Acta Naturae最新文献

Cancer is one of the leading causes of death worldwide. Traditional cancer treatments include surgery, radiotherapy, and chemotherapy, as well as combinations of these treatments. Despite significant advances in these fields, the search for innovative ways to treat malignant tumors, including the application of oncolytic viruses, remains relevant. One such virus is the vesicular stomatitis virus (VSV), which possess a number of useful oncolytic properties. However, VSV-based drugs are still in their infancy and are yet to be approved for clinical use. This review discusses the mechanisms of oncogenesis, the antiviral response of tumor and normal cells, and markers of tumor cell resistance to VSV virotherapy. In addition, it examines methods for producing and arming recombinant VSV and provides examples of clinical trials. The data presented will allow better assessment of the prospects of using VSV as an oncolytic.

Embryonic stem cells (ESCs) hold great promise for regenerative medicine thanks to their ability to self-renew and differentiate into somatic cells and the germline. ESCs correspond to pluripotent epiblast - the tissue from which the following three germ layers originate during embryonic gastrulation: the ectoderm, mesoderm, and endoderm. Importantly, ESCs can be induced to differentiate toward various cell types by varying culture conditions, which can be exploited for in vitro modeling of developmental processes such as gastrulation. The classical model of gastrulation postulates that mesoderm and endoderm specification is made possible through the FGF-, BMP-, Wnt-, and Nodal-signaling gradients. Hence, it can be expected that one of these signals should direct ESC differentiation towards specific germ layers. However, ESC specification appears to be more complicated, and the same signal can be interpreted differently depending on the readout. In this research, using chemically defined culture conditions, homogeneous naïve ESCs as a starting cell population, and the Foxa2 gene-driven EGFP reporter tool, we established a robust model of definitive endoderm (DE) specification. This in vitro model features formative pluripotency as an intermediate state acquired by the epiblast in vivo shortly after implantation. Despite the initially homogeneous state of the cells in the model and high Activin concentration during endodermal specification, there remains a cell subpopulation that does not reach the endodermal state. This simple model developed by us can be used to study the origins of cellular heterogeneity during germ layer specification.

The replenishment of our stock of substances that possess a therapeutic potential is an important objective in modern biomedicine. Despite the important advances achieved in chemical synthesis, the natural diversity of organisms and microorganisms remains an important source of biologically active compounds. Here, we report the results of our study of a unique collection containing more than 3,000 samples of yeasts found on the Kamchatka Peninsula, the Kuril Islands, and Sakhalin Island, Russia. Since yeast and bacteria coexist in a variety of habitats and can interact with each other, we analyzed the antibacterial activity of the collection of yeast strains towards E. coli cells using a fluorescent bacterial reporter. It was uncovered that the Sakhalin strains for the most part stimulate bacterial growth, while most of the strains found on the Kamchatka Peninsula possess inhibitory properties. Moreover, the samples with the most pronounced antibacterial activity, identified as members of the genus Cryptococcus (Naganishia), were found in a gorge in the vicinity of Pauzhetka village on the Kamchatka Peninsula on wormwood (Artemisia vulgaris) and thistle (Onopordum acanthium). Our data indicate that the combination of a plant and its growth site is important for the emergence of yeast strains capable of secreting antibacterial compounds.

Analytical electron microscopy techniques, including energy-dispersive X-ray spectroscopy (EDX) and electron energy-loss spectroscopy (EELS), are employed in materials science and biology to visualize and chemically map diverse elements. This review presents cases of successful identification of nucleic acids in cells and in DNA- and RNA-containing viruses that use the chemical element phosphorus as a marker.

The growing incidence of infections caused by antibiotic-resistant strains of pathogens is one of the key challenges of the 21^st century. The development of novel technological platforms based on single-cell analysis of antibacterial activity at the whole-microbiome level enables the transition to massive screening of antimicrobial agents with various mechanisms of action. The microbiome of wild animals remains largely underinvestigated. It can be considered a natural reservoir of biodiversity for antibiotic discovery. Here, the Staphylococcus pseudintermedius E18 strain was isolated from the oral microbiome of a raccoon dog (Nyctereutes procyonoides) using a microfluidic ultrahigh-throughput screening platform. S. pseudintermedius E18 efficiently inhibited the growth of pathogenic methicillin-resistant Staphylococcus aureus (MRSA). It was established that the main active substance of the S. pseudintermedius E18 strain was a bacteriocin with a molecular weight of 27 kDa. The identified bacteriocin had a high positive charge and an extremely narrow spectrum of activity. Bacteriocin S. pseudintermedius E18 was inactivated by elevated temperature, proteinase K, and EDTA. Further investigation on the structure of the bacteriocin produced by S. pseudintermedius E18 will provide a comprehensive understanding of its mechanism of action, which will open up prospects for developing novel DNA-encoded antimicrobials.

Amyotrophic lateral sclerosis (ALS) is a severe disease of the central nervous system (CNS) characterized by motor neuron damage leading to death from respiratory failure. The neurodegenerative process in ALS is characterized by an accumulation of aberrant proteins (TDP-43, SOD1, etc.) in CNS cells. The trans-synaptic transmission of these proteins via exosomes may be one of the mechanisms through which the pathology progresses. The aim of this work was to study the effect of an intraventricular injection of exosomes obtained from the cerebrospinal fluid (CSF) of ALS patients on the motor activity and CNS pathomorphology of mice. The exosomes were obtained from two ALS patients and a healthy donor. Exosome suspensions at high and low concentrations were injected into the lateral brain ventricles of male BALB/c mice (n = 45). Motor activity and physiological parameters were evaluated twice a month; morphological examination of the spinal cord was performed 14 months after the start of the experiment. Nine months after administration of exosomes from the ALS patients, the animals started exhibiting a pathological motor phenotype; i.e., altered locomotion with paresis of hind limbs, coordination impairment, and increasing episodes of immobility. The motor symptoms accelerated after administration of a higher concentration of exosomes. The experimental group showed a significant decrease in motor neuron density in the ventral horns of the spinal cord, a significant increase in the number of microglial cells, and microglia activation. The TDP43 protein in the control animals was localized in the nuclei of motor neurons. TDP43 mislocation with its accumulation in the cytoplasm was observed in the experimental group. Thus, the triggering effect of the exosomal proteins derived from the CSF of ALS patients in the development of a motor neuron pathology in the experimental animals was established. This confirms the pathogenetic role of exosomes in neurodegenerative progression and makes it possible to identify a new target for ALS therapy.

The gradually increasing age of the world population implies that the prevalence of neurodegenerative diseases also continues to rise. These diseases are characterized by a progressive loss of cognitive and motor functions. Parkinson's disease, which involves the gradual death of specialized neural tissue, is a striking example of a neurodegenerative process. The pathomorphological analysis shows that chronic cerebral ischemia is accompanied by extensive complex neurodegeneration; parkinsonism is its clinical manifestation in 20-30% of cases. Although Parkinson's disease and vascular parkinsonism are similar, these two pathologies have fundamentally different etiopathogeneses. But their set of differential diagnosis traits is confined to some features of the neurological status. There currently exist no diagnostic markers for individual neurodegenerative pathologies or the neurodegeneration phenomenon in general. Metabolomic profiling can be a promising means for finding a unique "fingerprint" of the disease. Identifying the biomarkers of various neurodegenerative diseases will help shorten the time to the diagnosis, forecast the course of the disease, and personalize the therapeutic approach. This review summarizes and compares the current concepts of metabolomics research into Parkinson's disease and vascular parkinsonism, as well as the respective animal models.

The secreted human protein SLURP-2 is a regulator of epithelial homeostasis, which enhances the viability and migration of keratinocytes. The targets of SLURP-2 in keratinocytes are nicotinic and muscarinic acetylcholine receptors. This work is devoted to the search for the SLURP-2 functional regions responsible for enhancing keratinocyte viability and migration. We produced synthetic peptides corresponding to the SLURP-2 loop regions and studied their effect on the viability and migration of HaCaT skin keratinocytes using the WST-8 test and scratch-test, respectively. The highest activity was exhibited by a loop II-mimicking peptide that enhanced the viability of keratinocytes and stimulated their migration. The peptide activity was mediated by interactions with α7- and α3β2-nAChRs and suppression of the p38 MAPK intracellular signaling pathway. Thus, we obtained new data that explain the mechanisms underlying SLURP-2 regulatory activity and indicate the promise of further research into loop II-mimicking peptides as prototypes of wound healing drugs.

Living organisms exhibit an impressive ability to expand the basic information encoded in their genome, specifically regarding the structure and function of protein. Two basic strategies are employed to increase protein diversity and functionality: alternative mRNA splicing and post-translational protein modifications (PTMs). Enzymatic regulation is responsible for the majority of the chemical reactions occurring within living cells. However, plants redox metabolism perpetually generates reactive byproducts that spontaneously interact with and modify biomolecules, including proteins. Reactive carbonyls resulted from the oxidative metabolism of carbohydrates and lipids carbonylate proteins, leading to the latter inactivation and deposition in the form of glycation and lipoxidation end products. The protein nitrosylation caused by reactive nitrogen species plays a crucial role in plant morphogenesis and stress reactions. The redox state of protein thiol groups modified by reactive oxygen species is regulated through the interplay of thioredoxins and glutaredoxins, thereby influencing processes such as protein folding, enzyme activity, and calcium and hormone signaling. This review provides a summary of the PTMs caused by chemically active metabolites and explores their functional consequences in plant proteins.

Dairy production facilities represent a unique ecological niche for bacteriophages of lactic acid bacteria. Throughout evolution, bacteria have developed a wide range of defense mechanisms against viral infections caused by bacteriophages. The CRISPR-Cas system is of particular interest due to its adaptive nature. It allows bacteria to acquire and maintain specific resistance to certain bacteriophages. In this study, we investigated the CRISPR-Cas systems of lactic acid bacteria. Special attention was paid to the specificity of the spacers in CRISPR cassettes. CRISPR-Cas systems were found in the genomes of 43% of the lactic acid bacteria studied. Additionally, only 13.1% of the total number of CRISPR cassette spacers matched bacteriophage genomes, indicating that many predicted spacers either lack known phage targets or are directed against other types of mobile genetic elements, such as plasmids.