Acta Naturae最新文献

{"title":"Cooperation and Competition of RNA Secondary Structure and RNA-Protein Interactions in the Regulation of Alternative Splicing.","authors":"M A Vorobeva, D A Skvortsov, D D Pervouchine","doi":"10.32607/actanaturae.26826","DOIUrl":"10.32607/actanaturae.26826","url":null,"abstract":"<p><p>The regulation of alternative splicing in eukaryotic cells is carried out through the coordinated action of a large number of factors, including RNA-binding proteins and RNA structure. The RNA structure influences alternative splicing by blocking <i>cis</i>-regulatory elements, or bringing them closer or farther apart. In combination with RNA-binding proteins, it generates transcript conformations that help to achieve the necessary splicing outcome. However, the binding of regulatory proteins depends on RNA structure and, vice versa, the formation of RNA structure depends on the interaction with regulators. Therefore, RNA structure and RNA-binding proteins are inseparable components of common regulatory mechanisms. This review highlights examples of alternative splicing regulation by RNA-binding proteins, the regulation through local and long-range RNA structures, as well as how these elements work together, cooperate, and compete.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"15 4","pages":"23-31"},"PeriodicalIF":2.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10790352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139484921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Muscarinic Cholinoreceptors in Skeletal Muscle: Localization and Functional Role.","authors":"I V Kovyazina, A A Khamidullina","doi":"10.32607/actanaturae.25259","DOIUrl":"10.32607/actanaturae.25259","url":null,"abstract":"<p><p>The review focuses on the modern concepts of the functions of muscarinic cholinoreceptors in skeletal muscles, particularly, in neuromuscular contacts, and that of the signaling pathways associated with the activation of various subtypes of muscarinic receptors in the skeletal muscles of cold-blooded and warm-blooded animals. Despite the long history of research into the involvement of muscarinic receptors in the modulation of neuromuscular transmission, many aspects of such regulation and the associated intracellular mechanisms remain unclear. Now it is obvious that the functions of muscarinic receptors in skeletal muscle are not limited to the autoregulation of neurosecretion from motor nerve endings but also extend to the development and morphological rearrangements of the synaptic apparatus, coordinating them with the degree of activity. The review discusses various approaches to the study of the functions of muscarinic receptors in motor synapses, as well as the problems arising when interpreting experimental data. The final part of the review is devoted to an analysis of some of the intracellular mechanisms and signaling pathways that mediate the effects of muscarinic agents on neuromuscular transmission.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"15 4","pages":"44-55"},"PeriodicalIF":2.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10790362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139486934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modern Approaches to the Genome Editing of Antibiotic Biosynthetic Clusters in Actinomycetes.","authors":"J A Buyuklyan, Yu V Zakalyukina, I A Osterman, M V Biryukov","doi":"10.32607/actanaturae.23426","DOIUrl":"10.32607/actanaturae.23426","url":null,"abstract":"<p><p>Representatives of the phylum <i>Actinomycetota</i> are one of the main sources of secondary metabolites, including antibiotics of various classes. Modern studies using high-throughput sequencing techniques enable the detection of dozens of potential antibiotic biosynthetic genome clusters in many actinomycetes; however, under laboratory conditions, production of secondary metabolites amounts to less than 5% of the total coding potential of producer strains. However, many of these antibiotics have already been described. There is a continuous \"rediscovery\" of known antibiotics, and new molecules become almost invisible against the general background. The established approaches aimed at increasing the production of novel antibiotics include: selection of optimal cultivation conditions by modifying the composition of nutrient media; co-cultivation methods; microfluidics, and the use of various transcription factors to activate silent genes. Unfortunately, these tools are non-universal for various actinomycete strains, stochastic in nature, and therefore do not always lead to success. The use of genetic engineering technologies is much more efficient, because they allow for a directed and controlled change in the production of target metabolites. One example of such technologies is mutagenesis-based genome editing of antibiotic biosynthetic clusters. This targeted approach allows one to alter gene expression, suppressing the production of previously characterized molecules, and thereby promoting the synthesis of other unknown antibiotic variants. In addition, mutagenesis techniques can be successfully applied both to new producer strains and to the genes of known isolates to identify new compounds.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"15 3","pages":"4-16"},"PeriodicalIF":2.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10615194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71419622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Attenuating Neuronal Autophagy Alleviates Inflammatory Injury in OGDDeprived Co-culture of HT22 with BV2.","authors":"Z W Huang,&nbsp;Y Y Liu,&nbsp;X M Chen,&nbsp;C L Yu,&nbsp;H Y He,&nbsp;Y H Deng","doi":"10.32607/actanaturae.11830","DOIUrl":"https://doi.org/10.32607/actanaturae.11830","url":null,"abstract":"<p><p>Neuronal CX3CL1 suppressed microglial inflammation by binding to its receptor CX3CR1 expressed on microglia. Neuronal autophagy was prominently activated by cerebral ischemia, whereas CX3CL1 expression in autophagic neurons was conversely down-regulated to exacerbate microglial inflammation. Accordingly, this study was meant to investigate whether ischemia-activated microglial inflammation could be repressed by promoting CX3CL1 expression via the attenuation of neuronal autophagy. Immunofluorescence showed that autophagy predominantly occurred in neurons but barely in microglia. Western blot and immunofluorescence demonstrated that attenuating HT22 autophagy significantly increased its CX3CL1 expression and subsequently mitigated the BV2-mediated inflammatory responses, as indicated by decreased inflammatory factors of NF-κB-p65, IL-6, IL-1β, TNF-α, and PGE2. Meanwhile, CCK-8, Nissl staining, and FJC staining showed that an OGD (Oxygen-glycogen deprivation)-created neuronal injury was greatly alleviated by CX3CL1-suppressed microglial inflammation. Contrarily, elevating HT22 autophagy markedly decreased its CX3CL1 expression, which consequently worsened microglial inflammation and the neuronal injury. Our data suggests that attenuating neuronal autophagy may be an effective method to alleviate a microglial inflammatory injury after an ischemic stroke.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"15 3","pages":"91-99"},"PeriodicalIF":2.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10615190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71419618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A DNA Replication Stress-Based Prognostic Model for Lung Adenocarcinoma.","authors":"S Shi, G Wen, C Lei, J Chang, X Yin, X Liu, S Huang","doi":"10.32607/actanaturae.25112","DOIUrl":"10.32607/actanaturae.25112","url":null,"abstract":"<p><p>Tumor cells endure continuous DNA replication stress, which opens the way to cancer development. Despite previous research, the prognostic implications of DNA replication stress on lung adenocarcinoma (LUAD) have yet to be investigated. Here, we aimed to investigate the potential of DNA replication stress-related genes (DNARSs) in predicting the prognosis of individuals with LUAD. Differentially expressed genes (DEGs) originated from the TCGA-LUAD dataset, and we constructed a 10-gene LUAD prognostic model based on DNARSs-related DEGs (DRSDs) using Cox regression analysis. The receiver operating characteristic (ROC) curve demonstrated excellent predictive capability for the LUAD prognostic model, while the Kaplan-Meier survival curve indicated a poorer prognosis in a high-risk (HR) group. Combined with clinical data, the Riskscore was found to be an independent predictor of LUAD prognosis. By incorporating Riskscore and clinical data, we developed a nomogram that demonstrated a capacity to predict overall survival and exhibited clinical utility, which was validated through the calibration curve, ROC curve, and decision curve analysis curve tests, confirming its effectiveness in prognostic evaluation. Immune analysis revealed that individuals belonging to the low-risk (LR) group exhibited a greater abundance of immune cell infiltration and higher levels of immune function. We calculated the immunopheno score and TIDE scores and tested them on the IMvigor210 and GSE78220 cohorts and found that individuals categorized in the LR group exhibited a higher likelihood of deriving therapeutic benefits from immunotherapy intervention. Additionally, we predicted that patients classified in the HR group would demonstrate enhanced sensitivity to Docetaxel using anti-tumor drugs. To summarize, we successfully developed and validated a prognostic model for LUAD by incorporating DNA replication stress as a key factor.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"15 3","pages":"100-110"},"PeriodicalIF":2.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10615186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71419616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromosomal Aberrations As a Biological Phenomenon in Human Embryonic Development.","authors":"A D Ivanova, M L Semenova","doi":"10.32607/actanaturae.25255","DOIUrl":"10.32607/actanaturae.25255","url":null,"abstract":"<p><p>Frequent chromosomal abnormalities are a distinctive feature of early embryonic development in mammals, especially humans. Aneuploidy is considered as a contributing factor to failed embryo implantation and spontaneous abortions. In the case of chromosomal mosaicism, its effect on the potency of embryos to normally develop has not been sufficiently studied. Although, a significant percentage of chromosomal defects in early human embryos are currently believed to be associated with the features of clinical and laboratory protocols, in this review, we focus on the biological mechanisms associated with chromosomal abnormalities. In particular, we address the main events in oocyte meiosis that affects not only the genetic status of an unfertilized oocyte, but also further embryo viability, and analyze the features of first cleavage divisions and the causes of frequent chromosomal errors in early embryonic development. In addition, we discuss current data on self-correction of the chromosomal status in early embryos.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"15 3","pages":"27-36"},"PeriodicalIF":2.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10615189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71419619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein Tyrosine Phosphatase CD45 As an Immunity Regulator and a Potential Effector of CAR-T therapy.","authors":"D V Volkov,&nbsp;V M Stepanova,&nbsp;Y P Rubtsov,&nbsp;A V Stepanov,&nbsp;A G Gabibov","doi":"10.32607/actanaturae.25438","DOIUrl":"https://doi.org/10.32607/actanaturae.25438","url":null,"abstract":"<p><p>The leukocyte common antigen CD45 is a receptor tyrosine phosphatase and one of the most prevalent antigens found on the surface of blood cells. CD45 plays a crucial role in the initial stages of signal transmission from receptors of various immune cell types. Immunodeficiency, autoimmune disorders, and oncological diseases are frequently caused by gene expression disorders and imbalances in CD45 isoforms. Despite extensive research into the structure and functions of CD45, the molecular mechanisms behind its role in transmitting signals from T-cell receptors and chimeric antigen receptors remain not fully understood. It is of utmost importance to comprehend the structural features of CD45 and its function in regulating immune system cell activation to study oncological diseases and the impact of CD45 on lymphocytes and T cells modified by chimeric antigen receptors.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"15 3","pages":"17-26"},"PeriodicalIF":2.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10615191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71419623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tirs dérogatoires de loups en France : évaluation des effets sur les dommages aux troupeaux","authors":"Oksana Grente, Christophe Duchamp, Sarah Bauduin, Simon Chamaillé-Jammes, Nolwenn Drouet-Hoguet, Olivier Gimenez","doi":"10.5852/naturae2023a5","DOIUrl":"https://doi.org/10.5852/naturae2023a5","url":null,"abstract":"L’efficacité des tirs létaux de Loups gris (Canis lupus Linnaeus, 1758) à réduire la prédation de cette espèce sur les troupeaux domestiques est débattue, que cela soit en France ou ailleurs où ces mesures sont appliquées. Dans cet article, nous résumons les résultats de la thèse d’Oksana Grente, réalisée sous la direction de l’Office français de la Biodiversité (OFB) et du Centre d’Écologie fonctionnelle et évolutive (CEFE-CNRS), qui a étudié les effets des tirs dérogatoires de loup sur les attaques aux troupeaux ovins dans l’arc alpin français. Deux approches complémentaires ont été adoptées pour répondre à cette question. Tout d’abord, les données administratives des constats d’attaques ont été analysées en comparant les situations avant et après les tirs. Il s’est avéré que les effets des tirs pouvaient être multiples et dépendaient des contextes dans lesquels ils étaient réalisés. La disparité dans ces résultats reste difficile à comprendre avec les données disponibles. Afin de pallier aux lacunes de l’analyse des tirs réalisés, un modèle théorique a été développé, dans lequel les comportements de prédation du loup ont été simulés selon différentes hypothèses, afin d’améliorer notre compréhension des interactions entre loups, troupeaux et tirs dérogatoires. Les simulations indiquent que le contrôle létal permettait de réduire la déprédation dans les contextes où les troupeaux domestiques sont protégés et moins vulnérables à la prédation que les proies sauvages. La difficulté réside à définir, sur le terrain, les contextes pastoraux et environnementaux qui régissent les comportements de prédation et donc les effets des tirs dérogatoires. L’une des solutions serait d’effectuer des expertises locales au sein de chaque ensemble de surfaces pastorales appartenant au même foyer de déprédation. La thèse propose une méthodologie statistique pour identifier ces groupes de pâturages. Cette méthode permet de tenir compte de l’utilisation des pâturages par les ovins, et donc du taux d’exposition au risque de déprédation qui diffère selon les troupeaux. Pour conclure, les résultats de la thèse invitent à adopter une gestion contextualisée des attaques par les tirs, c’est-à-dire ajustée aux situations locales, en complément des mesures de protection, elles aussi ajustées aux contextes locaux.","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"22 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2023-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81399537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship between the Gene Expression of Adenosine Kinase Isoforms and the Expression of CD39 and CD73 Ectonucleotidases in Colorectal Cancer.","authors":"G A Zhulai,&nbsp;M I Shibaev","doi":"10.32607/actanaturae.11871","DOIUrl":"10.32607/actanaturae.11871","url":null,"abstract":"<p><p>Tumor cells have the capacity to create an adenosine-rich immunosuppressive environment, which can interfere with antitumor immunotherapy. Approaches are currently being developed with a view to suppressing the production of adenosine or its signals. Such approaches include the use of antibodies to inhibit CD39, CD73, and adenosine-receptor antagonists. However, the abundance of enzymatic pathways that control the ATP-adenosine balance, as well as the still poorly understood intracellular adenosine regulation, makes the hoped-for success unlikely. In the present study, the enzyme adenosine kinase (ADK) needed to convert adenosine to adenosine monophosphate, thereby regulating its levels, was investigated. To do so, peripheral blood samples from patients with colorectal cancer (CRC) (<i>n</i> = 31) were collected with blood samples from healthy donors (<i>n</i> = 17) used as controls. ADK gene expression levels and those of its long (<i>ADK-L</i>) and short (<i>ADK-S</i>) isoforms were measured. The relationship between the levels of <i>ADK</i> gene expression and that of <i>CD39</i>, <i>CD73</i>, and <i>A2aR</i> genes was analyzed. It turned out that in the group of CRC patients (stages III-IV), the level of <i>ADK-L</i> mRNA was lower (<i>p</i> < 0.0011) when compared to that of the control. For the first time, an average correlation was found between the level of expression of <i>CD39</i> and <i>ADK-S</i> (<i>r</i> = -0.468 at <i>p</i> = 0.043) and between <i>CD73</i> and <i>ADK-L</i> (<i>r</i> = 0.518 at <i>p</i> = 0.0232) in CRC patients. Flow cytometry was used to assess the content of CD39/CD73-expressing CD8⁺, CD4⁺ and Treg lymphocytes, as well as their relationship with the level of ADK gene expression in CRC patients. But no significant correlations were found.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"15 2","pages":"42-49"},"PeriodicalIF":2.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10395772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9929761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"literammp-9 mRNA Expression and Bridging Fibrosis Progression in Toxic Liver Injury.","authors":"E I Lebedeva,&nbsp;A S Babenka,&nbsp;A T Shchastniy","doi":"10.32607/actanaturae.17856","DOIUrl":"10.32607/actanaturae.17856","url":null,"abstract":"<p><p>Developing liver disease treatments, in which fibrosis is a key pathogenetic link, still remains an urgent problem in hepatology. In the present study, the level of <i>mmp-9</i> mRNA expression and the number of FAP+, α-SMA+, CD45+ cells were analyzed at nine time points of fibrosis and cirrhosis. It was found that in the case of liver fibrosis, the choice of the optimal reference gene depended on the stage of fibrogenesis. When studying the specific stages rather than the entire process in a long-term experiment, it was shown that choosing an optimal reference gene has to be done additionally. In this case, the <i>mmp-9</i> mRNA expression level should be considered as a marker of liver fibrosis initiation and development but not as that of cirrhosis progression. In the liver, two morphologically heterogeneous populations of myofibroblasts were simultaneously identified as able to synthesize various types of immunohistochemical markers. It was found that the FAP+ cells were the main contributor to the development of portal fibrosis and the initial stages of bridging fibrosis. In the selected experimental model, fibrosis initiation and the development stages preceding parenchyma restructuring were accompanied by a low level of inflammation.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"15 2","pages":"50-58"},"PeriodicalIF":2.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10395773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9939454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}