystone taxa and highlighted structural differences in bacterial connectivity, with a notable disruption in the severe group. Our study highlights the diverse impacts of SARS-CoV-2 on the gut microbiome among both mild and severe COVID-19 patients, showcasing a spectrum of microbial responses to the virus. Importantly, these findings align, to some extent, with observations from other studies on COVID-19 gut microbiomes, despite variations in methodologies. The findings from this study, based on retrospective data, establish a foundation for future prospective research to confirm the role of the gut microbiome as a predictive biomarker for the severity of COVID-19.

G-Quadruplexes as Sensors of Intracellular Na+/K+ Ratio: Potential Role in Regulation of Transcription and Translation.

Data on the structure of G-quadruplexes, noncanonical nucleic acid forms, supporting an idea of their potential participation in regulation of gene expression in response to the change in intracellular Na+i/K+i ratio are considered in the review. Structural variety of G-quadruplexes, role of monovalent cations in formation of this structure, and thermodynamic stability of G-quadruplexes are described. Data on the methods of their identification in the cells and biological functions of these structures are presented. Analysis of information about specific interactions of G-quadruplexes with some proteins was conducted, and their potential participation in the development of some pathological conditions, in particular, cancer and neurodegenerative diseases, is considered. Special attention is given to the plausible role of G-quadruplexes as sensors of intracellular Na+i/K+i ratio, because alteration of this parameter affects folding of G-quadruplexes changing their stability and, thereby, organization of the regulatory elements of nucleic acids. The data presented in the conclusion section demonstrate significant change in the expression of some early response genes under certain physiological conditions of cells and tissues depending on the intracellular Na+i/K+i ratio.

CyVerse: Cyberinfrastructure for open science.

CyVerse, the largest publicly-funded open-source research cyberinfrastructure for life sciences, has played a crucial role in advancing data-driven research since the 2010s. As the technology landscape evolved with the emergence of cloud computing platforms, machine learning and artificial intelligence (AI) applications, CyVerse has enabled access by providing interfaces, Software as a Service (SaaS), and cloud-native Infrastructure as Code (IaC) to leverage new technologies. CyVerse services enable researchers to integrate institutional and private computational resources, custom software, perform analyses, and publish data in accordance with open science principles. Over the past 13 years, CyVerse has registered more than 124,000 verified accounts from 160 countries and was used for over 1,600 peer-reviewed publications. Since 2011, 45,000 students and researchers have been trained to use CyVerse. The platform has been replicated and deployed in three countries outside the US, with additional private deployments on commercial clouds for US government agencies and multinational corporations. In this manuscript, we present a strategic blueprint for creating and managing SaaS cyberinfrastructure and IaC as free and open-source software.

NaGaPO4F - a KTiOPO4-structured solid sodium-ion conductor.

Advanced ionic conductors are crucial for a large variety of contemporary technologies spanning solid state ion batteries, fuel cells, gas sensors, water desalination, etc. In this work, we report on a new member of KTiOPO4-structured materials, NaGaPO4F, with sodium-ion conductivity. NaGaPO4F has been obtained for the first time via a facile two-step synthesis consisting of a hydrothermal preparation of an ammonia-based precursor, NH4GaPO4F, followed by an ion exchange reaction with NaNO3. Its crystal structure was precisely refined using a combination of synchrotron X-ray powder diffraction and electron diffraction tomography. The material is thermally stable upon 450 °C showing no significant structural transformations or degradation but only a ∼1% cell volume expansion. Na-ion mobility in NaGaPO4F was investigated by a joint experimental and computational approach comprising solid-state nuclear magnetic resonance (NMR) and density functional theory (DFT). DFT and bond-valence site energy (BVSE) calculations reveal 3D diffusion of sodium in the [GaPO4F] framework with migration barriers amounting to 0.22 and 0.44 eV, respectively, while NMR yields 0.3-0.5 eV that, being coupled with a calculated bandgap of ∼4.25 eV, makes NaGaPO4F a promising fast Na-ion conductor.

Snapper: high-sensitive detection of methylation motifs based on Oxford Nanopore reads.

MOTIVATION: The Oxford Nanopore technology has a great potential for the analysis of methylated motifs in genomes, including whole-genome methylome profiling. However, we found that there are no methylation motifs detection algorithms, which would be sensitive enough and return deterministic results. Thus, the MEME suit does not extract all Helicobacter pylori methylation sites de novo even using the iterative approach implemented in the most up-to-date methylation analysis tool Nanodisco. RESULTS: We present Snapper, a new highly sensitive approach, to extract methylation motif sequences based on a greedy motif selection algorithm. Snapper does not require manual control during the enrichment process and has enrichment sensitivity higher than MEME coupled with Tombo or Nanodisco instruments that was demonstrated on H.pylori strain J99 studied earlier by the PacBio technology and on four external datasets representing different bacterial species. We used Snapper to characterize the total methylome of a new H.pylori strain A45. At least four methylation sites that have not been described for H.pylori earlier were revealed. We experimentally confirmed the presence of a new CCAG-specific methyltransferase and inferred a gene encoding a new CCAAK-specific methyltransferase. AVAILABILITY AND IMPLEMENTATION: Snapper is implemented using Python and is freely available as a pip package named "snapper-ont." Also, Snapper and the demo dataset are available in Zenodo (10.5281/zenodo.10117651).

Universal Pairwise Interatomic van der Waals Potentials Based on Quantum Drude Oscillators.

Repulsive short-range and attractive long-range van der Waals (vdW) forces play an appreciable role in the behavior of extended molecular systems. When using empirical force fields, the most popular computational methods applied to such systems, vdW forces are typically described by Lennard-Jones-like potentials, which unfortunately have a limited predictive power. Here, we present a universal parameterization of a quantum-mechanical vdW potential, which requires only two free-atom properties─the static dipole polarizability α1 and the dipole-dipole C6 dispersion coefficient. This is achieved by deriving the functional form of the potential from the quantum Drude oscillator (QDO) model, employing scaling laws for the equilibrium distance and the binding energy, and applying the microscopic law of corresponding states. The vdW-QDO potential is shown to be accurate for vdW binding energy curves, as demonstrated by comparing to the ab initio binding curves of 21 noble-gas dimers. The functional form of the vdW-QDO potential has the correct asymptotic behavior at both zero and infinite distances. In addition, it is shown that the damped vdW-QDO potential can accurately describe vdW interactions in dimers consisting of group II elements. Finally, we demonstrate the applicability of the atom-in-molecule vdW-QDO model for predicting accurate dispersion energies for molecular systems. The present work makes an important step toward constructing universal vdW potentials, which could benefit (bio)molecular computational studies.

Optimized Quantum Drude Oscillators for Atomic and Molecular Response Properties.

The quantum Drude oscillator (QDO) is an efficient yet accurate coarse-grained approach that has been widely used to model electronic and optical response properties of atoms and molecules as well as polarization and dispersion interactions between them. Three effective parameters (frequency, mass, and charge) fully characterize the QDO Hamiltonian and are adjusted to reproduce response properties. However, the soaring success of coupled QDOs for many-atom systems remains fundamentally unexplained, and the optimal mapping between atoms/molecules and oscillators has not been established. Here we present an optimized parametrization (OQDO) where the parameters are fixed by using only dipolar properties. For the periodic table of elements as well as small molecules, our model accurately reproduces atomic (spatial) polarization potentials and multipolar dispersion coefficients, elucidating the high promise of the presented model in the development of next-generation quantum-mechanical force fields for (bio)molecular simulations.

Pharmacological Modulation of Excitotoxicity through the Combined Use of NMDA Receptor Inhibition and Group III mGlu Activation Reduces TMT-Induced Neurodegeneration in the Rat Hippocampus.

We studied the neuroprotective properties of the non-competitive NMDA receptor antagonist memantine, in combination with a positive allosteric modulator of metabotropic glutamate receptors of Group III, VU 0422288. The treatment was started 48 h after the injection of neurotoxic agent trimethyltin (TMT) at 7.5 mg/kg. Three weeks after TMT injection, functional and morphological changes in a rat hippocampus were evaluated, including the expression level of genes characterizing glutamate transmission and neuroinflammation, animal behavior, and hippocampal cell morphology. Significant neuronal cell death occurred in the CA3 and CA4 regions, and to a lesser extent, in the CA1 and CA2 regions. The death of neurons in the CA1 field was significantly reduced in animals with a combined use of memantine and VU 0422288. In the hippocampus of these animals, the level of expression of genes characterizing glutamatergic synaptic transmission (Grin2b, Gria1, EAAT2) did not differ from the level in control animals, as well as the expression of genes characterizing neuroinflammation (IL1b, TGF beta 1, Aif1, and GFAP). However, the expression of genes characterizing neuroinflammation was markedly increased in the hippocampus of animals treated with memantine or VU 0422288 alone after TMT. The results of immunohistochemical studies confirmed a significant activation of microglia in the hippocampus three weeks after TMT injection. In contrast to the hilus, microglia in the CA1 region had an increase in rod-like cells. Moreover, in the CA1 field of the hippocampus of the animals of the MEM + VU group, the amount of such microglia was close to the control. Thus, the short-term modulation of glutamatergic synaptic transmission by memantine and subsequent activation of Group III mGluR significantly affected the dynamics of neurodegeneration in the hippocampus.

Bayesian compositional regression with microbiome features via variational inference.

The microbiome plays a key role in the health of the human body. Interest often lies in finding features of the microbiome, alongside other covariates, which are associated with a phenotype of interest. One important property of microbiome data, which is often overlooked, is its compositionality as it can only provide information about the relative abundance of its constituting components. Typically, these proportions vary by several orders of magnitude in datasets of high dimensions. To address these challenges we develop a Bayesian hierarchical linear log-contrast model which is estimated by mean field Monte-Carlo co-ordinate ascent variational inference (CAVI-MC) and easily scales to high dimensional data. We use novel priors which account for the large differences in scale and constrained parameter space associated with the compositional covariates. A reversible jump Monte Carlo Markov chain guided by the data through univariate approximations of the variational posterior probability of inclusion, with proposal parameters informed by approximating variational densities via auxiliary parameters, is used to estimate intractable marginal expectations. We demonstrate that our proposed Bayesian method performs favourably against existing frequentist state of the art compositional data analysis methods. We then apply the CAVI-MC to the analysis of real data exploring the relationship of the gut microbiome to body mass index.

Consistent Stool Metagenomic Biomarkers Associated with the Response To Melanoma Immunotherapy.

The human gut microbiome plays an important role in both health and disease. Recent studies have demonstrated a strong influence of the gut microbiome composition on the efficacy of cancer immunotherapy. However, available studies have not yet succeeded in finding reliable and consistent metagenomic markers that are associated with the response to immunotherapy. Therefore, the reanalysis of the published data may improve our understanding of the association between the composition of the gut microbiome and the treatment response. In this study, we focused on melanoma-related metagenomic data, which are more abundant than are data from other tumor types. We analyzed the metagenomes of 680 stool samples from 7 studies that were published earlier. The taxonomic and functional biomarkers were selected after comparing the metagenomes of patients showing different treatment responses. The list of selected biomarkers was also validated on additional metagenomic data sets that were dedicated to the influence of fecal microbiota transplantation on the response to melanoma immunotherapy. According to our analysis, the resulting cross-study taxonomic biomarkers included three bacterial species: Faecalibacterium prausnitzii, Bifidobacterium adolescentis, and Eubacterium rectale. 101 groups of genes were identified to be functional biomarkers, including those potentially involved in the production of immune-stimulating molecules and metabolites. Moreover, we ranked the microbial species by the number of genes encoding functionally relevant biomarkers that they contained. Thus, we put together a list of potentially the most beneficial bacteria for immunotherapy success. F. prausnitzii, E. rectale, and three species of bifidobacteria stood out as the most beneficial species, even though some useful functions were also present in other bacterial species. IMPORTANCE In this study, we put together a list of potentially the most beneficial bacteria that were associated with a responsiveness to melanoma immunotherapy. Another important result of this study is the list of functional biomarkers of responsiveness to immunotherapy, which are dispersed among different bacterial species. This result possibly explains the existing irregularities between studies regarding the bacterial species that are beneficial to melanoma immunotherapy. Overall, these findings can be utilized to issue recommendations for gut microbiome correction in cancer immunotherapy, and the resulting list of biomarkers might serve as a good stepping stone for the development of a diagnostic test that is aimed at predicting patients' responses to melanoma immunotherapy.

Casimir Self-Interaction Energy Density of Quantum Electrodynamic Fields.

Quantum electrodynamic fields possess fluctuations corresponding to transient particle-antiparticle dipoles, which can be characterized by a nonvanishing polarizability density. Here, we extend a recently proposed quantum scaling law to describe the volumetric and radial polarizability density of a quantum field corresponding to electrons and positrons and derive the Casimir self-interaction energy (SIE) density of the field, E[over ¯]_{SIE}, in terms of the fine-structure constant. The proposed model obeys the cosmological equation of state w=-1 and the magnitude of the calculated E[over ¯]_{SIE} lies in between the two recent measurements of the cosmological constant Λ obtained by the Planck Mission and the Hubble Space Telescope.

Mitochondrial genome of Pseudopotamilla reniformis (Annelida: Sabellidae).

Here, we report the complete mitochondrial genome of sabellid Pseudopotamilla reniformis (Bruguière, 1789) (16,408 bp) and comprised of two ribosomal RNAs, the ubiquitous set of 13 protein-coding sequences, and 22 tRNAs. The order of protein-coding genes is consistent with the proposed conserved pattern, which contradicts recent discovery in other members of the family (Sabella spallanzanii in Daffe et al., 2021 and Bispira melanostigma in Hornfeck et al., 2022).

Isolation and Characterization of Homologically Expressed Methanol Dehydrogenase from Methylorubrum extorquens AM1 for the Development of Bioelectrocatalytical Systems.

(Ca2+)-dependent pyrroloquinolinequinone (PQQ)-dependent methanol dehydrogenase (MDH) (EC: 1.1.2.7) is one of the key enzymes of primary C1-compound metabolism in methylotrophy. PQQ-MDH is a promising catalyst for electrochemical biosensors and biofuel cells. However, the large-scale use of PQQ-MDH in bioelectrocatalysis is not possible due to the low yield of the native enzyme. Homologously overexpressed MDH was obtained from methylotrophic bacterium Methylorubrum extorquens AM1 by cloning the gene of only one subunit, mxaF. The His-tagged enzyme was easily purified by immobilized metal ion affinity chromatography (36% yield). A multimeric form (α6ß6) of recombinant PQQ-MDH possessing enzymatic activity (0.54 U/mg) and high stability was demonstrated for the first time. pH-optimum of the purified protein was about 9-10; the enzyme was activated by ammonium ions. It had the highest affinity toward methanol (KM = 0.36 mM). The recombinant MDH was used for the fabrication of an amperometric biosensor. Its linear range for methanol concentrations was 0.002-0.1 mM, the detection limit was 0.7 µM. The properties of the invented biosensor are competitive to the analogs, meaning that this enzyme is a promising catalyst for industrial methanol biosensors. The developed simplified technology for PQQ-MDH production opens up new opportunities for the development of bioelectrocatalytic systems.

Increased Extracellular Sodium Concentration as a Factor Regulating Gene Expression in Endothelium.

Hyperosmotic stimulation of endothelial cells often leads to its dysfunction accompanied, among other things, by proinflammatory response. The mechanisms of this phenomenon are not fully understood. It may arise due to increase in the plasma Na+ concentration, due to increase in the extracellular osmolarity, increase in the intracellular Na+i/K+i ratio, and/or change in the cell stiffness. In the present study we investigated the effects of short-term increase in osmolarity of extracellular medium on the mRNA content of some genes important for endothelial function (including Na+i/K+i-sensitive ones) and the equivalent elasticity constant of human umbilical vein endothelial cells membranes. Hyperosmotic stimulation of these cells with NaCl but not mannitol resulted in accumulation of Na+ ions inside the cells despite the Na,K-ATPase activation, and was also accompanied by the decrease in their equivalent elasticity constant. The amount of IL1α mRNA decreased with increasing osmolarity of the extracellular medium, whereas the amount of ATF3, PAR2, and PTGS2 mRNAs increased only in response to the increasing NaCl concentration. At the same time, under the conditions of our experiments, we did not detect changes in the expression of the osmoprotective transcription factor NFAT5. The obtained data indicate that the increase of extracellular Na+ concentration in the physiological range is an independent factor that affects intracellular Na+i/K+i ratio and regulates expression of some genes (in particular, ATF3, PAR2, PTGS2) in endothelial cells.

AcdR protein is an activator of transcription of 1-aminocyclopropane-1-carboxylate deaminase in Methylobacterium radiotolerans JCM 2831.

It has been previously shown that a number of plant associated methylotrophic bacteria contain an enzyme aminocyclopropane carboxylate (ACC) deaminase (AcdS) hydrolyzing ACC, the immediate precursor of ethylene in plants. The genome of the epiphytic methylotroph Methylobacterium radiotolerans JCM2831 contains an open reading frame encoding a protein homologous to transcriptional regulatory protein AcdR of the Lrp (leucine-responsive regulatory protein) family. The acdR gene of M. radiotolerans was heterologously expressed in Escherichia coli and purified. The results of gel retardation experiments have shown that AcdR specifically binds the DNA fragment containing the promoter-operator region of the acdS gene. ACC decreased electrophoretic mobility of the AcdR-DNA complex whereas leucine had no effect on the complex mobility. The mutant strains of M. radiotolerans obtained by insertion of a tetracycline cassette in the acdS or acdR gene lost the ACC-deaminase activity but the strains with complementation of the mutation recovered this function. The acdS- mutant but not acdR- strain expressed the xylE reporter gene under the control of acdS promoter region thus resulting in a catechol 2,3-dioxygenase activity. This suggested that AcdR in vivo functions as activator of transcription of the acdS gene. The results obtained in this study showed that in phytosymbiotic methylotroph Methylobacterium radiotolerans AcdR mediates activation of the acdS gene transcription in the presence of an inducer ACC or 2-aminoisobutyrate and the excess of the regulatory protein assists in transcription initiation even in the absence of the inducer. The model of regulation of acdS transcription in M. radiotolerans was proposed.

Molecular Interactions Induced by a Static Electric Field in Quantum Mechanics and Quantum Electrodynamics.

By means of quantum mechanics and quantum electrodynamics applied to coupled harmonic Drude oscillators, we study the interaction between two neutral atoms or molecules subject to a uniform static electric field. Our focus is to understand the interplay between leading contributions to field-induced electrostatics/polarization and dispersion interactions, as considered within the employed Drude model for both non-retarded and retarded regimes. For the first case, we present an exact solution for two coupled oscillators obtained by diagonalizing the corresponding quantum-mechanical Hamiltonian and demonstrate that the external field can control the strength of different intermolecular interactions and relative orientations of the molecules. In the retarded regime described by quantum electrodynamics, our analysis shows that field-induced electrostatic and polarization energies remain unchanged (in isotropic and homogeneous vacuum) compared to the non-retarded case. For interacting species modeled by quantum Drude oscillators, the developed framework based on quantum mechanics and quantum electrodynamics yields the leading contributions to molecular interactions under the combined action of external and vacuum fields.

Four-Dimensional Scaling of Dipole Polarizability in Quantum Systems.

Polarizability is a key response property of physical and chemical systems, which has an impact on intermolecular interactions, spectroscopic observables, and vacuum polarization. The calculation of polarizability for quantum systems involves an infinite sum over all excited (bound and continuum) states, concealing the physical interpretation of polarization mechanisms and complicating the derivation of efficient response models. Approximate expressions for the dipole polarizability, α, rely on different scaling laws α∝R^{3}, R^{4}, or R^{7}, for various definitions of the system radius R. Here, we consider a range of single-particle quantum systems of varying spatial dimensionality and having qualitatively different spectra, demonstrating that their polarizability follows a universal four-dimensional scaling law α=C(4µq^{2}/ℏ^{2})L^{4}, where µ and q are the (effective) particle mass and charge, C is a dimensionless excitation-energy ratio, and the characteristic length L is defined via the L^{2} norm of the position operator. This unified formula is also applicable to many-particle systems, as shown by accurately predicting the dipole polarizability of 36 atoms, 1641 small organic molecules, and Bloch electrons in periodic systems.

16S rRNA gene sequencing data of the upper respiratory tract microbiome in the SARS-CoV-2 infected patients.

The SARS-CoV-2 pandemic is a big challenge for humanity. The COVID-19 severity differs significantly from patient to patient, and it is important to study the factors protecting from severe forms of the disease. Respiratory microbiota may influence the patient's susceptibility to infection and disease severity due to its ability to modulate the immune system response of the host organism. This data article describes the microbiome dataset from the upper respiratory tract of SARS-CoV-2 positive patients from Russia. This dataset reports the microbial community profile of 335 human nasopharyngeal swabs collected between 2020-05 and 2021-03 during the first and the second epidemic waves. Samples were collected from both inpatients and outpatients in 4 cities of the Russian Federation (Moscow, Kazan, Irkutsk, Nizhny Novgorod) and sequenced using the 16S rRNA gene amplicon sequencing of V3-V4 region. Data contains information about the patient such as age, sex, hospitalization status, percent of damaged lung tissue, oxygen saturation (SpO2), respiratory rate, need for supplemental oxygen, chest computer tomography severity score, SARS-CoV-2 lineage, and also information about smoking and comorbidities. The amplicon sequencing data were deposited at NCBI SRA as BioProject PRJNA751478.

The Improvement of Functional State of Brain Mitochondria with Astaxanthin in Rats after Heart Failure.

The relationship between neurological damage and cardiovascular disease is often observed. This type of damage is both a cause and an effect of cardiovascular disease. Mitochondria are the key organelles of the cell and are primarily subject to oxidative stress. Mitochondrial dysfunctions are involved in the etiology of various diseases. A decrease in the efficiency of the heart muscle can lead to impaired blood flow and decreased oxygen supply to the brain. Astaxanthin (AST), a marine-derived xanthophyll carotenoid, has multiple functions and its effects have been shown in both experimental and clinical studies. We investigated the effects of AST on the functional state of brain mitochondria in rats after heart failure. Isoproterenol (ISO) was used to cause heart failure. In the present study, we found that ISO impaired the functional state of rat brain mitochondria (RBM), while the administration of AST resulted in an improvement in mitochondrial efficiency. The respiratory control index (RCI) in RBM decreased with the use of ISO, while AST administration led to an increase in this parameter. Ca2+ retention capacity (CRC) decreased in RBM isolated from rat brain after ISO injection, and AST enhanced CRC in RBM after heart failure. The study of changes in the content of regulatory proteins such as adenine nucleotide translocase 1 and 2 (ANT1/2), voltage dependent anion channel (VDAC), and cyclophilin D (CyP-D) of mitochondrial permeability transition pore (mPTP) showed that ISO reduced their level, while AST restored the content of these proteins almost to the control value. In general, AST improves the functional state of mitochondria and can be considered as a prophylactic drug in various therapeutic approaches.

Seebeck effect in nanomagnets.

We present a theory of the Seebeck effect in nanomagnets with dimensions smaller than the spin diffusion length, showing that the spin accumulation generated by a temperature gradient strongly affects the thermopower. We also identify a correction arising from the transverse temperature gradient induced by the anomalous Ettingshausen effect and an induced spin-heat accumulation gradient. The relevance of these effects for nanoscale magnets is illustrated byab initiocalculations on dilute magnetic alloys.