High heterogeneity of cross-reactive immunoglobulins in multiple sclerosis presumes combining of B-cell epitopes for diagnostics: a case-control study.

Background: Multiple sclerosis (MS) is a neuroinflammatory disease triggered by a combination of genetic traits and external factors. Autoimmune nature of MS is proven by the identification of pathogenic T cells, but the role of autoantibody-producing B cells is less clear. A comprehensive understanding of the development of neuroinflammation and the identification of targeted autoantigens are crucial for timely diagnosis and appropriate treatment.

Non-conventional toxin WTX and its disulfide-fixed synthetic fragments: Interaction with nicotinic acetylcholine receptors and reduction of blood pressure.

Non-conventional snake venom toxins, such as WTX from the cobra Naja kaouthia, are three-finger proteins containing a fifth disulfide bond in the N-terminal polypeptide loop I and inhibiting α7 and muscle-type nicotinic acetylcholine receptors (nAChRs). Because the central polypeptide loop II of non-conventional toxins plays an important role in their biological activity, we synthesized several WTX loop II fragments with two cysteine residues added at the N- and C-termini and oxidized to form a disulfide bond. The inhibition by peptides of several nAChRs subtypes was investigated using different methods and the effects of peptides on the rat arterial pressure and heart rate were analyzed.

Cyclic vinyl sulfones activate NRF2 to protect from oxidative stress-induced programmed necrosis.

The NRF2 transcriptional factor is a member of cellular stress response machinery and is activated in response to oxidative stress caused either by cellular homeostasis imbalance or by environmental challenges. NRF2 levels are stringently controlled by rapid and continuous proteasomal degradation. KEAP1 is a specific NRF2 binding protein that acts as a bridge between NRF2 and the E3 ligase Cullin-3.

Formation of the Native Topology of a Protein is due to the "Conserved but Non-Functional" Residues: A Case of Apomyoglobin Folding.

This paper is dedicated to the memory of Oleg B. Ptitsyn (1929-1999) and presents an answer to his question: "What is the role of conserved non-functional residues in protein folding?". This answer follows from the experimental works of three labs.

Phylogenetic Insights into H7Nx Influenza Viruses: Uncovering Reassortment Patterns and Geographic Variability.

Influenza A viruses (IAVs), which belong to the Orthomyxoviridae family, are RNA viruses characterized by a segmented genome that allows them to evolve and adapt rapidly. These viruses are mainly transmitted by wild waterfowl. In this study, we investigated the evolutionary processes of H7Nx (H7N1, H7N2, H7N3, H7N4, H7N5, H7N6, H7N7, H7N8, H7N9) viruses, which pose a significant pandemic risk due to the known cases of human infection and their potential for rapid genetic evolution and reassortment.

Climate Response and Radial Growth Dynamics of Pedunculate Oak ( L.) Plus Trees and Their Half-Sib Progeny in Periods of Severe Droughts in the Forest-Steppe Zone of Eastern Europe.

The dendrochronological parameters of 97 pedunculate oak ( L.) trees including 20 plus trees (142-year-old on average) and four half-sib families for four of them were analyzed considering also specifically years of the most severe droughts that were identified using average monthly air temperature and precipitation data. The tree-ring width (TRW) was mostly affected by air temperature that had the largest cross-dating indices (CDI), up to 78% maximum.

Discovery of Novel Thanatin-like Antimicrobial Peptides from Bean Bug .

Endogenous antimicrobial peptides (AMPs) are evolutionarily ancient molecular factors of innate immunity that play a key role in host defense. The study of the diversity of animal defense peptides has important applications in the context of the growing global antimicrobial resistance. In this study using a transcriptome mining approach, we found three novel thanatin-like β-hairpin AMPs in the bean bug , named Rip-2, Rip-3, and Rip-4.

Towards Aptamer-Targeted Drug Delivery to Brain Tumors: The Synthesis of Ramified Conjugates of an EGFR-Specific Aptamer with MMAE on a Cathepsin B-Cleavable Linker.

Targeted delivery of chemotherapeutic agents is a well-established approach to cancer therapy. Antibody-drug conjugates (ADCs) typically carry toxic payloads attached to a tumor-associated antigen-targeting IgG antibody via an enzyme-cleavable linker that releases the drug inside the cell. Aptamers are a promising alternative to antibodies in terms of antigen targeting; however, their polynucleotide nature and smaller size result in a completely different PK/PD profile compared to an IgG.

Immunomodulatory Effects of the Tobacco Defensin NaD1.

Defensins are important components of the innate plant immune system, exhibiting antimicrobial activity against phytopathogens, as well as against fungi pathogenic to humans. Along with antifungal activity, plant defensins are also capable of influencing various immune processes, but not much is known about these effects. In this study, we investigated the immunomodulatory effects of the tobacco defensin NaD1, which possesses a pronounced antifungal activity.

Computational Prediction and Structural Analysis of α-Hairpinins, a Ubiquitous Family of Antimicrobial Peptides, Using the Cysmotif Searcher Pipeline.

Background: α-Hairpinins are a family of antimicrobial peptides, promising antimicrobial agents, which includes only 12 currently revealed members with proven activity, although their real number is supposed to be much higher. α-Hairpinins are short peptides containing four cysteine residues arranged in a specific Cys-motif. These antimicrobial peptides (AMPs) have a characteristic helix-loop-helix structure with two disulfide bonds.

Forced Overexpression and Knockout Analysis of SLC30A and SLC39A Family Genes Suggests Their Involvement in Establishing Resistance to Cisplatin in Human Cancer Cells.

The metabolism of zinc and manganese plays a pivotal role in cancer progression by mediating cancer cell growth and metastasis. The SLC30A family proteins and mediate the efflux of zinc, manganese, and probably other transition element ions outside the cytoplasm to the extracellular space or into intracellular membrane compartments. The SLC39A family members and are their functional antagonists that transfer these ions into the cytoplasm.

Resveratrol Inhibits Nucleosome Binding and Catalytic Activity of PARP1.

The natural polyphenol resveratrol is a biologically active compound that interacts with DNA and affects the activity of some nuclear enzymes. Its effect on the interaction between nucleosomes and poly(ADP-ribose) polymerase-1 (PARP1) and on the catalytic activity of PARP1 was studied using Western blotting, spectrophotometry, electrophoretic mobility shift assay, and single particle Förster resonance energy transfer microscopy. Resveratrol inhibited PARP1 activity at micro- and sub-micromolar concentrations, but the inhibitory effect decreased at higher concentrations due to the aggregation of the polyphenol.

A New Approach of Detecting Fusion Oncogenes by RNA Sequencing Exon Coverage Analysis.

Background: In clinical practice, various methods are used to identify gene rearrangements in tumor samples, ranging from "classic" techniques, such as IHC, FISH, and RT-qPCR, to more advanced highly multiplexed approaches, such as NanoString technology and NGS panels. Each of these methods has its own advantages and disadvantages, but they share the drawback of detecting only a restricted (although sometimes quite extensive) set of preselected biomarkers. At the same time, whole transcriptome sequencing (WTS, RNAseq) can, in principle, be used to detect gene fusions while simultaneously analyzing an incomparably wide range of tumor characteristics.

Multiomics analysis of Staphylococcus aureus ST239 strains resistant to virulent Herelleviridae phages.

In the context of the antimicrobial therapy crisis, the significance of studying and implementing alternative treatment methods, particularly phage therapy, is increasingly evident. This study aimed to investigate the resistance of clinical Staphylococcus aureus ST239 strains to Herelleviridae phages through comparative genomics, transcriptomics, and proteomics. Analysis of resistant and sensitive S.

Animal Venoms and Their Components: Molecular Mechanisms of Action V 2.0.

The adaptation of living beings to natural environmental conditions occurs as a result of various adaptive mechanisms [...

Immunogenicity and Efficacy of Combined mRNA Vaccine Against Influenza and SARS-CoV-2 in Mice Animal Models.

The combined or multivalent vaccines are actively used in pediatric practice and offer a series of advantages, including a reduced number of injections and visits to the doctor, simplicity of the vaccination schedule and minimization of side effects, easier vaccine monitoring and storage, and lower vaccination costs. The practice of widespread use of the combined vaccines has shown the potential to increase vaccination coverage against single infections. The mRNA platform has been shown to be effective against the COVID-19 pandemic and enables the development of combined vaccines.

In Search of the Role of Three-Finger Starfish Proteins.

Three-finger proteins (TFPs), or Ly6/uPAR proteins, are characterized by the beta-structural LU domain containing three protruding "fingers" and stabilized by four conserved disulfide bonds. TFPs were initially characterized as snake alpha-neurotoxins, but later many studies showed their regulatory roles in different organisms. Despite a known expression of TFPs in vertebrates, they are poorly studied in other taxa.

Ppn2 Polyphosphatase Improves the Ability of to Grow in Mild Alkaline Medium.

Inorganic polyphosphates and respective metabolic pathways and enzymes are important factors for yeast active growth in unfavorable conditions. However, particular proteins of polyphosphate metabolism remain poorly explored in this context. Here we report biochemical and transcriptomic characterization of the CRN/PPN2 yeast strain (derived from Ppn1-lacking CRN strain) overexpressing poorly studied Ppn2 polyphosphatase.

Mesenchymal Properties of Glioma Cell Lines.

Screening of cell surface markers of three glioma cell lines (astrocytoma 1321N1, glioblastoma T98g, and glioblastoma astrocytoma U373 MG) was performed. Glioma cells expressed common mesenchymal cell markers, although the expression levels varied between the cell lines. The expression of proneural markers and glioma cancer stem cell markers was very low and also varied.

Antigen Presentation in an Artificial and Cell Membrane: Blood Group A Glycan Recognition.

Glycosphingolipids (GSL) are functionally important components of the cell membrane and recognition of their glycan "head" by the immune system is a key part of normal and pathological processes. Recognition of glycolipid antigens on a living cell, their structure, "context" (microenvironment and clustering), presentation including orientation and distance from the plasma membrane, as well as molecular dynamics are important. GSL antigens are targets for the development of anticancer vaccines and therapeutic antibodies, therefore, control of the presentation of their glycans by synthetic methods opens up new possibilities in medicine.

The completing of the second meiotic division by MII mouse oocytes correlates with the positioning of F-actin and mitochondria in the ooplasm.

Actin filaments play an essential role in the process of oocyte maturation and completion of meiosis. However, whether the localization of F-actin in the ooplasm is associated with normal completion of the second meiotic division remains unclear. Mitochondrial distribution is another important parameter correlating directly with MII oocyte capacity to finalize meiosis.