Progress and Prospects in Epigenetic Studies of Ancient DNA.

Development of technologies for high-throughput whole-genome sequencing and improvement of sample preparation techniques made it possible to study ancient DNA (aDNA) from archaeological samples over a million year old. The studies of aDNA have shed light on the history of human migration, replacement of populations, interbreeding of Cro-Magnons with Neanderthals and Denisovans, evolution of human pathogens, etc. Equally important is the possibility to investigate epigenetic modifications of ancient genomes, which has allowed to obtain previously inaccessible information on gene expression, nucleosome positioning, and DNA methylation.

Programmed Risks of Death in Male Patients with Diabetes.

Lifespan has been studied in a cohort of male patients with diabetes mellitus. It was shown that the rate of death displays significant fluctuations over the course of ontogenesis. On the curves of dependence of the rate of death on the age at time of death (differential mortality curves) these fluctuations are visualized as peaks.

Hepatitis C virus-specific markers in pediatric patients with chronic hepatitis C.

Background: The study aimed to investigate hepatitis C virus (HCV) specific markers in chronically infected children. The main objective was to explore the patterns of marker variability.

Methods: HCV RNA, core antigen, anti-HCV IgM, and antibodies to individual viral proteins were detected using commercially available assays or experimental ELISA.

A Strategy for the Rapid Development of a Safe Candidate Vaccine Strain.

Approximately 1/6 of humanity is at high risk of experiencing cholera epidemics. The development of effective and safe vaccines against the primary cause of cholera, is part of the public health measures to prevent cholera epidemics. Natural nontoxigenic isolates represent a source of new genetically improved and relatively safe vaccine strains.

Enhancement of thermostability of GH10 xylanase E Penicillium canescens directed by ΔΔG calculations and structure analysis.

Hydrolytic enzymes are highly demanded in the industry. Thermostability is an important property of enzymes that affects the economic costs of the industrial processes. The rational design of GH10 xylanase E (XylE) Penicillium canescens for the thermostability improvement was directed by ΔΔG calculations and structure analysis.

Two Sides of Quantum-Based Modeling of Enzyme-Catalyzed Reactions: Mechanistic and Electronic Structure Aspects of the Hydrolysis by Glutamate Carboxypeptidase.

We report the results of a computational study of the hydrolysis reaction mechanism of -acetyl-l-aspartyl-l-glutamate (NAAG) catalyzed by glutamate carboxypeptidase II. Analysis of both mechanistic and electronic structure aspects of this multistep reaction is in the focus of this work. In these simulations, model systems are constructed using the relevant crystal structure of the mutated inactive enzyme.

Expression and Refolding of the Plant Chitinase From for Applications as a Sustainable and Integrated Pest Management.

Recently, the study of chitinases has become an important target of numerous research projects due to their potential for applications, such as biocontrol pest agents. Plant chitinases from carnivorous plants of the genus are most aggressive against a wide range of phytopathogens. However, low solubility or insolubility of the target protein hampered application of chitinases as biofungicides.

Modeling Spectral Tuning in Red Fluorescent Proteins Using the Dipole Moment Variation upon Excitation.

We describe a model for spectral tuning in red fluorescent proteins (RFPs) based on the relation between an electronic structure descriptor, the dipole moment variation upon excitation (DMV), and the excitation energy of a protein. This approach aims to overcome the problem of accurate prediction of excitation energies in RFPs, which span a very narrow window of band maxima. The latter roughly corresponds to the energy range of 0.

Analysis of the structure and function of the tomato Solanum lycopersicum L. MADS-box gene SlMADS5.

At all stages of f lowering, a decisive role is played by the family of MADS-domain transcription factors, the combinatorial action of which is described by the ABCDE-model of f lower development. The current volume of data suggests a high conservatism of ABCDE genes in angiosperms. The E-proteins SEPALLATA are the central hub of the MADS-complexes, which determine the identity of the f loral organs.

Peroxidase-mimicking nanozyme with surface-dispersed Pt atoms for the colorimetric lateral flow immunoassay of C-reactive protein.

Platinum-containing nanozymes with peroxidase-mimicking activity (PMA) have found a broad application in bioanalytical methods and are potentially able to compete with enzymes as the labels. However, traditionally used methods for the synthesis of nanozymes result in only a small fraction of surface-exposed Pt atoms, which participate in catalysis. To overcome this limitation, we propose a new approach for the synthesis of nanozymes with the efficient dispersion of Pt atoms on particles' surfaces.

Kaiso Regulates DNA Methylation Homeostasis.

Gain and loss of DNA methylation in cells is a dynamic process that tends to achieve an equilibrium. Many factors are involved in maintaining the balance between DNA methylation and demethylation. Previously, it was shown that methyl-DNA protein Kaiso may attract NCoR, SMRT repressive complexes affecting histone modifications.

Mechanism of Guanosine Triphosphate Hydrolysis by the Visual Proteins Arl3-RP2: Free Energy Reaction Profiles Computed with Ab Initio Type QM/MM Potentials.

We report the results of calculations of the Gibbs energy profiles of the guanosine triphosphate (GTP) hydrolysis by the Arl3-RP2 protein complex using molecular dynamics (MD) simulations with ab initio type QM/MM potentials. The chemical reaction of GTP hydrolysis to guanosine diphosphate (GDP) and inorganic phosphate (Pi) is catalyzed by GTPases, the enzymes, which are responsible for signal transduction in live cells. A small GTPase Arl3, catalyzing the GTP → GDP reaction in complex with the activating protein RP2, constitute an essential part of the human vision cycle.

Pathogenesis-Related Genes of PR1, PR2, PR4, and PR5 Families Are Involved in the Response to Infection in Garlic ( L.).

Plants of the genus developed a diversity of defense mechanisms against pathogenic fungi of the genus , including transcriptional activation of pathogenesis-related (PR) genes. However, the information on the regulation of PR factors in garlic ( L.) is limited.

An engineered cellobiohydrolase I for sustainable degradation of lignocellulosic biomass.

This study provides computational-assisted engineering of the cellobiohydrolase I (CBH-I) from Penicillium verruculosum with simultaneous enhanced thermostability and tolerance in ionic liquids, deep eutectic solvent, and concentrated seawater without affecting its wild-type activity. Engineered triple variant CBH-I R1 (A65R-G415R-S181F) showed 2.48-fold higher thermostability in terms of relative activity at 65°C after 1 h of incubation when compared with CBH-I wild type.

[Molecular mechanism of chromogenic substrate hydrolysis in the active site of human carboxylesterase-1].

Human carboxylesterases are involved in the protective processes of detoxification during the hydrolytic metabolism of xenobiotics. Knowledge of the molecular mechanisms of substrates hydrolysis in the enzymes active site is necessary for the rational drug design. In this work, the molecular mechanism of the hydrolysis reaction of para-nitrophenyl acetate in the active site of human carboxylesterase was determined using modern methods of molecular modeling.

Growth of Mesenchymal Stem Cells on Poly(3-Hydroxybutyrate) Scaffolds Loaded with Simvastatin.

We studied the effect of porous composite scaffolds based on poly(3-hydroxybutyrate) (PHB) loaded with simvastatin on the growth and differentiation of mesenchymal stem cells. The scaffolds have a suitable microstructure (porosity and pore size) and physicochemical properties to support the growth of mesenchymal stem cells. Scaffold loading with simvastatin suppressed cell growth and increased alkaline phosphatase activity, which can attest to their osteoinductive properties.

Photoinactivation of mycobacteria to combat infection diseases: current state and perspectives.

The spread of multi-drug-resistant bacterial strains causing serious infectious diseases dictates the development of new approaches to combat these diseases. In addition to drug resistance, the important causative agent of tuberculosis (Mycobacterium tuberculosis (Mtb)) is able to persist asymptomatically in individuals for many years, causing latent forms of tuberculosis. In such a dormant state, Mtb cells are also resistant to known antibiotics.

Boronic Acids as Prospective Inhibitors of Metallo-β-Lactamases: Efficient Chemical Reaction in the Enzymatic Active Site Revealed by Molecular Modeling.

Boronic acids are prospective compounds in inhibition of metallo-β-lactamases as they form covalent adducts with the catalytic hydroxide anion in the enzymatic active site upon binding. We compare this chemical reaction in the active site of the New Delhi metallo-β-lactamase (NDM-1) with the hydrolysis of the antibacterial drug imipenem. The nucleophilic attack occurs with the energy barrier of 14 kcal/mol for imipenem and simultaneously upon binding a boronic acid inhibitor.

Bioconversion of Renewable Plant Biomass. Second-Generation Biofuels: Raw Materials, Biomass Pretreatment, Enzymes, Processes, and Cost Analysis.

The review discusses various aspects of renewable plant biomass conversion and production of the second-generation biofuels, including the types of plant biomass, its composition and reaction ability in the enzymatic hydrolysis, and various pretreatment methods for increasing the biomass reactivity. Conversion of plant biomass into sugars requires the use of a complex of enzymes, the composition of which should be adapted to the biomass type and the pretreatment method. The efficiency of enzymatic hydrolysis can be increased by optimizing the composition of the enzymatic complex and by increasing the catalytic activity and operational stability of its constituent enzymes.

CRISPR/Cas Genome Editing in Filamentous Fungi.

The review describes the CRISPR/CAS system and its adaptation for the genome editing in filamentous fungi commonly used for production of enzyme complexes, enzymes, secondary metabolites, and other compounds used in industrial biotechnology and agriculture. In the second part of this review, examples of the CRISPR/CAS technology application for improving properties of the industrial strains of fungi from the Trichoderma, Aspergillus, Penicillium, and other genera are presented. Particular attention is given to the efficiency of genome editing, as well as system optimization for specific industrial producers.

Small Noncoding RNAs and Their Role in the Pathogenesis of Mycobacterium tuberculosis Infection.

Mycobacterium tuberculosis possesses a significant arsenal of strategies to combat immune defense of the host organism. Small noncoding RNAs, which constitute the largest group of regulatory RNAs, play an important role in the host-pathogen interactions and represent one of the levels of the regulation of interactions of microbial cells with their environment. The regulatory role of small RNAs in pathogenic bacteria is essential when rapid adaptation to the changing environmental conditions with further synchronization of metabolic reactions are required to ensure microbial survival and infection progression.

Metallo-β-Lactamases: Influence of the Active Site Structure on the Mechanisms of Antibiotic Resistance and Inhibition.

The review focuses on bacterial metallo-β-lactamases (MβLs) responsible for the inactivation of β-lactams and associated antibiotic resistance. The diversity of the active site structure in the members of different MβL subclasses explains different mechanisms of antibiotic hydrolysis and should be taken into account when searching for potential MβL inhibitors. The review describes the features of the antibiotic inactivation mechanisms by various MβLs studied by X-ray crystallography, NMR, kinetic measurements, and molecular modeling.

Autotolerant ceruloplasmin based biocathodes for implanted biological power sources.

High-performance autotolerant bioelectrodes should be ideally suited to design implantable bioelectronic devices. Because of its high redox potential and ability to reduce oxygen directly to water, human ceruloplasmin, HCp, the only blue multicopper oxidase present in human plasma, appears to be the ultimate biocatalyst for oxygen biosensors and also biocathodes in biological power sources. In comparison to fungal and plant blue multicopper oxidases, e.