Insights into Mechanisms of Damage Recognition and Catalysis by APE1-like Enzymes.

Apurinic/apyrimidinic (AP) endonucleases are the key DNA repair enzymes in the base excision repair (BER) pathway, and are responsible for hydrolyzing phosphodiester bonds on the 5' side of an AP site. The enzymes can recognize not only AP sites but also some types of damaged bases, such as 1,-ethenoadenosine, α-adenosine, and 5,6-dihydrouridine. Here, to elucidate the mechanism underlying such a broad substrate specificity as that of AP endonucleases, we performed a computational study of four homologous APE1-like endonucleases: insect () Rrp1, amphibian () APE1 (xAPE1), fish () APE1 (zAPE1), and human APE1 (hAPE1).

Pairing nanoarchitectonics of oligodeoxyribonucleotides with complex diversity: concatemers and self-limited complexes.

The development of approaches to the design of two- and three-dimensional self-assembled DNA-based nanostructures with a controlled shape and size is an essential task for applied nanotechnology, therapy, biosensing, and bioimaging. We conducted a comprehensive study on the formation of various complexes from a pair of oligonucleotides with two transposed complementary blocks that can be linked through a nucleotide or non-nucleotide linker. A methodology is proposed to prove the formation of a self-limited complex and to determine its molecularity.

Cell Differentiation and Proliferation in the Bone Marrow and Other Organs of 2D2 Mice during Spontaneous Development of EAE Leading to the Production of Abzymes.

The exact cellular and molecular mechanisms of multiple sclerosis and other autoimmune diseases have not been established. Autoimmune pathologies are known to be associated with faults in the immune system and changes in the differentiation profiles of bone marrow stem cells. This study analyzed various characteristics of experimental autoimmune encephalomyelitis (EAE) in 2D2 mice.

Post-Immune Antibodies in HIV-1 Infection in the Context of Vaccine Development: A Variety of Biological Functions and Catalytic Activities.

Unlike many other viruses, HIV-1 is highly variable. The structure of the viral envelope changes as the infection progresses and is one of the biggest obstacles in developing an HIV-1 vaccine. HIV-1 infection can cause the production of various natural autoantibodies, including catalytic antibodies hydrolyzing DNA, myelin basic protein, histones, HIV-integrase, HIV-reverse transcriptase, β-casein, serum albumin, and some other natural substrates.

Multiplex Droplet Digital PCR Assay for Detection of and Genes Amplification in Non-Small Cell Lung Cancer.

Non-small-cell lung cancer (NSCLC), a subtype of lung cancer, remains one of the most common tumors with a high mortality and morbidity rate. Numerous targeted drugs were implemented or are now developed for the treatment of NSCLC. Two genes, and , are among targets for these specific therapeutic agents.

Triazine-Carbosilane Dendrimersomes Enhance Cellular Uptake and Phototoxic Activity of Rose Bengal in Basal Cell Skin Carcinoma Cells.

Background: The search for new formulations for photodynamic therapy is intended to improve the outcome of skin cancer treatment using significantly reduced doses of photosensitizer, thereby avoiding side effects. The incorporation of photosensitizers into nanoassemblies is a versatile way to increase the efficiency and specificity of drug delivery into target cells. Herein, we report the loading of rose bengal into vesicle-like constructs of amphiphilic triazine-carbosilane dendrons (dendrimersomes) as well as biophysical and in vitro characterization of this novel nanosystem.

Comparative Analysis of Exo- and Endonuclease Activities of APE1-like Enzymes.

Apurinic/apyrimidinic (AP)-endonucleases are multifunctional enzymes that are required for cell viability. AP-endonucleases incise DNA 5' to an AP-site; can recognize and process some damaged nucleosides; and possess 3'-phosphodiesterase, 3'-phosphatase, and endoribonuclease activities. To elucidate the mechanism of substrate cleavage in detail, we analyzed the effect of mono- and divalent metal ions on the exo- and endonuclease activities of four homologous APE1-like endonucleases (from an insect (Rrp1), amphibian (xAPE1), fish (zAPE1), and from humans (hAPE1)).

Complete Genome of Sinorhizobium meliloti AK76, a Symbiont of Wild Diploid Medicago lupulina from the Mugodgary Mountain Region.

Sinorhizobium meliloti is a symbiotic bacterial species forming nitrogen-fixing nodules on roots of annual and perennial spp. We report the full genome sequence of S. meliloti strain AK76, an effective symbiont of the wild diploid plant Medicago lupulina grown in the Mugodgary Mountain region, Kazakhstan.

Occurrence and clinical manifestations of tick-borne rickettsioses in Western Siberia: First Russian cases of Rickettsia aeschlimannii and Rickettsia slovaca infections.

Rickettsia sibirica subsp. sibirica is a main agent of tick-borne rickettsioses in Western Siberia, Russia. Recently, the first cases of Rickettsia raoultii infection in patients hospitalized in Novosibirsk Province were described.

A Low-Activity Polymorphic Variant of Human NEIL2 DNA Glycosylase.

Human NEIL2 DNA glycosylase (hNEIL2) is a base excision repair protein that removes oxidative lesions from DNA. A distinctive feature of hNEIL2 is its preference for the lesions in bubbles and other non-canonical DNA structures. Although a number of associations of polymorphisms in the gene were reported, there is little data on the functionality of the encoded protein variants, as follows: only hNEIL2 R103Q was described as unaffected, and R257L, as less proficient in supporting the repair in a reconstituted system.

Amphiphilic Triazine-Phosphorus Metallodendrons Possessing Anti-Cancer Stem Cell Activity.

Dendritic molecules bearing metal complexes in their structure (metallodendrimers and metallodendrons) are considered prospective therapeutic entities. In particular, metallodendrons raise interest as antitumor agents for the treatment of poorly curable or drug-resistant tumors. Herein, we have synthesized amphiphilic triazine-phosphorus dendrons bearing multiple copper (II) or gold (III) complexes on the periphery and a branched hydrophobic fragment at the focal point.

The Blood of the HIV-Infected Patients Contains κ-IgG, λ-IgG, and Bispecific κλ-IgG, Which Possess DNase and Amylolytic Activity.

Though hundreds of thousands of papers are currently being published on HIV/AIDS, only tens of hundreds of them are devoted to the antibodies generated during the disease. Most of these papers discuss antibodies in HIV/AIDS as a diagnostic tool, and some articles describe neutralizing antibodies as a promising treatment. In this paper, we used affinity chromatography and ELISA to isolate natural IgG from the blood of 26 HIV-infected patients.

Polymorphisms in DNA Repair and Xenobiotic Biotransformation Enzyme Genes and Lung Cancer Risk in Coal Mine Workers.

Background: Currently coal mining employs over 7 million miners globally. This occupational setting is associated with exposure to dust particles, heavy metals, polycyclic aromatic hydrocarbons and radioactive radon, significantly increasing the risk of lung cancer (LC). The susceptibility for LC is modified by genetic variations in xenobiotic detoxification and DNA repair capacity.

Application of W-band F electron nuclear double resonance (ENDOR) spectroscopy to distance measurement using a trityl spin probe and a fluorine label.

Recently, Marina Bennati and coworkers (M. Bennati , , 2020, , 373-379., M.

Probing the Dynamics of Cas9 Endonuclease Bound to the sgRNA Complex Using Hydrogen-Deuterium Exchange Mass Spectrometry.

The Cas9 endonuclease is an essential component of the CRISPR-Cas-based genome editing tools. The attainment of high specificity and efficiency of Cas9 during targetted DNA cleavage is the main problem that limits the clinical application of the CRISPR-Cas9 system. A deep understanding of the Cas9 mechanism and its structural-functional relationships is required to develop strategies for precise gene editing.

Do Sputnik V Vaccine-Induced Antibodies Protect Against Seasonal Coronaviruses? Case Study.

There are hundreds of coronaviruses, most of which circulate among animals, yet there are seven types that infect humans. Three of them can cause severe acute respiratory illness-SARS-CoV, SARS-CoV-2, and MERS-CoV. Other HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1 usually cause only mild to moderate upper respiratory tract infections.

Miscoding and DNA Polymerase Stalling by Methoxyamine-Adducted Abasic Sites.

Apurinic/apyrimidinic (AP) sites appear in DNA spontaneously and as intermediates of base excision DNA repair. AP sites are noninstructive lesions: they strongly block DNA polymerases, and if bypassed, the nature of the incorporated dNMP is mostly guided by the interactions within the polymerase-DNA active site. Many DNA polymerases follow the "A-rule", preferentially incorporating dAMP opposite to natural AP sites.

Dendriplex-Impregnated Hydrogels With Programmed Release Rate.

Hydrogels are biocompatible matrices for local delivery of nucleic acids; however, functional dopants are required to provide efficient delivery into cells. In particular, dendrimers, known as robust nucleic acid carriers, can be used as dopants. Herein, we report the first example of impregnating neutral hydrogels with siRNA-dendrimer complexes.

Delimitation of the tick-borne flaviviruses. Resolving the tick-borne encephalitis virus and louping-ill virus paraphyletic taxa.

The tick-borne flavivirus (TBFV) group contains at least 12 members where five of them are important pathogens of humans inducing diseases with varying severity (from mild fever forms to acute encephalitis). The taxonomy structure of TBFV is not fully clarified at present. In particular, there is a number of paraphyletic issues of tick-borne encephalitis virus (TBEV) and louping-ill virus (LIV).

Heteroleptic Pd(II) and Pt(II) Complexes with Redox-Active Ligands: Synthesis, Structure, and Multimodal Anticancer Mechanism.

A series of heteroleptic square-planar Pt and Pd complexes with bis(diisopropylphenyl) iminoacenaphtene (dpp-Bian) and Cl, 1,3-dithia-2-thione-4,5-dithiolate (dmit), or 1,3-dithia-2-thione-4,5-diselenolate (dsit) ligands have been prepared and characterized by spectroscopic techniques, elemental analysis, X-ray diffraction analysis, and cyclic voltammetry (CV). The intermolecular noncovalent interactions in the crystal structures were assessed by density functional theory (DFT) calculations. The anticancer activity of Pd complexes in breast cancer cell lines was limited by their solubility.

Investigation of Chemical Constituents of (Ranunculaceae): Coumarins and Furochromones.

Aqueous-ethanol extracts (70%) from the leaves of Regel. (Ranunculaceae Juss.)-collected from natural populations of Kyrgyzstan-were studied by liquid chromatography with high-resolution mass spectrometry (LC-HRMS).