Acta Naturae最新文献

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.

Pyridoxal 5'-phosphate-dependent enzymes play a crucial role in nitrogen metabolism. Carbonyl compounds, such as O-substituted hydroxylamines, stand out among numerous specific inhibitors of these enzymes, including those of practical importance, because they react with pyridoxal 5'-phosphate in the active site of the enzymes to form stable oximes. O-substituted hydroxylamines mimic the side group of amino acid substrates, thus providing highly potent and specific inhibition of the corresponding enzymes. The interaction between D-amino acid transaminase from bacterium Haliscomenobacter hydrossis and 3-aminooxypropionic acid was studied in the present work. The structural and spectral analyses of the complex of this transaminase with 3-aminooxypropionic acid allowed us to clarify some features of the organization and functioning of its active site and illustrate one of the mechanisms of inhibition by the specific substrate, D-glutamic acid.

Low-grade gliomas are divided into two main genetic phenotypes based on the presence or absence of mutations in the isocitrate dehydrogenase (IDH) genes. The mutated IDH phenotype (IDHmut), in contrast to the wild-type phenotype (IDHwt), is characterized by a more positive response to pharmacological intervention and a significantly longer survival time. In this study, we analyzed the differential co-expression of 225,000 microRNA-mRNA pairs at the level of correlations between microRNA levels and their potential mRNA targets. Analysis of the associative relationships of individual representatives of the selected pairs revealed that the level of mRNAs encoded by the ELN, ARL4C, C9orf64, PLAT, and FKBP9 genes associated with aggressive progression of glioma was increased in the IDHwt group. Meanwhile, the levels of miRNA-182, miRNA-455, and miRNA-891a associated with the negative prognosis in glioma were generally increased in the IDHmut group. Most (16/21) of the detected 21 microRNA-mRNA pairs with significant difference in regulation between IDHwt and IDHmut glioma samples had a weak or moderate positive correlation in IDHmut samples and a negative correlation in IDHwt samples. Therefore, our findings indicate that glioma samples from the IDHmut group with a positive prognosis potentially have a significantly less pronounced ability to microRNA-mediated regulation. We further suggest that such physiological disorders can lead to reduced tumor viability, resulting in an increased ability of the host to resist the spread of a malignant transformation of this genetic phenotype.

Fermented dairy products are produced using starter cultures. They ferment milk to create products with a certain texture, aroma, and taste. However, the lactic acid bacteria used in this production are prone to bacteriophage infection. We examined the genomes of two newly discovered bacteriophage species that were isolated from cheese whey during the cheesemaking process. We have determined the species and the lytic spectrum of these bacteriophages. Phages vL_20A and vL_296 were isolated using lactococcal indicator cultures. They have unique lytic spectra: of the 21 possible identified host bacteria, only four are shared amongst them. The vL_20A and vL_296 genomes comprise linear double-stranded DNA lengths with 21,909 and 22,667 nucleotide pairs, respectively. Lactococcus phage bIL67 (ANI 93.3 and 92.6, respectively) is the closest to the phages vL_20A and vL_296. The analysis of the CRISPR spacers in the genomes of starter cultures did not reveal any phage-specific vL_20A or vL_296 among them. This study highlights the biodiversity of L. lactis phages, their widespread presence in dairy products, and their virulence. However, the virulence of phages is balanced by the presence of a significant number of bacterial strains with different sensitivities to phages in the starter cultures due to the bacterial immune system.

Accumulation of neurotoxic aggregates of beta-amyloid peptides (Aβ) is a hallmark of Alzheimer's disease (AD) progression. Post-translational modifications (PTMs) increase Aβ aggregation and cytotoxicity, and the content of specific Aβ proteoforms is elevated in senile plaques of AD patients. The pathophysiological mechanisms of aggregate formation and the role of Aβ proteoforms need thorough study both to understand the role played by specific processes in the initiation of neuronal degradation and to find effective preventive means of therapeutic action. The present work investigates the dynamics of accumulation of phosphorylated serine-8 proteoform Aβ (pSer8-Aβ) using the 5xFAD mouse amyloid model. Aβ samples from human cerebrospinal fluid (CSF) and brain were also investigated. Western blot studies using 1E4E11 and 4G8 antibodies showed that accumulation of pSer8-Aβ in mouse brain starts as early as at the age of 3 months and reaches a maximum by the age of 14-17 months, which is generally similar to the dynamics of accumulation of the total pool of Aβ peptides. The pSer8-Aβ level in human CSF in AD patients can reach ~ 1-10% of the total amount of Aβ. Mass spectrometric analysis showed that Aβ phosphorylation by the Ser8, Tyr10, and Ser26 residues in brain tissues, as well as phosphorylation of the APP by Thr719 residue, is possible. These findings support the assumption that pSer8-Aβ proteoforms are involved in amyloidosis in AD. KEYWORDS Beta-amyloid, mass spectrometry, Alzheimer's disease, phosphorylation.

Sporadic Alzheimer's disease (sAD) is the most common of neurodegenerative disorders. The lack of effective therapy indicates that the mechanisms of sAD development remain poorly understood. To investigate this pathology in animals, intracerebroventricular injection of β-amyloid peptide (Aβ) using a Hamilton syringe, either during stereotactic surgery or through a pre-implanted cannula, is used. In this study, we analyzed the effect of chronic cannula implantation on the severity of Aβ effects at the behavioral, histological, and biochemical levels. The results showed that the local damage to neural tissue caused by cannulation has no bearing on the effect of Aβ on animal behavior and the microglial parameters of the unilateral hippocampus two weeks after the Aβ administration. However, cannula implantation fundamentally modifies some biochemical markers of the oxidative stress that occurs in the brain tissue in response to Aβ administration. Thus, the presence of a cannula reduces the severity of the Aβ impact on the levels of peroxidized lipids and glutathione two- and 10-fold, respectively. It is important to note that the detected changes are chronic and systemic. This is known because the homogenate of the entire contralateral (in relation to the cannula implantation site) hemisphere was analyzed, and the analysis was performed two weeks after implantation. At the same time, cannulation does not affect the rate of reactive oxygen species production. The obtained data indicate that chronic implantation of a cannula into the brain of experimental animals fundamentally distorts some parameters of oxidative stress in the neural tissue, which are widely used to assess the severity of experimental Alzheimer's-type diseases.

5'-Noraristeromycin as a racemic mixture of enantiomers was found to exhibit a pronounced cytotoxic effect on leukemia cells; IC₅₀ for the Jurkat, K562, and THP-1 cell lines was 7.3, 1.3, and 3.7 μM, respectively. The general toxicity of 5'-noraristeromycin was studied in experiments on white mice upon single-dose intragastric administration; toxicometric parameters were determined, and the clinical and pathomorphological presentation of acute intoxication was studied. LD₅₀ of the substance was shown to be 63.2 (52.7÷75.8) mg/kg; LD16, 44.7 mg/kg, and LD84, 89.4 mg/kg. Administration of the substance at a dose within the studied dose range is accompanied by systemic damage to the internal organs and tissues of the experimental animals.

In this analytical review, we explore the potential impact of the rapid proliferation of artificial intelligence (AI) tools on the biosphere and noosphere, suggesting that the trend may lead to a transformative event that could be termed "Human-AI integration." We argue that this integration could give rise to novel lifeforms, associations, and hierarchies, resulting in competitive advantages and increased complexity of structural organizations within both the biosphere and noosphere. Our central premise emphasizes the importance of human-AI integration as a global adaptive response crucial for our civilization's survival amidst a rapidly changing environment. The convergence may initially manifest itself through symbiotic, endosymbiotic, or other mutualistic relationships, such as domestication, contingent on the rate at which AI systems achieve autonomy and develop survival instincts akin to those of biological organisms. We investigate potential drivers of these scenarios, addressing the ethical and existential challenges arising from the AI-driven transformation of the biosphere and noosphere, and considering potential trade-offs. Additionally, we discuss the application of complexity and the balance between competition and cooperation to better comprehend and navigate these transformative scenarios.

Poly(ADP-ribose) polymerase (PARP) is the key enzyme in polyADP-ribosylation, one of the main post-translational modifications. This enzyme is abundant in eukaryotic organisms. However, information on the PARP structure and its functions in members of the Fungi kingdom is very limited. In this study, we performed a bioinformatic search for homologs of PARP and its antagonist, PARG, in the genomes of four Fusarium strains using their whole-genome sequences annotated and deposited in databases. The F. graminearum PH-1, F. proliferatum ET-1, and F. oxysporum Fo47 strains were shown to possess a single homolog of both PARP and PARG. In addition, the F. oxysporum f. sp. lycopersici strain 4287 contained four additional proteins comprising PARP catalytic domains whose structure was different from that of the remaining identified homologs. Partial nucleotide sequences encoding the catalytic domains of the PARP and PARG homologs were determined in 11 strains of 9 Fusarium species deposited in all-Russian collections, and the phylogenetic properties of the analyzed genes were evaluated. In the toxigenic F. graminearum strain, we demonstrated up-regulation of the gene encoding the PARP homolog upon culturing under conditions stimulating the production of the DON mycotoxin, as well as up-regulation of the gene encoding PARG at later stages of growth. These findings indirectly indicate involvement of the polyADP-ribosylation system in the regulation of the genes responsible for DON biosynthesis.

Cancer is a major global health problem. The type of malignant neoplasm and the potency of the immune response against tumors are two of the key factors influencing the outcome of the disease. The degree of tumor infiltration by lymphocytes plays an important role in antitumor response development, generally correlating with a favorable prognosis of treatment for certain cancers. We analyzed the abundance of tumor-infiltrating B cells (TIBs) in solid tumors of different cancers. TIBs were shown to be more abundant in colon and sigmoid colon cancer samples compared with cecal, rectal, and kidney cancer samples. The median and interquartile range of the TIB fraction were 11.5% and 4-20% in colon cancer, 6% and 3-11% in sigmoid colon cancer, 2.7% and 0.7-3.7% in cecal cancer, 2.5% and 0.9-3.6% in rectal cancer, 1.4% and 1.0-2.3% in kidney cancer, and 3.0% and 1.8-12% in lung cancer, respectively. However, there were no significant differences in the abundance of TIBs among samples at different stages of the cancer. Hence, investigation of the B cell response in colon cancer is of particular interest, since increased quantities of TIBs may indicate the existence of immunogenic tumor markers or the cell-cell interactions involved in disease progression. We believe that studying the diversity of TIBs in colon cancer will increaseour understanding of the mechanisms of the disease, contributing to the identification of new molecular targets for targeted oncotherapy.